Evidence-Based Reviews

Studies have found that 1 in 2 psychiatrists,^1-4 and 1 in 5 psychologists, clinical social workers, and other mental health professionals,⁵ will lose a patient to suicide in the course of their career. This statistic suggests that losing a patient to suicide constitutes a clear occupational hazard.^6,7 Despite this, most mental health professionals continue to view suicide loss as an aberration. Consequently, there is often a lack of preparedness for such an event when it does occur.

This 2-part article summarizes what is currently known about the unique personal and professional issues experienced by clinician-survivors (clinicians who have lost patients and/or loved ones to suicide). In Part 1, I cover:

• the impact of losing a patient to suicide
• confidentiality-related constraints on the ability to discuss and process the loss
• legal and ethical issues
• colleagues’ reactions and stigma
• the effects of a suicide loss on one’s clinical work.

Part 2 will discuss the opportunities for personal growth that can result from experiencing a suicide loss, guidelines for optimal postventions, and steps clinicians can take to help support colleagues who have lost a patient to suicide. 

A neglected topic

For psychiatrists and other mental health professionals, the loss of a patient to suicide is certainly not uncommon.^1-5 Despite this, coping with a patient’s suicide is a “neglected topic”⁸ in residency and general mental health training.

There are many published articles on clinicians experiencing suicide loss (for a comprehensive bibliography, see McIntosh⁹), and several authors^10-19 have developed suggestions, guidelines, and detailed postvention protocols to help clinicians navigate the often-complicated sequelae to such a loss. However, these resources have generally not been integrated into clinical training, and tend to be poorly disseminated. In a national survey of chief residents, Melton and Coverdale²⁰ found that only 25% of residency training programs covered topics related to postvention, and 72% of chief residents felt this topic needed more attention. Thus, despite the existence of guidelines for optimal postvention and support, clinicians are often left to cope with the consequences of this difficult loss on their own, and under less-than-optimal conditions.

A patient’s suicide typically affects clinicians on multiple levels, both personally and professionally. In this article, I highlight the range of normative responses, as well as the factors that may facilitate or inhibit subsequent healing and growth, with the hope that this knowledge may be utilized to help current and future generations of clinician-survivors obtain optimal support, and that institutions who treat potentially suicidal individuals will develop optimal postvention responses following a suicide loss. Many aspects of what this article discusses also apply to clinicians who have experienced a suicide loss in their personal or family life, as this also tends to “spill over” into one’s professional roles and identity.

Grief and other emotional effects

In many ways, clinicians’ responses after a patient’s suicide are similar to those of other survivors after the loss of a loved one to suicide.²¹ Chemtob et al² found that approximately one-half of psychiatrists who lost a patient to suicide had scores on the Impact of an Event Scale that were comparable to those of a clinical population seeking treatment after the death of a parent.

Continue to: Jordan and McIntosh have detailed...

Jordan and McIntosh²² have detailed several elements and themes that differentiate suicide loss and its associated reactions from other types of loss and grief. In general, suicide loss is considered traumatic, and is often accompanied by intense confusion and existential questioning, reflecting a negative impact on one’s core beliefs and assumptive world. The subsequent need to address the myriad of “why” questions left in its wake are often tinted with what Jordan and Baugher²³ term the “tyranny of hindsight,” and take the form of implicit guilt for “sins of omission or commission” in relation to the lost individual.

Responses to suicide loss typically include initial shock, denial and numbness, intense sadness, anxiety, anger, and intense distress. Consistent with the traumatic nature of the loss, survivors are also likely to experience posttraumatic stress disorder symptoms such as intrusive thoughts, avoidance, and dissociation. Survivors also commonly experience significant guilt and shame, and this is likely to be socially reinforced by the general stigma associated with suicide as well as the actual blaming and avoidance responses of others.^24-27

Clinicians’ unique reactions

For clinicians, there are additional components that may further complicate or exacerbate these reactions and extend their duration. First and foremost, such a loss affects clinicians on both personal and professional levels, a phenomenon that Plakun and Tillman¹³ have termed a “twin bereavement.” Thus, in addition to the personal grief and trauma reactions entailed in losing a patient to suicide, this loss is likely to impact clinicians’ professional identities, their relationships with colleagues, and their clinical work.

Clinicians’ professional identities are often predicated on generally shared assumptions and beliefs that, as trained professionals, they should have the power, aptitude, and competence to heal, or at least improve, the lives of patients, to reduce their distress, and to provide safety. In addition, such assumptions about clinicians’ responsibility and ability to prevent suicide are often reinforced in the clinical literature.^28,29

These assumptions are often challenged, if not shattered, when patients take their own lives. A clinician’s sense of professional responsibility, the guilt and self-blame that may accompany this, self-doubts about one’s skills and clinical competence, the fear of (and actual) blame of colleagues and family members, and the real or imagined threat of litigation may all greatly exacerbate a clinician’s distress.¹¹

Continue to: Hendin et al found...

Hendin et al³⁰ found that mental health therapists have described losing a patient as “the most profoundly disturbing event of their professional careers,” noting that one-third of these clinicians experienced severe distress that lasted at least 1 year beyond the initial loss. In a 2004 study, Ruskin et al⁴ similarly found that one-quarter of psychiatrists and psychiatric trainees noted that losing a patient had a “profound and enduring effect on them.” In her article on surviving a patient’s suicide, Rycroft³¹ describes a “professional void” following the loss of her patient, in which “the world had changed, nothing was predictable any more, and it was no longer safe to assume anything.” Additionally, many clinicians experience an “acute sense of aloneness and isolation” subsequent to the loss.³²

Many clinicians have noted that they considered leaving the field after such a loss,^33,34 and it is hypothesized that many may have done so.^35-37 Others have noted that, at least temporarily, they stopped treating patients who were potentially suicidal.^29,35

Box 1

After losing a patient to suicide, a clinician may experience grief that proceeds through specific stages (Box 1^33,38-41). Box 2^{2-4,6,16,24,29,30,33,34,40,42-45}  describes a wide range of factors that affect each clinician’s unique response to losing a patient to suicide.

Box 2

Continue to: Implications of confidentiality restrictions

Confidentiality issues, as well as advice from attorneys to limit the disclosure of information about a patient, are likely to preclude a clinician’s ability to talk freely about the patient, the therapeutic relationship, and his/her reactions to the loss, all of which are known to facilitate movement through the grief process.⁴⁶

The development of trust and the sharing of pain are just 2 factors that can make the clinical encounter an intense emotional experience for both parties. Recent trends in the psychodynamic literature acknowledge the profundity and depth of the personal impact that patients have on the clinician, an impact that is neither pathological nor an indication of poor boundaries in the therapy dyad, but instead a recognition of how all aspects of the clinician’s person, whether consciously or not, are used within the context of a therapeutic relationship. Yet when clinicians lose a patient, confidentiality restrictions often leave them wondering if and where any aspects of their experiences can be shared. Legal counsel may advise a clinician against speaking to consultants or supervisors or even surviving family members for fear that these non-privileged communications are subject to discovery should any legal proceedings ensue. Furthermore, the usual grief rituals that facilitate the healing of loss and the processing of grief (eg, gathering with others who knew the deceased, sharing feelings and memories, attending memorials) are usually denied to the clinician, and are often compounded by the reactions of one’s professional colleagues, who tend not to view the therapist’s grief as “legitimate.” Thus, clinician-survivors, despite having experienced a profound and traumatic loss, have very few places where this may be processed or even validated. As one clinician in a clinician-survivors support group stated, “I felt like I was grieving in a vacuum, that I wasn’t allowed to talk about how much my patient meant to me or how I’m feeling about it.” The isolation of grieving alone is likely to be compounded by the general lack of resources for supporting clinicians after such a loss. In contrast to the general suicide “survivor” network of support groups for family members who have experienced a suicide loss, there is an almost complete lack of supportive resources for clinicians following such a loss, and most clinicians are not aware of the resources that are available, such as the Clinician Survivor Task Force of the American Association of Suicidology (Box 3¹²).

Box 3

Continue to: Doka has described...

Doka⁴⁷ has described “disenfranchised grief” in which the bereaved person does not receive the type and quality of support accorded to other bereaved persons, and thus is likely to internalize the view that his/her grief is not legitimate, and to believe that sharing related distress is a shame-ridden liability. This clearly relates to the sense of profound isolation and distress often described by clinician-survivors.

Other legal/ethical issues

The clinician-survivor’s concern about litigation, or an actual lawsuit, is likely to produce intense anxiety. This common fear is both understandable and credible. According to Bongar,⁴⁸ the most common malpractice lawsuits filed against clinicians are those that involve a patient’s suicide. Peterson et al⁴⁹ found that 34% of surviving family members considered bringing a lawsuit against the clinician, and of these, 57% consulted a lawyer.

In addition, an institution’s concern about protecting itself from liability may compromise its ability to support the clinician or trainee who sustained the loss. As noted above, the potential prohibitions around discussing the case can compromise the grief process. Additionally, the fear of (or actual) legal reprisals against supervisors and the larger institution may engender angry and blaming responses toward the treating clinician. In a personal communication (April 2008), Quinnett described an incident in which a supervising psychologist stomped into the grieving therapist’s office unannounced and shouted, “Now look what you’ve done! You’re going to get me sued!”

Other studies^29,50,51 note that clinician-survivors fear losing their job, and that their colleagues and supervisors will be reluctant to assign new patients to them. Spiegleman and Werth¹⁷ also note that trainees grapple with additional concerns over negative evaluations, suspension or termination from clinical sites or training programs, and a potential interruption of obtaining a degree. Such supervisory and institutional reactions are likely to intensify a clinician’s sense of shame and distress, and are antithetical to postvention responses that promote optimal personal and professional growth. Such negative reactions are also likely to contribute to a clinician or trainee’s subsequent reluctance to work with suicidal individuals, or their decision to discontinue their clinical work altogether. Lastly, other ethical issues, such as contact with the patient’s family following the suicide, attending the funeral, etc., are likely to be a source of additional anxiety and distress, particularly if the clinician needs to address these issues in isolation.

Professional relationships/colleagues’ reactions

Many clinician-survivors have described reactions from colleagues and supervisors that are hurtful and unsupportive. According to Jobes and Maltsberger,⁵² “the suicide death of a patient in active treatment is commonly taken as prima facie evidence that the therapist, somehow or another, has mismanaged the case,” and thus the clinician often faces unwarranted blame and censure from colleagues and supervisors. Hendin et al³⁰ noted that many trainees found reactions by their institutions to be insensitive and unsupportive, one noting that the department’s review of the case “felt more like a tribunal or inquest.” In a personal communication (April 2008), Quinnett noted that many clinicians he interviewed following a suicide loss reported a pattern of isolation and interpersonal discomfort with their colleagues, who implicitly or explicitly expressed concerns about their competence. He described how a respected colleague received “no understanding, no support, only abuse” from her supervisors. Such responses, while perhaps surprising from mental health professionals, probably reflect the long-standing cultural attitude of social condemnation of suicide, and of those who are associated with it.

Continue to: Negative reactions from professional colleagues...

Negative reactions from professional colleagues are most likely to occur immediately after the suicide loss and/or during the course of a subsequent investigation or psychological autopsy. Castelli-Dransart et al⁵³ found that the lack of institutional support after a clinician experiences a suicide loss contributed to significantly higher stress responses for impacted clinicians, and may lead to a well-founded ambivalence about disclosure to colleagues, and consequent resistance to seeking out optimal supervision/consultation or even personal therapy that could help the clinician gain clarity on the effects of these issues. Many mental health professionals have described how, after the distressing experience of losing a patient to suicide, they moved through this process in relative isolation and loneliness, feeling abandoned by their colleagues and by their own hopes and expectations for support.

Stigmatization. In clinical settings, when a patient in treatment completes suicide, the treating clinician becomes an easy scapegoat for family members and colleagues. To the extent that mental health professionals are not immune from the effects and imposition of stigma, this might also affect their previously mentioned tendency to project judgment, overtly or covertly, onto the treating clinician.

Stigma around suicide is well documented.²⁵ In The Surgeon General’s Call to Action to Prevent Suicide,⁵⁴ former Surgeon General David Satcher specifically described stigma around suicide as one of the biggest barriers to prevention. Studies have shown that individuals bereaved by suicide are also stigmatized, and that those who were in caregiving roles (parents, clinicians) are believed to be more psychologically disturbed, less likable, more blameworthy, and less worthy of receiving support than other bereaved individuals.^25,55-63 These judgments often mirror survivors’ self-punitive assessments, which then become exacerbated by and intertwined with both externally imposed and internalized stigma. Hence, it is not uncommon for suicide survivors to question their own right to grieve, to report low expectations of social support, and to feel compelled to deny or hide the mode of death. Feigelman et al²⁶ found that stigmatization after a suicide loss was specifically associated with ongoing grief difficulties, depression, and suicidal thinking.

In my long-term work with clinician-survivors, I’ve come to believe that in addition to stigma around suicide, there may also be stigma projected by colleagues in relation to a clinician’s perceived emotional vulnerability. A traumatized clinician potentially challenges the notion of the implicit dichotomy/power imbalance between professionals and the patients we treat: “Us”—the professional, competent, healthy, and benevolent clinicians who have the care to offer, and “Them”—our patients, being needy, pathological, looking to us for care. This “us/them” distinction may serve to bolster a clinician’s professional esteem and identity. But when one of “us” becomes one of “them”—when a professional colleague is perceived as being emotionally vulnerable—this can be threatening to the predicates of this distinction, leading to the need to put the affected clinician firmly into the “them” camp. Thus, unwarranted condemnations of the clinician-survivor’s handling of the case, and/or the pathologizing of their normative grief reactions after the suicide loss, can seem justified.

Stigma associated both with suicide and with professional vulnerability is likely to be internalized and to have a profound effect on the clinician’s decisions about disclosure, asking for support, and ultimately on one’s ability to integrate the loss. When this occurs, it is likely to lead to even more isolation, shame, and self-blame. It is not surprising that many clinicians consider leaving the profession after this type of experience.

Continue to: Effects on clinical work

A suicide loss is also likely to affect a clinician’s therapeutic work. Many authors^12,52,64-67 have found that this commonly leads therapists to question their abilities as clinicians, and to experience a sharp loss of confidence in their work with patients. The shattered beliefs and assumptions around the efficacy of the therapeutic process, a sense of guilt or self-blame, and any perceived or actual negative judgment from colleagues can dramatically compromise a clinician’s sense of competence. Hendin et al³⁰ noted that even the most experienced therapists expressed difficulty in trusting their own clinical judgment, or accurately assessing risk after a suicide loss.

In addition, the common grief and trauma-related responses to a suicide loss (including shock, numbness, sadness, anxiety, and generalized distress) are likely to result in at least some temporary disruption of a clinician’s optimal functioning. If trauma-related symptoms are more pronounced, the effect and longevity of such impairment may be exacerbated, and are likely to “impair clinical response and therapeutic judgment.”¹⁵ In addition, because such symptoms and states may be triggered by exposure to other potentially suicidal patients, they are more likely to impact clinical functioning when the clinician works with suicidal individuals. Thus, the normative responses to a suicide loss are likely to impact a clinician’s work, just as they are likely to impact the personal and occupational functioning of any survivor of suicide loss.

In clinician-survivor discussions and support groups I’ve led, participants have identified many common areas of clinical impact. Perhaps one of the most common early responses reported by clinician-survivors who continued to work with potentially suicidal individuals was to become hypervigilant in relation to any perceived suicide risk, to interpret such risk in such a way as to warrant more conservative interventions than are necessary, and to consequently minimize the patient’s own capacities for self-care.⁶⁸ Conversely, others reported a tendency to minimize or deny suicidal potential by, for example, avoiding asking patients directly about suicidal ideation, even when they later realized that such questioning was indicated.⁶⁹

Suicide loss may also lead to more subtle clinical reactions that have been observed not only with suicidal patients, but also in relation to patients who struggle with loss or grief. These include avoidant or even dissociative reactions in relation to their patient’s pain, which in turn can impact the clinician’s ability to “be fully present” or empathic in clinical encounters.^50,69 Still, other clinicians noted that they tended to project residual feelings of anger onto their current suicidal patients, or envied patients who seemed to have mastered their grief. Consistent with Maltsberger’s description of “atonement reactions,”⁴⁰ some clinicians found themselves doing more than should be expected for their patients, even losing their sense of professional boundaries in the process. Anderson⁷⁰ noted that in pushing herself beyond what she knew were her optimal clinical boundaries, she was “punishing herself” for failing to prevent her patient’s suicide because, as she realized, “doing ‘penance’ was better than feeling helpless and powerless.” And Schultz¹⁶ described how therapists may have subsequent difficulty in trusting other patients, especially if patients who completed suicide did not disclose or denied their suicidal intent.

Working toward a supportive solution

In summary, unless clinicians who lose a patient to suicide have more supportive experiences, the combination of confidentiality-related restrictions, confusion about legal/ethical repercussions, unsupportive reactions from colleagues, and unexpected impairments in clinical work are likely to lead to intensified distress, isolation, the perceived need to “hide” the impact in professional settings, and consideration of leaving the profession. However, as I will describe in Part 2 (Current Psychiatry. November 2019), losing a patient to suicide can paradoxically present opportunities for clinicians to experience profound and personal transformation, and postvention protocols can help them navigate the often-complicated sequelae to a patient’s suicide. There is also much we can do to help support a clinician colleague who has lost a patient to suicide.

Bottom Line

For mental health clinicians, losing a patient to suicide is a clear occupational hazard. After a suicide loss, clinicians often experience unique personal and professional challenges, including the impact of the loss on clinical work and professional identity, legal/ethical issues, and confidentiality-related constraints on the ability to discuss and process the loss.

Related Resources

• American Association of Suicidology Clinician Survivor Task Force. www.cliniciansurvivor.org.
• Gutin N. Helping survivors in the aftermath of suicide loss. Current Psychiatry. 2018;17(8):27-33.

Studies have found that 1 in 2 psychiatrists,^1-4 and 1 in 5 psychologists, clinical social workers, and other mental health professionals,⁵ will lose a patient to suicide in the course of their career. This statistic suggests that losing a patient to suicide constitutes a clear occupational hazard.^6,7 Despite this, most mental health professionals continue to view suicide loss as an aberration. Consequently, there is often a lack of preparedness for such an event when it does occur.

This 2-part article summarizes what is currently known about the unique personal and professional issues experienced by clinician-survivors (clinicians who have lost patients and/or loved ones to suicide). In Part 1, I cover:

• the impact of losing a patient to suicide
• confidentiality-related constraints on the ability to discuss and process the loss
• legal and ethical issues
• colleagues’ reactions and stigma
• the effects of a suicide loss on one’s clinical work.

Part 2 will discuss the opportunities for personal growth that can result from experiencing a suicide loss, guidelines for optimal postventions, and steps clinicians can take to help support colleagues who have lost a patient to suicide. 

A neglected topic

For psychiatrists and other mental health professionals, the loss of a patient to suicide is certainly not uncommon.^1-5 Despite this, coping with a patient’s suicide is a “neglected topic”⁸ in residency and general mental health training.

There are many published articles on clinicians experiencing suicide loss (for a comprehensive bibliography, see McIntosh⁹), and several authors^10-19 have developed suggestions, guidelines, and detailed postvention protocols to help clinicians navigate the often-complicated sequelae to such a loss. However, these resources have generally not been integrated into clinical training, and tend to be poorly disseminated. In a national survey of chief residents, Melton and Coverdale²⁰ found that only 25% of residency training programs covered topics related to postvention, and 72% of chief residents felt this topic needed more attention. Thus, despite the existence of guidelines for optimal postvention and support, clinicians are often left to cope with the consequences of this difficult loss on their own, and under less-than-optimal conditions.

A patient’s suicide typically affects clinicians on multiple levels, both personally and professionally. In this article, I highlight the range of normative responses, as well as the factors that may facilitate or inhibit subsequent healing and growth, with the hope that this knowledge may be utilized to help current and future generations of clinician-survivors obtain optimal support, and that institutions who treat potentially suicidal individuals will develop optimal postvention responses following a suicide loss. Many aspects of what this article discusses also apply to clinicians who have experienced a suicide loss in their personal or family life, as this also tends to “spill over” into one’s professional roles and identity.

Grief and other emotional effects

In many ways, clinicians’ responses after a patient’s suicide are similar to those of other survivors after the loss of a loved one to suicide.²¹ Chemtob et al² found that approximately one-half of psychiatrists who lost a patient to suicide had scores on the Impact of an Event Scale that were comparable to those of a clinical population seeking treatment after the death of a parent.

Continue to: Jordan and McIntosh have detailed...

Jordan and McIntosh²² have detailed several elements and themes that differentiate suicide loss and its associated reactions from other types of loss and grief. In general, suicide loss is considered traumatic, and is often accompanied by intense confusion and existential questioning, reflecting a negative impact on one’s core beliefs and assumptive world. The subsequent need to address the myriad of “why” questions left in its wake are often tinted with what Jordan and Baugher²³ term the “tyranny of hindsight,” and take the form of implicit guilt for “sins of omission or commission” in relation to the lost individual.

Responses to suicide loss typically include initial shock, denial and numbness, intense sadness, anxiety, anger, and intense distress. Consistent with the traumatic nature of the loss, survivors are also likely to experience posttraumatic stress disorder symptoms such as intrusive thoughts, avoidance, and dissociation. Survivors also commonly experience significant guilt and shame, and this is likely to be socially reinforced by the general stigma associated with suicide as well as the actual blaming and avoidance responses of others.^24-27

Clinicians’ unique reactions

For clinicians, there are additional components that may further complicate or exacerbate these reactions and extend their duration. First and foremost, such a loss affects clinicians on both personal and professional levels, a phenomenon that Plakun and Tillman¹³ have termed a “twin bereavement.” Thus, in addition to the personal grief and trauma reactions entailed in losing a patient to suicide, this loss is likely to impact clinicians’ professional identities, their relationships with colleagues, and their clinical work.

Clinicians’ professional identities are often predicated on generally shared assumptions and beliefs that, as trained professionals, they should have the power, aptitude, and competence to heal, or at least improve, the lives of patients, to reduce their distress, and to provide safety. In addition, such assumptions about clinicians’ responsibility and ability to prevent suicide are often reinforced in the clinical literature.^28,29

These assumptions are often challenged, if not shattered, when patients take their own lives. A clinician’s sense of professional responsibility, the guilt and self-blame that may accompany this, self-doubts about one’s skills and clinical competence, the fear of (and actual) blame of colleagues and family members, and the real or imagined threat of litigation may all greatly exacerbate a clinician’s distress.¹¹

Continue to: Hendin et al found...

Hendin et al³⁰ found that mental health therapists have described losing a patient as “the most profoundly disturbing event of their professional careers,” noting that one-third of these clinicians experienced severe distress that lasted at least 1 year beyond the initial loss. In a 2004 study, Ruskin et al⁴ similarly found that one-quarter of psychiatrists and psychiatric trainees noted that losing a patient had a “profound and enduring effect on them.” In her article on surviving a patient’s suicide, Rycroft³¹ describes a “professional void” following the loss of her patient, in which “the world had changed, nothing was predictable any more, and it was no longer safe to assume anything.” Additionally, many clinicians experience an “acute sense of aloneness and isolation” subsequent to the loss.³²

Many clinicians have noted that they considered leaving the field after such a loss,^33,34 and it is hypothesized that many may have done so.^35-37 Others have noted that, at least temporarily, they stopped treating patients who were potentially suicidal.^29,35

Box 1

After losing a patient to suicide, a clinician may experience grief that proceeds through specific stages (Box 1^33,38-41). Box 2^{2-4,6,16,24,29,30,33,34,40,42-45}  describes a wide range of factors that affect each clinician’s unique response to losing a patient to suicide.

Box 2

Continue to: Implications of confidentiality restrictions

Confidentiality issues, as well as advice from attorneys to limit the disclosure of information about a patient, are likely to preclude a clinician’s ability to talk freely about the patient, the therapeutic relationship, and his/her reactions to the loss, all of which are known to facilitate movement through the grief process.⁴⁶

The development of trust and the sharing of pain are just 2 factors that can make the clinical encounter an intense emotional experience for both parties. Recent trends in the psychodynamic literature acknowledge the profundity and depth of the personal impact that patients have on the clinician, an impact that is neither pathological nor an indication of poor boundaries in the therapy dyad, but instead a recognition of how all aspects of the clinician’s person, whether consciously or not, are used within the context of a therapeutic relationship. Yet when clinicians lose a patient, confidentiality restrictions often leave them wondering if and where any aspects of their experiences can be shared. Legal counsel may advise a clinician against speaking to consultants or supervisors or even surviving family members for fear that these non-privileged communications are subject to discovery should any legal proceedings ensue. Furthermore, the usual grief rituals that facilitate the healing of loss and the processing of grief (eg, gathering with others who knew the deceased, sharing feelings and memories, attending memorials) are usually denied to the clinician, and are often compounded by the reactions of one’s professional colleagues, who tend not to view the therapist’s grief as “legitimate.” Thus, clinician-survivors, despite having experienced a profound and traumatic loss, have very few places where this may be processed or even validated. As one clinician in a clinician-survivors support group stated, “I felt like I was grieving in a vacuum, that I wasn’t allowed to talk about how much my patient meant to me or how I’m feeling about it.” The isolation of grieving alone is likely to be compounded by the general lack of resources for supporting clinicians after such a loss. In contrast to the general suicide “survivor” network of support groups for family members who have experienced a suicide loss, there is an almost complete lack of supportive resources for clinicians following such a loss, and most clinicians are not aware of the resources that are available, such as the Clinician Survivor Task Force of the American Association of Suicidology (Box 3¹²).

Box 3

Continue to: Doka has described...

Doka⁴⁷ has described “disenfranchised grief” in which the bereaved person does not receive the type and quality of support accorded to other bereaved persons, and thus is likely to internalize the view that his/her grief is not legitimate, and to believe that sharing related distress is a shame-ridden liability. This clearly relates to the sense of profound isolation and distress often described by clinician-survivors.

Other legal/ethical issues

The clinician-survivor’s concern about litigation, or an actual lawsuit, is likely to produce intense anxiety. This common fear is both understandable and credible. According to Bongar,⁴⁸ the most common malpractice lawsuits filed against clinicians are those that involve a patient’s suicide. Peterson et al⁴⁹ found that 34% of surviving family members considered bringing a lawsuit against the clinician, and of these, 57% consulted a lawyer.

In addition, an institution’s concern about protecting itself from liability may compromise its ability to support the clinician or trainee who sustained the loss. As noted above, the potential prohibitions around discussing the case can compromise the grief process. Additionally, the fear of (or actual) legal reprisals against supervisors and the larger institution may engender angry and blaming responses toward the treating clinician. In a personal communication (April 2008), Quinnett described an incident in which a supervising psychologist stomped into the grieving therapist’s office unannounced and shouted, “Now look what you’ve done! You’re going to get me sued!”

Other studies^29,50,51 note that clinician-survivors fear losing their job, and that their colleagues and supervisors will be reluctant to assign new patients to them. Spiegleman and Werth¹⁷ also note that trainees grapple with additional concerns over negative evaluations, suspension or termination from clinical sites or training programs, and a potential interruption of obtaining a degree. Such supervisory and institutional reactions are likely to intensify a clinician’s sense of shame and distress, and are antithetical to postvention responses that promote optimal personal and professional growth. Such negative reactions are also likely to contribute to a clinician or trainee’s subsequent reluctance to work with suicidal individuals, or their decision to discontinue their clinical work altogether. Lastly, other ethical issues, such as contact with the patient’s family following the suicide, attending the funeral, etc., are likely to be a source of additional anxiety and distress, particularly if the clinician needs to address these issues in isolation.

Professional relationships/colleagues’ reactions

Many clinician-survivors have described reactions from colleagues and supervisors that are hurtful and unsupportive. According to Jobes and Maltsberger,⁵² “the suicide death of a patient in active treatment is commonly taken as prima facie evidence that the therapist, somehow or another, has mismanaged the case,” and thus the clinician often faces unwarranted blame and censure from colleagues and supervisors. Hendin et al³⁰ noted that many trainees found reactions by their institutions to be insensitive and unsupportive, one noting that the department’s review of the case “felt more like a tribunal or inquest.” In a personal communication (April 2008), Quinnett noted that many clinicians he interviewed following a suicide loss reported a pattern of isolation and interpersonal discomfort with their colleagues, who implicitly or explicitly expressed concerns about their competence. He described how a respected colleague received “no understanding, no support, only abuse” from her supervisors. Such responses, while perhaps surprising from mental health professionals, probably reflect the long-standing cultural attitude of social condemnation of suicide, and of those who are associated with it.

Continue to: Negative reactions from professional colleagues...

Negative reactions from professional colleagues are most likely to occur immediately after the suicide loss and/or during the course of a subsequent investigation or psychological autopsy. Castelli-Dransart et al⁵³ found that the lack of institutional support after a clinician experiences a suicide loss contributed to significantly higher stress responses for impacted clinicians, and may lead to a well-founded ambivalence about disclosure to colleagues, and consequent resistance to seeking out optimal supervision/consultation or even personal therapy that could help the clinician gain clarity on the effects of these issues. Many mental health professionals have described how, after the distressing experience of losing a patient to suicide, they moved through this process in relative isolation and loneliness, feeling abandoned by their colleagues and by their own hopes and expectations for support.

Stigmatization. In clinical settings, when a patient in treatment completes suicide, the treating clinician becomes an easy scapegoat for family members and colleagues. To the extent that mental health professionals are not immune from the effects and imposition of stigma, this might also affect their previously mentioned tendency to project judgment, overtly or covertly, onto the treating clinician.

Stigma around suicide is well documented.²⁵ In The Surgeon General’s Call to Action to Prevent Suicide,⁵⁴ former Surgeon General David Satcher specifically described stigma around suicide as one of the biggest barriers to prevention. Studies have shown that individuals bereaved by suicide are also stigmatized, and that those who were in caregiving roles (parents, clinicians) are believed to be more psychologically disturbed, less likable, more blameworthy, and less worthy of receiving support than other bereaved individuals.^25,55-63 These judgments often mirror survivors’ self-punitive assessments, which then become exacerbated by and intertwined with both externally imposed and internalized stigma. Hence, it is not uncommon for suicide survivors to question their own right to grieve, to report low expectations of social support, and to feel compelled to deny or hide the mode of death. Feigelman et al²⁶ found that stigmatization after a suicide loss was specifically associated with ongoing grief difficulties, depression, and suicidal thinking.

In my long-term work with clinician-survivors, I’ve come to believe that in addition to stigma around suicide, there may also be stigma projected by colleagues in relation to a clinician’s perceived emotional vulnerability. A traumatized clinician potentially challenges the notion of the implicit dichotomy/power imbalance between professionals and the patients we treat: “Us”—the professional, competent, healthy, and benevolent clinicians who have the care to offer, and “Them”—our patients, being needy, pathological, looking to us for care. This “us/them” distinction may serve to bolster a clinician’s professional esteem and identity. But when one of “us” becomes one of “them”—when a professional colleague is perceived as being emotionally vulnerable—this can be threatening to the predicates of this distinction, leading to the need to put the affected clinician firmly into the “them” camp. Thus, unwarranted condemnations of the clinician-survivor’s handling of the case, and/or the pathologizing of their normative grief reactions after the suicide loss, can seem justified.

Stigma associated both with suicide and with professional vulnerability is likely to be internalized and to have a profound effect on the clinician’s decisions about disclosure, asking for support, and ultimately on one’s ability to integrate the loss. When this occurs, it is likely to lead to even more isolation, shame, and self-blame. It is not surprising that many clinicians consider leaving the profession after this type of experience.

Continue to: Effects on clinical work

A suicide loss is also likely to affect a clinician’s therapeutic work. Many authors^12,52,64-67 have found that this commonly leads therapists to question their abilities as clinicians, and to experience a sharp loss of confidence in their work with patients. The shattered beliefs and assumptions around the efficacy of the therapeutic process, a sense of guilt or self-blame, and any perceived or actual negative judgment from colleagues can dramatically compromise a clinician’s sense of competence. Hendin et al³⁰ noted that even the most experienced therapists expressed difficulty in trusting their own clinical judgment, or accurately assessing risk after a suicide loss.

In addition, the common grief and trauma-related responses to a suicide loss (including shock, numbness, sadness, anxiety, and generalized distress) are likely to result in at least some temporary disruption of a clinician’s optimal functioning. If trauma-related symptoms are more pronounced, the effect and longevity of such impairment may be exacerbated, and are likely to “impair clinical response and therapeutic judgment.”¹⁵ In addition, because such symptoms and states may be triggered by exposure to other potentially suicidal patients, they are more likely to impact clinical functioning when the clinician works with suicidal individuals. Thus, the normative responses to a suicide loss are likely to impact a clinician’s work, just as they are likely to impact the personal and occupational functioning of any survivor of suicide loss.

In clinician-survivor discussions and support groups I’ve led, participants have identified many common areas of clinical impact. Perhaps one of the most common early responses reported by clinician-survivors who continued to work with potentially suicidal individuals was to become hypervigilant in relation to any perceived suicide risk, to interpret such risk in such a way as to warrant more conservative interventions than are necessary, and to consequently minimize the patient’s own capacities for self-care.⁶⁸ Conversely, others reported a tendency to minimize or deny suicidal potential by, for example, avoiding asking patients directly about suicidal ideation, even when they later realized that such questioning was indicated.⁶⁹

Suicide loss may also lead to more subtle clinical reactions that have been observed not only with suicidal patients, but also in relation to patients who struggle with loss or grief. These include avoidant or even dissociative reactions in relation to their patient’s pain, which in turn can impact the clinician’s ability to “be fully present” or empathic in clinical encounters.^50,69 Still, other clinicians noted that they tended to project residual feelings of anger onto their current suicidal patients, or envied patients who seemed to have mastered their grief. Consistent with Maltsberger’s description of “atonement reactions,”⁴⁰ some clinicians found themselves doing more than should be expected for their patients, even losing their sense of professional boundaries in the process. Anderson⁷⁰ noted that in pushing herself beyond what she knew were her optimal clinical boundaries, she was “punishing herself” for failing to prevent her patient’s suicide because, as she realized, “doing ‘penance’ was better than feeling helpless and powerless.” And Schultz¹⁶ described how therapists may have subsequent difficulty in trusting other patients, especially if patients who completed suicide did not disclose or denied their suicidal intent.

Working toward a supportive solution

In summary, unless clinicians who lose a patient to suicide have more supportive experiences, the combination of confidentiality-related restrictions, confusion about legal/ethical repercussions, unsupportive reactions from colleagues, and unexpected impairments in clinical work are likely to lead to intensified distress, isolation, the perceived need to “hide” the impact in professional settings, and consideration of leaving the profession. However, as I will describe in Part 2 (Current Psychiatry. November 2019), losing a patient to suicide can paradoxically present opportunities for clinicians to experience profound and personal transformation, and postvention protocols can help them navigate the often-complicated sequelae to a patient’s suicide. There is also much we can do to help support a clinician colleague who has lost a patient to suicide.

Bottom Line

For mental health clinicians, losing a patient to suicide is a clear occupational hazard. After a suicide loss, clinicians often experience unique personal and professional challenges, including the impact of the loss on clinical work and professional identity, legal/ethical issues, and confidentiality-related constraints on the ability to discuss and process the loss.

Related Resources

• American Association of Suicidology Clinician Survivor Task Force. www.cliniciansurvivor.org.
• Gutin N. Helping survivors in the aftermath of suicide loss. Current Psychiatry. 2018;17(8):27-33.

Studies have found that 1 in 2 psychiatrists,^1-4 and 1 in 5 psychologists, clinical social workers, and other mental health professionals,⁵ will lose a patient to suicide in the course of their career. This statistic suggests that losing a patient to suicide constitutes a clear occupational hazard.^6,7 Despite this, most mental health professionals continue to view suicide loss as an aberration. Consequently, there is often a lack of preparedness for such an event when it does occur.

This 2-part article summarizes what is currently known about the unique personal and professional issues experienced by clinician-survivors (clinicians who have lost patients and/or loved ones to suicide). In Part 1, I cover:

• the impact of losing a patient to suicide
• confidentiality-related constraints on the ability to discuss and process the loss
• legal and ethical issues
• colleagues’ reactions and stigma
• the effects of a suicide loss on one’s clinical work.

Part 2 will discuss the opportunities for personal growth that can result from experiencing a suicide loss, guidelines for optimal postventions, and steps clinicians can take to help support colleagues who have lost a patient to suicide. 

A neglected topic

For psychiatrists and other mental health professionals, the loss of a patient to suicide is certainly not uncommon.^1-5 Despite this, coping with a patient’s suicide is a “neglected topic”⁸ in residency and general mental health training.

There are many published articles on clinicians experiencing suicide loss (for a comprehensive bibliography, see McIntosh⁹), and several authors^10-19 have developed suggestions, guidelines, and detailed postvention protocols to help clinicians navigate the often-complicated sequelae to such a loss. However, these resources have generally not been integrated into clinical training, and tend to be poorly disseminated. In a national survey of chief residents, Melton and Coverdale²⁰ found that only 25% of residency training programs covered topics related to postvention, and 72% of chief residents felt this topic needed more attention. Thus, despite the existence of guidelines for optimal postvention and support, clinicians are often left to cope with the consequences of this difficult loss on their own, and under less-than-optimal conditions.

A patient’s suicide typically affects clinicians on multiple levels, both personally and professionally. In this article, I highlight the range of normative responses, as well as the factors that may facilitate or inhibit subsequent healing and growth, with the hope that this knowledge may be utilized to help current and future generations of clinician-survivors obtain optimal support, and that institutions who treat potentially suicidal individuals will develop optimal postvention responses following a suicide loss. Many aspects of what this article discusses also apply to clinicians who have experienced a suicide loss in their personal or family life, as this also tends to “spill over” into one’s professional roles and identity.

Grief and other emotional effects

In many ways, clinicians’ responses after a patient’s suicide are similar to those of other survivors after the loss of a loved one to suicide.²¹ Chemtob et al² found that approximately one-half of psychiatrists who lost a patient to suicide had scores on the Impact of an Event Scale that were comparable to those of a clinical population seeking treatment after the death of a parent.

Continue to: Jordan and McIntosh have detailed...

Jordan and McIntosh²² have detailed several elements and themes that differentiate suicide loss and its associated reactions from other types of loss and grief. In general, suicide loss is considered traumatic, and is often accompanied by intense confusion and existential questioning, reflecting a negative impact on one’s core beliefs and assumptive world. The subsequent need to address the myriad of “why” questions left in its wake are often tinted with what Jordan and Baugher²³ term the “tyranny of hindsight,” and take the form of implicit guilt for “sins of omission or commission” in relation to the lost individual.

Responses to suicide loss typically include initial shock, denial and numbness, intense sadness, anxiety, anger, and intense distress. Consistent with the traumatic nature of the loss, survivors are also likely to experience posttraumatic stress disorder symptoms such as intrusive thoughts, avoidance, and dissociation. Survivors also commonly experience significant guilt and shame, and this is likely to be socially reinforced by the general stigma associated with suicide as well as the actual blaming and avoidance responses of others.^24-27

Clinicians’ unique reactions

For clinicians, there are additional components that may further complicate or exacerbate these reactions and extend their duration. First and foremost, such a loss affects clinicians on both personal and professional levels, a phenomenon that Plakun and Tillman¹³ have termed a “twin bereavement.” Thus, in addition to the personal grief and trauma reactions entailed in losing a patient to suicide, this loss is likely to impact clinicians’ professional identities, their relationships with colleagues, and their clinical work.

Clinicians’ professional identities are often predicated on generally shared assumptions and beliefs that, as trained professionals, they should have the power, aptitude, and competence to heal, or at least improve, the lives of patients, to reduce their distress, and to provide safety. In addition, such assumptions about clinicians’ responsibility and ability to prevent suicide are often reinforced in the clinical literature.^28,29

These assumptions are often challenged, if not shattered, when patients take their own lives. A clinician’s sense of professional responsibility, the guilt and self-blame that may accompany this, self-doubts about one’s skills and clinical competence, the fear of (and actual) blame of colleagues and family members, and the real or imagined threat of litigation may all greatly exacerbate a clinician’s distress.¹¹

Continue to: Hendin et al found...

Hendin et al³⁰ found that mental health therapists have described losing a patient as “the most profoundly disturbing event of their professional careers,” noting that one-third of these clinicians experienced severe distress that lasted at least 1 year beyond the initial loss. In a 2004 study, Ruskin et al⁴ similarly found that one-quarter of psychiatrists and psychiatric trainees noted that losing a patient had a “profound and enduring effect on them.” In her article on surviving a patient’s suicide, Rycroft³¹ describes a “professional void” following the loss of her patient, in which “the world had changed, nothing was predictable any more, and it was no longer safe to assume anything.” Additionally, many clinicians experience an “acute sense of aloneness and isolation” subsequent to the loss.³²

Many clinicians have noted that they considered leaving the field after such a loss,^33,34 and it is hypothesized that many may have done so.^35-37 Others have noted that, at least temporarily, they stopped treating patients who were potentially suicidal.^29,35

Box 1

After losing a patient to suicide, a clinician may experience grief that proceeds through specific stages (Box 1^33,38-41). Box 2^{2-4,6,16,24,29,30,33,34,40,42-45}  describes a wide range of factors that affect each clinician’s unique response to losing a patient to suicide.

Box 2

Continue to: Implications of confidentiality restrictions

Confidentiality issues, as well as advice from attorneys to limit the disclosure of information about a patient, are likely to preclude a clinician’s ability to talk freely about the patient, the therapeutic relationship, and his/her reactions to the loss, all of which are known to facilitate movement through the grief process.⁴⁶

The development of trust and the sharing of pain are just 2 factors that can make the clinical encounter an intense emotional experience for both parties. Recent trends in the psychodynamic literature acknowledge the profundity and depth of the personal impact that patients have on the clinician, an impact that is neither pathological nor an indication of poor boundaries in the therapy dyad, but instead a recognition of how all aspects of the clinician’s person, whether consciously or not, are used within the context of a therapeutic relationship. Yet when clinicians lose a patient, confidentiality restrictions often leave them wondering if and where any aspects of their experiences can be shared. Legal counsel may advise a clinician against speaking to consultants or supervisors or even surviving family members for fear that these non-privileged communications are subject to discovery should any legal proceedings ensue. Furthermore, the usual grief rituals that facilitate the healing of loss and the processing of grief (eg, gathering with others who knew the deceased, sharing feelings and memories, attending memorials) are usually denied to the clinician, and are often compounded by the reactions of one’s professional colleagues, who tend not to view the therapist’s grief as “legitimate.” Thus, clinician-survivors, despite having experienced a profound and traumatic loss, have very few places where this may be processed or even validated. As one clinician in a clinician-survivors support group stated, “I felt like I was grieving in a vacuum, that I wasn’t allowed to talk about how much my patient meant to me or how I’m feeling about it.” The isolation of grieving alone is likely to be compounded by the general lack of resources for supporting clinicians after such a loss. In contrast to the general suicide “survivor” network of support groups for family members who have experienced a suicide loss, there is an almost complete lack of supportive resources for clinicians following such a loss, and most clinicians are not aware of the resources that are available, such as the Clinician Survivor Task Force of the American Association of Suicidology (Box 3¹²).

Box 3

Continue to: Doka has described...

Doka⁴⁷ has described “disenfranchised grief” in which the bereaved person does not receive the type and quality of support accorded to other bereaved persons, and thus is likely to internalize the view that his/her grief is not legitimate, and to believe that sharing related distress is a shame-ridden liability. This clearly relates to the sense of profound isolation and distress often described by clinician-survivors.

Other legal/ethical issues

The clinician-survivor’s concern about litigation, or an actual lawsuit, is likely to produce intense anxiety. This common fear is both understandable and credible. According to Bongar,⁴⁸ the most common malpractice lawsuits filed against clinicians are those that involve a patient’s suicide. Peterson et al⁴⁹ found that 34% of surviving family members considered bringing a lawsuit against the clinician, and of these, 57% consulted a lawyer.

In addition, an institution’s concern about protecting itself from liability may compromise its ability to support the clinician or trainee who sustained the loss. As noted above, the potential prohibitions around discussing the case can compromise the grief process. Additionally, the fear of (or actual) legal reprisals against supervisors and the larger institution may engender angry and blaming responses toward the treating clinician. In a personal communication (April 2008), Quinnett described an incident in which a supervising psychologist stomped into the grieving therapist’s office unannounced and shouted, “Now look what you’ve done! You’re going to get me sued!”

Other studies^29,50,51 note that clinician-survivors fear losing their job, and that their colleagues and supervisors will be reluctant to assign new patients to them. Spiegleman and Werth¹⁷ also note that trainees grapple with additional concerns over negative evaluations, suspension or termination from clinical sites or training programs, and a potential interruption of obtaining a degree. Such supervisory and institutional reactions are likely to intensify a clinician’s sense of shame and distress, and are antithetical to postvention responses that promote optimal personal and professional growth. Such negative reactions are also likely to contribute to a clinician or trainee’s subsequent reluctance to work with suicidal individuals, or their decision to discontinue their clinical work altogether. Lastly, other ethical issues, such as contact with the patient’s family following the suicide, attending the funeral, etc., are likely to be a source of additional anxiety and distress, particularly if the clinician needs to address these issues in isolation.

Professional relationships/colleagues’ reactions

Many clinician-survivors have described reactions from colleagues and supervisors that are hurtful and unsupportive. According to Jobes and Maltsberger,⁵² “the suicide death of a patient in active treatment is commonly taken as prima facie evidence that the therapist, somehow or another, has mismanaged the case,” and thus the clinician often faces unwarranted blame and censure from colleagues and supervisors. Hendin et al³⁰ noted that many trainees found reactions by their institutions to be insensitive and unsupportive, one noting that the department’s review of the case “felt more like a tribunal or inquest.” In a personal communication (April 2008), Quinnett noted that many clinicians he interviewed following a suicide loss reported a pattern of isolation and interpersonal discomfort with their colleagues, who implicitly or explicitly expressed concerns about their competence. He described how a respected colleague received “no understanding, no support, only abuse” from her supervisors. Such responses, while perhaps surprising from mental health professionals, probably reflect the long-standing cultural attitude of social condemnation of suicide, and of those who are associated with it.

Continue to: Negative reactions from professional colleagues...

Negative reactions from professional colleagues are most likely to occur immediately after the suicide loss and/or during the course of a subsequent investigation or psychological autopsy. Castelli-Dransart et al⁵³ found that the lack of institutional support after a clinician experiences a suicide loss contributed to significantly higher stress responses for impacted clinicians, and may lead to a well-founded ambivalence about disclosure to colleagues, and consequent resistance to seeking out optimal supervision/consultation or even personal therapy that could help the clinician gain clarity on the effects of these issues. Many mental health professionals have described how, after the distressing experience of losing a patient to suicide, they moved through this process in relative isolation and loneliness, feeling abandoned by their colleagues and by their own hopes and expectations for support.

Stigmatization. In clinical settings, when a patient in treatment completes suicide, the treating clinician becomes an easy scapegoat for family members and colleagues. To the extent that mental health professionals are not immune from the effects and imposition of stigma, this might also affect their previously mentioned tendency to project judgment, overtly or covertly, onto the treating clinician.

Stigma around suicide is well documented.²⁵ In The Surgeon General’s Call to Action to Prevent Suicide,⁵⁴ former Surgeon General David Satcher specifically described stigma around suicide as one of the biggest barriers to prevention. Studies have shown that individuals bereaved by suicide are also stigmatized, and that those who were in caregiving roles (parents, clinicians) are believed to be more psychologically disturbed, less likable, more blameworthy, and less worthy of receiving support than other bereaved individuals.^25,55-63 These judgments often mirror survivors’ self-punitive assessments, which then become exacerbated by and intertwined with both externally imposed and internalized stigma. Hence, it is not uncommon for suicide survivors to question their own right to grieve, to report low expectations of social support, and to feel compelled to deny or hide the mode of death. Feigelman et al²⁶ found that stigmatization after a suicide loss was specifically associated with ongoing grief difficulties, depression, and suicidal thinking.

In my long-term work with clinician-survivors, I’ve come to believe that in addition to stigma around suicide, there may also be stigma projected by colleagues in relation to a clinician’s perceived emotional vulnerability. A traumatized clinician potentially challenges the notion of the implicit dichotomy/power imbalance between professionals and the patients we treat: “Us”—the professional, competent, healthy, and benevolent clinicians who have the care to offer, and “Them”—our patients, being needy, pathological, looking to us for care. This “us/them” distinction may serve to bolster a clinician’s professional esteem and identity. But when one of “us” becomes one of “them”—when a professional colleague is perceived as being emotionally vulnerable—this can be threatening to the predicates of this distinction, leading to the need to put the affected clinician firmly into the “them” camp. Thus, unwarranted condemnations of the clinician-survivor’s handling of the case, and/or the pathologizing of their normative grief reactions after the suicide loss, can seem justified.

Stigma associated both with suicide and with professional vulnerability is likely to be internalized and to have a profound effect on the clinician’s decisions about disclosure, asking for support, and ultimately on one’s ability to integrate the loss. When this occurs, it is likely to lead to even more isolation, shame, and self-blame. It is not surprising that many clinicians consider leaving the profession after this type of experience.

Continue to: Effects on clinical work

A suicide loss is also likely to affect a clinician’s therapeutic work. Many authors^12,52,64-67 have found that this commonly leads therapists to question their abilities as clinicians, and to experience a sharp loss of confidence in their work with patients. The shattered beliefs and assumptions around the efficacy of the therapeutic process, a sense of guilt or self-blame, and any perceived or actual negative judgment from colleagues can dramatically compromise a clinician’s sense of competence. Hendin et al³⁰ noted that even the most experienced therapists expressed difficulty in trusting their own clinical judgment, or accurately assessing risk after a suicide loss.

In addition, the common grief and trauma-related responses to a suicide loss (including shock, numbness, sadness, anxiety, and generalized distress) are likely to result in at least some temporary disruption of a clinician’s optimal functioning. If trauma-related symptoms are more pronounced, the effect and longevity of such impairment may be exacerbated, and are likely to “impair clinical response and therapeutic judgment.”¹⁵ In addition, because such symptoms and states may be triggered by exposure to other potentially suicidal patients, they are more likely to impact clinical functioning when the clinician works with suicidal individuals. Thus, the normative responses to a suicide loss are likely to impact a clinician’s work, just as they are likely to impact the personal and occupational functioning of any survivor of suicide loss.

In clinician-survivor discussions and support groups I’ve led, participants have identified many common areas of clinical impact. Perhaps one of the most common early responses reported by clinician-survivors who continued to work with potentially suicidal individuals was to become hypervigilant in relation to any perceived suicide risk, to interpret such risk in such a way as to warrant more conservative interventions than are necessary, and to consequently minimize the patient’s own capacities for self-care.⁶⁸ Conversely, others reported a tendency to minimize or deny suicidal potential by, for example, avoiding asking patients directly about suicidal ideation, even when they later realized that such questioning was indicated.⁶⁹

Suicide loss may also lead to more subtle clinical reactions that have been observed not only with suicidal patients, but also in relation to patients who struggle with loss or grief. These include avoidant or even dissociative reactions in relation to their patient’s pain, which in turn can impact the clinician’s ability to “be fully present” or empathic in clinical encounters.^50,69 Still, other clinicians noted that they tended to project residual feelings of anger onto their current suicidal patients, or envied patients who seemed to have mastered their grief. Consistent with Maltsberger’s description of “atonement reactions,”⁴⁰ some clinicians found themselves doing more than should be expected for their patients, even losing their sense of professional boundaries in the process. Anderson⁷⁰ noted that in pushing herself beyond what she knew were her optimal clinical boundaries, she was “punishing herself” for failing to prevent her patient’s suicide because, as she realized, “doing ‘penance’ was better than feeling helpless and powerless.” And Schultz¹⁶ described how therapists may have subsequent difficulty in trusting other patients, especially if patients who completed suicide did not disclose or denied their suicidal intent.

Working toward a supportive solution

In summary, unless clinicians who lose a patient to suicide have more supportive experiences, the combination of confidentiality-related restrictions, confusion about legal/ethical repercussions, unsupportive reactions from colleagues, and unexpected impairments in clinical work are likely to lead to intensified distress, isolation, the perceived need to “hide” the impact in professional settings, and consideration of leaving the profession. However, as I will describe in Part 2 (Current Psychiatry. November 2019), losing a patient to suicide can paradoxically present opportunities for clinicians to experience profound and personal transformation, and postvention protocols can help them navigate the often-complicated sequelae to a patient’s suicide. There is also much we can do to help support a clinician colleague who has lost a patient to suicide.

Bottom Line

For mental health clinicians, losing a patient to suicide is a clear occupational hazard. After a suicide loss, clinicians often experience unique personal and professional challenges, including the impact of the loss on clinical work and professional identity, legal/ethical issues, and confidentiality-related constraints on the ability to discuss and process the loss.

Related Resources

• American Association of Suicidology Clinician Survivor Task Force. www.cliniciansurvivor.org.
• Gutin N. Helping survivors in the aftermath of suicide loss. Current Psychiatry. 2018;17(8):27-33.

Ms. B, age 31, is brought to the emergency department (ED) via ambulance after emergency medical technicians used naloxone nasal spray to revive her following an overdose on heroin. She reports daily IV heroin use for the last 4 years as well as frequent use of other illicit substances, including marijuana and alprazolam, for which she does not have a prescription. She is unemployed, estranged from her family, and does not have stable housing. She refuses to be admitted to a drug rehabilitation facility for detoxification and asks to be immediately discharged.

How can you determine if Ms. B has the capacity to make decisions regarding her care?

Decisional capacity is defined as a patient’s ability to use information about an illness and the proposed treatment options to make a choice that is congruent with one’s own values and preferences.¹ Determining whether a patient has adequate capacity to make decisions regarding their care is an inherent aspect of all clinician-patient interactions.

Published reports have focused on the challenges clinicians face when assessing decisional capacity in patients with psychiatric and cognitive disorders. However, there is little evidence about assessing decisional capacity in patients with substance use disorders (SUDs), even though increasing numbers of patients with SUDs are presenting to EDs² and being admitted as inpatients in general hospitals.³ In this article, I discuss:

• the biologic basis for impaired decision-making in patients with SUDs
• common substance use–related conditions that may impact a patient’s decisional capacity
• the clinical challenges and legal considerations clinicians face when assessing decisional capacity in patients with SUDs
• how to assess decisional capacity in such patients.

Decisional capacity vs competence

“Capacity” and “competence” are not the same. Decisional capacity, which refers to the ability to make decisions, is a clinical construct that is determined by clinicians and is generally used in the acute clinical setting. Because cognition is the main determinant of capacity, conditions or treatments that affect cognition can impair an individual’s decision-making capacity.¹ Decisional capacity is not a global concept but a decision-specific one, subject to fluctuations depending on the time and the nature of the decision at hand. Therefore, requests for determination of decisional capacity in the clinical setting should be specific to an individual decision or set of decisions.

In contrast, competence is an enduring legal determination of incapacitation, typically made by a probate judge. It refers to the ability of an individual to perform actions needed to put decisions into effect. Decisional capacity as assessed by a clinician often serves as the basis for petitions submitted for the purpose of competency adjudication by the judicial system.

A biologic basis for impaired decision-making?

Jeste and Saks⁴ suggested that addiction itself is characterized by impaired decision-making because individuals keep using a substance despite experiencing recurrent physical, psychologic, or social problems caused or worsened by the substance. Several studies suggest there may be a biologic basis for impaired decision-making in these patients, even in the absence of severe psychiatric or cognitive disorders.

Continue to: Bechara and Damasio found...

Bechara and Damasio⁵ found that the decision-making impairment seen in some patients with SUDs was similar to that observed in patients who have lesions of the ventromedial prefrontal cortex. In both groups of patients, the impaired decision-making was characterized by a preference to opt for high immediate reward despite even higher future losses.

These deficits were also observed by Grant et al.⁶ In this study, patients with SUDs displayed markedly impaired performance on the Gambling Task, which examines decisions that result in long-term losses that exceed short-term gains. However, patients with SUDs performed similarly to controls on the Wisconsin Card Sorting Test, which evaluates the ability to form abstract concepts and to shift from established response sets.

MacDonald et al⁷ used a laboratory experiment and 2 field studies to test the hypothesis that alcohol affects attitudes and intentions toward drinking and driving. Their findings support the concept that alcohol intoxication decreases cognitive capacity such that people are more likely to attend to only the most salient cues.⁷

Whether the impairment documented in such studies is a contributing factor in addiction or is a result of addiction remains uncertain. While individuals with SUDs may have some level of impairment in decision-making in general, particularly in regard to their substance use, their decisional capacity on specific clinical decisions should be assessed carefully. In a study of 300 consecutive psychiatric consultations for decisional capacity at an urban hospital, Boettger et al⁸ found that 41% were related to SUDs. Of these, 37% were found to have impaired decisional capacity.

Impaired decision-making in patients with SUDs may specifically pertain to choices related to their addiction, including⁹:

• consent for addiction treatment
• consistency in maintaining a choice of recovery
• changing values regarding treatment over time
• capacity to participate in addiction research involving the use of addictive substances.

Continue to: It is important to recognize...

It is important to recognize that this impairment may not necessarily translate into altered decisional capacity regarding other health care decisions, such as consenting to surgery or other necessary medical interventions.⁹

Substance-related disorders that affect decisional capacity

Substance-related syndromes can affect mood, reality testing, and/or cognitive function, thereby directly impacting a patient’s decisional capacity. Substance-related syndromes can be divided into 2 categories: 1) disorders resulting from the direct effects of the substance, and 2) secondary disorders resulting from/or associated with substance use.

Disorders resulting from the direct effects of the substance

Temporary/reversible incapacitation

• Acute intoxication or intoxication delirium may be the most frequent type of temporary incapacitation. It can result from toxic levels of licit or illicit substances; alcohol is likely the most frequent offending agent. Although some individuals who are intoxicated may appear to be alert, oriented, and able to engage in lengthy conversations, the majority do not possess adequate decisional capacity.¹⁰
• Withdrawal delirium, associated with longstanding alcohol, sedative-hypnotic, or barbiturate dependence, is typically prolonged, but usually resolves, either spontaneously or with treatment. Although most deliria resolve once the underlying etiology is corrected, vulnerable individuals may experience irreversible cognitive impairment and permanent decisional incapacitation.^11,12
• Severe substance-induced depressive disorders, especially if accompanied by frank psychotic symptoms or severe depressive distortions of reality, may result in decisional incapacity. Substance abuse treatment that incorporates multiple strategies, sometimes in conjunction with pharmacotherapy to manage depression, should lead to sufficient recovery and restoration of decisional capacity.
• Transient psychotic disorders such as those associated with the use of stimulants are often treatable. Patients may recover decisional capacity spontaneously or with treatment.

Permanent incapacitation

• Dementia is associated with substance use, particularly alcohol use.¹³ For a patient who develops dementia, no appreciable recovery can be expected, even with prolonged abstinence.
• Persistent amnestic disorders (eg, Korsakoff syndrome) resulting from undiagnosed or untreated severe thiamine deficiency (Wernicke’s encephalopathy). Although an isolated Korsakoff syndrome consists primarily of anterograde amnesia, these patients may experience additional cognitive impairment resulting from years of alcohol consumption or associated with other neurodegenerative processes, and therefore are sufficiently impaired and lack decisional capacity. Even in the absence of such concomitant cognitive deficits, a very severe anterograde amnestic disorder directly impacts a patient’s capacity to perform the necessary tasks required to give informed consent. The inability to consolidate information about new medical developments, treatments, and procedures, even when they are thoroughly explained by the medical team, can pose serious challenges. For example, a patient may protest to being taken to surgery because he/she does not recall signing a consent form the previous day.
• Enduring severe and treatment-refractory psychotic disorders associated with drug use, specifically stimulants, can result in permanent incapacitation similar to that seen in severe primary psychotic disorders (such as treatment-resistant schizophrenia).

Secondary disorders resulting from/or associated with substance use

• Hepatic encephalopathy may be seen in patients with advanced cirrhosis of the liver (due to hepatitis C resulting from IV drug use, and/or alcohol use). In late stages of cirrhosis, the confusional state patients experience may become severe and may no longer be reversible unless liver transplantation is available and successful. This would therefore constitute a basis for permanent decisional incapacitation.
• Human immunodeficiency virus encephalitis or dementia can result from IV drug use.

Continue to: Clinical challenges

In intensive care settings, where a patient with a SUD may be treated for acute life-threatening intoxication or severe withdrawal delirium, an assumption of decisional incapacitation often exists as a result of medical acuity and impaired mentation. In these situations, treatment usually proceeds with consent obtained from next-of-kin, a guardian, or an administrative (hospital) authority when other substitute decision makers are unavailable or unwilling. In such cases, psychiatric consultation can play a dual role in documenting the patient’s decisional capacity and also in contributing to the care of patients with SUDs.

It is critical to perform a cognitive evaluation and mental status examination in a medically compromised patient with an SUD. Unfortunately, serious cognitive disorders can often be concealed by a superficially jovial or verbally skilled patient, or by an uncooperative individual who refuses to engage in a thorough conversation with his/her clinicians. These scenarios present significant challenges and may result in missed opportunities for care or premature discharges. Negative countertransference by clinicians toward patients with SUDs may also promote poor outcomes. For difficult cases, legal and ethical consultations may help mitigate risk and guide management approaches (Box¹⁴).

Box

How to assess decisional capacity

A direct conclusion of incapacity in an individual cannot be determined solely on the knowledge of the patient having a SUD-related clinical condition. (The possible exception to this may be a patient with severe dementia.) Evidence suggests that clinicians must conduct a specific assessment to determine the severity of the psychiatric or cognitive impairment and whether it directly impacts a patient’s ability to:

• understand the decision at hand
• discuss its benefits and risks
• describe alternatives
• demonstrate an appreciation of the implications of treatment or lack thereof
• communicate a clear and consistent choice.

Continue to: While most clinicians...

While most clinicians rely on a psychi­atric interview (with or without a cognitive examination) to make these determinations, several instruments have been developed to aid these evaluations, such as the MacArthur Competence Assessment Tool for Treatment (Mac-CAT-T).¹⁵ In patients with potentially reversible incapacitating conditions, serial examinations over time, especially re-evaluation when a patient has achieved and maintained sobriety, may be necessary and helpful.

The Table offers a guide to assessing decisional capacity in a patient with an SUD.

Who should conduct the assessment?

Mental health professionals—usually psychiatrists or psychologists—are consulted when there is uncertainty about a patient’s decisional capacity, and when a more thorough mental status examination is warranted to formulate an informed opinion.¹⁶ Unfortunately, this typically occurs only if a patient refuses treatment or demands to be discharged before treatment has been completed, or there is a high level of risk to the patient or others after discharge.

In acute settings, when a patient consents to treatment, a psychiatric consultation regarding decisional capacity is rarely requested. While it is often tempting for medical or surgical teams to proceed with an intervention in a cooperative patient who willingly signs a consent form without a formal assessment of his/her decisional capacity, doing so raises challenging ethical and legal questions in the event of an adverse outcome. It is therefore prudent to strongly recommend that medical and surgical colleagues obtain a psychiatric consultation when an individual’s decisional capacity is uncertain, especially when a patient is known to have a psychiatric or neurocognitive disorder, or exhibits evidence of recent mental status changes. In cases of potentially reversible impairment (eg, delirium, psychosis, or acute anxiety), targeted interventions may help restore capacity and allow treatment to proceed.

No jurisdictions mandate that the determination of decisional capacity should be made exclusively by a mental health professional. Any treating health care professional (usually the attending physician) can make a determination of decisional capacity in scenarios where there is no overt evidence the patient has a mental or cognitive disorder and the patient is communicating clear and reasoned choices, or when a patient is profoundly impaired and no meaningful communication can take place.

Continue to: CASE CONTINUED

The emergency physician requests a psychi­atric consultation. You assess Ms. B’s decisional capacity using the Mac-CAT-T along with a standard psychiatric evaluation. Her score of 14 reflects that she is able to understand the risks associated with her opioid use, and although irritated by engaging in such a discussion, is capable of reasoning through the various medical and psychosocial aspects of her addiction, and shows moderate appreciation of the impact of her choices on her future and that of significant others. The psychiatric evaluation fails to elicit any substantial mood, anxiety, or psychotic disorders associated with/or resulting from her addiction, and her cognitive examination is within normal limits. She does not exhibit severe withdrawal and is not delirious on examination. Finally, she did not harbor thoughts of intentional harm to self or others and is not deemed imminently dangerous.

You document that in your opinion, despite Ms. B’s unfortunate choices and questionable judgment, she does have the capacity to make informed decisions regarding her care and could be released against medical advice if she so chooses, while providing her with information about available resources should she decide to seek rehabilitation in the future.

An increasingly common scenario

Decisional capacity assessment in patients with SUDs is an increasingly common reason for psychiatric consultations. Primary and secondary conditions related to substance use can affect a patient’s decisional capacity on a temporary or permanent basis. The same principles that guide the assessment of decisional capacity in patients with other psychiatric or cognitive disorders should be applied to compromised individuals with SUDs. In challenging cases, a skilled psychiatric evaluation that is supported by a thorough cognitive examination and, when required, complemented by a legal or ethical consultation, can help clinicians make safe and judicious decisions.

Bottom Line

Assessing the decisional capacity of a patient with a substance use disorder can be challenging. Primary or secondary conditions related to substance use can affect a patient’s decisional capacity on a temporary or permanent basis. A skilled psychiatric evaluation that includes a thorough cognitive examination and is complemented by legal or ethical consultation can help in making judicious decisions.

Related Resources

• Tan SY. Determining patients’ decisional capacity. Clinical Psychiatry News. https://www.mdedge.com/psychiatry/article/137939/practice-management/determining-patients-decisional-capacity. Published May 10, 2017.
• Sorrentino R. Performing capacity evaluations: What’s expected from your consult. Current Psychiatry. 2014;13(1):41-44.

Drug Brand Names

Alprazolam • Xanax
Naloxone nasal spray • Narcan

Ms. B, age 31, is brought to the emergency department (ED) via ambulance after emergency medical technicians used naloxone nasal spray to revive her following an overdose on heroin. She reports daily IV heroin use for the last 4 years as well as frequent use of other illicit substances, including marijuana and alprazolam, for which she does not have a prescription. She is unemployed, estranged from her family, and does not have stable housing. She refuses to be admitted to a drug rehabilitation facility for detoxification and asks to be immediately discharged.

How can you determine if Ms. B has the capacity to make decisions regarding her care?

Decisional capacity is defined as a patient’s ability to use information about an illness and the proposed treatment options to make a choice that is congruent with one’s own values and preferences.¹ Determining whether a patient has adequate capacity to make decisions regarding their care is an inherent aspect of all clinician-patient interactions.

Published reports have focused on the challenges clinicians face when assessing decisional capacity in patients with psychiatric and cognitive disorders. However, there is little evidence about assessing decisional capacity in patients with substance use disorders (SUDs), even though increasing numbers of patients with SUDs are presenting to EDs² and being admitted as inpatients in general hospitals.³ In this article, I discuss:

• the biologic basis for impaired decision-making in patients with SUDs
• common substance use–related conditions that may impact a patient’s decisional capacity
• the clinical challenges and legal considerations clinicians face when assessing decisional capacity in patients with SUDs
• how to assess decisional capacity in such patients.

Decisional capacity vs competence

“Capacity” and “competence” are not the same. Decisional capacity, which refers to the ability to make decisions, is a clinical construct that is determined by clinicians and is generally used in the acute clinical setting. Because cognition is the main determinant of capacity, conditions or treatments that affect cognition can impair an individual’s decision-making capacity.¹ Decisional capacity is not a global concept but a decision-specific one, subject to fluctuations depending on the time and the nature of the decision at hand. Therefore, requests for determination of decisional capacity in the clinical setting should be specific to an individual decision or set of decisions.

In contrast, competence is an enduring legal determination of incapacitation, typically made by a probate judge. It refers to the ability of an individual to perform actions needed to put decisions into effect. Decisional capacity as assessed by a clinician often serves as the basis for petitions submitted for the purpose of competency adjudication by the judicial system.

A biologic basis for impaired decision-making?

Jeste and Saks⁴ suggested that addiction itself is characterized by impaired decision-making because individuals keep using a substance despite experiencing recurrent physical, psychologic, or social problems caused or worsened by the substance. Several studies suggest there may be a biologic basis for impaired decision-making in these patients, even in the absence of severe psychiatric or cognitive disorders.

Continue to: Bechara and Damasio found...

Bechara and Damasio⁵ found that the decision-making impairment seen in some patients with SUDs was similar to that observed in patients who have lesions of the ventromedial prefrontal cortex. In both groups of patients, the impaired decision-making was characterized by a preference to opt for high immediate reward despite even higher future losses.

These deficits were also observed by Grant et al.⁶ In this study, patients with SUDs displayed markedly impaired performance on the Gambling Task, which examines decisions that result in long-term losses that exceed short-term gains. However, patients with SUDs performed similarly to controls on the Wisconsin Card Sorting Test, which evaluates the ability to form abstract concepts and to shift from established response sets.

MacDonald et al⁷ used a laboratory experiment and 2 field studies to test the hypothesis that alcohol affects attitudes and intentions toward drinking and driving. Their findings support the concept that alcohol intoxication decreases cognitive capacity such that people are more likely to attend to only the most salient cues.⁷

Whether the impairment documented in such studies is a contributing factor in addiction or is a result of addiction remains uncertain. While individuals with SUDs may have some level of impairment in decision-making in general, particularly in regard to their substance use, their decisional capacity on specific clinical decisions should be assessed carefully. In a study of 300 consecutive psychiatric consultations for decisional capacity at an urban hospital, Boettger et al⁸ found that 41% were related to SUDs. Of these, 37% were found to have impaired decisional capacity.

Impaired decision-making in patients with SUDs may specifically pertain to choices related to their addiction, including⁹:

• consent for addiction treatment
• consistency in maintaining a choice of recovery
• changing values regarding treatment over time
• capacity to participate in addiction research involving the use of addictive substances.

Continue to: It is important to recognize...

It is important to recognize that this impairment may not necessarily translate into altered decisional capacity regarding other health care decisions, such as consenting to surgery or other necessary medical interventions.⁹

Substance-related disorders that affect decisional capacity

Substance-related syndromes can affect mood, reality testing, and/or cognitive function, thereby directly impacting a patient’s decisional capacity. Substance-related syndromes can be divided into 2 categories: 1) disorders resulting from the direct effects of the substance, and 2) secondary disorders resulting from/or associated with substance use.

Disorders resulting from the direct effects of the substance

Temporary/reversible incapacitation

• Acute intoxication or intoxication delirium may be the most frequent type of temporary incapacitation. It can result from toxic levels of licit or illicit substances; alcohol is likely the most frequent offending agent. Although some individuals who are intoxicated may appear to be alert, oriented, and able to engage in lengthy conversations, the majority do not possess adequate decisional capacity.¹⁰
• Withdrawal delirium, associated with longstanding alcohol, sedative-hypnotic, or barbiturate dependence, is typically prolonged, but usually resolves, either spontaneously or with treatment. Although most deliria resolve once the underlying etiology is corrected, vulnerable individuals may experience irreversible cognitive impairment and permanent decisional incapacitation.^11,12
• Severe substance-induced depressive disorders, especially if accompanied by frank psychotic symptoms or severe depressive distortions of reality, may result in decisional incapacity. Substance abuse treatment that incorporates multiple strategies, sometimes in conjunction with pharmacotherapy to manage depression, should lead to sufficient recovery and restoration of decisional capacity.
• Transient psychotic disorders such as those associated with the use of stimulants are often treatable. Patients may recover decisional capacity spontaneously or with treatment.

Permanent incapacitation

• Dementia is associated with substance use, particularly alcohol use.¹³ For a patient who develops dementia, no appreciable recovery can be expected, even with prolonged abstinence.
• Persistent amnestic disorders (eg, Korsakoff syndrome) resulting from undiagnosed or untreated severe thiamine deficiency (Wernicke’s encephalopathy). Although an isolated Korsakoff syndrome consists primarily of anterograde amnesia, these patients may experience additional cognitive impairment resulting from years of alcohol consumption or associated with other neurodegenerative processes, and therefore are sufficiently impaired and lack decisional capacity. Even in the absence of such concomitant cognitive deficits, a very severe anterograde amnestic disorder directly impacts a patient’s capacity to perform the necessary tasks required to give informed consent. The inability to consolidate information about new medical developments, treatments, and procedures, even when they are thoroughly explained by the medical team, can pose serious challenges. For example, a patient may protest to being taken to surgery because he/she does not recall signing a consent form the previous day.
• Enduring severe and treatment-refractory psychotic disorders associated with drug use, specifically stimulants, can result in permanent incapacitation similar to that seen in severe primary psychotic disorders (such as treatment-resistant schizophrenia).

Secondary disorders resulting from/or associated with substance use

• Hepatic encephalopathy may be seen in patients with advanced cirrhosis of the liver (due to hepatitis C resulting from IV drug use, and/or alcohol use). In late stages of cirrhosis, the confusional state patients experience may become severe and may no longer be reversible unless liver transplantation is available and successful. This would therefore constitute a basis for permanent decisional incapacitation.
• Human immunodeficiency virus encephalitis or dementia can result from IV drug use.

Continue to: Clinical challenges

In intensive care settings, where a patient with a SUD may be treated for acute life-threatening intoxication or severe withdrawal delirium, an assumption of decisional incapacitation often exists as a result of medical acuity and impaired mentation. In these situations, treatment usually proceeds with consent obtained from next-of-kin, a guardian, or an administrative (hospital) authority when other substitute decision makers are unavailable or unwilling. In such cases, psychiatric consultation can play a dual role in documenting the patient’s decisional capacity and also in contributing to the care of patients with SUDs.

It is critical to perform a cognitive evaluation and mental status examination in a medically compromised patient with an SUD. Unfortunately, serious cognitive disorders can often be concealed by a superficially jovial or verbally skilled patient, or by an uncooperative individual who refuses to engage in a thorough conversation with his/her clinicians. These scenarios present significant challenges and may result in missed opportunities for care or premature discharges. Negative countertransference by clinicians toward patients with SUDs may also promote poor outcomes. For difficult cases, legal and ethical consultations may help mitigate risk and guide management approaches (Box¹⁴).

Box

How to assess decisional capacity

A direct conclusion of incapacity in an individual cannot be determined solely on the knowledge of the patient having a SUD-related clinical condition. (The possible exception to this may be a patient with severe dementia.) Evidence suggests that clinicians must conduct a specific assessment to determine the severity of the psychiatric or cognitive impairment and whether it directly impacts a patient’s ability to:

• understand the decision at hand
• discuss its benefits and risks
• describe alternatives
• demonstrate an appreciation of the implications of treatment or lack thereof
• communicate a clear and consistent choice.

Continue to: While most clinicians...

While most clinicians rely on a psychi­atric interview (with or without a cognitive examination) to make these determinations, several instruments have been developed to aid these evaluations, such as the MacArthur Competence Assessment Tool for Treatment (Mac-CAT-T).¹⁵ In patients with potentially reversible incapacitating conditions, serial examinations over time, especially re-evaluation when a patient has achieved and maintained sobriety, may be necessary and helpful.

The Table offers a guide to assessing decisional capacity in a patient with an SUD.

Who should conduct the assessment?

Mental health professionals—usually psychiatrists or psychologists—are consulted when there is uncertainty about a patient’s decisional capacity, and when a more thorough mental status examination is warranted to formulate an informed opinion.¹⁶ Unfortunately, this typically occurs only if a patient refuses treatment or demands to be discharged before treatment has been completed, or there is a high level of risk to the patient or others after discharge.

In acute settings, when a patient consents to treatment, a psychiatric consultation regarding decisional capacity is rarely requested. While it is often tempting for medical or surgical teams to proceed with an intervention in a cooperative patient who willingly signs a consent form without a formal assessment of his/her decisional capacity, doing so raises challenging ethical and legal questions in the event of an adverse outcome. It is therefore prudent to strongly recommend that medical and surgical colleagues obtain a psychiatric consultation when an individual’s decisional capacity is uncertain, especially when a patient is known to have a psychiatric or neurocognitive disorder, or exhibits evidence of recent mental status changes. In cases of potentially reversible impairment (eg, delirium, psychosis, or acute anxiety), targeted interventions may help restore capacity and allow treatment to proceed.

No jurisdictions mandate that the determination of decisional capacity should be made exclusively by a mental health professional. Any treating health care professional (usually the attending physician) can make a determination of decisional capacity in scenarios where there is no overt evidence the patient has a mental or cognitive disorder and the patient is communicating clear and reasoned choices, or when a patient is profoundly impaired and no meaningful communication can take place.

Continue to: CASE CONTINUED

The emergency physician requests a psychi­atric consultation. You assess Ms. B’s decisional capacity using the Mac-CAT-T along with a standard psychiatric evaluation. Her score of 14 reflects that she is able to understand the risks associated with her opioid use, and although irritated by engaging in such a discussion, is capable of reasoning through the various medical and psychosocial aspects of her addiction, and shows moderate appreciation of the impact of her choices on her future and that of significant others. The psychiatric evaluation fails to elicit any substantial mood, anxiety, or psychotic disorders associated with/or resulting from her addiction, and her cognitive examination is within normal limits. She does not exhibit severe withdrawal and is not delirious on examination. Finally, she did not harbor thoughts of intentional harm to self or others and is not deemed imminently dangerous.

You document that in your opinion, despite Ms. B’s unfortunate choices and questionable judgment, she does have the capacity to make informed decisions regarding her care and could be released against medical advice if she so chooses, while providing her with information about available resources should she decide to seek rehabilitation in the future.

An increasingly common scenario

Decisional capacity assessment in patients with SUDs is an increasingly common reason for psychiatric consultations. Primary and secondary conditions related to substance use can affect a patient’s decisional capacity on a temporary or permanent basis. The same principles that guide the assessment of decisional capacity in patients with other psychiatric or cognitive disorders should be applied to compromised individuals with SUDs. In challenging cases, a skilled psychiatric evaluation that is supported by a thorough cognitive examination and, when required, complemented by a legal or ethical consultation, can help clinicians make safe and judicious decisions.

Bottom Line

Assessing the decisional capacity of a patient with a substance use disorder can be challenging. Primary or secondary conditions related to substance use can affect a patient’s decisional capacity on a temporary or permanent basis. A skilled psychiatric evaluation that includes a thorough cognitive examination and is complemented by legal or ethical consultation can help in making judicious decisions.

Related Resources

• Tan SY. Determining patients’ decisional capacity. Clinical Psychiatry News. https://www.mdedge.com/psychiatry/article/137939/practice-management/determining-patients-decisional-capacity. Published May 10, 2017.
• Sorrentino R. Performing capacity evaluations: What’s expected from your consult. Current Psychiatry. 2014;13(1):41-44.

Drug Brand Names

Alprazolam • Xanax
Naloxone nasal spray • Narcan

Ms. B, age 31, is brought to the emergency department (ED) via ambulance after emergency medical technicians used naloxone nasal spray to revive her following an overdose on heroin. She reports daily IV heroin use for the last 4 years as well as frequent use of other illicit substances, including marijuana and alprazolam, for which she does not have a prescription. She is unemployed, estranged from her family, and does not have stable housing. She refuses to be admitted to a drug rehabilitation facility for detoxification and asks to be immediately discharged.

How can you determine if Ms. B has the capacity to make decisions regarding her care?

Decisional capacity is defined as a patient’s ability to use information about an illness and the proposed treatment options to make a choice that is congruent with one’s own values and preferences.¹ Determining whether a patient has adequate capacity to make decisions regarding their care is an inherent aspect of all clinician-patient interactions.

Published reports have focused on the challenges clinicians face when assessing decisional capacity in patients with psychiatric and cognitive disorders. However, there is little evidence about assessing decisional capacity in patients with substance use disorders (SUDs), even though increasing numbers of patients with SUDs are presenting to EDs² and being admitted as inpatients in general hospitals.³ In this article, I discuss:

• the biologic basis for impaired decision-making in patients with SUDs
• common substance use–related conditions that may impact a patient’s decisional capacity
• the clinical challenges and legal considerations clinicians face when assessing decisional capacity in patients with SUDs
• how to assess decisional capacity in such patients.

Decisional capacity vs competence

“Capacity” and “competence” are not the same. Decisional capacity, which refers to the ability to make decisions, is a clinical construct that is determined by clinicians and is generally used in the acute clinical setting. Because cognition is the main determinant of capacity, conditions or treatments that affect cognition can impair an individual’s decision-making capacity.¹ Decisional capacity is not a global concept but a decision-specific one, subject to fluctuations depending on the time and the nature of the decision at hand. Therefore, requests for determination of decisional capacity in the clinical setting should be specific to an individual decision or set of decisions.

In contrast, competence is an enduring legal determination of incapacitation, typically made by a probate judge. It refers to the ability of an individual to perform actions needed to put decisions into effect. Decisional capacity as assessed by a clinician often serves as the basis for petitions submitted for the purpose of competency adjudication by the judicial system.

A biologic basis for impaired decision-making?

Jeste and Saks⁴ suggested that addiction itself is characterized by impaired decision-making because individuals keep using a substance despite experiencing recurrent physical, psychologic, or social problems caused or worsened by the substance. Several studies suggest there may be a biologic basis for impaired decision-making in these patients, even in the absence of severe psychiatric or cognitive disorders.

Continue to: Bechara and Damasio found...

Bechara and Damasio⁵ found that the decision-making impairment seen in some patients with SUDs was similar to that observed in patients who have lesions of the ventromedial prefrontal cortex. In both groups of patients, the impaired decision-making was characterized by a preference to opt for high immediate reward despite even higher future losses.

These deficits were also observed by Grant et al.⁶ In this study, patients with SUDs displayed markedly impaired performance on the Gambling Task, which examines decisions that result in long-term losses that exceed short-term gains. However, patients with SUDs performed similarly to controls on the Wisconsin Card Sorting Test, which evaluates the ability to form abstract concepts and to shift from established response sets.

MacDonald et al⁷ used a laboratory experiment and 2 field studies to test the hypothesis that alcohol affects attitudes and intentions toward drinking and driving. Their findings support the concept that alcohol intoxication decreases cognitive capacity such that people are more likely to attend to only the most salient cues.⁷

Whether the impairment documented in such studies is a contributing factor in addiction or is a result of addiction remains uncertain. While individuals with SUDs may have some level of impairment in decision-making in general, particularly in regard to their substance use, their decisional capacity on specific clinical decisions should be assessed carefully. In a study of 300 consecutive psychiatric consultations for decisional capacity at an urban hospital, Boettger et al⁸ found that 41% were related to SUDs. Of these, 37% were found to have impaired decisional capacity.

Impaired decision-making in patients with SUDs may specifically pertain to choices related to their addiction, including⁹:

• consent for addiction treatment
• consistency in maintaining a choice of recovery
• changing values regarding treatment over time
• capacity to participate in addiction research involving the use of addictive substances.

Continue to: It is important to recognize...

It is important to recognize that this impairment may not necessarily translate into altered decisional capacity regarding other health care decisions, such as consenting to surgery or other necessary medical interventions.⁹

Substance-related disorders that affect decisional capacity

Substance-related syndromes can affect mood, reality testing, and/or cognitive function, thereby directly impacting a patient’s decisional capacity. Substance-related syndromes can be divided into 2 categories: 1) disorders resulting from the direct effects of the substance, and 2) secondary disorders resulting from/or associated with substance use.

Disorders resulting from the direct effects of the substance

Temporary/reversible incapacitation

• Acute intoxication or intoxication delirium may be the most frequent type of temporary incapacitation. It can result from toxic levels of licit or illicit substances; alcohol is likely the most frequent offending agent. Although some individuals who are intoxicated may appear to be alert, oriented, and able to engage in lengthy conversations, the majority do not possess adequate decisional capacity.¹⁰
• Withdrawal delirium, associated with longstanding alcohol, sedative-hypnotic, or barbiturate dependence, is typically prolonged, but usually resolves, either spontaneously or with treatment. Although most deliria resolve once the underlying etiology is corrected, vulnerable individuals may experience irreversible cognitive impairment and permanent decisional incapacitation.^11,12
• Severe substance-induced depressive disorders, especially if accompanied by frank psychotic symptoms or severe depressive distortions of reality, may result in decisional incapacity. Substance abuse treatment that incorporates multiple strategies, sometimes in conjunction with pharmacotherapy to manage depression, should lead to sufficient recovery and restoration of decisional capacity.
• Transient psychotic disorders such as those associated with the use of stimulants are often treatable. Patients may recover decisional capacity spontaneously or with treatment.

Permanent incapacitation

• Dementia is associated with substance use, particularly alcohol use.¹³ For a patient who develops dementia, no appreciable recovery can be expected, even with prolonged abstinence.
• Persistent amnestic disorders (eg, Korsakoff syndrome) resulting from undiagnosed or untreated severe thiamine deficiency (Wernicke’s encephalopathy). Although an isolated Korsakoff syndrome consists primarily of anterograde amnesia, these patients may experience additional cognitive impairment resulting from years of alcohol consumption or associated with other neurodegenerative processes, and therefore are sufficiently impaired and lack decisional capacity. Even in the absence of such concomitant cognitive deficits, a very severe anterograde amnestic disorder directly impacts a patient’s capacity to perform the necessary tasks required to give informed consent. The inability to consolidate information about new medical developments, treatments, and procedures, even when they are thoroughly explained by the medical team, can pose serious challenges. For example, a patient may protest to being taken to surgery because he/she does not recall signing a consent form the previous day.
• Enduring severe and treatment-refractory psychotic disorders associated with drug use, specifically stimulants, can result in permanent incapacitation similar to that seen in severe primary psychotic disorders (such as treatment-resistant schizophrenia).

Secondary disorders resulting from/or associated with substance use

• Hepatic encephalopathy may be seen in patients with advanced cirrhosis of the liver (due to hepatitis C resulting from IV drug use, and/or alcohol use). In late stages of cirrhosis, the confusional state patients experience may become severe and may no longer be reversible unless liver transplantation is available and successful. This would therefore constitute a basis for permanent decisional incapacitation.
• Human immunodeficiency virus encephalitis or dementia can result from IV drug use.

Continue to: Clinical challenges

In intensive care settings, where a patient with a SUD may be treated for acute life-threatening intoxication or severe withdrawal delirium, an assumption of decisional incapacitation often exists as a result of medical acuity and impaired mentation. In these situations, treatment usually proceeds with consent obtained from next-of-kin, a guardian, or an administrative (hospital) authority when other substitute decision makers are unavailable or unwilling. In such cases, psychiatric consultation can play a dual role in documenting the patient’s decisional capacity and also in contributing to the care of patients with SUDs.

It is critical to perform a cognitive evaluation and mental status examination in a medically compromised patient with an SUD. Unfortunately, serious cognitive disorders can often be concealed by a superficially jovial or verbally skilled patient, or by an uncooperative individual who refuses to engage in a thorough conversation with his/her clinicians. These scenarios present significant challenges and may result in missed opportunities for care or premature discharges. Negative countertransference by clinicians toward patients with SUDs may also promote poor outcomes. For difficult cases, legal and ethical consultations may help mitigate risk and guide management approaches (Box¹⁴).

Box

How to assess decisional capacity

A direct conclusion of incapacity in an individual cannot be determined solely on the knowledge of the patient having a SUD-related clinical condition. (The possible exception to this may be a patient with severe dementia.) Evidence suggests that clinicians must conduct a specific assessment to determine the severity of the psychiatric or cognitive impairment and whether it directly impacts a patient’s ability to:

• understand the decision at hand
• discuss its benefits and risks
• describe alternatives
• demonstrate an appreciation of the implications of treatment or lack thereof
• communicate a clear and consistent choice.

Continue to: While most clinicians...

While most clinicians rely on a psychi­atric interview (with or without a cognitive examination) to make these determinations, several instruments have been developed to aid these evaluations, such as the MacArthur Competence Assessment Tool for Treatment (Mac-CAT-T).¹⁵ In patients with potentially reversible incapacitating conditions, serial examinations over time, especially re-evaluation when a patient has achieved and maintained sobriety, may be necessary and helpful.

The Table offers a guide to assessing decisional capacity in a patient with an SUD.

Who should conduct the assessment?

Mental health professionals—usually psychiatrists or psychologists—are consulted when there is uncertainty about a patient’s decisional capacity, and when a more thorough mental status examination is warranted to formulate an informed opinion.¹⁶ Unfortunately, this typically occurs only if a patient refuses treatment or demands to be discharged before treatment has been completed, or there is a high level of risk to the patient or others after discharge.

In acute settings, when a patient consents to treatment, a psychiatric consultation regarding decisional capacity is rarely requested. While it is often tempting for medical or surgical teams to proceed with an intervention in a cooperative patient who willingly signs a consent form without a formal assessment of his/her decisional capacity, doing so raises challenging ethical and legal questions in the event of an adverse outcome. It is therefore prudent to strongly recommend that medical and surgical colleagues obtain a psychiatric consultation when an individual’s decisional capacity is uncertain, especially when a patient is known to have a psychiatric or neurocognitive disorder, or exhibits evidence of recent mental status changes. In cases of potentially reversible impairment (eg, delirium, psychosis, or acute anxiety), targeted interventions may help restore capacity and allow treatment to proceed.

No jurisdictions mandate that the determination of decisional capacity should be made exclusively by a mental health professional. Any treating health care professional (usually the attending physician) can make a determination of decisional capacity in scenarios where there is no overt evidence the patient has a mental or cognitive disorder and the patient is communicating clear and reasoned choices, or when a patient is profoundly impaired and no meaningful communication can take place.

Continue to: CASE CONTINUED

The emergency physician requests a psychi­atric consultation. You assess Ms. B’s decisional capacity using the Mac-CAT-T along with a standard psychiatric evaluation. Her score of 14 reflects that she is able to understand the risks associated with her opioid use, and although irritated by engaging in such a discussion, is capable of reasoning through the various medical and psychosocial aspects of her addiction, and shows moderate appreciation of the impact of her choices on her future and that of significant others. The psychiatric evaluation fails to elicit any substantial mood, anxiety, or psychotic disorders associated with/or resulting from her addiction, and her cognitive examination is within normal limits. She does not exhibit severe withdrawal and is not delirious on examination. Finally, she did not harbor thoughts of intentional harm to self or others and is not deemed imminently dangerous.

You document that in your opinion, despite Ms. B’s unfortunate choices and questionable judgment, she does have the capacity to make informed decisions regarding her care and could be released against medical advice if she so chooses, while providing her with information about available resources should she decide to seek rehabilitation in the future.

An increasingly common scenario

Decisional capacity assessment in patients with SUDs is an increasingly common reason for psychiatric consultations. Primary and secondary conditions related to substance use can affect a patient’s decisional capacity on a temporary or permanent basis. The same principles that guide the assessment of decisional capacity in patients with other psychiatric or cognitive disorders should be applied to compromised individuals with SUDs. In challenging cases, a skilled psychiatric evaluation that is supported by a thorough cognitive examination and, when required, complemented by a legal or ethical consultation, can help clinicians make safe and judicious decisions.

Bottom Line

Assessing the decisional capacity of a patient with a substance use disorder can be challenging. Primary or secondary conditions related to substance use can affect a patient’s decisional capacity on a temporary or permanent basis. A skilled psychiatric evaluation that includes a thorough cognitive examination and is complemented by legal or ethical consultation can help in making judicious decisions.

Related Resources

• Tan SY. Determining patients’ decisional capacity. Clinical Psychiatry News. https://www.mdedge.com/psychiatry/article/137939/practice-management/determining-patients-decisional-capacity. Published May 10, 2017.
• Sorrentino R. Performing capacity evaluations: What’s expected from your consult. Current Psychiatry. 2014;13(1):41-44.

Drug Brand Names

Alprazolam • Xanax
Naloxone nasal spray • Narcan

Psychotherapy is among the evidence-based treatment options for treating various psychiatric disorders. How we approach psychiatric disorders via psycho­therapy has been shaped by numerous theories of personality and psychopathology, including psychodynamic, behavioral, cognitive, systems, and existential-humanistic approaches. Whether used as primary treatment or in conjunction with medication, psychotherapy has played a pivotal role in shaping psychiatric disease management and treatment. Several evidence-based therapy modalities have been used throughout the years and continue to significantly improve and impact our patients’ lives. In the armamentarium of treatment modalities, therapy takes the leading role for several conditions. Here we review 4 studies from current psychotherapy literature; these studies are summarized in the Table.^1-4

1. Pompoli A, Furukawa TA, Efthimiou O, et al. Dismantling cognitive-behaviour therapy for panic disorder: a systematic review and component network meta-analysis. Psychol Med. 2018;48(12):1945-1953.

Panic disorder has a lifetime prevalence of 3.7% in the general population. Three treatment modalities recommended for patients with panic disorder are psychological therapy, pharmacologic therapy, and self-help. Among the psychological therapies, cognitive-behavioral therapy (CBT) is one of the most widely used.¹

Cognitive-behavioral therapy for panic disorder has been proven to be an efficacious and impactful treatment. For panic disorder, CBT may consist of different combinations of several therapeutic components, such as relaxation, breathing retraining, cognitive restructuring, interoceptive exposure, and/or in vivo exposure. It is therefore important, both theoretically and clinically, to examine whether specific components of CBT or their combinations are superior to others for treating panic disorder.¹

Pompoli et al¹ conducted a component network meta-analysis (NMA) of 72 studies in order to determine which CBT components were the most efficacious in treating patients with panic disorder. Component NMA is an extension of standard NMA; it is used to disentangle the treatment effects of different components included in composite interventions.¹

The aim of this study was to determine which specific component or combination of components was superior to others when treating panic disorder.¹

Study design

• Researchers reviewed 2,526 references from Medline, EMBASE, PsycINFO, and Cochrane Central and selected 72 studies that included 4,064 patients with panic disorder.¹
• The primary outcome was remission of panic disorder with or without agoraphobia in the short term (3 to 6 months). Remission was defined as achieving a score of ≤7 on the Panic Disorder Severity Scale (PDSS).¹
• Secondary outcomes included response (≥40% reduction in PDSS score from baseline) and dropout for any reason in the short term.¹

Continue to: Outcomes

Outcomes

• Using component NMA, researchers determined that interoceptive exposure and face-to-face setting (administration of therapeutic components in a face-to-face setting rather than through self-help means) led to better efficacy and acceptability. Muscle relaxation and virtual reality exposure corresponded to lower efficacy. Breathing retraining and in vivo exposure improved treatment acceptability, but had small effects on efficacy.¹
• Based on an analysis of remission rates, the most efficacious CBT incorporated cognitive restructuring and interoceptive exposure. The least efficacious CBT incorporated breathing retraining, muscle relaxation, in vivo exposure, and virtual reality exposure.¹
• Application of cognitive and behavioral therapeutic elements was superior to administration of behavioral elements alone. When administering CBT, face-to-face therapy led to better outcomes in response and remission rates. Dropout rates occurred at a lower frequency when CBT was administered face-to-face when compared with self-help groups. The placebo effect was associated with the highest dropout rate.¹

Conclusion

• Findings from this meta-analysis have high practical utility. Which CBT components are used can significantly alter CBT’s efficacy and acceptability in patients with panic disorder.¹
• The “most efficacious CBT” would include cognitive restructuring and interoceptive exposure delivered in a face-to-face setting. Breathing retraining, muscle relaxation, and virtual reality may have a minimal or even negative impact.¹
• Limitations of this meta-analysis include the high number of studies used for the data analysis, complex statistical analysis, inability to include unpublished studies, and limited relevant studies. A future implication of this study is the consideration of formal methodology based on the clinical application of efficacious CBT components when treating patients with panic disorder.¹

2. Sloan DM, Marx BP, Lee DJ, et al. A brief exposure-based treatment vs cognitive processing therapy for posttraumatic stress disorder: a randomized noninferiority clinical trial. JAMA Psychiatry. 2018;75(3):233-239.

Psychotherapy is also a useful modality for treating posttraumatic stress disorder (PTSD). Sloan et al² compared brief exposure-based treatment with cognitive processing therapy (CPT) for PTSD. 

Clinical practice guidelines for the management of PTSD and acute stress disorder recommend the use of individual, trauma-focused therapies that focus on exposure and cognitive restructuring, such as prolonged exposure, CPT, and written narrative exposure.⁵

Continue to: One type of written narrative...

One type of written narrative exposure treatment is written exposure therapy (WET), which consists of 5 sessions during which patients write about their trauma. The first session is comprised of psychoeducation about PTSD and a review of treatment reasoning, followed by 30 minutes of writing. The therapist provides feedback and instructions. Written exposure therapy requires less therapist training and less supervision than prolonged exposure or CPT. Prior studies have suggested that WET can significantly reduce PTSD symptoms in various trauma survivors.²

Although efficacious for PTSD, WET had not been compared with CPT, which is the most commonly used first-line treatment of PTSD. The aim of this study was to determine whether WET is noninferior to CPT.²

Study design

• In this randomized noninferiority clinical trial conducted in Boston, Massachusetts from February 28, 2013 to November 6, 2016, 126 veterans and non-veteran adults were randomized to WET or CPT. Participants met DSM-5 criteria for PTSD and were taking stable doses of their medications for at least 4 weeks.² 
• Participants assigned to CPT (n = 63) underwent 12 sessions, and participants assigned to WET (n = 63) received 5 sessions. Cognitive processing therapy was conducted over 60-minute weekly sessions. Written exposure therapy consisted of an initial session that was 60 minutes long and four 40-minute follow-up sessions.²
• Interviews were conducted by 4 independent evaluators at baseline and 6, 12, 24, and 36 weeks. During the WET sessions, participants wrote about a traumatic event while focusing on details, thoughts, and feelings associated with the event.²
• Cognitive processing therapy involved 12 trauma-focused therapy sessions during which participants learn how to become aware of and address problematic cognitions about the trauma as well as thoughts about themselves and others. Between sessions, participants were required to write 2 trauma accounts and complete other assignments.²

Outcomes

• The primary outcome was change in total score on the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5). The CAPS-5 scores for participants in the WET group were noninferior to those for participants in the CPT group at all assessment points.²
• Participants did not significantly differ in age, education, income, or PTSD severity. Participants in the 2 groups did not differ in treatment expectations or level of satisfaction with treatment. Individuals assigned to CPT were more likely to drop out of the study: 20 participants in the CPT group dropped out in the first 5 sessions, whereas only 4 dropped out of the WET group. The dropout rate in the CPT group was 39.7%. Improvements in PTSD symptoms in the WET group were noninferior to improvements in the CPT group.²
• Written exposure therapy showed no difference compared with CPT in decreasing PTSD symptoms. Furthermore, this study demonstrated that PTSD symptoms can decrease with a smaller number of shorter therapeutic sessions.²

Conclusion

• This study demonstrated noninferiority between an established, commonly used PTSD therapy (CPT) and a version of exposure therapy that is briefer, simpler, and requires less homework and less therapist training and expertise. This “lower-dose” approach may improve access for the expanding number of patients who require treatment for PTSD, especially in the Veterans Affairs system.²
• In summary, WET is well tolerated and time-efficient. Although it requires fewer sessions, WET was noninferior to CPT.²

Continue to: Multisystemic therapy versus management as usual...

3. Fonagy P, Butler S, Cottrell D, et al. Multisystemic therapy versus management as usual in the treatment of adolescent antisocial behaviour (START): a pragmatic, randomised controlled, superiority trial. Lancet Psychiatry. 2018;5(2):119-133.

Multisystemic therapy (MST) is an intensive, family-based, home-based intervention for young people with serious antisocial behavior. It has been found effective for childhood conduct disorders in the United States. However, previous studies that supported its efficacy were conducted by the therapy’s developers and used noncomprehensive comparators, such as individual therapy. Fonagy et al³ assessed the effectiveness and cost-effectiveness of MST vs management as usual for treating adolescent antisocial behavior. This is the first study that was performed by independent investigators and used a comprehensive control.³

Study design

• This 18-month, multisite, pragmatic, randomized controlled superiority trial was conducted in England.³
• Participants were age 11 to 17, with moderate to severe antisocial behavior. They had at least 3 severity criteria indicating difficulties across several settings and at least one of the 5 inclusion criteria for antisocial behavior. Six hundred eighty-four families were randomly assigned to MST or management as usual, and 491 families completed the study.³
• For the MST intervention, therapists worked with the adolescent’s caregiver 3 times a week for 3 to 5 months to improve parenting skills, enhance family relationships, increase support from social networks, develop skills and resources, address communication problems, increase school attendance and achievement, and reduce the adolescent’s association with delinquent peers.³
• For the management as usual intervention, management was based on local services for young people and was designed to be in line with current community practice.³

Outcomes

• The primary outcome was the proportion of participants in out-of-home placements at 18 months. The secondary outcomes were time to first criminal offense and the total number of offenses.³
• In terms of the risk of out-of-home placement, MST had no effect: 13% of participants in the MST group had out-of-home placement at 18 months, compared with 11% in the management-as-usual group.³
• Multisystemic therapy also did not significantly delay the time to first offense (hazard ratio, 1.06; 95% confidence interval, 0.84 to 1.33). Also, at 18-month follow-up, participants in the MST group had committed more offenses than those in the management-as-usual group, although the difference was not statistically significant.³
• Parents in the MST group reported increased parental support and involvement and reduced problems at 6 months, but the adolescents’ reports of parenting behavior indicated no significant effect for MST vs management as usual at any time point.³

Conclusion

• Multisystemic therapy was not superior to management as usual in reducing out-of-home placements. Although the parents believed that MST brought about a rapid and effective change, this was not reflected in objective indicators of antisocial behavior. These results are contrary to previous studies in the United States. The substantial improvements observed in both groups reflected the effectiveness of routinely offered interventions for this group of young people, at least when observed in clinical trials.³

Continue to: Mindfulness-based cognitive therapy...

4. Janssen L, Kan CC, Carpentier PJ, et al. Mindfulness-based cognitive therapy v. treatment as usual in adults with ADHD: a multicentre, single-blind, randomised controlled trial. Psychol Med. 2019;49(1):55-65.

There is empirical support for using psychotherapy to treat attention-deficit/hyperactivity disorder (ADHD). Although medication management plays a leading role in treating ADHD, Janssen et al⁴ conducted a multicenter, single-blind trial comparing mindfulness-based cognitive therapy (MBCT) vs treatment as usual (TAU) for ADHD.

The aim of this study was to determine the efficacy of MBCT plus TAU vs TAU only in decreasing symptoms of adults with ADHD.⁴

Study design

• This multicenter, single-blind randomized controlled trial was conducted in the Netherlands. Participants (N = 120) met criteria for ADHD and were age ≥18. Patients were randomly assigned to MBCT plus TAU (n = 60) or TAU only (n = 60). Patients in the MBCT plus TAU group received weekly group therapy sessions, meditation exercises, psychoeducation, and group discussions. Patients in the TAU-only group received pharmacotherapy and psychoeducation.⁴ 
• Blinded clinicians used the Connors’ Adult ADHD Rating Scale to assess ADHD symptoms.⁴
• Secondary outcomes were determined by self-reported questionnaires that patients completed online.⁴
• All statistical analyses were performed on an intention-to-treat sample as well as the per protocol sample.⁴

Outcomes

• The primary outcome was ADHD symptoms rated by clinicians. Secondary outcomes included self-reported ADHD symptoms, executive functioning, mindfulness skills, positive mental health, and general functioning. Outcomes were examined at baseline and then at post treatment and 3- and 6-month follow-up.⁴
• Patients in the MBCT plus TAU group had a significant decrease in clinician-rated ADHD symptoms that was maintained at 6-month follow-up. More patients in the MBCT plus TAU group (27%) vs patients in the TAU group (4%) showed a ≥30% reduction in ADHD symptoms. Compared with patients in the TAU group, patients in the MBCT plus TAU group had significant improvements in ADHD symptoms, mindfulness skills, and positive mental health at post treatment and at 6-month follow-up. Compared with those receiving TAU only, patients treated with MBCT plus TAU reported no improvement in executive functioning at post treatment, but did improve at 6-month follow-up.⁴

Continue to: Conclusion

Conclusion

• Compared with TAU only, MBCT plus TAU is more effective in reducing ADHD symptoms, with a lasting effect at 6-month follow-up. In terms of secondary outcomes, MBCT plus TAU proved to be effective in improving mindfulness, self-compassion, positive mental health, and executive functioning. The results of this trial demonstrate that psychosocial treatments can be effective in addition to TAU in patients with ADHD, and MBCT holds promise for adult ADHD.⁴

Psychotherapy is among the evidence-based treatment options for treating various psychiatric disorders. How we approach psychiatric disorders via psycho­therapy has been shaped by numerous theories of personality and psychopathology, including psychodynamic, behavioral, cognitive, systems, and existential-humanistic approaches. Whether used as primary treatment or in conjunction with medication, psychotherapy has played a pivotal role in shaping psychiatric disease management and treatment. Several evidence-based therapy modalities have been used throughout the years and continue to significantly improve and impact our patients’ lives. In the armamentarium of treatment modalities, therapy takes the leading role for several conditions. Here we review 4 studies from current psychotherapy literature; these studies are summarized in the Table.^1-4

1. Pompoli A, Furukawa TA, Efthimiou O, et al. Dismantling cognitive-behaviour therapy for panic disorder: a systematic review and component network meta-analysis. Psychol Med. 2018;48(12):1945-1953.

Panic disorder has a lifetime prevalence of 3.7% in the general population. Three treatment modalities recommended for patients with panic disorder are psychological therapy, pharmacologic therapy, and self-help. Among the psychological therapies, cognitive-behavioral therapy (CBT) is one of the most widely used.¹

Cognitive-behavioral therapy for panic disorder has been proven to be an efficacious and impactful treatment. For panic disorder, CBT may consist of different combinations of several therapeutic components, such as relaxation, breathing retraining, cognitive restructuring, interoceptive exposure, and/or in vivo exposure. It is therefore important, both theoretically and clinically, to examine whether specific components of CBT or their combinations are superior to others for treating panic disorder.¹

Pompoli et al¹ conducted a component network meta-analysis (NMA) of 72 studies in order to determine which CBT components were the most efficacious in treating patients with panic disorder. Component NMA is an extension of standard NMA; it is used to disentangle the treatment effects of different components included in composite interventions.¹

The aim of this study was to determine which specific component or combination of components was superior to others when treating panic disorder.¹

Study design

• Researchers reviewed 2,526 references from Medline, EMBASE, PsycINFO, and Cochrane Central and selected 72 studies that included 4,064 patients with panic disorder.¹
• The primary outcome was remission of panic disorder with or without agoraphobia in the short term (3 to 6 months). Remission was defined as achieving a score of ≤7 on the Panic Disorder Severity Scale (PDSS).¹
• Secondary outcomes included response (≥40% reduction in PDSS score from baseline) and dropout for any reason in the short term.¹

Continue to: Outcomes

Outcomes

• Using component NMA, researchers determined that interoceptive exposure and face-to-face setting (administration of therapeutic components in a face-to-face setting rather than through self-help means) led to better efficacy and acceptability. Muscle relaxation and virtual reality exposure corresponded to lower efficacy. Breathing retraining and in vivo exposure improved treatment acceptability, but had small effects on efficacy.¹
• Based on an analysis of remission rates, the most efficacious CBT incorporated cognitive restructuring and interoceptive exposure. The least efficacious CBT incorporated breathing retraining, muscle relaxation, in vivo exposure, and virtual reality exposure.¹
• Application of cognitive and behavioral therapeutic elements was superior to administration of behavioral elements alone. When administering CBT, face-to-face therapy led to better outcomes in response and remission rates. Dropout rates occurred at a lower frequency when CBT was administered face-to-face when compared with self-help groups. The placebo effect was associated with the highest dropout rate.¹

Conclusion

• Findings from this meta-analysis have high practical utility. Which CBT components are used can significantly alter CBT’s efficacy and acceptability in patients with panic disorder.¹
• The “most efficacious CBT” would include cognitive restructuring and interoceptive exposure delivered in a face-to-face setting. Breathing retraining, muscle relaxation, and virtual reality may have a minimal or even negative impact.¹
• Limitations of this meta-analysis include the high number of studies used for the data analysis, complex statistical analysis, inability to include unpublished studies, and limited relevant studies. A future implication of this study is the consideration of formal methodology based on the clinical application of efficacious CBT components when treating patients with panic disorder.¹

2. Sloan DM, Marx BP, Lee DJ, et al. A brief exposure-based treatment vs cognitive processing therapy for posttraumatic stress disorder: a randomized noninferiority clinical trial. JAMA Psychiatry. 2018;75(3):233-239.

Psychotherapy is also a useful modality for treating posttraumatic stress disorder (PTSD). Sloan et al² compared brief exposure-based treatment with cognitive processing therapy (CPT) for PTSD. 

Clinical practice guidelines for the management of PTSD and acute stress disorder recommend the use of individual, trauma-focused therapies that focus on exposure and cognitive restructuring, such as prolonged exposure, CPT, and written narrative exposure.⁵

Continue to: One type of written narrative...

One type of written narrative exposure treatment is written exposure therapy (WET), which consists of 5 sessions during which patients write about their trauma. The first session is comprised of psychoeducation about PTSD and a review of treatment reasoning, followed by 30 minutes of writing. The therapist provides feedback and instructions. Written exposure therapy requires less therapist training and less supervision than prolonged exposure or CPT. Prior studies have suggested that WET can significantly reduce PTSD symptoms in various trauma survivors.²

Although efficacious for PTSD, WET had not been compared with CPT, which is the most commonly used first-line treatment of PTSD. The aim of this study was to determine whether WET is noninferior to CPT.²

Study design

• In this randomized noninferiority clinical trial conducted in Boston, Massachusetts from February 28, 2013 to November 6, 2016, 126 veterans and non-veteran adults were randomized to WET or CPT. Participants met DSM-5 criteria for PTSD and were taking stable doses of their medications for at least 4 weeks.² 
• Participants assigned to CPT (n = 63) underwent 12 sessions, and participants assigned to WET (n = 63) received 5 sessions. Cognitive processing therapy was conducted over 60-minute weekly sessions. Written exposure therapy consisted of an initial session that was 60 minutes long and four 40-minute follow-up sessions.²
• Interviews were conducted by 4 independent evaluators at baseline and 6, 12, 24, and 36 weeks. During the WET sessions, participants wrote about a traumatic event while focusing on details, thoughts, and feelings associated with the event.²
• Cognitive processing therapy involved 12 trauma-focused therapy sessions during which participants learn how to become aware of and address problematic cognitions about the trauma as well as thoughts about themselves and others. Between sessions, participants were required to write 2 trauma accounts and complete other assignments.²

Outcomes

• The primary outcome was change in total score on the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5). The CAPS-5 scores for participants in the WET group were noninferior to those for participants in the CPT group at all assessment points.²
• Participants did not significantly differ in age, education, income, or PTSD severity. Participants in the 2 groups did not differ in treatment expectations or level of satisfaction with treatment. Individuals assigned to CPT were more likely to drop out of the study: 20 participants in the CPT group dropped out in the first 5 sessions, whereas only 4 dropped out of the WET group. The dropout rate in the CPT group was 39.7%. Improvements in PTSD symptoms in the WET group were noninferior to improvements in the CPT group.²
• Written exposure therapy showed no difference compared with CPT in decreasing PTSD symptoms. Furthermore, this study demonstrated that PTSD symptoms can decrease with a smaller number of shorter therapeutic sessions.²

Conclusion

• This study demonstrated noninferiority between an established, commonly used PTSD therapy (CPT) and a version of exposure therapy that is briefer, simpler, and requires less homework and less therapist training and expertise. This “lower-dose” approach may improve access for the expanding number of patients who require treatment for PTSD, especially in the Veterans Affairs system.²
• In summary, WET is well tolerated and time-efficient. Although it requires fewer sessions, WET was noninferior to CPT.²

Continue to: Multisystemic therapy versus management as usual...

3. Fonagy P, Butler S, Cottrell D, et al. Multisystemic therapy versus management as usual in the treatment of adolescent antisocial behaviour (START): a pragmatic, randomised controlled, superiority trial. Lancet Psychiatry. 2018;5(2):119-133.

Multisystemic therapy (MST) is an intensive, family-based, home-based intervention for young people with serious antisocial behavior. It has been found effective for childhood conduct disorders in the United States. However, previous studies that supported its efficacy were conducted by the therapy’s developers and used noncomprehensive comparators, such as individual therapy. Fonagy et al³ assessed the effectiveness and cost-effectiveness of MST vs management as usual for treating adolescent antisocial behavior. This is the first study that was performed by independent investigators and used a comprehensive control.³

Study design

• This 18-month, multisite, pragmatic, randomized controlled superiority trial was conducted in England.³
• Participants were age 11 to 17, with moderate to severe antisocial behavior. They had at least 3 severity criteria indicating difficulties across several settings and at least one of the 5 inclusion criteria for antisocial behavior. Six hundred eighty-four families were randomly assigned to MST or management as usual, and 491 families completed the study.³
• For the MST intervention, therapists worked with the adolescent’s caregiver 3 times a week for 3 to 5 months to improve parenting skills, enhance family relationships, increase support from social networks, develop skills and resources, address communication problems, increase school attendance and achievement, and reduce the adolescent’s association with delinquent peers.³
• For the management as usual intervention, management was based on local services for young people and was designed to be in line with current community practice.³

Outcomes

• The primary outcome was the proportion of participants in out-of-home placements at 18 months. The secondary outcomes were time to first criminal offense and the total number of offenses.³
• In terms of the risk of out-of-home placement, MST had no effect: 13% of participants in the MST group had out-of-home placement at 18 months, compared with 11% in the management-as-usual group.³
• Multisystemic therapy also did not significantly delay the time to first offense (hazard ratio, 1.06; 95% confidence interval, 0.84 to 1.33). Also, at 18-month follow-up, participants in the MST group had committed more offenses than those in the management-as-usual group, although the difference was not statistically significant.³
• Parents in the MST group reported increased parental support and involvement and reduced problems at 6 months, but the adolescents’ reports of parenting behavior indicated no significant effect for MST vs management as usual at any time point.³

Conclusion

• Multisystemic therapy was not superior to management as usual in reducing out-of-home placements. Although the parents believed that MST brought about a rapid and effective change, this was not reflected in objective indicators of antisocial behavior. These results are contrary to previous studies in the United States. The substantial improvements observed in both groups reflected the effectiveness of routinely offered interventions for this group of young people, at least when observed in clinical trials.³

Continue to: Mindfulness-based cognitive therapy...

4. Janssen L, Kan CC, Carpentier PJ, et al. Mindfulness-based cognitive therapy v. treatment as usual in adults with ADHD: a multicentre, single-blind, randomised controlled trial. Psychol Med. 2019;49(1):55-65.

There is empirical support for using psychotherapy to treat attention-deficit/hyperactivity disorder (ADHD). Although medication management plays a leading role in treating ADHD, Janssen et al⁴ conducted a multicenter, single-blind trial comparing mindfulness-based cognitive therapy (MBCT) vs treatment as usual (TAU) for ADHD.

The aim of this study was to determine the efficacy of MBCT plus TAU vs TAU only in decreasing symptoms of adults with ADHD.⁴

Study design

• This multicenter, single-blind randomized controlled trial was conducted in the Netherlands. Participants (N = 120) met criteria for ADHD and were age ≥18. Patients were randomly assigned to MBCT plus TAU (n = 60) or TAU only (n = 60). Patients in the MBCT plus TAU group received weekly group therapy sessions, meditation exercises, psychoeducation, and group discussions. Patients in the TAU-only group received pharmacotherapy and psychoeducation.⁴ 
• Blinded clinicians used the Connors’ Adult ADHD Rating Scale to assess ADHD symptoms.⁴
• Secondary outcomes were determined by self-reported questionnaires that patients completed online.⁴
• All statistical analyses were performed on an intention-to-treat sample as well as the per protocol sample.⁴

Outcomes

• The primary outcome was ADHD symptoms rated by clinicians. Secondary outcomes included self-reported ADHD symptoms, executive functioning, mindfulness skills, positive mental health, and general functioning. Outcomes were examined at baseline and then at post treatment and 3- and 6-month follow-up.⁴
• Patients in the MBCT plus TAU group had a significant decrease in clinician-rated ADHD symptoms that was maintained at 6-month follow-up. More patients in the MBCT plus TAU group (27%) vs patients in the TAU group (4%) showed a ≥30% reduction in ADHD symptoms. Compared with patients in the TAU group, patients in the MBCT plus TAU group had significant improvements in ADHD symptoms, mindfulness skills, and positive mental health at post treatment and at 6-month follow-up. Compared with those receiving TAU only, patients treated with MBCT plus TAU reported no improvement in executive functioning at post treatment, but did improve at 6-month follow-up.⁴

Continue to: Conclusion

Conclusion

• Compared with TAU only, MBCT plus TAU is more effective in reducing ADHD symptoms, with a lasting effect at 6-month follow-up. In terms of secondary outcomes, MBCT plus TAU proved to be effective in improving mindfulness, self-compassion, positive mental health, and executive functioning. The results of this trial demonstrate that psychosocial treatments can be effective in addition to TAU in patients with ADHD, and MBCT holds promise for adult ADHD.⁴

Psychotherapy is among the evidence-based treatment options for treating various psychiatric disorders. How we approach psychiatric disorders via psycho­therapy has been shaped by numerous theories of personality and psychopathology, including psychodynamic, behavioral, cognitive, systems, and existential-humanistic approaches. Whether used as primary treatment or in conjunction with medication, psychotherapy has played a pivotal role in shaping psychiatric disease management and treatment. Several evidence-based therapy modalities have been used throughout the years and continue to significantly improve and impact our patients’ lives. In the armamentarium of treatment modalities, therapy takes the leading role for several conditions. Here we review 4 studies from current psychotherapy literature; these studies are summarized in the Table.^1-4

1. Pompoli A, Furukawa TA, Efthimiou O, et al. Dismantling cognitive-behaviour therapy for panic disorder: a systematic review and component network meta-analysis. Psychol Med. 2018;48(12):1945-1953.

Panic disorder has a lifetime prevalence of 3.7% in the general population. Three treatment modalities recommended for patients with panic disorder are psychological therapy, pharmacologic therapy, and self-help. Among the psychological therapies, cognitive-behavioral therapy (CBT) is one of the most widely used.¹

Cognitive-behavioral therapy for panic disorder has been proven to be an efficacious and impactful treatment. For panic disorder, CBT may consist of different combinations of several therapeutic components, such as relaxation, breathing retraining, cognitive restructuring, interoceptive exposure, and/or in vivo exposure. It is therefore important, both theoretically and clinically, to examine whether specific components of CBT or their combinations are superior to others for treating panic disorder.¹

Pompoli et al¹ conducted a component network meta-analysis (NMA) of 72 studies in order to determine which CBT components were the most efficacious in treating patients with panic disorder. Component NMA is an extension of standard NMA; it is used to disentangle the treatment effects of different components included in composite interventions.¹

The aim of this study was to determine which specific component or combination of components was superior to others when treating panic disorder.¹

Study design

• Researchers reviewed 2,526 references from Medline, EMBASE, PsycINFO, and Cochrane Central and selected 72 studies that included 4,064 patients with panic disorder.¹
• The primary outcome was remission of panic disorder with or without agoraphobia in the short term (3 to 6 months). Remission was defined as achieving a score of ≤7 on the Panic Disorder Severity Scale (PDSS).¹
• Secondary outcomes included response (≥40% reduction in PDSS score from baseline) and dropout for any reason in the short term.¹

Continue to: Outcomes

Outcomes

• Using component NMA, researchers determined that interoceptive exposure and face-to-face setting (administration of therapeutic components in a face-to-face setting rather than through self-help means) led to better efficacy and acceptability. Muscle relaxation and virtual reality exposure corresponded to lower efficacy. Breathing retraining and in vivo exposure improved treatment acceptability, but had small effects on efficacy.¹
• Based on an analysis of remission rates, the most efficacious CBT incorporated cognitive restructuring and interoceptive exposure. The least efficacious CBT incorporated breathing retraining, muscle relaxation, in vivo exposure, and virtual reality exposure.¹
• Application of cognitive and behavioral therapeutic elements was superior to administration of behavioral elements alone. When administering CBT, face-to-face therapy led to better outcomes in response and remission rates. Dropout rates occurred at a lower frequency when CBT was administered face-to-face when compared with self-help groups. The placebo effect was associated with the highest dropout rate.¹

Conclusion

• Findings from this meta-analysis have high practical utility. Which CBT components are used can significantly alter CBT’s efficacy and acceptability in patients with panic disorder.¹
• The “most efficacious CBT” would include cognitive restructuring and interoceptive exposure delivered in a face-to-face setting. Breathing retraining, muscle relaxation, and virtual reality may have a minimal or even negative impact.¹
• Limitations of this meta-analysis include the high number of studies used for the data analysis, complex statistical analysis, inability to include unpublished studies, and limited relevant studies. A future implication of this study is the consideration of formal methodology based on the clinical application of efficacious CBT components when treating patients with panic disorder.¹

2. Sloan DM, Marx BP, Lee DJ, et al. A brief exposure-based treatment vs cognitive processing therapy for posttraumatic stress disorder: a randomized noninferiority clinical trial. JAMA Psychiatry. 2018;75(3):233-239.

Psychotherapy is also a useful modality for treating posttraumatic stress disorder (PTSD). Sloan et al² compared brief exposure-based treatment with cognitive processing therapy (CPT) for PTSD. 

Clinical practice guidelines for the management of PTSD and acute stress disorder recommend the use of individual, trauma-focused therapies that focus on exposure and cognitive restructuring, such as prolonged exposure, CPT, and written narrative exposure.⁵

Continue to: One type of written narrative...

One type of written narrative exposure treatment is written exposure therapy (WET), which consists of 5 sessions during which patients write about their trauma. The first session is comprised of psychoeducation about PTSD and a review of treatment reasoning, followed by 30 minutes of writing. The therapist provides feedback and instructions. Written exposure therapy requires less therapist training and less supervision than prolonged exposure or CPT. Prior studies have suggested that WET can significantly reduce PTSD symptoms in various trauma survivors.²

Although efficacious for PTSD, WET had not been compared with CPT, which is the most commonly used first-line treatment of PTSD. The aim of this study was to determine whether WET is noninferior to CPT.²

Study design

• In this randomized noninferiority clinical trial conducted in Boston, Massachusetts from February 28, 2013 to November 6, 2016, 126 veterans and non-veteran adults were randomized to WET or CPT. Participants met DSM-5 criteria for PTSD and were taking stable doses of their medications for at least 4 weeks.² 
• Participants assigned to CPT (n = 63) underwent 12 sessions, and participants assigned to WET (n = 63) received 5 sessions. Cognitive processing therapy was conducted over 60-minute weekly sessions. Written exposure therapy consisted of an initial session that was 60 minutes long and four 40-minute follow-up sessions.²
• Interviews were conducted by 4 independent evaluators at baseline and 6, 12, 24, and 36 weeks. During the WET sessions, participants wrote about a traumatic event while focusing on details, thoughts, and feelings associated with the event.²
• Cognitive processing therapy involved 12 trauma-focused therapy sessions during which participants learn how to become aware of and address problematic cognitions about the trauma as well as thoughts about themselves and others. Between sessions, participants were required to write 2 trauma accounts and complete other assignments.²

Outcomes

• The primary outcome was change in total score on the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5). The CAPS-5 scores for participants in the WET group were noninferior to those for participants in the CPT group at all assessment points.²
• Participants did not significantly differ in age, education, income, or PTSD severity. Participants in the 2 groups did not differ in treatment expectations or level of satisfaction with treatment. Individuals assigned to CPT were more likely to drop out of the study: 20 participants in the CPT group dropped out in the first 5 sessions, whereas only 4 dropped out of the WET group. The dropout rate in the CPT group was 39.7%. Improvements in PTSD symptoms in the WET group were noninferior to improvements in the CPT group.²
• Written exposure therapy showed no difference compared with CPT in decreasing PTSD symptoms. Furthermore, this study demonstrated that PTSD symptoms can decrease with a smaller number of shorter therapeutic sessions.²

Conclusion

• This study demonstrated noninferiority between an established, commonly used PTSD therapy (CPT) and a version of exposure therapy that is briefer, simpler, and requires less homework and less therapist training and expertise. This “lower-dose” approach may improve access for the expanding number of patients who require treatment for PTSD, especially in the Veterans Affairs system.²
• In summary, WET is well tolerated and time-efficient. Although it requires fewer sessions, WET was noninferior to CPT.²

Continue to: Multisystemic therapy versus management as usual...

3. Fonagy P, Butler S, Cottrell D, et al. Multisystemic therapy versus management as usual in the treatment of adolescent antisocial behaviour (START): a pragmatic, randomised controlled, superiority trial. Lancet Psychiatry. 2018;5(2):119-133.

Multisystemic therapy (MST) is an intensive, family-based, home-based intervention for young people with serious antisocial behavior. It has been found effective for childhood conduct disorders in the United States. However, previous studies that supported its efficacy were conducted by the therapy’s developers and used noncomprehensive comparators, such as individual therapy. Fonagy et al³ assessed the effectiveness and cost-effectiveness of MST vs management as usual for treating adolescent antisocial behavior. This is the first study that was performed by independent investigators and used a comprehensive control.³

Study design

• This 18-month, multisite, pragmatic, randomized controlled superiority trial was conducted in England.³
• Participants were age 11 to 17, with moderate to severe antisocial behavior. They had at least 3 severity criteria indicating difficulties across several settings and at least one of the 5 inclusion criteria for antisocial behavior. Six hundred eighty-four families were randomly assigned to MST or management as usual, and 491 families completed the study.³
• For the MST intervention, therapists worked with the adolescent’s caregiver 3 times a week for 3 to 5 months to improve parenting skills, enhance family relationships, increase support from social networks, develop skills and resources, address communication problems, increase school attendance and achievement, and reduce the adolescent’s association with delinquent peers.³
• For the management as usual intervention, management was based on local services for young people and was designed to be in line with current community practice.³

Outcomes

• The primary outcome was the proportion of participants in out-of-home placements at 18 months. The secondary outcomes were time to first criminal offense and the total number of offenses.³
• In terms of the risk of out-of-home placement, MST had no effect: 13% of participants in the MST group had out-of-home placement at 18 months, compared with 11% in the management-as-usual group.³
• Multisystemic therapy also did not significantly delay the time to first offense (hazard ratio, 1.06; 95% confidence interval, 0.84 to 1.33). Also, at 18-month follow-up, participants in the MST group had committed more offenses than those in the management-as-usual group, although the difference was not statistically significant.³
• Parents in the MST group reported increased parental support and involvement and reduced problems at 6 months, but the adolescents’ reports of parenting behavior indicated no significant effect for MST vs management as usual at any time point.³

Conclusion

• Multisystemic therapy was not superior to management as usual in reducing out-of-home placements. Although the parents believed that MST brought about a rapid and effective change, this was not reflected in objective indicators of antisocial behavior. These results are contrary to previous studies in the United States. The substantial improvements observed in both groups reflected the effectiveness of routinely offered interventions for this group of young people, at least when observed in clinical trials.³

Continue to: Mindfulness-based cognitive therapy...

4. Janssen L, Kan CC, Carpentier PJ, et al. Mindfulness-based cognitive therapy v. treatment as usual in adults with ADHD: a multicentre, single-blind, randomised controlled trial. Psychol Med. 2019;49(1):55-65.

There is empirical support for using psychotherapy to treat attention-deficit/hyperactivity disorder (ADHD). Although medication management plays a leading role in treating ADHD, Janssen et al⁴ conducted a multicenter, single-blind trial comparing mindfulness-based cognitive therapy (MBCT) vs treatment as usual (TAU) for ADHD.

The aim of this study was to determine the efficacy of MBCT plus TAU vs TAU only in decreasing symptoms of adults with ADHD.⁴

Study design

• This multicenter, single-blind randomized controlled trial was conducted in the Netherlands. Participants (N = 120) met criteria for ADHD and were age ≥18. Patients were randomly assigned to MBCT plus TAU (n = 60) or TAU only (n = 60). Patients in the MBCT plus TAU group received weekly group therapy sessions, meditation exercises, psychoeducation, and group discussions. Patients in the TAU-only group received pharmacotherapy and psychoeducation.⁴ 
• Blinded clinicians used the Connors’ Adult ADHD Rating Scale to assess ADHD symptoms.⁴
• Secondary outcomes were determined by self-reported questionnaires that patients completed online.⁴
• All statistical analyses were performed on an intention-to-treat sample as well as the per protocol sample.⁴

Outcomes

• The primary outcome was ADHD symptoms rated by clinicians. Secondary outcomes included self-reported ADHD symptoms, executive functioning, mindfulness skills, positive mental health, and general functioning. Outcomes were examined at baseline and then at post treatment and 3- and 6-month follow-up.⁴
• Patients in the MBCT plus TAU group had a significant decrease in clinician-rated ADHD symptoms that was maintained at 6-month follow-up. More patients in the MBCT plus TAU group (27%) vs patients in the TAU group (4%) showed a ≥30% reduction in ADHD symptoms. Compared with patients in the TAU group, patients in the MBCT plus TAU group had significant improvements in ADHD symptoms, mindfulness skills, and positive mental health at post treatment and at 6-month follow-up. Compared with those receiving TAU only, patients treated with MBCT plus TAU reported no improvement in executive functioning at post treatment, but did improve at 6-month follow-up.⁴

Continue to: Conclusion

Conclusion

• Compared with TAU only, MBCT plus TAU is more effective in reducing ADHD symptoms, with a lasting effect at 6-month follow-up. In terms of secondary outcomes, MBCT plus TAU proved to be effective in improving mindfulness, self-compassion, positive mental health, and executive functioning. The results of this trial demonstrate that psychosocial treatments can be effective in addition to TAU in patients with ADHD, and MBCT holds promise for adult ADHD.⁴

Major depressive disorder (MDD) is a significant pediatric health problem, with a lifetime prevalence as high as 20% by the end of adolescence.^1-3 Major depressive disorder in adolescence is associated with significant morbidity, including poor social functioning, school difficulties, early pregnancy, and increased risk of physical illness and substance abuse.^4-6 It is also linked with significant mortality, with increased risk for suicide, which is now the second leading cause of death in individuals age 10 to 24 years.^1,7,8

As their name suggests, antidepressants comprise a group of medications that are used to treat MDD; they are also, however, first-line agents for generalized anxiety disorder (GAD), posttraumatic stress disorder (PTSD), and obsessive-compulsive disorder (OCD) in adults. Anxiety disorders (including GAD and other anxiety diagnoses) and PTSD are also common in childhood and adolescence with a combined lifetime prevalence ranging from 15% to 30%.^9,10 These disorders are also associated with increased risk of suicide.¹¹ For all of these disorders, depending on the severity of presentation and the preference of the patient, treatments are often a combination of psychotherapy and psychopharmacology.

Clinicians face several challenges when considering antidepressants for pediatric patients. Pediatricians and psychiatrists need to understand whether these medications work in children and adolescents, and whether there are unique developmental safety and tolerability issues. The evidence base in child psychiatry is considerably smaller compared with that of adult psychiatry. From this more limited evidence base also came the controversial “black-box” warning regarding a risk of emergent suicidality when starting antidepressants that accompanies all antidepressants for pediatric, but not adult, patients. This warning has had major effects on clinical encounters with children experiencing depression, including altering clinician prescribing behavior.¹²

In this article, we review the current evidence for antidepressant efficacy, tolerability, and safety in pediatric patients. We also suggest ways in which clinicians might choose, start, and stop antidepressants in children, as well as how to talk with parents about benefits, risks, and the black-box warning.

Do antidepressants work in children?

Selective serotonin reuptake inhibitors. Selective serotonin reuptake inhibitors (SSRIs) are the most commonly used class of antidepressants in both children and adults.¹³ While only a few SSRIs are FDA-approved for pediatric indications, the lack of FDA approval is typically related to a lack of sufficient testing in randomized controlled trials (RCTs) for specific pediatric indications, rather than to demonstrable differences in efficacy between antidepressant agents. Since there is currently no data to suggest inferiority of one agent compared to another in children or adults,^14,15 efficacy data will be discussed here as applied to the class of SSRIs, generalizing from RCTs conducted on individual drugs. Table 1 lists FDA indications and dosing information for individual antidepressants.

There is strong evidence that SSRIs are effective for treating pediatric anxiety disorders (eg, social anxiety disorder and GAD)¹⁶ and OCD,¹⁷ with numbers needed to treat (NNT) between 3 and 5. For both of these disorders, SSRIs combined with cognitive-behavioral therapy (CBT) have the highest likelihood of improving symptoms or achieving remission.^17,18

Selective serotonin reuptake inhibitors are also effective for treating pediatric MDD; however, the literature is more complex for this disorder compared to GAD and OCD as there are considerable differences in effect sizes between National Institute of Mental Health (NIMH)–funded studies and industry-sponsored trials.¹³ The major NIMH-sponsored adolescent depression trial, TADS (Treatment for Adolescents and Depression Study), showed that SSRIs (fluoxetine in this case) were quite effective, with an NNT of 4 over the acute phase (12 weeks).¹⁹ Ultimately, approximately 80% of adolescents improved over 9 months. Many industry-sponsored trials for MDD in pediatric patients had large placebo response rates (approximately 60%), which resulted in smaller between-group differences, and estimates of an NNT closer to 12,¹³ which has muddied the waters in meta-analyses that include all trials.²⁰ Improvement in depressive symptoms also appears to be bolstered by concomitant CBT in MDD,¹⁹ but not as robustly as in GAD and OCD. While the full benefit of SSRIs for depression may take as long as 8 weeks, a meta-analysis of depression studies of pediatric patients suggests that significant benefits from placebo are observed as early as 2 weeks, and that further treatment gains are minimal after 4 weeks.¹⁵ Thus, we recommend at least a 4- to 6-week trial at therapeutic dosing before deeming a medication a treatment failure.

Continue to: Posttraumatic stress disorder...

Posttraumatic stress disorder is a fourth disorder in which SSRIs are a first-line treatment in adults. The data for using SSRIs to treat pediatric patients with PTSD is scant, with only a few RCTs, and no large NIMH-funded trials. Randomized controlled trials have not demonstrated significant differences between SSRIs and placebo^21,22 and thus the current first-line recommendation in pediatric PTSD remains trauma-focused therapy, with good evidence for trauma-focused CBT.²³ Practically speaking, there can be considerable overlap of PTSD, depression, and anxiety symptoms in children,²³ and children with a history of trauma who also have comorbid MDD may benefit from medication if their symptoms persist despite an adequate trial of psychotherapy.

Taken together, the current evidence suggests that SSRIs are often effective in pediatric GAD, OCD, and MDD, with low NNTs (ranging from 3 to 5 based on NIMH-funded trials) for all of these disorders; there is not yet sufficient evidence of efficacy in pediatric patients with PTSD.

Fluoxetine has been studied more intensively than other SSRIs (for example, it was the antidepressant used in the TADS trial), and thus has the largest evidence base. For this reason, fluoxetine is often considered the first of the first-line options. Additionally, fluoxetine has a longer half-life than other antidepressants, which may make it more effective in situations where patients are likely to miss doses, and results in a lower risk of withdrawal symptoms when stopped due to “self-tapering.”

SNRIs and atypical antidepressants. Other antidepressants commonly used in pediatric patients but with far less evidence of efficacy include serotonin-norepinephrine reuptake inhibitors (SNRIs) and the atypical antidepressants bupropion and mirtazapine. The SNRI duloxetine is FDA-approved for treating GAD in children age 7 to 17, but there are no other pediatric indications for duloxetine, or for the other SNRIs.

In general, adverse effect profiles are worse for SNRIs compared to SSRIs, further limiting their utility. While there are no pediatric studies demonstrating SNRI efficacy for neuropathic pain, good data exists in adults.²⁴ Thus, an SNRI could be a reasonable option if a pediatric patient has failed prior adequate SSRI trials and also has comorbid neuropathic pain.

Continue to: Neither bupropion nor mirtazapine...

Neither bupropion nor mirtazapine have undergone rigorous testing in pediatric patients, and therefore these agents should generally be considered only once other first-line treatments have failed. Bupropion has been evaluated for attention-deficit/hyperactivity disorder (ADHD)²⁵ and for adolescent smoking cessation.²⁶ However, the evidence is weak, and bupropion is not considered a first-line option for children and adolescents.

Tricyclic antidepressants. Randomized controlled trials have demonstrated that tricyclic antidepressants (TCAs) are efficacious for treating several pediatric conditions; however, their significant side effect profile, their monitoring requirements, as well as their lethality in overdose has left them replaced by SSRIs in most cases. That said, they can be appropriate in refractory ADHD (desipramine^27,28) and refractory OCD (clomipramine is FDA-approved for this indication²⁹); they are considered a third-line treatment for enuresis.³⁰

Why did my patient stop the medication?

Common adverse effects. Although the greatest benefit of antidepressant medications compared with placebo is achieved relatively early on in treatment, it generally takes time for these benefits to accrue and become clinically apparent.^15,31 By contrast, most adverse effects of antidepressants present and are at their most severe early in treatment. The combination of early adverse effects and delayed efficacy leads many patients, families, and clinicians to discontinue medications before they have an adequate chance to work. Thus, it is imperative to provide psychoeducation before starting a medication about the typical time-course of improvement and adverse effects (Table 2).

Adverse effects of SSRIs often appear or worsen transiently during initiation of a medication, during a dose increase,³² or, theoretically, with the addition of a medication that interferes with SSRI metabolism (eg, cimetidine inhibition of cytochrome P450 2D6).³³ If families are prepared for this phenomenon and the therapeutic alliance is adequate, adverse effects can be tolerated to allow for a full medication trial. Common adverse effects of SSRIs include sleep problems (insomnia/sedation), gastrointestinal upset, sexual dysfunction, dry mouth, and hyperhidrosis. Although SSRIs differ somewhat in the frequency of these effects, as a class, they are more similar than different. Adequate psychoeducation is especially imperative in the treatment of OCD and anxiety disorders, where there is limited evidence of efficacy for any non-serotonergic antidepressants.

Serotonin-norepinephrine reuptake inhibitors are not considered first-line medications because of the reduced evidence base compared to SSRIs and their enhanced adverse effect profiles. Because SNRIs partially share a mechanism of action with SSRIs, they also share portions of the adverse effects profile. However, SNRIs have the additional adverse effect of hypertension, which is related to their noradrenergic activity. Thus, it is reasonable to obtain a baseline blood pressure before initiating an SNRI, as well as periodically after initiation and during dose increases, particularly if the patient has other risk factors for hypertension.³⁴

Continue to: Although TCAs have efficacy...

Although TCAs have efficacy in some pediatric disorders,^27-29,35 their adverse effect profile limits their use. Tricyclic antidepressants are highly anticholinergic (causing dizziness secondary to orthostatic hypotension, dry mouth, and urinary retention) and antihistaminergic (causing sedation and weight gain). Additionally, TCAs lower the seizure threshold and have adverse cardiac effects relating to their anti-alpha-1 adrenergic activity, resulting in dose-dependent increases in the QTc and cardiac toxicity in overdose that could lead to arrhythmia and death. These medications have their place, but their use requires careful informed consent, clear treatment goals, and baseline and periodic cardiac monitoring (via electrocardiogram).

Serious adverse effects. Clinicians may be hesitant to prescribe antidepressants for pediatric patients because of the potential for more serious adverse effects, including severe behavioral activation syndromes, serotonin syndrome, and emergent suicidality. However, current FDA-approved antidepressants arguably have one of the most positive risk/benefit profiles of any orally-administered medication approved for pediatric patients. Having a strong understanding of the evidence is critical to evaluating when it is appropriate to prescribe an antidepressant, how to properly monitor the patient, and how to obtain accurate informed consent.

Pediatric behavioral activation syndrome. Many clinicians report that children receiving antidepressants experience a pediatric behavioral activation syndrome, which exists along a spectrum from mild activation, increased energy, insomnia, or irritability up through more severe presentations of agitation, hyperactivity, or possibly mania. A recent meta-analysis suggested a positive association between antidepressant use and activation events on the milder end of this spectrum in pediatric patients with non-OCD anxiety disorders,¹⁶ and it is thought that compared with adolescents, younger children are more susceptible to activation adverse effects.³⁶ The likelihood of activation events has been associated with higher antidepressant plasma levels,³⁷ suggesting that dose or individual differences in metabolism may play a role. At the severe end of the spectrum, the risk of induction of mania in pediatric patients with depression or anxiety is relatively rare (<2%) and not statistically different from placebo in RCTs of pediatric participants.³⁸ Meta-analyses of larger randomized, placebo-controlled trials of adults do not support the idea that SSRIs and other second-generation antidepressants carry an increased risk of mania compared with placebo.^39,40 Children or adolescents with bona fide bipolar disorder (ie, patients who have had observed mania that meets all DSM-5 criteria) should be treated with a mood-stabilizing agent or antipsychotic if prescribed an antidepressant.⁴¹ These clear-cut cases are, however, relatively rare, and more often clinicians are confronted with ambiguous cases that include a family history of bipolar disorder along with “softer” symptoms of irritability, intrusiveness, or aggression. In these children, SSRIs may be appropriate for depressive, OCD, or anxiety symptoms, and should be strongly considered before prescribing antipsychotics or mood stabilizers, as long as initiated with proper monitoring.

Serotonin syndrome is a life-threatening condition caused by excess synaptic serotonin. It is characterized by confusion, sweating, diarrhea, hypertension, hyperthermia, and tachycardia. At its most severe, serotonin syndrome can result in seizures, arrhythmias, and death. The risk of serotonin syndrome is very low when using an SSRI as monotherapy. Risk increases with polypharmacy, particularly unexamined polypharmacy when multiple serotonergic agents are inadvertently on board. Commonly used serotonergic agents include other antidepressants, migraine medications (eg, triptans), some pain medications, and the cough suppressant dextromethorphan.

The easiest way to mitigate the risk of serotonin syndrome is to use an interaction index computer program, which can help ensure that the interacting agents are not prescribed without first discussing the risks and benefits. It is important to teach adolescents that certain recreational drugs are highly serotonergic and can cause serious interactions with antidepressants. For example, recreational use of dextrometh­orphan or 3,4-methylenedioxymethamphetamine (MDMA; commonly known as “ecstasy”) has been associated with serotonin syndrome in adolescents taking antidepressant medications.^42,43

Continue to: Suicidality

Suicidality. The black-box warning regarding a risk of emergent suicidality when starting antidepressant treatment in children is controversial.⁴⁴ The prospect that a medication intended to ameliorate depression might instead risk increasing suicidal thinking is alarming to parents and clinicians alike. To appropriately weigh and discuss the risks and benefits with families, it is important to understand the data upon which the warning is based.

In 2004, the FDA commissioned a review of 23 antidepressant trials, both published and unpublished, pooling studies across multiple indications (MDD, OCD, anxiety, and ADHD) and multiple antidepressant classes. This meta-analysis, which included nearly 4,400 pediatric patients, found a small but statistically significant increase in spontaneously-reported suicidal thoughts or actions, with a risk difference of 1% (95% confidence interval [CI], 1% to 2%).⁴⁵ These data suggest that if one treats 100 pediatric patients, 1 to 2 of them may experience short-term increases in suicidal thinking or behavior.⁴⁵ There were no differences in suicidal thinking when assessed systematically (ie, when all subjects reported symptoms of suicidal ideation on structured rating scales), and there were no completed suicides.⁴⁵ A subsequent analysis that included 27 pediatric trials suggested an even lower, although still significant, risk difference (<1%), yielding a number needed to harm (NNH) of 143.⁴⁶ Thus, with low NNT for efficacy (3 to 6) and relatively high NNH for emergent suicidal thoughts or behaviors (100 to 143), for many patients the benefits will outweigh the risks.

Figure 1, Figure 2, and Figure 3 are Cates plots that depict the absolute benefits of antidepressants compared with the risk of suicidality for pediatric patients with MDD, OCD, and anxiety disorders. Recent meta-analyses have suggested that the increased risk of suicidality in antidepressant trials is specific to studies that included children and adolescents, and is not observed in adult studies. A meta-analysis of 70 trials involving 18,526 participants suggested that the odds ratio of suicidality in trials of children and adolescents was 2.39 (95% CI, 1.31 to 4.33) compared with 0.81 (95% CI, 0.51 to 1.28) in adults.⁴⁷ Additionally, a network meta-analysis exclusively focusing on pediatric antidepressant trials in MDD reported significantly higher suicidality-related adverse events in venlafaxine trials compared with placebo, duloxetine, and several SSRIs (fluoxetine, paroxetine, and escitalopram).²⁰ These data should be interpreted with caution as differences in suicidality detected between agents is quite possibly related to differences in the method of assessment between trials, as opposed to actual differences in risk between agents.

Epidemiologic data further support the use of antidepressants in pediatric patients, showing that antidepressant use is associated with decreased teen suicide attempts and completions,⁴⁸ and the decline in prescriptions that occurred following the black-box warning was accompanied by a 14% increase in teen suicides.⁴⁹ Multiple hypotheses have been proposed to explain the pediatric clinical trial findings. One idea is that potential adverse effects of activation, or the intended effects of restoring the motivation, energy, and social engagement that is often impaired in depression, increases the likelihood of thinking about suicide or acting on thoughts. Another theory is that reporting of suicidality may be increased, rather than increased de novo suicidality itself. Antidepressants are effective for treating pediatric anxiety disorders, including social anxiety disorder,¹⁶ which could result in more willingness to report. Also, the manner in which adverse effects are generally ascertained in trials might have led to increased spontaneous reporting. In many trials, investigators ask whether participants have any adverse effects in general, and inquire about specific adverse effects only if the family answers affirmatively. Thus, the increased rate of other adverse effects associated with antidepressants (sleep problems, gastrointestinal upset, dry mouth, etc.) might trigger a specific question regarding suicidal ideation, which the child or family then may be more likely to report. Alternatively, any type of psychiatric treatment could increase an individual’s propensity to report; in adolescent psychotherapy trials, non-medicated participants have reported emergent suicidality at similar frequencies as those described in drug trials.⁵⁰ Regardless of the mechanism, the possibility of treatment-emergent suicidality is a low-frequency but serious event that necessitates careful monitoring when starting medication. Current guidelines suggest seeing children weekly for the first month after medication initiation, every 2 weeks for the following month, and monthly thereafter.⁵¹

Continue to: How long should the antidepressant be continued?

How long should the antidepressant be continued?

Many patients are concerned about how long they may be taking medication, and whether they will be taking an antidepressant “forever.” A treatment course can be broken into an acute phase, wherein remission is achieved and maintained for 6 to 8 weeks. This is followed by a continuation phase, with the goal of relapse prevention, lasting 16 to 20 weeks. The length of the last phase—the maintenance phase—depends both on the child’s history, the underlying therapeutic indication, the adverse effect burden experienced, and the family’s preferences/values. In general, for a first depressive episode, after treating for 1 year, a trial of discontinuation can be attempted with close monitoring. For a second depressive episode, we recommend 2 years of remission on antidepressant therapy before attempting discontinuation. In patients who have had 3 depressive episodes, or have had episodes of high severity, we recommend continuing antidepressant treatment indefinitely. Although much less well studied, the risk of relapse following SSRI discontinuation appears much more significant in OCD, whereas anxiety disorders and MDD have a relatively comparable risk.⁵²

In general, stopping an antidepressant should be done carefully and slowly. The speed with which a specific antidepressant can be stopped is largely related to its half-life. Agents with very long half-lives, such as fluoxetine (half-life of 5 days for the parent compound and 9 days for active metabolite), can often be stopped altogether, being “auto-tapered” by the long half-life. One might still consider a taper if the patient were taking high doses. Medications with shorter half-lives must be more carefully tapered to avoid discontinuation syndromes. Discontinuation syndromes are characterized by flu-like symptoms (nausea, myalgias, fatigue, dizziness) and worsening mood. Medications with short half-lives (eg, paroxetine and venlafaxine) have the highest potential for this syndrome in children,⁵³ and thus are used less frequently.

What to do when first-line treatments fail

When a child does not experience sufficient improvement from first-line treatments, it is crucial to determine whether they have experienced an adequate dosing, duration, and quality of medication and psychotherapy.

Adequate psychotherapy? To determine whether children are receiving adequate CBT, ask:

1. if the child receives homework from psychotherapy
2. if the parents are included in treatment
3. if therapy has involved identifying thought patterns that may be contributing to the child’s illness, and
4. if the therapist has ever exposed the child to a challenge likely to produce anxiety or distress in a supervised environment and has developed an exposure hierarchy (for conditions with primarily exposure-based therapies, such as OCD or anxiety disorders).

If a family is not receiving most of these elements in psychotherapy, this is a good indicator that they may not be receiving evidence-based CBT.

Continue to: Adequate pharmacotherapy?

Adequate pharmacotherapy? Similarly, when determining the adequacy of previous pharmacotherapy, it is critical to determine whether the child received an adequate dose of medications (at least the FDA-recommended minimum dose) for an adequate duration of time at therapeutic dosing (at least 6 weeks for MDD, 8 weeks for anxiety disorders, and 8 to 12 weeks for pediatric patients with OCD), and that the child actually took the medication regularly during that period. Patient compliance can typically be tracked through checking refill requests or intervals through the patient’s pharmacy. Ensuring proper delivery of first-line treatments is imperative because (1) the adverse effects associated with second-line treatments are often more substantial; (2) the cost in terms of time and money is considerably higher with second-line treatments, and; (3) the evidence regarding the benefits of these treatments is much less certain.

Inadequate dosing is a common reason for non-response in pediatric patients. Therapeutic dose ranges for common antidepressants are displayed in Table 1. Many clinicians underdose antidepressants for pediatric patients initially (and often throughout treatment) because they fear that the typical dose titration used in clinical trials will increase the risk of adverse effects compared with more conservative dosing. There is limited evidence to suggest that this underdosing strategy is likely to be successful; adverse effects attributable to these medications are modest, and most that are experienced early in treatment (eg, headache, increased anxiety or irritability, sleep problems, gastrointestinal upset) are self-limiting and may be coincidental rather than medication-induced. Furthermore, there is no evidence for efficacy of subtherapeutic dosing in children in the acute phase of treatment or for preventing relapse.¹⁴ Thus, from an efficacy standpoint, a medication trial has not officially begun until the therapeutic dose range is reached.

Once dosing is within the therapeutic range, however, pediatric data differs from the adult literature. In most adult psychi­atric conditions, higher doses of SSRIs within the therapeutic range are associated with an increased response rate.^14,54 In pediatrics, there are few fixed dose trials, and once within the recommended therapeutic range, minimal data supports an association between higher dosing and higher efficacy.¹⁴ In general, pediatric guidelines are silent regarding optimal dosing of SSRIs within the recommended dose range, and higher antidepressant doses often result in a more significant adverse effect burden for children. One exception is pediatric OCD, where, similar to adults, the guidelines suggest that higher dosing of SSRIs often is required to induce a therapeutic response as compared to MDD and GAD.^31,55

If a child does not respond to adequate first-line treatment (or has a treatment history that cannot be fully verified), repeating these first-line interventions carries little risk and can be quite effective. For example, 60% of adolescents with MDD who did not initially respond to an SSRI demonstrated a significant response when prescribed a second SSRI or venlafaxine (with or without CBT).⁵⁶

When pediatric patients continue to experience significantly distressing and/or debilitating symptoms (particularly in MDD) despite multiple trials of antidepressants and psychotherapy, practitioners should consider a careful referral to interventional psychiatry services, which can include the more intensive treatments of electroconvulsive therapy, repetitive transcranial magnetic stimulation, or ketamine (see Box 1). Given the substantial morbidity and mortality associated with adolescent depression, interventional psychiatry treatments are under-researched and under-utilized clinically in pediatric populations.

Continue to: Antidepressants in general...

Antidepressants in general, and SSRIs in particular, are the first-line pharmacotherapy for pediatric anxiety, OCD, and MDD. For PTSD, although they are a first-line treatment in adults, their efficacy has not been demonstrated in children and adolescents. Antidepressants are generally safe, well-tolerated, and effective, with low NNTs (3 to 5 for anxiety and OCD; 4 to 12 in MDD, depending on whether industry trials are included). It is important that clinicians and families be educated about possible adverse effects and their time course in order to anticipate difficulties, ensure adequate informed consent, and monitor appropriately. The black-box warning regarding treatment-emergent suicidal thoughts or behaviors must be discussed (for suggested talking points, see Box 2). The NNH is large (100 to 143), and for many patients, the benefits will outweigh the risks. For pediatric patients who fail to respond to multiple adequate trials of antidepressants and psychotherapy, referrals for interventional psychiatry consultation should be considered.

Bottom Line

Although the evidence base for prescribing antidepressants for children and adolescents is smaller compared to the adult literature, properly understanding and prescribing these agents, and explaining their risks and benefits to families, can make a major difference in patient compliance, satisfaction, and outcomes. Antidepressants (particularly selective serotonin reuptake inhibitors) are the firstline pharmacologic intervention for pediatric patients with anxiety disorders, obsessive-compulsive disorder, or major depressive disorder.

Related Resource

• Bonin L, Moreland CS. Overview of prevention and treatment for pediatric depression. https://www.uptodate.com/contents/overview-of-prevention-and-treatment-for-pediatric-depression. Last reviewed July 2019.

Drug Brand Names

Bupropion • Wellbutrin, Zyban
Cimetidine • Tagamet
Citalopram • Celexa
Clomipramine • Anafranil
Desipramine • Norpramin
Desvenlafaxine • Pristiq
Duloxetine • Cymbalta
Escitalopram • Lexapro
Fluoxetine • Prozac
Fluvoxamine • Luvox
Imipramine • Tofranil
Mirtazapine • Remeron
Nortriptyline • Pamelor
Paroxetine • Paxil
Sertraline • Zoloft
Venlafaxine • Effexor
Vilazodone • Viibryd
Vortioxetine • Trintellix

Box 1

Box 2

Major depressive disorder (MDD) is a significant pediatric health problem, with a lifetime prevalence as high as 20% by the end of adolescence.^1-3 Major depressive disorder in adolescence is associated with significant morbidity, including poor social functioning, school difficulties, early pregnancy, and increased risk of physical illness and substance abuse.^4-6 It is also linked with significant mortality, with increased risk for suicide, which is now the second leading cause of death in individuals age 10 to 24 years.^1,7,8

As their name suggests, antidepressants comprise a group of medications that are used to treat MDD; they are also, however, first-line agents for generalized anxiety disorder (GAD), posttraumatic stress disorder (PTSD), and obsessive-compulsive disorder (OCD) in adults. Anxiety disorders (including GAD and other anxiety diagnoses) and PTSD are also common in childhood and adolescence with a combined lifetime prevalence ranging from 15% to 30%.^9,10 These disorders are also associated with increased risk of suicide.¹¹ For all of these disorders, depending on the severity of presentation and the preference of the patient, treatments are often a combination of psychotherapy and psychopharmacology.

Clinicians face several challenges when considering antidepressants for pediatric patients. Pediatricians and psychiatrists need to understand whether these medications work in children and adolescents, and whether there are unique developmental safety and tolerability issues. The evidence base in child psychiatry is considerably smaller compared with that of adult psychiatry. From this more limited evidence base also came the controversial “black-box” warning regarding a risk of emergent suicidality when starting antidepressants that accompanies all antidepressants for pediatric, but not adult, patients. This warning has had major effects on clinical encounters with children experiencing depression, including altering clinician prescribing behavior.¹²

In this article, we review the current evidence for antidepressant efficacy, tolerability, and safety in pediatric patients. We also suggest ways in which clinicians might choose, start, and stop antidepressants in children, as well as how to talk with parents about benefits, risks, and the black-box warning.

Do antidepressants work in children?

Selective serotonin reuptake inhibitors. Selective serotonin reuptake inhibitors (SSRIs) are the most commonly used class of antidepressants in both children and adults.¹³ While only a few SSRIs are FDA-approved for pediatric indications, the lack of FDA approval is typically related to a lack of sufficient testing in randomized controlled trials (RCTs) for specific pediatric indications, rather than to demonstrable differences in efficacy between antidepressant agents. Since there is currently no data to suggest inferiority of one agent compared to another in children or adults,^14,15 efficacy data will be discussed here as applied to the class of SSRIs, generalizing from RCTs conducted on individual drugs. Table 1 lists FDA indications and dosing information for individual antidepressants.

There is strong evidence that SSRIs are effective for treating pediatric anxiety disorders (eg, social anxiety disorder and GAD)¹⁶ and OCD,¹⁷ with numbers needed to treat (NNT) between 3 and 5. For both of these disorders, SSRIs combined with cognitive-behavioral therapy (CBT) have the highest likelihood of improving symptoms or achieving remission.^17,18

Selective serotonin reuptake inhibitors are also effective for treating pediatric MDD; however, the literature is more complex for this disorder compared to GAD and OCD as there are considerable differences in effect sizes between National Institute of Mental Health (NIMH)–funded studies and industry-sponsored trials.¹³ The major NIMH-sponsored adolescent depression trial, TADS (Treatment for Adolescents and Depression Study), showed that SSRIs (fluoxetine in this case) were quite effective, with an NNT of 4 over the acute phase (12 weeks).¹⁹ Ultimately, approximately 80% of adolescents improved over 9 months. Many industry-sponsored trials for MDD in pediatric patients had large placebo response rates (approximately 60%), which resulted in smaller between-group differences, and estimates of an NNT closer to 12,¹³ which has muddied the waters in meta-analyses that include all trials.²⁰ Improvement in depressive symptoms also appears to be bolstered by concomitant CBT in MDD,¹⁹ but not as robustly as in GAD and OCD. While the full benefit of SSRIs for depression may take as long as 8 weeks, a meta-analysis of depression studies of pediatric patients suggests that significant benefits from placebo are observed as early as 2 weeks, and that further treatment gains are minimal after 4 weeks.¹⁵ Thus, we recommend at least a 4- to 6-week trial at therapeutic dosing before deeming a medication a treatment failure.

Continue to: Posttraumatic stress disorder...

Posttraumatic stress disorder is a fourth disorder in which SSRIs are a first-line treatment in adults. The data for using SSRIs to treat pediatric patients with PTSD is scant, with only a few RCTs, and no large NIMH-funded trials. Randomized controlled trials have not demonstrated significant differences between SSRIs and placebo^21,22 and thus the current first-line recommendation in pediatric PTSD remains trauma-focused therapy, with good evidence for trauma-focused CBT.²³ Practically speaking, there can be considerable overlap of PTSD, depression, and anxiety symptoms in children,²³ and children with a history of trauma who also have comorbid MDD may benefit from medication if their symptoms persist despite an adequate trial of psychotherapy.

Taken together, the current evidence suggests that SSRIs are often effective in pediatric GAD, OCD, and MDD, with low NNTs (ranging from 3 to 5 based on NIMH-funded trials) for all of these disorders; there is not yet sufficient evidence of efficacy in pediatric patients with PTSD.

Fluoxetine has been studied more intensively than other SSRIs (for example, it was the antidepressant used in the TADS trial), and thus has the largest evidence base. For this reason, fluoxetine is often considered the first of the first-line options. Additionally, fluoxetine has a longer half-life than other antidepressants, which may make it more effective in situations where patients are likely to miss doses, and results in a lower risk of withdrawal symptoms when stopped due to “self-tapering.”

SNRIs and atypical antidepressants. Other antidepressants commonly used in pediatric patients but with far less evidence of efficacy include serotonin-norepinephrine reuptake inhibitors (SNRIs) and the atypical antidepressants bupropion and mirtazapine. The SNRI duloxetine is FDA-approved for treating GAD in children age 7 to 17, but there are no other pediatric indications for duloxetine, or for the other SNRIs.

In general, adverse effect profiles are worse for SNRIs compared to SSRIs, further limiting their utility. While there are no pediatric studies demonstrating SNRI efficacy for neuropathic pain, good data exists in adults.²⁴ Thus, an SNRI could be a reasonable option if a pediatric patient has failed prior adequate SSRI trials and also has comorbid neuropathic pain.

Continue to: Neither bupropion nor mirtazapine...

Neither bupropion nor mirtazapine have undergone rigorous testing in pediatric patients, and therefore these agents should generally be considered only once other first-line treatments have failed. Bupropion has been evaluated for attention-deficit/hyperactivity disorder (ADHD)²⁵ and for adolescent smoking cessation.²⁶ However, the evidence is weak, and bupropion is not considered a first-line option for children and adolescents.

Tricyclic antidepressants. Randomized controlled trials have demonstrated that tricyclic antidepressants (TCAs) are efficacious for treating several pediatric conditions; however, their significant side effect profile, their monitoring requirements, as well as their lethality in overdose has left them replaced by SSRIs in most cases. That said, they can be appropriate in refractory ADHD (desipramine^27,28) and refractory OCD (clomipramine is FDA-approved for this indication²⁹); they are considered a third-line treatment for enuresis.³⁰

Why did my patient stop the medication?

Common adverse effects. Although the greatest benefit of antidepressant medications compared with placebo is achieved relatively early on in treatment, it generally takes time for these benefits to accrue and become clinically apparent.^15,31 By contrast, most adverse effects of antidepressants present and are at their most severe early in treatment. The combination of early adverse effects and delayed efficacy leads many patients, families, and clinicians to discontinue medications before they have an adequate chance to work. Thus, it is imperative to provide psychoeducation before starting a medication about the typical time-course of improvement and adverse effects (Table 2).

Adverse effects of SSRIs often appear or worsen transiently during initiation of a medication, during a dose increase,³² or, theoretically, with the addition of a medication that interferes with SSRI metabolism (eg, cimetidine inhibition of cytochrome P450 2D6).³³ If families are prepared for this phenomenon and the therapeutic alliance is adequate, adverse effects can be tolerated to allow for a full medication trial. Common adverse effects of SSRIs include sleep problems (insomnia/sedation), gastrointestinal upset, sexual dysfunction, dry mouth, and hyperhidrosis. Although SSRIs differ somewhat in the frequency of these effects, as a class, they are more similar than different. Adequate psychoeducation is especially imperative in the treatment of OCD and anxiety disorders, where there is limited evidence of efficacy for any non-serotonergic antidepressants.

Serotonin-norepinephrine reuptake inhibitors are not considered first-line medications because of the reduced evidence base compared to SSRIs and their enhanced adverse effect profiles. Because SNRIs partially share a mechanism of action with SSRIs, they also share portions of the adverse effects profile. However, SNRIs have the additional adverse effect of hypertension, which is related to their noradrenergic activity. Thus, it is reasonable to obtain a baseline blood pressure before initiating an SNRI, as well as periodically after initiation and during dose increases, particularly if the patient has other risk factors for hypertension.³⁴

Continue to: Although TCAs have efficacy...

Although TCAs have efficacy in some pediatric disorders,^27-29,35 their adverse effect profile limits their use. Tricyclic antidepressants are highly anticholinergic (causing dizziness secondary to orthostatic hypotension, dry mouth, and urinary retention) and antihistaminergic (causing sedation and weight gain). Additionally, TCAs lower the seizure threshold and have adverse cardiac effects relating to their anti-alpha-1 adrenergic activity, resulting in dose-dependent increases in the QTc and cardiac toxicity in overdose that could lead to arrhythmia and death. These medications have their place, but their use requires careful informed consent, clear treatment goals, and baseline and periodic cardiac monitoring (via electrocardiogram).

Serious adverse effects. Clinicians may be hesitant to prescribe antidepressants for pediatric patients because of the potential for more serious adverse effects, including severe behavioral activation syndromes, serotonin syndrome, and emergent suicidality. However, current FDA-approved antidepressants arguably have one of the most positive risk/benefit profiles of any orally-administered medication approved for pediatric patients. Having a strong understanding of the evidence is critical to evaluating when it is appropriate to prescribe an antidepressant, how to properly monitor the patient, and how to obtain accurate informed consent.

Pediatric behavioral activation syndrome. Many clinicians report that children receiving antidepressants experience a pediatric behavioral activation syndrome, which exists along a spectrum from mild activation, increased energy, insomnia, or irritability up through more severe presentations of agitation, hyperactivity, or possibly mania. A recent meta-analysis suggested a positive association between antidepressant use and activation events on the milder end of this spectrum in pediatric patients with non-OCD anxiety disorders,¹⁶ and it is thought that compared with adolescents, younger children are more susceptible to activation adverse effects.³⁶ The likelihood of activation events has been associated with higher antidepressant plasma levels,³⁷ suggesting that dose or individual differences in metabolism may play a role. At the severe end of the spectrum, the risk of induction of mania in pediatric patients with depression or anxiety is relatively rare (<2%) and not statistically different from placebo in RCTs of pediatric participants.³⁸ Meta-analyses of larger randomized, placebo-controlled trials of adults do not support the idea that SSRIs and other second-generation antidepressants carry an increased risk of mania compared with placebo.^39,40 Children or adolescents with bona fide bipolar disorder (ie, patients who have had observed mania that meets all DSM-5 criteria) should be treated with a mood-stabilizing agent or antipsychotic if prescribed an antidepressant.⁴¹ These clear-cut cases are, however, relatively rare, and more often clinicians are confronted with ambiguous cases that include a family history of bipolar disorder along with “softer” symptoms of irritability, intrusiveness, or aggression. In these children, SSRIs may be appropriate for depressive, OCD, or anxiety symptoms, and should be strongly considered before prescribing antipsychotics or mood stabilizers, as long as initiated with proper monitoring.

Serotonin syndrome is a life-threatening condition caused by excess synaptic serotonin. It is characterized by confusion, sweating, diarrhea, hypertension, hyperthermia, and tachycardia. At its most severe, serotonin syndrome can result in seizures, arrhythmias, and death. The risk of serotonin syndrome is very low when using an SSRI as monotherapy. Risk increases with polypharmacy, particularly unexamined polypharmacy when multiple serotonergic agents are inadvertently on board. Commonly used serotonergic agents include other antidepressants, migraine medications (eg, triptans), some pain medications, and the cough suppressant dextromethorphan.

The easiest way to mitigate the risk of serotonin syndrome is to use an interaction index computer program, which can help ensure that the interacting agents are not prescribed without first discussing the risks and benefits. It is important to teach adolescents that certain recreational drugs are highly serotonergic and can cause serious interactions with antidepressants. For example, recreational use of dextrometh­orphan or 3,4-methylenedioxymethamphetamine (MDMA; commonly known as “ecstasy”) has been associated with serotonin syndrome in adolescents taking antidepressant medications.^42,43

Continue to: Suicidality

Suicidality. The black-box warning regarding a risk of emergent suicidality when starting antidepressant treatment in children is controversial.⁴⁴ The prospect that a medication intended to ameliorate depression might instead risk increasing suicidal thinking is alarming to parents and clinicians alike. To appropriately weigh and discuss the risks and benefits with families, it is important to understand the data upon which the warning is based.

In 2004, the FDA commissioned a review of 23 antidepressant trials, both published and unpublished, pooling studies across multiple indications (MDD, OCD, anxiety, and ADHD) and multiple antidepressant classes. This meta-analysis, which included nearly 4,400 pediatric patients, found a small but statistically significant increase in spontaneously-reported suicidal thoughts or actions, with a risk difference of 1% (95% confidence interval [CI], 1% to 2%).⁴⁵ These data suggest that if one treats 100 pediatric patients, 1 to 2 of them may experience short-term increases in suicidal thinking or behavior.⁴⁵ There were no differences in suicidal thinking when assessed systematically (ie, when all subjects reported symptoms of suicidal ideation on structured rating scales), and there were no completed suicides.⁴⁵ A subsequent analysis that included 27 pediatric trials suggested an even lower, although still significant, risk difference (<1%), yielding a number needed to harm (NNH) of 143.⁴⁶ Thus, with low NNT for efficacy (3 to 6) and relatively high NNH for emergent suicidal thoughts or behaviors (100 to 143), for many patients the benefits will outweigh the risks.

Figure 1, Figure 2, and Figure 3 are Cates plots that depict the absolute benefits of antidepressants compared with the risk of suicidality for pediatric patients with MDD, OCD, and anxiety disorders. Recent meta-analyses have suggested that the increased risk of suicidality in antidepressant trials is specific to studies that included children and adolescents, and is not observed in adult studies. A meta-analysis of 70 trials involving 18,526 participants suggested that the odds ratio of suicidality in trials of children and adolescents was 2.39 (95% CI, 1.31 to 4.33) compared with 0.81 (95% CI, 0.51 to 1.28) in adults.⁴⁷ Additionally, a network meta-analysis exclusively focusing on pediatric antidepressant trials in MDD reported significantly higher suicidality-related adverse events in venlafaxine trials compared with placebo, duloxetine, and several SSRIs (fluoxetine, paroxetine, and escitalopram).²⁰ These data should be interpreted with caution as differences in suicidality detected between agents is quite possibly related to differences in the method of assessment between trials, as opposed to actual differences in risk between agents.

Epidemiologic data further support the use of antidepressants in pediatric patients, showing that antidepressant use is associated with decreased teen suicide attempts and completions,⁴⁸ and the decline in prescriptions that occurred following the black-box warning was accompanied by a 14% increase in teen suicides.⁴⁹ Multiple hypotheses have been proposed to explain the pediatric clinical trial findings. One idea is that potential adverse effects of activation, or the intended effects of restoring the motivation, energy, and social engagement that is often impaired in depression, increases the likelihood of thinking about suicide or acting on thoughts. Another theory is that reporting of suicidality may be increased, rather than increased de novo suicidality itself. Antidepressants are effective for treating pediatric anxiety disorders, including social anxiety disorder,¹⁶ which could result in more willingness to report. Also, the manner in which adverse effects are generally ascertained in trials might have led to increased spontaneous reporting. In many trials, investigators ask whether participants have any adverse effects in general, and inquire about specific adverse effects only if the family answers affirmatively. Thus, the increased rate of other adverse effects associated with antidepressants (sleep problems, gastrointestinal upset, dry mouth, etc.) might trigger a specific question regarding suicidal ideation, which the child or family then may be more likely to report. Alternatively, any type of psychiatric treatment could increase an individual’s propensity to report; in adolescent psychotherapy trials, non-medicated participants have reported emergent suicidality at similar frequencies as those described in drug trials.⁵⁰ Regardless of the mechanism, the possibility of treatment-emergent suicidality is a low-frequency but serious event that necessitates careful monitoring when starting medication. Current guidelines suggest seeing children weekly for the first month after medication initiation, every 2 weeks for the following month, and monthly thereafter.⁵¹

Continue to: How long should the antidepressant be continued?

How long should the antidepressant be continued?

Many patients are concerned about how long they may be taking medication, and whether they will be taking an antidepressant “forever.” A treatment course can be broken into an acute phase, wherein remission is achieved and maintained for 6 to 8 weeks. This is followed by a continuation phase, with the goal of relapse prevention, lasting 16 to 20 weeks. The length of the last phase—the maintenance phase—depends both on the child’s history, the underlying therapeutic indication, the adverse effect burden experienced, and the family’s preferences/values. In general, for a first depressive episode, after treating for 1 year, a trial of discontinuation can be attempted with close monitoring. For a second depressive episode, we recommend 2 years of remission on antidepressant therapy before attempting discontinuation. In patients who have had 3 depressive episodes, or have had episodes of high severity, we recommend continuing antidepressant treatment indefinitely. Although much less well studied, the risk of relapse following SSRI discontinuation appears much more significant in OCD, whereas anxiety disorders and MDD have a relatively comparable risk.⁵²

In general, stopping an antidepressant should be done carefully and slowly. The speed with which a specific antidepressant can be stopped is largely related to its half-life. Agents with very long half-lives, such as fluoxetine (half-life of 5 days for the parent compound and 9 days for active metabolite), can often be stopped altogether, being “auto-tapered” by the long half-life. One might still consider a taper if the patient were taking high doses. Medications with shorter half-lives must be more carefully tapered to avoid discontinuation syndromes. Discontinuation syndromes are characterized by flu-like symptoms (nausea, myalgias, fatigue, dizziness) and worsening mood. Medications with short half-lives (eg, paroxetine and venlafaxine) have the highest potential for this syndrome in children,⁵³ and thus are used less frequently.

What to do when first-line treatments fail

When a child does not experience sufficient improvement from first-line treatments, it is crucial to determine whether they have experienced an adequate dosing, duration, and quality of medication and psychotherapy.

Adequate psychotherapy? To determine whether children are receiving adequate CBT, ask:

1. if the child receives homework from psychotherapy
2. if the parents are included in treatment
3. if therapy has involved identifying thought patterns that may be contributing to the child’s illness, and
4. if the therapist has ever exposed the child to a challenge likely to produce anxiety or distress in a supervised environment and has developed an exposure hierarchy (for conditions with primarily exposure-based therapies, such as OCD or anxiety disorders).

If a family is not receiving most of these elements in psychotherapy, this is a good indicator that they may not be receiving evidence-based CBT.

Continue to: Adequate pharmacotherapy?

Adequate pharmacotherapy? Similarly, when determining the adequacy of previous pharmacotherapy, it is critical to determine whether the child received an adequate dose of medications (at least the FDA-recommended minimum dose) for an adequate duration of time at therapeutic dosing (at least 6 weeks for MDD, 8 weeks for anxiety disorders, and 8 to 12 weeks for pediatric patients with OCD), and that the child actually took the medication regularly during that period. Patient compliance can typically be tracked through checking refill requests or intervals through the patient’s pharmacy. Ensuring proper delivery of first-line treatments is imperative because (1) the adverse effects associated with second-line treatments are often more substantial; (2) the cost in terms of time and money is considerably higher with second-line treatments, and; (3) the evidence regarding the benefits of these treatments is much less certain.

Inadequate dosing is a common reason for non-response in pediatric patients. Therapeutic dose ranges for common antidepressants are displayed in Table 1. Many clinicians underdose antidepressants for pediatric patients initially (and often throughout treatment) because they fear that the typical dose titration used in clinical trials will increase the risk of adverse effects compared with more conservative dosing. There is limited evidence to suggest that this underdosing strategy is likely to be successful; adverse effects attributable to these medications are modest, and most that are experienced early in treatment (eg, headache, increased anxiety or irritability, sleep problems, gastrointestinal upset) are self-limiting and may be coincidental rather than medication-induced. Furthermore, there is no evidence for efficacy of subtherapeutic dosing in children in the acute phase of treatment or for preventing relapse.¹⁴ Thus, from an efficacy standpoint, a medication trial has not officially begun until the therapeutic dose range is reached.

Once dosing is within the therapeutic range, however, pediatric data differs from the adult literature. In most adult psychi­atric conditions, higher doses of SSRIs within the therapeutic range are associated with an increased response rate.^14,54 In pediatrics, there are few fixed dose trials, and once within the recommended therapeutic range, minimal data supports an association between higher dosing and higher efficacy.¹⁴ In general, pediatric guidelines are silent regarding optimal dosing of SSRIs within the recommended dose range, and higher antidepressant doses often result in a more significant adverse effect burden for children. One exception is pediatric OCD, where, similar to adults, the guidelines suggest that higher dosing of SSRIs often is required to induce a therapeutic response as compared to MDD and GAD.^31,55

If a child does not respond to adequate first-line treatment (or has a treatment history that cannot be fully verified), repeating these first-line interventions carries little risk and can be quite effective. For example, 60% of adolescents with MDD who did not initially respond to an SSRI demonstrated a significant response when prescribed a second SSRI or venlafaxine (with or without CBT).⁵⁶

When pediatric patients continue to experience significantly distressing and/or debilitating symptoms (particularly in MDD) despite multiple trials of antidepressants and psychotherapy, practitioners should consider a careful referral to interventional psychiatry services, which can include the more intensive treatments of electroconvulsive therapy, repetitive transcranial magnetic stimulation, or ketamine (see Box 1). Given the substantial morbidity and mortality associated with adolescent depression, interventional psychiatry treatments are under-researched and under-utilized clinically in pediatric populations.

Continue to: Antidepressants in general...

Antidepressants in general, and SSRIs in particular, are the first-line pharmacotherapy for pediatric anxiety, OCD, and MDD. For PTSD, although they are a first-line treatment in adults, their efficacy has not been demonstrated in children and adolescents. Antidepressants are generally safe, well-tolerated, and effective, with low NNTs (3 to 5 for anxiety and OCD; 4 to 12 in MDD, depending on whether industry trials are included). It is important that clinicians and families be educated about possible adverse effects and their time course in order to anticipate difficulties, ensure adequate informed consent, and monitor appropriately. The black-box warning regarding treatment-emergent suicidal thoughts or behaviors must be discussed (for suggested talking points, see Box 2). The NNH is large (100 to 143), and for many patients, the benefits will outweigh the risks. For pediatric patients who fail to respond to multiple adequate trials of antidepressants and psychotherapy, referrals for interventional psychiatry consultation should be considered.

Bottom Line

Although the evidence base for prescribing antidepressants for children and adolescents is smaller compared to the adult literature, properly understanding and prescribing these agents, and explaining their risks and benefits to families, can make a major difference in patient compliance, satisfaction, and outcomes. Antidepressants (particularly selective serotonin reuptake inhibitors) are the firstline pharmacologic intervention for pediatric patients with anxiety disorders, obsessive-compulsive disorder, or major depressive disorder.

Related Resource

• Bonin L, Moreland CS. Overview of prevention and treatment for pediatric depression. https://www.uptodate.com/contents/overview-of-prevention-and-treatment-for-pediatric-depression. Last reviewed July 2019.

Drug Brand Names

Bupropion • Wellbutrin, Zyban
Cimetidine • Tagamet
Citalopram • Celexa
Clomipramine • Anafranil
Desipramine • Norpramin
Desvenlafaxine • Pristiq
Duloxetine • Cymbalta
Escitalopram • Lexapro
Fluoxetine • Prozac
Fluvoxamine • Luvox
Imipramine • Tofranil
Mirtazapine • Remeron
Nortriptyline • Pamelor
Paroxetine • Paxil
Sertraline • Zoloft
Venlafaxine • Effexor
Vilazodone • Viibryd
Vortioxetine • Trintellix

Box 1

Box 2

Major depressive disorder (MDD) is a significant pediatric health problem, with a lifetime prevalence as high as 20% by the end of adolescence.^1-3 Major depressive disorder in adolescence is associated with significant morbidity, including poor social functioning, school difficulties, early pregnancy, and increased risk of physical illness and substance abuse.^4-6 It is also linked with significant mortality, with increased risk for suicide, which is now the second leading cause of death in individuals age 10 to 24 years.^1,7,8

As their name suggests, antidepressants comprise a group of medications that are used to treat MDD; they are also, however, first-line agents for generalized anxiety disorder (GAD), posttraumatic stress disorder (PTSD), and obsessive-compulsive disorder (OCD) in adults. Anxiety disorders (including GAD and other anxiety diagnoses) and PTSD are also common in childhood and adolescence with a combined lifetime prevalence ranging from 15% to 30%.^9,10 These disorders are also associated with increased risk of suicide.¹¹ For all of these disorders, depending on the severity of presentation and the preference of the patient, treatments are often a combination of psychotherapy and psychopharmacology.

Clinicians face several challenges when considering antidepressants for pediatric patients. Pediatricians and psychiatrists need to understand whether these medications work in children and adolescents, and whether there are unique developmental safety and tolerability issues. The evidence base in child psychiatry is considerably smaller compared with that of adult psychiatry. From this more limited evidence base also came the controversial “black-box” warning regarding a risk of emergent suicidality when starting antidepressants that accompanies all antidepressants for pediatric, but not adult, patients. This warning has had major effects on clinical encounters with children experiencing depression, including altering clinician prescribing behavior.¹²

In this article, we review the current evidence for antidepressant efficacy, tolerability, and safety in pediatric patients. We also suggest ways in which clinicians might choose, start, and stop antidepressants in children, as well as how to talk with parents about benefits, risks, and the black-box warning.

Do antidepressants work in children?

Selective serotonin reuptake inhibitors. Selective serotonin reuptake inhibitors (SSRIs) are the most commonly used class of antidepressants in both children and adults.¹³ While only a few SSRIs are FDA-approved for pediatric indications, the lack of FDA approval is typically related to a lack of sufficient testing in randomized controlled trials (RCTs) for specific pediatric indications, rather than to demonstrable differences in efficacy between antidepressant agents. Since there is currently no data to suggest inferiority of one agent compared to another in children or adults,^14,15 efficacy data will be discussed here as applied to the class of SSRIs, generalizing from RCTs conducted on individual drugs. Table 1 lists FDA indications and dosing information for individual antidepressants.

There is strong evidence that SSRIs are effective for treating pediatric anxiety disorders (eg, social anxiety disorder and GAD)¹⁶ and OCD,¹⁷ with numbers needed to treat (NNT) between 3 and 5. For both of these disorders, SSRIs combined with cognitive-behavioral therapy (CBT) have the highest likelihood of improving symptoms or achieving remission.^17,18

Selective serotonin reuptake inhibitors are also effective for treating pediatric MDD; however, the literature is more complex for this disorder compared to GAD and OCD as there are considerable differences in effect sizes between National Institute of Mental Health (NIMH)–funded studies and industry-sponsored trials.¹³ The major NIMH-sponsored adolescent depression trial, TADS (Treatment for Adolescents and Depression Study), showed that SSRIs (fluoxetine in this case) were quite effective, with an NNT of 4 over the acute phase (12 weeks).¹⁹ Ultimately, approximately 80% of adolescents improved over 9 months. Many industry-sponsored trials for MDD in pediatric patients had large placebo response rates (approximately 60%), which resulted in smaller between-group differences, and estimates of an NNT closer to 12,¹³ which has muddied the waters in meta-analyses that include all trials.²⁰ Improvement in depressive symptoms also appears to be bolstered by concomitant CBT in MDD,¹⁹ but not as robustly as in GAD and OCD. While the full benefit of SSRIs for depression may take as long as 8 weeks, a meta-analysis of depression studies of pediatric patients suggests that significant benefits from placebo are observed as early as 2 weeks, and that further treatment gains are minimal after 4 weeks.¹⁵ Thus, we recommend at least a 4- to 6-week trial at therapeutic dosing before deeming a medication a treatment failure.

Continue to: Posttraumatic stress disorder...

Posttraumatic stress disorder is a fourth disorder in which SSRIs are a first-line treatment in adults. The data for using SSRIs to treat pediatric patients with PTSD is scant, with only a few RCTs, and no large NIMH-funded trials. Randomized controlled trials have not demonstrated significant differences between SSRIs and placebo^21,22 and thus the current first-line recommendation in pediatric PTSD remains trauma-focused therapy, with good evidence for trauma-focused CBT.²³ Practically speaking, there can be considerable overlap of PTSD, depression, and anxiety symptoms in children,²³ and children with a history of trauma who also have comorbid MDD may benefit from medication if their symptoms persist despite an adequate trial of psychotherapy.

Taken together, the current evidence suggests that SSRIs are often effective in pediatric GAD, OCD, and MDD, with low NNTs (ranging from 3 to 5 based on NIMH-funded trials) for all of these disorders; there is not yet sufficient evidence of efficacy in pediatric patients with PTSD.

Fluoxetine has been studied more intensively than other SSRIs (for example, it was the antidepressant used in the TADS trial), and thus has the largest evidence base. For this reason, fluoxetine is often considered the first of the first-line options. Additionally, fluoxetine has a longer half-life than other antidepressants, which may make it more effective in situations where patients are likely to miss doses, and results in a lower risk of withdrawal symptoms when stopped due to “self-tapering.”

SNRIs and atypical antidepressants. Other antidepressants commonly used in pediatric patients but with far less evidence of efficacy include serotonin-norepinephrine reuptake inhibitors (SNRIs) and the atypical antidepressants bupropion and mirtazapine. The SNRI duloxetine is FDA-approved for treating GAD in children age 7 to 17, but there are no other pediatric indications for duloxetine, or for the other SNRIs.

In general, adverse effect profiles are worse for SNRIs compared to SSRIs, further limiting their utility. While there are no pediatric studies demonstrating SNRI efficacy for neuropathic pain, good data exists in adults.²⁴ Thus, an SNRI could be a reasonable option if a pediatric patient has failed prior adequate SSRI trials and also has comorbid neuropathic pain.

Continue to: Neither bupropion nor mirtazapine...

Neither bupropion nor mirtazapine have undergone rigorous testing in pediatric patients, and therefore these agents should generally be considered only once other first-line treatments have failed. Bupropion has been evaluated for attention-deficit/hyperactivity disorder (ADHD)²⁵ and for adolescent smoking cessation.²⁶ However, the evidence is weak, and bupropion is not considered a first-line option for children and adolescents.

Tricyclic antidepressants. Randomized controlled trials have demonstrated that tricyclic antidepressants (TCAs) are efficacious for treating several pediatric conditions; however, their significant side effect profile, their monitoring requirements, as well as their lethality in overdose has left them replaced by SSRIs in most cases. That said, they can be appropriate in refractory ADHD (desipramine^27,28) and refractory OCD (clomipramine is FDA-approved for this indication²⁹); they are considered a third-line treatment for enuresis.³⁰

Why did my patient stop the medication?

Common adverse effects. Although the greatest benefit of antidepressant medications compared with placebo is achieved relatively early on in treatment, it generally takes time for these benefits to accrue and become clinically apparent.^15,31 By contrast, most adverse effects of antidepressants present and are at their most severe early in treatment. The combination of early adverse effects and delayed efficacy leads many patients, families, and clinicians to discontinue medications before they have an adequate chance to work. Thus, it is imperative to provide psychoeducation before starting a medication about the typical time-course of improvement and adverse effects (Table 2).

Adverse effects of SSRIs often appear or worsen transiently during initiation of a medication, during a dose increase,³² or, theoretically, with the addition of a medication that interferes with SSRI metabolism (eg, cimetidine inhibition of cytochrome P450 2D6).³³ If families are prepared for this phenomenon and the therapeutic alliance is adequate, adverse effects can be tolerated to allow for a full medication trial. Common adverse effects of SSRIs include sleep problems (insomnia/sedation), gastrointestinal upset, sexual dysfunction, dry mouth, and hyperhidrosis. Although SSRIs differ somewhat in the frequency of these effects, as a class, they are more similar than different. Adequate psychoeducation is especially imperative in the treatment of OCD and anxiety disorders, where there is limited evidence of efficacy for any non-serotonergic antidepressants.

Serotonin-norepinephrine reuptake inhibitors are not considered first-line medications because of the reduced evidence base compared to SSRIs and their enhanced adverse effect profiles. Because SNRIs partially share a mechanism of action with SSRIs, they also share portions of the adverse effects profile. However, SNRIs have the additional adverse effect of hypertension, which is related to their noradrenergic activity. Thus, it is reasonable to obtain a baseline blood pressure before initiating an SNRI, as well as periodically after initiation and during dose increases, particularly if the patient has other risk factors for hypertension.³⁴

Continue to: Although TCAs have efficacy...

Although TCAs have efficacy in some pediatric disorders,^27-29,35 their adverse effect profile limits their use. Tricyclic antidepressants are highly anticholinergic (causing dizziness secondary to orthostatic hypotension, dry mouth, and urinary retention) and antihistaminergic (causing sedation and weight gain). Additionally, TCAs lower the seizure threshold and have adverse cardiac effects relating to their anti-alpha-1 adrenergic activity, resulting in dose-dependent increases in the QTc and cardiac toxicity in overdose that could lead to arrhythmia and death. These medications have their place, but their use requires careful informed consent, clear treatment goals, and baseline and periodic cardiac monitoring (via electrocardiogram).

Serious adverse effects. Clinicians may be hesitant to prescribe antidepressants for pediatric patients because of the potential for more serious adverse effects, including severe behavioral activation syndromes, serotonin syndrome, and emergent suicidality. However, current FDA-approved antidepressants arguably have one of the most positive risk/benefit profiles of any orally-administered medication approved for pediatric patients. Having a strong understanding of the evidence is critical to evaluating when it is appropriate to prescribe an antidepressant, how to properly monitor the patient, and how to obtain accurate informed consent.

Pediatric behavioral activation syndrome. Many clinicians report that children receiving antidepressants experience a pediatric behavioral activation syndrome, which exists along a spectrum from mild activation, increased energy, insomnia, or irritability up through more severe presentations of agitation, hyperactivity, or possibly mania. A recent meta-analysis suggested a positive association between antidepressant use and activation events on the milder end of this spectrum in pediatric patients with non-OCD anxiety disorders,¹⁶ and it is thought that compared with adolescents, younger children are more susceptible to activation adverse effects.³⁶ The likelihood of activation events has been associated with higher antidepressant plasma levels,³⁷ suggesting that dose or individual differences in metabolism may play a role. At the severe end of the spectrum, the risk of induction of mania in pediatric patients with depression or anxiety is relatively rare (<2%) and not statistically different from placebo in RCTs of pediatric participants.³⁸ Meta-analyses of larger randomized, placebo-controlled trials of adults do not support the idea that SSRIs and other second-generation antidepressants carry an increased risk of mania compared with placebo.^39,40 Children or adolescents with bona fide bipolar disorder (ie, patients who have had observed mania that meets all DSM-5 criteria) should be treated with a mood-stabilizing agent or antipsychotic if prescribed an antidepressant.⁴¹ These clear-cut cases are, however, relatively rare, and more often clinicians are confronted with ambiguous cases that include a family history of bipolar disorder along with “softer” symptoms of irritability, intrusiveness, or aggression. In these children, SSRIs may be appropriate for depressive, OCD, or anxiety symptoms, and should be strongly considered before prescribing antipsychotics or mood stabilizers, as long as initiated with proper monitoring.

Serotonin syndrome is a life-threatening condition caused by excess synaptic serotonin. It is characterized by confusion, sweating, diarrhea, hypertension, hyperthermia, and tachycardia. At its most severe, serotonin syndrome can result in seizures, arrhythmias, and death. The risk of serotonin syndrome is very low when using an SSRI as monotherapy. Risk increases with polypharmacy, particularly unexamined polypharmacy when multiple serotonergic agents are inadvertently on board. Commonly used serotonergic agents include other antidepressants, migraine medications (eg, triptans), some pain medications, and the cough suppressant dextromethorphan.

The easiest way to mitigate the risk of serotonin syndrome is to use an interaction index computer program, which can help ensure that the interacting agents are not prescribed without first discussing the risks and benefits. It is important to teach adolescents that certain recreational drugs are highly serotonergic and can cause serious interactions with antidepressants. For example, recreational use of dextrometh­orphan or 3,4-methylenedioxymethamphetamine (MDMA; commonly known as “ecstasy”) has been associated with serotonin syndrome in adolescents taking antidepressant medications.^42,43

Continue to: Suicidality

Suicidality. The black-box warning regarding a risk of emergent suicidality when starting antidepressant treatment in children is controversial.⁴⁴ The prospect that a medication intended to ameliorate depression might instead risk increasing suicidal thinking is alarming to parents and clinicians alike. To appropriately weigh and discuss the risks and benefits with families, it is important to understand the data upon which the warning is based.

In 2004, the FDA commissioned a review of 23 antidepressant trials, both published and unpublished, pooling studies across multiple indications (MDD, OCD, anxiety, and ADHD) and multiple antidepressant classes. This meta-analysis, which included nearly 4,400 pediatric patients, found a small but statistically significant increase in spontaneously-reported suicidal thoughts or actions, with a risk difference of 1% (95% confidence interval [CI], 1% to 2%).⁴⁵ These data suggest that if one treats 100 pediatric patients, 1 to 2 of them may experience short-term increases in suicidal thinking or behavior.⁴⁵ There were no differences in suicidal thinking when assessed systematically (ie, when all subjects reported symptoms of suicidal ideation on structured rating scales), and there were no completed suicides.⁴⁵ A subsequent analysis that included 27 pediatric trials suggested an even lower, although still significant, risk difference (<1%), yielding a number needed to harm (NNH) of 143.⁴⁶ Thus, with low NNT for efficacy (3 to 6) and relatively high NNH for emergent suicidal thoughts or behaviors (100 to 143), for many patients the benefits will outweigh the risks.

Figure 1, Figure 2, and Figure 3 are Cates plots that depict the absolute benefits of antidepressants compared with the risk of suicidality for pediatric patients with MDD, OCD, and anxiety disorders. Recent meta-analyses have suggested that the increased risk of suicidality in antidepressant trials is specific to studies that included children and adolescents, and is not observed in adult studies. A meta-analysis of 70 trials involving 18,526 participants suggested that the odds ratio of suicidality in trials of children and adolescents was 2.39 (95% CI, 1.31 to 4.33) compared with 0.81 (95% CI, 0.51 to 1.28) in adults.⁴⁷ Additionally, a network meta-analysis exclusively focusing on pediatric antidepressant trials in MDD reported significantly higher suicidality-related adverse events in venlafaxine trials compared with placebo, duloxetine, and several SSRIs (fluoxetine, paroxetine, and escitalopram).²⁰ These data should be interpreted with caution as differences in suicidality detected between agents is quite possibly related to differences in the method of assessment between trials, as opposed to actual differences in risk between agents.

Epidemiologic data further support the use of antidepressants in pediatric patients, showing that antidepressant use is associated with decreased teen suicide attempts and completions,⁴⁸ and the decline in prescriptions that occurred following the black-box warning was accompanied by a 14% increase in teen suicides.⁴⁹ Multiple hypotheses have been proposed to explain the pediatric clinical trial findings. One idea is that potential adverse effects of activation, or the intended effects of restoring the motivation, energy, and social engagement that is often impaired in depression, increases the likelihood of thinking about suicide or acting on thoughts. Another theory is that reporting of suicidality may be increased, rather than increased de novo suicidality itself. Antidepressants are effective for treating pediatric anxiety disorders, including social anxiety disorder,¹⁶ which could result in more willingness to report. Also, the manner in which adverse effects are generally ascertained in trials might have led to increased spontaneous reporting. In many trials, investigators ask whether participants have any adverse effects in general, and inquire about specific adverse effects only if the family answers affirmatively. Thus, the increased rate of other adverse effects associated with antidepressants (sleep problems, gastrointestinal upset, dry mouth, etc.) might trigger a specific question regarding suicidal ideation, which the child or family then may be more likely to report. Alternatively, any type of psychiatric treatment could increase an individual’s propensity to report; in adolescent psychotherapy trials, non-medicated participants have reported emergent suicidality at similar frequencies as those described in drug trials.⁵⁰ Regardless of the mechanism, the possibility of treatment-emergent suicidality is a low-frequency but serious event that necessitates careful monitoring when starting medication. Current guidelines suggest seeing children weekly for the first month after medication initiation, every 2 weeks for the following month, and monthly thereafter.⁵¹

Continue to: How long should the antidepressant be continued?

How long should the antidepressant be continued?

Many patients are concerned about how long they may be taking medication, and whether they will be taking an antidepressant “forever.” A treatment course can be broken into an acute phase, wherein remission is achieved and maintained for 6 to 8 weeks. This is followed by a continuation phase, with the goal of relapse prevention, lasting 16 to 20 weeks. The length of the last phase—the maintenance phase—depends both on the child’s history, the underlying therapeutic indication, the adverse effect burden experienced, and the family’s preferences/values. In general, for a first depressive episode, after treating for 1 year, a trial of discontinuation can be attempted with close monitoring. For a second depressive episode, we recommend 2 years of remission on antidepressant therapy before attempting discontinuation. In patients who have had 3 depressive episodes, or have had episodes of high severity, we recommend continuing antidepressant treatment indefinitely. Although much less well studied, the risk of relapse following SSRI discontinuation appears much more significant in OCD, whereas anxiety disorders and MDD have a relatively comparable risk.⁵²

In general, stopping an antidepressant should be done carefully and slowly. The speed with which a specific antidepressant can be stopped is largely related to its half-life. Agents with very long half-lives, such as fluoxetine (half-life of 5 days for the parent compound and 9 days for active metabolite), can often be stopped altogether, being “auto-tapered” by the long half-life. One might still consider a taper if the patient were taking high doses. Medications with shorter half-lives must be more carefully tapered to avoid discontinuation syndromes. Discontinuation syndromes are characterized by flu-like symptoms (nausea, myalgias, fatigue, dizziness) and worsening mood. Medications with short half-lives (eg, paroxetine and venlafaxine) have the highest potential for this syndrome in children,⁵³ and thus are used less frequently.

What to do when first-line treatments fail

When a child does not experience sufficient improvement from first-line treatments, it is crucial to determine whether they have experienced an adequate dosing, duration, and quality of medication and psychotherapy.

Adequate psychotherapy? To determine whether children are receiving adequate CBT, ask:

1. if the child receives homework from psychotherapy
2. if the parents are included in treatment
3. if therapy has involved identifying thought patterns that may be contributing to the child’s illness, and
4. if the therapist has ever exposed the child to a challenge likely to produce anxiety or distress in a supervised environment and has developed an exposure hierarchy (for conditions with primarily exposure-based therapies, such as OCD or anxiety disorders).

If a family is not receiving most of these elements in psychotherapy, this is a good indicator that they may not be receiving evidence-based CBT.

Continue to: Adequate pharmacotherapy?

Adequate pharmacotherapy? Similarly, when determining the adequacy of previous pharmacotherapy, it is critical to determine whether the child received an adequate dose of medications (at least the FDA-recommended minimum dose) for an adequate duration of time at therapeutic dosing (at least 6 weeks for MDD, 8 weeks for anxiety disorders, and 8 to 12 weeks for pediatric patients with OCD), and that the child actually took the medication regularly during that period. Patient compliance can typically be tracked through checking refill requests or intervals through the patient’s pharmacy. Ensuring proper delivery of first-line treatments is imperative because (1) the adverse effects associated with second-line treatments are often more substantial; (2) the cost in terms of time and money is considerably higher with second-line treatments, and; (3) the evidence regarding the benefits of these treatments is much less certain.

Inadequate dosing is a common reason for non-response in pediatric patients. Therapeutic dose ranges for common antidepressants are displayed in Table 1. Many clinicians underdose antidepressants for pediatric patients initially (and often throughout treatment) because they fear that the typical dose titration used in clinical trials will increase the risk of adverse effects compared with more conservative dosing. There is limited evidence to suggest that this underdosing strategy is likely to be successful; adverse effects attributable to these medications are modest, and most that are experienced early in treatment (eg, headache, increased anxiety or irritability, sleep problems, gastrointestinal upset) are self-limiting and may be coincidental rather than medication-induced. Furthermore, there is no evidence for efficacy of subtherapeutic dosing in children in the acute phase of treatment or for preventing relapse.¹⁴ Thus, from an efficacy standpoint, a medication trial has not officially begun until the therapeutic dose range is reached.

Once dosing is within the therapeutic range, however, pediatric data differs from the adult literature. In most adult psychi­atric conditions, higher doses of SSRIs within the therapeutic range are associated with an increased response rate.^14,54 In pediatrics, there are few fixed dose trials, and once within the recommended therapeutic range, minimal data supports an association between higher dosing and higher efficacy.¹⁴ In general, pediatric guidelines are silent regarding optimal dosing of SSRIs within the recommended dose range, and higher antidepressant doses often result in a more significant adverse effect burden for children. One exception is pediatric OCD, where, similar to adults, the guidelines suggest that higher dosing of SSRIs often is required to induce a therapeutic response as compared to MDD and GAD.^31,55

If a child does not respond to adequate first-line treatment (or has a treatment history that cannot be fully verified), repeating these first-line interventions carries little risk and can be quite effective. For example, 60% of adolescents with MDD who did not initially respond to an SSRI demonstrated a significant response when prescribed a second SSRI or venlafaxine (with or without CBT).⁵⁶

When pediatric patients continue to experience significantly distressing and/or debilitating symptoms (particularly in MDD) despite multiple trials of antidepressants and psychotherapy, practitioners should consider a careful referral to interventional psychiatry services, which can include the more intensive treatments of electroconvulsive therapy, repetitive transcranial magnetic stimulation, or ketamine (see Box 1). Given the substantial morbidity and mortality associated with adolescent depression, interventional psychiatry treatments are under-researched and under-utilized clinically in pediatric populations.

Continue to: Antidepressants in general...

Antidepressants in general, and SSRIs in particular, are the first-line pharmacotherapy for pediatric anxiety, OCD, and MDD. For PTSD, although they are a first-line treatment in adults, their efficacy has not been demonstrated in children and adolescents. Antidepressants are generally safe, well-tolerated, and effective, with low NNTs (3 to 5 for anxiety and OCD; 4 to 12 in MDD, depending on whether industry trials are included). It is important that clinicians and families be educated about possible adverse effects and their time course in order to anticipate difficulties, ensure adequate informed consent, and monitor appropriately. The black-box warning regarding treatment-emergent suicidal thoughts or behaviors must be discussed (for suggested talking points, see Box 2). The NNH is large (100 to 143), and for many patients, the benefits will outweigh the risks. For pediatric patients who fail to respond to multiple adequate trials of antidepressants and psychotherapy, referrals for interventional psychiatry consultation should be considered.

Bottom Line

Although the evidence base for prescribing antidepressants for children and adolescents is smaller compared to the adult literature, properly understanding and prescribing these agents, and explaining their risks and benefits to families, can make a major difference in patient compliance, satisfaction, and outcomes. Antidepressants (particularly selective serotonin reuptake inhibitors) are the firstline pharmacologic intervention for pediatric patients with anxiety disorders, obsessive-compulsive disorder, or major depressive disorder.

Related Resource

• Bonin L, Moreland CS. Overview of prevention and treatment for pediatric depression. https://www.uptodate.com/contents/overview-of-prevention-and-treatment-for-pediatric-depression. Last reviewed July 2019.

Drug Brand Names

Bupropion • Wellbutrin, Zyban
Cimetidine • Tagamet
Citalopram • Celexa
Clomipramine • Anafranil
Desipramine • Norpramin
Desvenlafaxine • Pristiq
Duloxetine • Cymbalta
Escitalopram • Lexapro
Fluoxetine • Prozac
Fluvoxamine • Luvox
Imipramine • Tofranil
Mirtazapine • Remeron
Nortriptyline • Pamelor
Paroxetine • Paxil
Sertraline • Zoloft
Venlafaxine • Effexor
Vilazodone • Viibryd
Vortioxetine • Trintellix

Box 1

Box 2

Urine drug tests (UDTs) are useful clinical tools for assessing and monitoring the risk of misuse, abuse, and diversion when prescribing controlled substances, or for monitoring abstinence in patients with substance use disorders (SUDs). However, UDTs have been underutilized, and have been used without systematic documentation of reasons and results.^1,2 In addition, many clinicians may lack the knowledge needed to effectively interpret test results.^3,4 Although the reported use of UDTs is much higher among clinicians who are members of American Society of Addiction Medicine (ASAM), there is still a need for improved education.⁵

The appropriate use of UDTs strengthens the therapeutic relationship and promotes healthy behaviors and patients’ recovery. On the other hand, incorrect interpretation of test results may lead to missing potential aberrant behaviors, or inappropriate consequences for patients, such as discontinuing necessary medications or discharging them from care secondary to a perceived violation of a treatment contract due to unexpected positive or negative drug screening results.⁶ In this article, we review the basic concepts of UDTs and provide an algorithm to determine when to order these tests, how to interpret the results, and how to modify treatment accordingly.

Urine drug tests 101

Urine drug tests include rapid urine drug screening (UDS) and confirmatory tests. Urine drug screenings are usually based on various types of immunoassays. They are fast, sensitive, and cost-effective. Because immunoassays are antibody-mediated, they have significant false-positive and false-negative rates due to cross-reactivity and sensitivity of antibodies.⁷ For example, antibodies used in immunoassays to detect opioids are essentially morphine antibodies, and are not able to detect semisynthetic opioids or synthetic opioids (except hydrocodone).⁷ However, immunoassays specifically developed to detect oxycodone, buprenorphine, fentanyl, and methadone are available. On the other hand, antibodies can cross-react with molecules unrelated to proto-medicines or drug metabolites, but with similar antigenic determinants. For example, amphetamine immunoassays have high false-positive rates with many different classes of medications or substances.⁷

Urine drug tests based on mass spectrometry, gas chromatography/mass spectrometry (GC/MS), and liquid chromatography/mass spectrometry (LC/MS) are gold standards to confirm toxicology results. They are highly sensitive and specific, with accurate quantitative measurement. However, they are more expensive than UDS and usually need to be sent to a laboratory with capacity to perform GC/MS or LC/MS, with a turnaround time of up to 1 week.⁸ In clinical practice, we usually start with UDS tests and order confirmatory tests when needed.

When to order UDTs in outpatient psychiatry

On December 12, 2013, the ASAM released a white paper that suggests the use of drug testing as a primary prevention, diagnostic, and monitoring tool in the management of addiction or drug misuse and its application in a wide variety of medical settings.⁹ Many clinicians use treatment contracts when prescribing controlled substances as a part of a risk-mitigation strategy, and these contracts often include the use of UDTs. Urine drug tests provide objective evidence to support or negate self-report, because many people may underreport their use.¹⁰ The literature has shown significant “abnormal” urine test results, ranging from 9% to 53%, in patients receiving chronic opioid therapy.^2,11

The CDC and the American Academy of Pain Medicine recommend UDS before initiating any controlled substance for pain therapy.^12,13 They also suggest random drug testing at least once or twice a year for low-risk patients, and more frequent screening for high-risk patients, such as those with a history of addiction.^12,13 For example, for patients with opioid use disorder who participate in a methadone program, weekly UDTs are mandated for the first 90 days, and at least 8 UDTs a year are required after that.

However, UDTs carry significant stigma due to their association with SUDs. Talking with patients from the start of treatment helps to reduce this stigma, and makes it easier to have further discussions when patients have unexpected results during treatment. For example, clinicians can explain to patients that monitoring UDTs when prescribing controlled substances is similar to monitoring thyroid function with lithium use because treatment with a controlled substance carries an inherent risk of misuse, abuse, and diversion. For patients with SUDs, clinicians can explain that using UDTs to monitor their abstinence is similar to monitoring HbA_1c for glucose control in patients with diabetes.

Continue to: Factors that can affect UDT results

In addition to knowing when to order UDT, it is critical to know how to interpret the results of UDS and follow up with confirmatory tests when needed. Other than the limitations of the tests, the following factors could contribute to unexpected UDT results:

• the drug itself, including its half-life, metabolic pathways, and potential interactions with other medications
• how patients take their medications, including dose, frequency, and pattern of drug use
• all the medications that patients are taking, including prescription, over-the-counter, and herbal and supplemental preparations
• when the last dose of a prescribed controlled substance was taken. Always ask when the patient’s last dose was taken before you consider ordering a UDT.

To help better understand UDT results, Figure 1¹⁴ and Figure 2¹⁵ demonstrate metabolic pathways of commonly used benzodiazepines and opioids, respectively. There are several comprehensive reviews on commonly seen false positives and negatives for each drug or each class of drugs in immunoassays.^16-21 Confirmatory tests are usually very accurate. However, chiral analysis is needed to differentiate enantiomers, such as methamphetamine (active R-enantiomer) and selegiline, which is metabolized into L-methamphetamine (inactive S-enantiomer).²² In addition, detection of tetrahydrocannabivarin (THCV), an ingredient of the cannabis plant, via GC/MS can be used to distinguish between consumption of dronabinol and natural cannabis products.²³ The Table^16-21 summarizes the proto­type agents, other detectable agents in the same class, and false positives and negatives in immunoassays.

Interpreting UDT results and management strategies

Our Algorithm outlines how to interpret UDT results, and management strategies to consider based on whether the results are as expected or unexpected, with a few key caveats as described below.

Expected results

If there are no concerns based on the patient’s clinical presentation or collateral information, simply continue the current treatment. However, for patients taking medications that are undetectable by UDS (for example, regular use of clonazepam or oxycodone), consider ordering confirmatory tests at least once to ensure compliance, even when UDS results are negative.

Unexpected positive results, including the presence of illicit drugs and/or unprescribed licit drugs

Drug misuse, abuse, or dependence. The first step is to talk with the patient, who may acknowledge drug misuse, abuse, or dependence. Next, consider modifying the treatment plan; this may include more frequent monitoring and visits, limiting or discontinuing prescribed controlled substances, or referring the patient to inpatient or outpatient SUD treatment, as appropriate.

Continue to: Interference from medications or diet

Interference from medications or diets. One example of a positive opioid screening result due to interference from diet is the consumption of foods that contain poppy seeds. Because of this potential interference, the cutoff value for a positive opioid immunoassay in workplace drug testing was increased from 300 to 2,000 ug/L.²⁴ Educating patients regarding medication and lifestyle choices can help them avoid any interference with drug monitoring. Confirmatory tests can be ordered at the clinician’s discretion. The same principle applies to medication choice when prescribing. For example, a patient taking bupropion may experience a false positive result on a UDS for amphetamines, and a different antidepressant might be a better choice (Box 1).

Box 1

Urine sample tampering. Consider the possibility that urine samples could be substituted, especially when there are signs or indications of tampering, such as a positive pregnancy test for a male patient, or the presence of multiple prescription medications not prescribed to the patient. If there is high suspicion of urine sample tampering, consider observed urine sample collection.

When to order confirmatory tests for unexpected positive results.

Order a confirmatory test if a patient adamantly denies taking the substance(s) for which he/she has screened positive, and there’s no other explanation for the positive result. Continue the patient’s current treatment if the confirmatory test is negative. However, if the confirmatory test is positive, then modify the treatment plan (Algorithm).

Special circumstances.

A positive opioid screen in a patient who has been prescribed a synthetic or semisynthetic opioid indicates the patient is likely using opioids other than the one he/she has been prescribed. Similarly, clonazepam is expected to be negative in a benzodiazepine immunoassay. If such testing is positive, consider the possibility that the patient is taking other benzodiazepines, such as diazepam. The results of UDTs can also be complicated by common metabolites in the same class of drugs. For example, the presence of hydromorphone for patients taking hydrocodone does not necessarily indicate the use of hydromorphone, because hydromorphone is a metabolite of hydrocodone (Figure 2¹⁵).

Unexpected negative results

Prescribed medications exist in low concentration that are below the UDS detection threshold. This unexpected UDS result could occur if patients:

• take their medications less often than prescribed (because of financial difficulties or the patient feels better and does not think he/she needs it, etc.)
• hydrate too much (intentionally or unintentionally), are pregnant, or are fast metabolizers (Box 2)
• take other medications that increase the metabolism of the prescribed medication.

Box 2

Continue to: Further inquiry will...

Further inquiry will clarify these concerns. Clinicians should educate patients and manage accordingly. Confirmatory tests may be ordered upon clinicians’ discretion.

Urine sample tampering. Dilution or substitution of urine samples may lead to unexpected negative results. Usually, the urine sample will have abnormal parameters, including temperature, pH, specific gravity, urine creatinine level, or detection of adulterants. If needed, consider observed urine sample collection. Jaffee et al²⁵ reviewed tampering methods in urine drug testing.

Diversion or binge use of medications. If patients adamantly deny diverting or binge using their medication, order confirmatory tests. If the confirmatory test also is negative, modify the treatment plan accordingly, and consider the following options:

• adjust the medication dosage or frequency
• discontinue the medication
• conduct pill counts for more definitive evidence of diversion or misuse, especially if discontinuation may lead to potential harm (for example, for patients prescribed buprenorphine for opioid use disorder).

When to order confirmatory tests for unexpected negative results.

Because confirmatory tests also measure drug concentrations, clinicians sometimes order serial confirmatory testing to monitor lipophilic drugs after a patient reports discontinuation, such as in the case of a patient using marijuana, ketamine, or alprazolam. The level of a lipophilic drug, such as these 3, should continue to decline if the patient has discontinued using it. However, because the drug level is affected by how concentrated the urine samples are, it is necessary to compare the ratios of drug levels over urine creatinine levels.²⁶ Another use for confirmatory-quantitative testing is to detect “urine spiking,”^27,28 when a patient adds an unconsumed drug to his/her urine sample to produce a positive result without actually taking the drug (Box 3).

Box 3

When to consult lab specialists

Because many clinicians may find it challenging to stay abreast of all of the factors necessary to properly interpret UDT results, consulting with qualified laboratory professionals is appropriate when needed. For example, a patient was prescribed codeine, and his UDTs showed morphine as anticipated; however, the prescribing clinician suspected that the patient was also using heroin. In this case, consultation with a specialist may be warranted to look for 6-mono-acetylemorphine (6-MAM, a unique heroin metabolite) and/or the ratio of morphine to codeine.

Continue to: In summary...

In summary, UDTs are important tools to use in general psychiatry practice, especially when prescribing controlled substances. To use UDTs effectively, it is essential to possess knowledge of drug metabolism and the limitations of these tests. All immunoassay results should be considered as presumptive, and confirmatory tests are often needed for making treatment decisions. Many clinicians are unlikely to possess all the knowledge needed to correctly interpret UDTs, and in some cases, communication with qualified laboratory professionals may be necessary. In addition, the patient’s history and clinical presentation, collateral information, and data from prescription drug monitoring programs are all important factors to consider.

The cost of UDTs, variable insurance coverage, and a lack of on-site laboratory services can be deterrents to implementing UDTs as recommended. These factors vary significantly across regions, facilities, and insurance providers (see Related Resources). If faced with these issues and you expect to often need UDTs in your practice, consider using point-of-care UDTs as an alternative to improve access, convenience, and possibly cost.

Bottom Line

Urine drug tests (UDTs) should be standard clinical practice when prescribing controlled substances and treating patients with substance use disorders in the outpatient setting. Clinicians need to be knowledgeable about the limitations of UDTs, drug metabolism, and relevant patient history to interpret UDTs proficiently for optimal patient care. Consult laboratory specialists when needed to help interpret the results.

Related Resources

• Islam FA, Choudhry Z. Urine drug screens: Not just for job applicants. Current Psychiatry. 2018;17(12):43-44.
• HealthCare.gov. Health benefits & coverage: Mental health & substance abuse coverage. www.healthcare.gov/coverage/mental-health-substance-abuse-coverage/.

Drug Brand Names

Alprazolam • Xanax
Amphetamine • Adderall
Atomoxetine • Strattera
Buprenorphine • Subutex
Buprenorphine/naloxone • Suboxone, Zubsolv
Bupropion • Wellbutrin, Zyban
Chlordiazepoxide • Librium
Chlorpromazine • Thorazine
Clonazepam • Klonopin
Desipramine • Norpramin
Dextroamphetamine • Dexedrine, ProCentra
Diazepam • Valium
Doxepin • Silenor
Dronabinol • Marinol
Efavirenz • Sustiva
Ephedrine • Akovaz
Fentanyl • Actiq, Duragesic
Flurazepam • Dalmane
Hydrocodone • Hysingla, Zohydro ER
Hydromorphone • Dilaudid, Exalgo
Labetalol • Normodyne, Trandate
Lamotrigine • Lamictal
Lisdexamfetamine • Vyvanse
Lithium • Eskalith, Lithobid
Lorazepam • Ativan
Meperidine • Demerol
Metformin • Fortamet, Glucophage
Methadone • Dolophine, Methadose
Methylphenidate • Ritalin
Midazolam • Versed
Morphine • Kadian, MorphaBond
Nabilone • Cesamet
Naltrexone • Vivitrol
Oxaprozin • Daypro
Oxazepam • Serax
Oxycodone • Oxycontin
Oxymorphone • Opana
Phentermine • Adipex-P, Ionamin
Promethazine • Phenergan
Quetiapine • Seroquel
Ranitidine • Zantac
Rifampicin • Rifadin
Selegiline • Eldepryl, Zelapar
Sertraline • Zoloft
Temazepam • Restoril
Thioridazine • Mellaril
Tramadol • Conzip, Ultram
Trazodone • Desyrel
Triazolam • Halcion
Venlafaxine • Effexor
Verapamil • Calan, Verelan
Zolpidem • Ambien

Urine drug tests (UDTs) are useful clinical tools for assessing and monitoring the risk of misuse, abuse, and diversion when prescribing controlled substances, or for monitoring abstinence in patients with substance use disorders (SUDs). However, UDTs have been underutilized, and have been used without systematic documentation of reasons and results.^1,2 In addition, many clinicians may lack the knowledge needed to effectively interpret test results.^3,4 Although the reported use of UDTs is much higher among clinicians who are members of American Society of Addiction Medicine (ASAM), there is still a need for improved education.⁵

The appropriate use of UDTs strengthens the therapeutic relationship and promotes healthy behaviors and patients’ recovery. On the other hand, incorrect interpretation of test results may lead to missing potential aberrant behaviors, or inappropriate consequences for patients, such as discontinuing necessary medications or discharging them from care secondary to a perceived violation of a treatment contract due to unexpected positive or negative drug screening results.⁶ In this article, we review the basic concepts of UDTs and provide an algorithm to determine when to order these tests, how to interpret the results, and how to modify treatment accordingly.

Urine drug tests 101

Urine drug tests include rapid urine drug screening (UDS) and confirmatory tests. Urine drug screenings are usually based on various types of immunoassays. They are fast, sensitive, and cost-effective. Because immunoassays are antibody-mediated, they have significant false-positive and false-negative rates due to cross-reactivity and sensitivity of antibodies.⁷ For example, antibodies used in immunoassays to detect opioids are essentially morphine antibodies, and are not able to detect semisynthetic opioids or synthetic opioids (except hydrocodone).⁷ However, immunoassays specifically developed to detect oxycodone, buprenorphine, fentanyl, and methadone are available. On the other hand, antibodies can cross-react with molecules unrelated to proto-medicines or drug metabolites, but with similar antigenic determinants. For example, amphetamine immunoassays have high false-positive rates with many different classes of medications or substances.⁷

Urine drug tests based on mass spectrometry, gas chromatography/mass spectrometry (GC/MS), and liquid chromatography/mass spectrometry (LC/MS) are gold standards to confirm toxicology results. They are highly sensitive and specific, with accurate quantitative measurement. However, they are more expensive than UDS and usually need to be sent to a laboratory with capacity to perform GC/MS or LC/MS, with a turnaround time of up to 1 week.⁸ In clinical practice, we usually start with UDS tests and order confirmatory tests when needed.

When to order UDTs in outpatient psychiatry

On December 12, 2013, the ASAM released a white paper that suggests the use of drug testing as a primary prevention, diagnostic, and monitoring tool in the management of addiction or drug misuse and its application in a wide variety of medical settings.⁹ Many clinicians use treatment contracts when prescribing controlled substances as a part of a risk-mitigation strategy, and these contracts often include the use of UDTs. Urine drug tests provide objective evidence to support or negate self-report, because many people may underreport their use.¹⁰ The literature has shown significant “abnormal” urine test results, ranging from 9% to 53%, in patients receiving chronic opioid therapy.^2,11

The CDC and the American Academy of Pain Medicine recommend UDS before initiating any controlled substance for pain therapy.^12,13 They also suggest random drug testing at least once or twice a year for low-risk patients, and more frequent screening for high-risk patients, such as those with a history of addiction.^12,13 For example, for patients with opioid use disorder who participate in a methadone program, weekly UDTs are mandated for the first 90 days, and at least 8 UDTs a year are required after that.

However, UDTs carry significant stigma due to their association with SUDs. Talking with patients from the start of treatment helps to reduce this stigma, and makes it easier to have further discussions when patients have unexpected results during treatment. For example, clinicians can explain to patients that monitoring UDTs when prescribing controlled substances is similar to monitoring thyroid function with lithium use because treatment with a controlled substance carries an inherent risk of misuse, abuse, and diversion. For patients with SUDs, clinicians can explain that using UDTs to monitor their abstinence is similar to monitoring HbA_1c for glucose control in patients with diabetes.

Continue to: Factors that can affect UDT results

In addition to knowing when to order UDT, it is critical to know how to interpret the results of UDS and follow up with confirmatory tests when needed. Other than the limitations of the tests, the following factors could contribute to unexpected UDT results:

• the drug itself, including its half-life, metabolic pathways, and potential interactions with other medications
• how patients take their medications, including dose, frequency, and pattern of drug use
• all the medications that patients are taking, including prescription, over-the-counter, and herbal and supplemental preparations
• when the last dose of a prescribed controlled substance was taken. Always ask when the patient’s last dose was taken before you consider ordering a UDT.

To help better understand UDT results, Figure 1¹⁴ and Figure 2¹⁵ demonstrate metabolic pathways of commonly used benzodiazepines and opioids, respectively. There are several comprehensive reviews on commonly seen false positives and negatives for each drug or each class of drugs in immunoassays.^16-21 Confirmatory tests are usually very accurate. However, chiral analysis is needed to differentiate enantiomers, such as methamphetamine (active R-enantiomer) and selegiline, which is metabolized into L-methamphetamine (inactive S-enantiomer).²² In addition, detection of tetrahydrocannabivarin (THCV), an ingredient of the cannabis plant, via GC/MS can be used to distinguish between consumption of dronabinol and natural cannabis products.²³ The Table^16-21 summarizes the proto­type agents, other detectable agents in the same class, and false positives and negatives in immunoassays.

Interpreting UDT results and management strategies

Our Algorithm outlines how to interpret UDT results, and management strategies to consider based on whether the results are as expected or unexpected, with a few key caveats as described below.

Expected results

If there are no concerns based on the patient’s clinical presentation or collateral information, simply continue the current treatment. However, for patients taking medications that are undetectable by UDS (for example, regular use of clonazepam or oxycodone), consider ordering confirmatory tests at least once to ensure compliance, even when UDS results are negative.

Unexpected positive results, including the presence of illicit drugs and/or unprescribed licit drugs

Drug misuse, abuse, or dependence. The first step is to talk with the patient, who may acknowledge drug misuse, abuse, or dependence. Next, consider modifying the treatment plan; this may include more frequent monitoring and visits, limiting or discontinuing prescribed controlled substances, or referring the patient to inpatient or outpatient SUD treatment, as appropriate.

Continue to: Interference from medications or diet

Interference from medications or diets. One example of a positive opioid screening result due to interference from diet is the consumption of foods that contain poppy seeds. Because of this potential interference, the cutoff value for a positive opioid immunoassay in workplace drug testing was increased from 300 to 2,000 ug/L.²⁴ Educating patients regarding medication and lifestyle choices can help them avoid any interference with drug monitoring. Confirmatory tests can be ordered at the clinician’s discretion. The same principle applies to medication choice when prescribing. For example, a patient taking bupropion may experience a false positive result on a UDS for amphetamines, and a different antidepressant might be a better choice (Box 1).

Box 1

Urine sample tampering. Consider the possibility that urine samples could be substituted, especially when there are signs or indications of tampering, such as a positive pregnancy test for a male patient, or the presence of multiple prescription medications not prescribed to the patient. If there is high suspicion of urine sample tampering, consider observed urine sample collection.

When to order confirmatory tests for unexpected positive results.

Order a confirmatory test if a patient adamantly denies taking the substance(s) for which he/she has screened positive, and there’s no other explanation for the positive result. Continue the patient’s current treatment if the confirmatory test is negative. However, if the confirmatory test is positive, then modify the treatment plan (Algorithm).

Special circumstances.

A positive opioid screen in a patient who has been prescribed a synthetic or semisynthetic opioid indicates the patient is likely using opioids other than the one he/she has been prescribed. Similarly, clonazepam is expected to be negative in a benzodiazepine immunoassay. If such testing is positive, consider the possibility that the patient is taking other benzodiazepines, such as diazepam. The results of UDTs can also be complicated by common metabolites in the same class of drugs. For example, the presence of hydromorphone for patients taking hydrocodone does not necessarily indicate the use of hydromorphone, because hydromorphone is a metabolite of hydrocodone (Figure 2¹⁵).

Unexpected negative results

Prescribed medications exist in low concentration that are below the UDS detection threshold. This unexpected UDS result could occur if patients:

• take their medications less often than prescribed (because of financial difficulties or the patient feels better and does not think he/she needs it, etc.)
• hydrate too much (intentionally or unintentionally), are pregnant, or are fast metabolizers (Box 2)
• take other medications that increase the metabolism of the prescribed medication.

Box 2

Continue to: Further inquiry will...

Further inquiry will clarify these concerns. Clinicians should educate patients and manage accordingly. Confirmatory tests may be ordered upon clinicians’ discretion.

Urine sample tampering. Dilution or substitution of urine samples may lead to unexpected negative results. Usually, the urine sample will have abnormal parameters, including temperature, pH, specific gravity, urine creatinine level, or detection of adulterants. If needed, consider observed urine sample collection. Jaffee et al²⁵ reviewed tampering methods in urine drug testing.

Diversion or binge use of medications. If patients adamantly deny diverting or binge using their medication, order confirmatory tests. If the confirmatory test also is negative, modify the treatment plan accordingly, and consider the following options:

• adjust the medication dosage or frequency
• discontinue the medication
• conduct pill counts for more definitive evidence of diversion or misuse, especially if discontinuation may lead to potential harm (for example, for patients prescribed buprenorphine for opioid use disorder).

When to order confirmatory tests for unexpected negative results.

Because confirmatory tests also measure drug concentrations, clinicians sometimes order serial confirmatory testing to monitor lipophilic drugs after a patient reports discontinuation, such as in the case of a patient using marijuana, ketamine, or alprazolam. The level of a lipophilic drug, such as these 3, should continue to decline if the patient has discontinued using it. However, because the drug level is affected by how concentrated the urine samples are, it is necessary to compare the ratios of drug levels over urine creatinine levels.²⁶ Another use for confirmatory-quantitative testing is to detect “urine spiking,”^27,28 when a patient adds an unconsumed drug to his/her urine sample to produce a positive result without actually taking the drug (Box 3).

Box 3

When to consult lab specialists

Because many clinicians may find it challenging to stay abreast of all of the factors necessary to properly interpret UDT results, consulting with qualified laboratory professionals is appropriate when needed. For example, a patient was prescribed codeine, and his UDTs showed morphine as anticipated; however, the prescribing clinician suspected that the patient was also using heroin. In this case, consultation with a specialist may be warranted to look for 6-mono-acetylemorphine (6-MAM, a unique heroin metabolite) and/or the ratio of morphine to codeine.

Continue to: In summary...

In summary, UDTs are important tools to use in general psychiatry practice, especially when prescribing controlled substances. To use UDTs effectively, it is essential to possess knowledge of drug metabolism and the limitations of these tests. All immunoassay results should be considered as presumptive, and confirmatory tests are often needed for making treatment decisions. Many clinicians are unlikely to possess all the knowledge needed to correctly interpret UDTs, and in some cases, communication with qualified laboratory professionals may be necessary. In addition, the patient’s history and clinical presentation, collateral information, and data from prescription drug monitoring programs are all important factors to consider.

The cost of UDTs, variable insurance coverage, and a lack of on-site laboratory services can be deterrents to implementing UDTs as recommended. These factors vary significantly across regions, facilities, and insurance providers (see Related Resources). If faced with these issues and you expect to often need UDTs in your practice, consider using point-of-care UDTs as an alternative to improve access, convenience, and possibly cost.

Bottom Line

Urine drug tests (UDTs) should be standard clinical practice when prescribing controlled substances and treating patients with substance use disorders in the outpatient setting. Clinicians need to be knowledgeable about the limitations of UDTs, drug metabolism, and relevant patient history to interpret UDTs proficiently for optimal patient care. Consult laboratory specialists when needed to help interpret the results.

Related Resources

• Islam FA, Choudhry Z. Urine drug screens: Not just for job applicants. Current Psychiatry. 2018;17(12):43-44.
• HealthCare.gov. Health benefits & coverage: Mental health & substance abuse coverage. www.healthcare.gov/coverage/mental-health-substance-abuse-coverage/.

Drug Brand Names

Alprazolam • Xanax
Amphetamine • Adderall
Atomoxetine • Strattera
Buprenorphine • Subutex
Buprenorphine/naloxone • Suboxone, Zubsolv
Bupropion • Wellbutrin, Zyban
Chlordiazepoxide • Librium
Chlorpromazine • Thorazine
Clonazepam • Klonopin
Desipramine • Norpramin
Dextroamphetamine • Dexedrine, ProCentra
Diazepam • Valium
Doxepin • Silenor
Dronabinol • Marinol
Efavirenz • Sustiva
Ephedrine • Akovaz
Fentanyl • Actiq, Duragesic
Flurazepam • Dalmane
Hydrocodone • Hysingla, Zohydro ER
Hydromorphone • Dilaudid, Exalgo
Labetalol • Normodyne, Trandate
Lamotrigine • Lamictal
Lisdexamfetamine • Vyvanse
Lithium • Eskalith, Lithobid
Lorazepam • Ativan
Meperidine • Demerol
Metformin • Fortamet, Glucophage
Methadone • Dolophine, Methadose
Methylphenidate • Ritalin
Midazolam • Versed
Morphine • Kadian, MorphaBond
Nabilone • Cesamet
Naltrexone • Vivitrol
Oxaprozin • Daypro
Oxazepam • Serax
Oxycodone • Oxycontin
Oxymorphone • Opana
Phentermine • Adipex-P, Ionamin
Promethazine • Phenergan
Quetiapine • Seroquel
Ranitidine • Zantac
Rifampicin • Rifadin
Selegiline • Eldepryl, Zelapar
Sertraline • Zoloft
Temazepam • Restoril
Thioridazine • Mellaril
Tramadol • Conzip, Ultram
Trazodone • Desyrel
Triazolam • Halcion
Venlafaxine • Effexor
Verapamil • Calan, Verelan
Zolpidem • Ambien

Urine drug tests (UDTs) are useful clinical tools for assessing and monitoring the risk of misuse, abuse, and diversion when prescribing controlled substances, or for monitoring abstinence in patients with substance use disorders (SUDs). However, UDTs have been underutilized, and have been used without systematic documentation of reasons and results.^1,2 In addition, many clinicians may lack the knowledge needed to effectively interpret test results.^3,4 Although the reported use of UDTs is much higher among clinicians who are members of American Society of Addiction Medicine (ASAM), there is still a need for improved education.⁵

The appropriate use of UDTs strengthens the therapeutic relationship and promotes healthy behaviors and patients’ recovery. On the other hand, incorrect interpretation of test results may lead to missing potential aberrant behaviors, or inappropriate consequences for patients, such as discontinuing necessary medications or discharging them from care secondary to a perceived violation of a treatment contract due to unexpected positive or negative drug screening results.⁶ In this article, we review the basic concepts of UDTs and provide an algorithm to determine when to order these tests, how to interpret the results, and how to modify treatment accordingly.

Urine drug tests 101

Urine drug tests include rapid urine drug screening (UDS) and confirmatory tests. Urine drug screenings are usually based on various types of immunoassays. They are fast, sensitive, and cost-effective. Because immunoassays are antibody-mediated, they have significant false-positive and false-negative rates due to cross-reactivity and sensitivity of antibodies.⁷ For example, antibodies used in immunoassays to detect opioids are essentially morphine antibodies, and are not able to detect semisynthetic opioids or synthetic opioids (except hydrocodone).⁷ However, immunoassays specifically developed to detect oxycodone, buprenorphine, fentanyl, and methadone are available. On the other hand, antibodies can cross-react with molecules unrelated to proto-medicines or drug metabolites, but with similar antigenic determinants. For example, amphetamine immunoassays have high false-positive rates with many different classes of medications or substances.⁷

Urine drug tests based on mass spectrometry, gas chromatography/mass spectrometry (GC/MS), and liquid chromatography/mass spectrometry (LC/MS) are gold standards to confirm toxicology results. They are highly sensitive and specific, with accurate quantitative measurement. However, they are more expensive than UDS and usually need to be sent to a laboratory with capacity to perform GC/MS or LC/MS, with a turnaround time of up to 1 week.⁸ In clinical practice, we usually start with UDS tests and order confirmatory tests when needed.

When to order UDTs in outpatient psychiatry

On December 12, 2013, the ASAM released a white paper that suggests the use of drug testing as a primary prevention, diagnostic, and monitoring tool in the management of addiction or drug misuse and its application in a wide variety of medical settings.⁹ Many clinicians use treatment contracts when prescribing controlled substances as a part of a risk-mitigation strategy, and these contracts often include the use of UDTs. Urine drug tests provide objective evidence to support or negate self-report, because many people may underreport their use.¹⁰ The literature has shown significant “abnormal” urine test results, ranging from 9% to 53%, in patients receiving chronic opioid therapy.^2,11

The CDC and the American Academy of Pain Medicine recommend UDS before initiating any controlled substance for pain therapy.^12,13 They also suggest random drug testing at least once or twice a year for low-risk patients, and more frequent screening for high-risk patients, such as those with a history of addiction.^12,13 For example, for patients with opioid use disorder who participate in a methadone program, weekly UDTs are mandated for the first 90 days, and at least 8 UDTs a year are required after that.

However, UDTs carry significant stigma due to their association with SUDs. Talking with patients from the start of treatment helps to reduce this stigma, and makes it easier to have further discussions when patients have unexpected results during treatment. For example, clinicians can explain to patients that monitoring UDTs when prescribing controlled substances is similar to monitoring thyroid function with lithium use because treatment with a controlled substance carries an inherent risk of misuse, abuse, and diversion. For patients with SUDs, clinicians can explain that using UDTs to monitor their abstinence is similar to monitoring HbA_1c for glucose control in patients with diabetes.

Continue to: Factors that can affect UDT results

In addition to knowing when to order UDT, it is critical to know how to interpret the results of UDS and follow up with confirmatory tests when needed. Other than the limitations of the tests, the following factors could contribute to unexpected UDT results:

• the drug itself, including its half-life, metabolic pathways, and potential interactions with other medications
• how patients take their medications, including dose, frequency, and pattern of drug use
• all the medications that patients are taking, including prescription, over-the-counter, and herbal and supplemental preparations
• when the last dose of a prescribed controlled substance was taken. Always ask when the patient’s last dose was taken before you consider ordering a UDT.

To help better understand UDT results, Figure 1¹⁴ and Figure 2¹⁵ demonstrate metabolic pathways of commonly used benzodiazepines and opioids, respectively. There are several comprehensive reviews on commonly seen false positives and negatives for each drug or each class of drugs in immunoassays.^16-21 Confirmatory tests are usually very accurate. However, chiral analysis is needed to differentiate enantiomers, such as methamphetamine (active R-enantiomer) and selegiline, which is metabolized into L-methamphetamine (inactive S-enantiomer).²² In addition, detection of tetrahydrocannabivarin (THCV), an ingredient of the cannabis plant, via GC/MS can be used to distinguish between consumption of dronabinol and natural cannabis products.²³ The Table^16-21 summarizes the proto­type agents, other detectable agents in the same class, and false positives and negatives in immunoassays.

Interpreting UDT results and management strategies

Our Algorithm outlines how to interpret UDT results, and management strategies to consider based on whether the results are as expected or unexpected, with a few key caveats as described below.

Expected results

If there are no concerns based on the patient’s clinical presentation or collateral information, simply continue the current treatment. However, for patients taking medications that are undetectable by UDS (for example, regular use of clonazepam or oxycodone), consider ordering confirmatory tests at least once to ensure compliance, even when UDS results are negative.

Unexpected positive results, including the presence of illicit drugs and/or unprescribed licit drugs

Drug misuse, abuse, or dependence. The first step is to talk with the patient, who may acknowledge drug misuse, abuse, or dependence. Next, consider modifying the treatment plan; this may include more frequent monitoring and visits, limiting or discontinuing prescribed controlled substances, or referring the patient to inpatient or outpatient SUD treatment, as appropriate.

Continue to: Interference from medications or diet

Interference from medications or diets. One example of a positive opioid screening result due to interference from diet is the consumption of foods that contain poppy seeds. Because of this potential interference, the cutoff value for a positive opioid immunoassay in workplace drug testing was increased from 300 to 2,000 ug/L.²⁴ Educating patients regarding medication and lifestyle choices can help them avoid any interference with drug monitoring. Confirmatory tests can be ordered at the clinician’s discretion. The same principle applies to medication choice when prescribing. For example, a patient taking bupropion may experience a false positive result on a UDS for amphetamines, and a different antidepressant might be a better choice (Box 1).

Box 1

Urine sample tampering. Consider the possibility that urine samples could be substituted, especially when there are signs or indications of tampering, such as a positive pregnancy test for a male patient, or the presence of multiple prescription medications not prescribed to the patient. If there is high suspicion of urine sample tampering, consider observed urine sample collection.

When to order confirmatory tests for unexpected positive results.

Order a confirmatory test if a patient adamantly denies taking the substance(s) for which he/she has screened positive, and there’s no other explanation for the positive result. Continue the patient’s current treatment if the confirmatory test is negative. However, if the confirmatory test is positive, then modify the treatment plan (Algorithm).

Special circumstances.

A positive opioid screen in a patient who has been prescribed a synthetic or semisynthetic opioid indicates the patient is likely using opioids other than the one he/she has been prescribed. Similarly, clonazepam is expected to be negative in a benzodiazepine immunoassay. If such testing is positive, consider the possibility that the patient is taking other benzodiazepines, such as diazepam. The results of UDTs can also be complicated by common metabolites in the same class of drugs. For example, the presence of hydromorphone for patients taking hydrocodone does not necessarily indicate the use of hydromorphone, because hydromorphone is a metabolite of hydrocodone (Figure 2¹⁵).

Unexpected negative results

Prescribed medications exist in low concentration that are below the UDS detection threshold. This unexpected UDS result could occur if patients:

• take their medications less often than prescribed (because of financial difficulties or the patient feels better and does not think he/she needs it, etc.)
• hydrate too much (intentionally or unintentionally), are pregnant, or are fast metabolizers (Box 2)
• take other medications that increase the metabolism of the prescribed medication.

Box 2

Continue to: Further inquiry will...

Further inquiry will clarify these concerns. Clinicians should educate patients and manage accordingly. Confirmatory tests may be ordered upon clinicians’ discretion.

Urine sample tampering. Dilution or substitution of urine samples may lead to unexpected negative results. Usually, the urine sample will have abnormal parameters, including temperature, pH, specific gravity, urine creatinine level, or detection of adulterants. If needed, consider observed urine sample collection. Jaffee et al²⁵ reviewed tampering methods in urine drug testing.

Diversion or binge use of medications. If patients adamantly deny diverting or binge using their medication, order confirmatory tests. If the confirmatory test also is negative, modify the treatment plan accordingly, and consider the following options:

• adjust the medication dosage or frequency
• discontinue the medication
• conduct pill counts for more definitive evidence of diversion or misuse, especially if discontinuation may lead to potential harm (for example, for patients prescribed buprenorphine for opioid use disorder).

When to order confirmatory tests for unexpected negative results.

Because confirmatory tests also measure drug concentrations, clinicians sometimes order serial confirmatory testing to monitor lipophilic drugs after a patient reports discontinuation, such as in the case of a patient using marijuana, ketamine, or alprazolam. The level of a lipophilic drug, such as these 3, should continue to decline if the patient has discontinued using it. However, because the drug level is affected by how concentrated the urine samples are, it is necessary to compare the ratios of drug levels over urine creatinine levels.²⁶ Another use for confirmatory-quantitative testing is to detect “urine spiking,”^27,28 when a patient adds an unconsumed drug to his/her urine sample to produce a positive result without actually taking the drug (Box 3).

Box 3

When to consult lab specialists

Because many clinicians may find it challenging to stay abreast of all of the factors necessary to properly interpret UDT results, consulting with qualified laboratory professionals is appropriate when needed. For example, a patient was prescribed codeine, and his UDTs showed morphine as anticipated; however, the prescribing clinician suspected that the patient was also using heroin. In this case, consultation with a specialist may be warranted to look for 6-mono-acetylemorphine (6-MAM, a unique heroin metabolite) and/or the ratio of morphine to codeine.

Continue to: In summary...

In summary, UDTs are important tools to use in general psychiatry practice, especially when prescribing controlled substances. To use UDTs effectively, it is essential to possess knowledge of drug metabolism and the limitations of these tests. All immunoassay results should be considered as presumptive, and confirmatory tests are often needed for making treatment decisions. Many clinicians are unlikely to possess all the knowledge needed to correctly interpret UDTs, and in some cases, communication with qualified laboratory professionals may be necessary. In addition, the patient’s history and clinical presentation, collateral information, and data from prescription drug monitoring programs are all important factors to consider.

The cost of UDTs, variable insurance coverage, and a lack of on-site laboratory services can be deterrents to implementing UDTs as recommended. These factors vary significantly across regions, facilities, and insurance providers (see Related Resources). If faced with these issues and you expect to often need UDTs in your practice, consider using point-of-care UDTs as an alternative to improve access, convenience, and possibly cost.

Bottom Line

Urine drug tests (UDTs) should be standard clinical practice when prescribing controlled substances and treating patients with substance use disorders in the outpatient setting. Clinicians need to be knowledgeable about the limitations of UDTs, drug metabolism, and relevant patient history to interpret UDTs proficiently for optimal patient care. Consult laboratory specialists when needed to help interpret the results.

Related Resources

• Islam FA, Choudhry Z. Urine drug screens: Not just for job applicants. Current Psychiatry. 2018;17(12):43-44.
• HealthCare.gov. Health benefits & coverage: Mental health & substance abuse coverage. www.healthcare.gov/coverage/mental-health-substance-abuse-coverage/.

Drug Brand Names

Alprazolam • Xanax
Amphetamine • Adderall
Atomoxetine • Strattera
Buprenorphine • Subutex
Buprenorphine/naloxone • Suboxone, Zubsolv
Bupropion • Wellbutrin, Zyban
Chlordiazepoxide • Librium
Chlorpromazine • Thorazine
Clonazepam • Klonopin
Desipramine • Norpramin
Dextroamphetamine • Dexedrine, ProCentra
Diazepam • Valium
Doxepin • Silenor
Dronabinol • Marinol
Efavirenz • Sustiva
Ephedrine • Akovaz
Fentanyl • Actiq, Duragesic
Flurazepam • Dalmane
Hydrocodone • Hysingla, Zohydro ER
Hydromorphone • Dilaudid, Exalgo
Labetalol • Normodyne, Trandate
Lamotrigine • Lamictal
Lisdexamfetamine • Vyvanse
Lithium • Eskalith, Lithobid
Lorazepam • Ativan
Meperidine • Demerol
Metformin • Fortamet, Glucophage
Methadone • Dolophine, Methadose
Methylphenidate • Ritalin
Midazolam • Versed
Morphine • Kadian, MorphaBond
Nabilone • Cesamet
Naltrexone • Vivitrol
Oxaprozin • Daypro
Oxazepam • Serax
Oxycodone • Oxycontin
Oxymorphone • Opana
Phentermine • Adipex-P, Ionamin
Promethazine • Phenergan
Quetiapine • Seroquel
Ranitidine • Zantac
Rifampicin • Rifadin
Selegiline • Eldepryl, Zelapar
Sertraline • Zoloft
Temazepam • Restoril
Thioridazine • Mellaril
Tramadol • Conzip, Ultram
Trazodone • Desyrel
Triazolam • Halcion
Venlafaxine • Effexor
Verapamil • Calan, Verelan
Zolpidem • Ambien

Attention-deficit/hyperactivity disorder (ADHD) is the most common childhood neurodevelopmental disorder, affecting 8% to 12% of school-aged children in the United States^1-3 with significant impairments that often persist into adulthood.^4-8 Current guidelines recommend stimulant medication and/or behavioral therapies as first-line treatments for ADHD.^9,10 There is a wealth of evidence on the efficacy of stimulants in ADHD, with the most significant effects noted on core ADHD symptoms.^11,12 Additional evidence links stimulants to decreased long-term negative outcomes, including reduced school absences and grade retention,¹³ as well as modestly but significantly improved reading and math scores.¹⁴ Other studies have reported that individuals with ADHD who receive medication have decreased criminality,^15,16 motor vehicle accidents,^17,18 injuries,¹⁹ substance abuse,^20-22 and risk for subsequent and concurrent depression.²³ Therefore, the evidence suggests that consistent medication treatment helps improve outcomes for individuals with ADHD.

Adherence is defined as “the extent to which a person’s behavior (eg, taking medication) corresponds with agreed recommendations from a clinician.”²⁴ Unfortunately, pediatric ADHD medication adherence has been found to be poor (approximately 64%).^25-30 Nonadherence to ADHD medication has been linked to multiple factors, including caregiver/family and child/adolescent factors (Table 1), medication-related factors (Table 2), and health care/system factors (Table 3). Understanding and addressing these factors is essential to maximizing long-term outcomes. In this article, we review the factors associated with nonadherence to ADHD medication, and outline strategies to improve adherence.

Caregiver/family characteristics

Caregiver beliefs about ADHD and their attitudes toward treatment have been associated with the initiation of and adherence to ADHD medication. For example, caregivers who view a child’s difficulties as a medical disorder that requires a biologic intervention are more likely to accept and adhere to medication.³¹ Similarly, caregivers who perceive ADHD medication as safe, effective, and socially acceptable are more likely to be treatment-adherent.^32-35Other caregiver-related factors associated with improved ADHD medication adherence include:

• increased caregiver knowledge about ADHD³³
• receiving an ADHD diagnosis based on a thorough diagnostic process (ie, comprehensive psychological testing)³⁶
• satisfaction with information about medicine
• comfort with the treatment plan.³⁴

Socioeconomic status, family functioning, and caregiver mental health diagnoses (eg, ADHD, depression) have also been linked to ADHD medication adherence. Several studies, including the Multimodal Treatment Study of Children with ADHD,¹¹ a landmark study of stimulant medication for children with ADHD, have found an association between low income and decreased likelihood of receiving ADHD medication.^2,37-39 Further, Gau et al⁴⁰ found that negative caregiver-child relationships and family dysfunction were associated with poor medication adherence in children with ADHD.⁹ Prior studies have also shown that mothers of children with ADHD are more likely to have depression and/or anxiety,^41,42 and that caregivers with a history of mental health diagnoses are more accepting of initiating medication treatment for their children.⁴³ However, additional studies have found that caregiver mental health diagnoses decreased the likelihood of ADHD medication adherence.^40,44

Child characteristics

Child characteristics associated with decreased ADHD medication adherence include older age (eg, adolescents vs school-aged children),^{29,30,34,40,45-47} non-White race, Hispanic ethnicity,^29,33,48-51 female gender,^29,33,52 lower baseline ADHD symptom severity,^30,37 and child unwillingness to take medications.³⁴ However, prior studies have not been completely consistent about the relationship between child comorbid conditions (eg, oppositional defiant disorder [ODD], conduct disorder) and ADHD medication adherence. A few studies found that child comorbid conditions, especially ODD, mediate poor ADHD medication adherence, possibly secondary to an increased caregiver-child conflict.^30,53,54 However, other studies have reported that the presence of comorbid ODD, depression, and anxiety predicted increased adherence to ADHD medications.^37,46

Medication-related factors

Adverse effects of medications are the most commonly cited reason for ADHD medication nonadherence.^5,33,54-56 The adverse effects most often linked to nonadherence are reduced weight/appetite, increased aggressive behavior/irritability, and sleep difficulties.^54,57 Studies comparing methylphenidates and amphetamines, including 2 recent meta-analyses, suggest that amphetamines may be less well-tolerated on average, particularly with regard to emotional lability and irritability.^45,58,59 Therefore, clinicians might consider using methylphenidate-based preparations as first-line psychopharmacologic interventions in children with ADHD, as is consistent with the findings and conclusions drawn by a recent systematic review and meta-analysis of the comparative efficacy and tolerability of ADHD medications.⁶⁰

On the other hand, increased ADHD medication effectiveness has been associated with improved medication adherence.^5,34,54-56 Medication titration and dosing factors have also been shown to affect adherence. Specifically, adherence has been improved when ADHD medications are titrated in a systematic manner soon after starting treatment, and when families have an early first contact with a physician after starting medication (within 3 months).²⁸ In addition, use of a simplified dose regimen has been linked to better adherence: patients who are prescribed long-acting stimulants are more likely to adhere to treatment compared with patients who take short-acting formulations.^{26,40,49,61-63} It is possible that long-acting stimulants increase adherence because they produce more even and sustained effects on ADHD symptoms throughout the day, compared with short-acting formulations.⁶⁴ Furthermore, the inconvenience of taking multiple doses throughout the day, as well as the potential social stigma of mid-school day dosing, may negatively impact adherence to short-acting formulations.¹⁰

Continue to: Health care/system factors

Several studies have investigated the influence of health services factors on ADHD medication adherence. Specifically, limited transportation services and lack of mental health providers in the community have been linked to decreased ADHD medication adherence.^47,65,66 Furthermore, limited insurance coverage and higher costs of ADHD medications, which lead to substantial out-of-pocket payments for families, have been associated with decreased likelihood of ADHD medication adherence.^29,67

Clinician-related factors also can affect ADHD medication adherence. For example, a clinician’s lack knowledge of ADHD care can negatively impact ADHD medication adherence.⁶⁸ Two studies have documented improved ADHD medication adherence when treatment is provided by specialists (eg, child psychiatrists) rather than by community primary care providers, possibly because specialists are more likely to provide close stimulant titration and monitoring (ie, ≥ 3 visits in the first 90 days) and use higher maximum doses.^62,69 Furthermore, ADHD medication initiation and adherence are increased when patients have a strong working alliance with their clinician and trust the health care system,^31,34,35 as well as when there is a match between the caregiver’s and clinician’s perception of the cause, course, and best treatment practices for a child’s ADHD.⁶⁵

Strategies to improve medication adherence

A number of strategies to improve ADHD medication adherence can be derived from our knowledge of the factors that influence adherence.

Patient/family education. Unanswered questions about ADHD diagnosis, etiology, and medication adverse effects can negatively impact the ADHD treatment process. Therefore, patient/family education regarding ADHD and its management is necessary to improve medication adherence, because it helps families attain the knowledge, confidence, and motivation to manage their child’s condition.

Clinicians have an important role in educating patients about⁷⁰:

• the medications they are taking
• why they are taking them
• what the medications look like
• the time of medication administration
• the potential adverse effects
• what to do if adverse effects occur
• what regular testing/monitoring is necessary.

Clinicians can provide appropriate psychoeducation by sharing written materials and trusted websites with families (see Related Resources).

Behavioral strategies. Behavioral interventions have been among the most effective strategies for improving medication adherence in other chronic conditions.⁷¹ Behavioral strategies are likely to be particularly important for families of children with ADHD and comorbid conditions such as ODD because these families experience considerable caregiver-child conflict.⁷² Moreover, parents of children with ADHD are at higher risk for having ADHD and depression themselves,⁷³ both of which may interfere with a parent’s ability to obtain and administer medications consistently. Thus, for these families, using a combination of psychoeducation and behavioral strategies will be necessary to affect change in attitude and behavior. Behavioral strategies that can be used to improve medication adherence include:

• Technology-based interventions can reduce the impact of environmental barriers to adherence. For example, pharmacy automatic prescription renewal systems can reduce the likelihood of families failing to obtain ADHD medication refills. Pill reminder boxes, smartphone alerts, and setting various alarms can effectively prompt caregivers/patients to administer medication. In particular, these methods can be crucial in families for which multiple members have ADHD and its attendant difficulties with organization and task completion.
• Caregiver training may assist families in developing specific behavioral management skills that support adherence. This training can be as straightforward as instructing caregivers on the use of positive reinforcement when teaching their children to swallow pills. It may also encompass structured behavioral interventions aimed at training caregivers to utilize rewards and consequences in order to maximize medication adherence.⁷⁴

Continue to: Clinician interventions

Clinician interventions. Clinicians can use decision aids to help inform families about treatment options, promote shared decision making, and decrease uncertainty about the treatment plan⁷⁵ (see Related Resources). Early titration of ADHD medications and early first contact (within months of starting medication treatment) between caregivers and clinicians, whether via in-person visit, telephone, or email, have also been related to improved adherence.²⁸ Furthermore, clinicians can improve adherence by prescribing a simplified medication regimen (ie, long-acting formulations that provide full-day coverage). To address the negative impact of high out-of-pocket ADHD medication costs on adherence, clinicians can also prescribe generic preparations and/or “preferred” medications options on an individual patient’s formulary.

Because clinician knowledge and expertise in ADHD care has been linked to improved patient medication adherence,⁶⁸ clinicians are encouraged to use the American Academy of Pediatrics (AAP) guideline for diagnosis and treatment of ADHD, which includes a supplemental process of care algorithm (last published in 2011,¹⁰ with an updated guideline anticipated in 2019), as well as the AAP/National Institute for Children’s Health Quality (NICHQ) ADHD Toolkit,⁷⁶ which includes items helpful for ADHD diagnosis and treatment. The Society for Developmental and Behavioral Pediatrics is also developing a clinical practice guideline for the diagnosis and treatment of complex ADHD (ie, ADHD complicated by coexisting mental health, developmental, and/or psychosocial conditions or issues), with publication anticipated in 2019. Primary care providers can also improve their expertise in ADHD care by pursuing additional mental health–related trainings (such as those conducted by the REACH Institute).⁷⁷

Because receiving ADHD care from a specialist has been shown to improve medication initiation and adherence,^62,69 other strategies to address the short supply of child psychiatrists include offering incentives to medical students to pursue a career in child psychiatry (eg, loan forgiveness). Telepsychiatry and co-location of mental health specialists and primary care providers are additional innovative ways in which ADHD specialty care can be delivered to more patients.⁶⁴

Finally, providing culturally-sensitive care can strengthen the clinician-caregiver relationship and promote adherence to treatment. For example, clinicians can partner with local groups to increase their understanding of how different racial/ethnic groups perceive ADHD and its treatment.⁶⁴

Peer support models. Peers are credible role models who have a valued role in facilitating the use of mental health services by empowering families and enhancing service satisfaction.⁷⁸ In several communities in the United States, peer models using family advocates have been introduced.⁷⁹ Family advocates are typically caregivers of children who have special needs or have been involved in the mental health system. Their perspective—as peers and first-hand consumers of the health care and/or mental health system—can make them powerful and effective coaches to families of children with ADHD. By helping families to navigate ADHD care systems successfully, family advocates can play an important role in enhancing ADHD medication adherence, although further investigation is needed. In addition, the stigma around ADHD medication use, which adversely impacts adherence, can be mitigated if caregivers participate in organized ADHD-related support groups (eg, Children and Adults with ADHD [CHADD]).

Continue to: Health disparity-reducing interventions

Health disparity-reducing interventions. Successful health disparity-reducing interventions—such as those developed to enhance care of other chronic disorders including asthma and diabetes—can be applied to improve ADHD care. These interventions, which include medical-legal partnerships (eg, between clinicians, social workers, legal advocates, and community partners) in primary care centers, have been shown to improve health insurance coverage and therefore health care access.^80,81 Although some hardships linked to nonadherence (eg, low socioeconomic status) may not be amenable to health care–related interventions, screening for these hardships can identify children who are most at risk for poor adherence. This would alert clinicians to proactively identify barriers to adherence and implement mitigation strategies. This might include developing more streamlined, easier-to-follow management plans for these patients, such as those that can be delivered through pharmacist-physician collaborative programs⁸² and school-based therapy programs.^83-85

Bottom Line

Suboptimal adherence to medications for attention-deficit/hyperactivity disorder (ADHD) can be addressed through patient/family education, behavioral strategies, clinician interventions, peer support models, and health disparity-reducing interventions. By improving ADHD treatment adherence, these interventions have the potential to maximize long-term outcomes.

Related Resources

• Cohen Children’s Medical Center Northwell Health. The ADHD Medication Guide. www.ADHDMedicationGuide.com. Revised December 31, 2017.
• Cincinnati Children’s Hospital Medical Center. Decision aids to facilitate shared decision making in practice. www.cincinnatichildrens.org/service/j/anderson-center/ evidence-based-care/decision-aids.
• CHADD. Children and Adults with attention-deficit/ hyperactivity disorder. www.chadd.org.

Drug Brand Name

Methylphenidate • Concerta, Ritalin

Attention-deficit/hyperactivity disorder (ADHD) is the most common childhood neurodevelopmental disorder, affecting 8% to 12% of school-aged children in the United States^1-3 with significant impairments that often persist into adulthood.^4-8 Current guidelines recommend stimulant medication and/or behavioral therapies as first-line treatments for ADHD.^9,10 There is a wealth of evidence on the efficacy of stimulants in ADHD, with the most significant effects noted on core ADHD symptoms.^11,12 Additional evidence links stimulants to decreased long-term negative outcomes, including reduced school absences and grade retention,¹³ as well as modestly but significantly improved reading and math scores.¹⁴ Other studies have reported that individuals with ADHD who receive medication have decreased criminality,^15,16 motor vehicle accidents,^17,18 injuries,¹⁹ substance abuse,^20-22 and risk for subsequent and concurrent depression.²³ Therefore, the evidence suggests that consistent medication treatment helps improve outcomes for individuals with ADHD.

Adherence is defined as “the extent to which a person’s behavior (eg, taking medication) corresponds with agreed recommendations from a clinician.”²⁴ Unfortunately, pediatric ADHD medication adherence has been found to be poor (approximately 64%).^25-30 Nonadherence to ADHD medication has been linked to multiple factors, including caregiver/family and child/adolescent factors (Table 1), medication-related factors (Table 2), and health care/system factors (Table 3). Understanding and addressing these factors is essential to maximizing long-term outcomes. In this article, we review the factors associated with nonadherence to ADHD medication, and outline strategies to improve adherence.

Caregiver/family characteristics

Caregiver beliefs about ADHD and their attitudes toward treatment have been associated with the initiation of and adherence to ADHD medication. For example, caregivers who view a child’s difficulties as a medical disorder that requires a biologic intervention are more likely to accept and adhere to medication.³¹ Similarly, caregivers who perceive ADHD medication as safe, effective, and socially acceptable are more likely to be treatment-adherent.^32-35Other caregiver-related factors associated with improved ADHD medication adherence include:

• increased caregiver knowledge about ADHD³³
• receiving an ADHD diagnosis based on a thorough diagnostic process (ie, comprehensive psychological testing)³⁶
• satisfaction with information about medicine
• comfort with the treatment plan.³⁴

Socioeconomic status, family functioning, and caregiver mental health diagnoses (eg, ADHD, depression) have also been linked to ADHD medication adherence. Several studies, including the Multimodal Treatment Study of Children with ADHD,¹¹ a landmark study of stimulant medication for children with ADHD, have found an association between low income and decreased likelihood of receiving ADHD medication.^2,37-39 Further, Gau et al⁴⁰ found that negative caregiver-child relationships and family dysfunction were associated with poor medication adherence in children with ADHD.⁹ Prior studies have also shown that mothers of children with ADHD are more likely to have depression and/or anxiety,^41,42 and that caregivers with a history of mental health diagnoses are more accepting of initiating medication treatment for their children.⁴³ However, additional studies have found that caregiver mental health diagnoses decreased the likelihood of ADHD medication adherence.^40,44

Child characteristics

Child characteristics associated with decreased ADHD medication adherence include older age (eg, adolescents vs school-aged children),^{29,30,34,40,45-47} non-White race, Hispanic ethnicity,^29,33,48-51 female gender,^29,33,52 lower baseline ADHD symptom severity,^30,37 and child unwillingness to take medications.³⁴ However, prior studies have not been completely consistent about the relationship between child comorbid conditions (eg, oppositional defiant disorder [ODD], conduct disorder) and ADHD medication adherence. A few studies found that child comorbid conditions, especially ODD, mediate poor ADHD medication adherence, possibly secondary to an increased caregiver-child conflict.^30,53,54 However, other studies have reported that the presence of comorbid ODD, depression, and anxiety predicted increased adherence to ADHD medications.^37,46

Medication-related factors

Adverse effects of medications are the most commonly cited reason for ADHD medication nonadherence.^5,33,54-56 The adverse effects most often linked to nonadherence are reduced weight/appetite, increased aggressive behavior/irritability, and sleep difficulties.^54,57 Studies comparing methylphenidates and amphetamines, including 2 recent meta-analyses, suggest that amphetamines may be less well-tolerated on average, particularly with regard to emotional lability and irritability.^45,58,59 Therefore, clinicians might consider using methylphenidate-based preparations as first-line psychopharmacologic interventions in children with ADHD, as is consistent with the findings and conclusions drawn by a recent systematic review and meta-analysis of the comparative efficacy and tolerability of ADHD medications.⁶⁰

On the other hand, increased ADHD medication effectiveness has been associated with improved medication adherence.^5,34,54-56 Medication titration and dosing factors have also been shown to affect adherence. Specifically, adherence has been improved when ADHD medications are titrated in a systematic manner soon after starting treatment, and when families have an early first contact with a physician after starting medication (within 3 months).²⁸ In addition, use of a simplified dose regimen has been linked to better adherence: patients who are prescribed long-acting stimulants are more likely to adhere to treatment compared with patients who take short-acting formulations.^{26,40,49,61-63} It is possible that long-acting stimulants increase adherence because they produce more even and sustained effects on ADHD symptoms throughout the day, compared with short-acting formulations.⁶⁴ Furthermore, the inconvenience of taking multiple doses throughout the day, as well as the potential social stigma of mid-school day dosing, may negatively impact adherence to short-acting formulations.¹⁰

Continue to: Health care/system factors

Several studies have investigated the influence of health services factors on ADHD medication adherence. Specifically, limited transportation services and lack of mental health providers in the community have been linked to decreased ADHD medication adherence.^47,65,66 Furthermore, limited insurance coverage and higher costs of ADHD medications, which lead to substantial out-of-pocket payments for families, have been associated with decreased likelihood of ADHD medication adherence.^29,67

Clinician-related factors also can affect ADHD medication adherence. For example, a clinician’s lack knowledge of ADHD care can negatively impact ADHD medication adherence.⁶⁸ Two studies have documented improved ADHD medication adherence when treatment is provided by specialists (eg, child psychiatrists) rather than by community primary care providers, possibly because specialists are more likely to provide close stimulant titration and monitoring (ie, ≥ 3 visits in the first 90 days) and use higher maximum doses.^62,69 Furthermore, ADHD medication initiation and adherence are increased when patients have a strong working alliance with their clinician and trust the health care system,^31,34,35 as well as when there is a match between the caregiver’s and clinician’s perception of the cause, course, and best treatment practices for a child’s ADHD.⁶⁵

Strategies to improve medication adherence

A number of strategies to improve ADHD medication adherence can be derived from our knowledge of the factors that influence adherence.

Patient/family education. Unanswered questions about ADHD diagnosis, etiology, and medication adverse effects can negatively impact the ADHD treatment process. Therefore, patient/family education regarding ADHD and its management is necessary to improve medication adherence, because it helps families attain the knowledge, confidence, and motivation to manage their child’s condition.

Clinicians have an important role in educating patients about⁷⁰:

• the medications they are taking
• why they are taking them
• what the medications look like
• the time of medication administration
• the potential adverse effects
• what to do if adverse effects occur
• what regular testing/monitoring is necessary.

Clinicians can provide appropriate psychoeducation by sharing written materials and trusted websites with families (see Related Resources).

Behavioral strategies. Behavioral interventions have been among the most effective strategies for improving medication adherence in other chronic conditions.⁷¹ Behavioral strategies are likely to be particularly important for families of children with ADHD and comorbid conditions such as ODD because these families experience considerable caregiver-child conflict.⁷² Moreover, parents of children with ADHD are at higher risk for having ADHD and depression themselves,⁷³ both of which may interfere with a parent’s ability to obtain and administer medications consistently. Thus, for these families, using a combination of psychoeducation and behavioral strategies will be necessary to affect change in attitude and behavior. Behavioral strategies that can be used to improve medication adherence include:

• Technology-based interventions can reduce the impact of environmental barriers to adherence. For example, pharmacy automatic prescription renewal systems can reduce the likelihood of families failing to obtain ADHD medication refills. Pill reminder boxes, smartphone alerts, and setting various alarms can effectively prompt caregivers/patients to administer medication. In particular, these methods can be crucial in families for which multiple members have ADHD and its attendant difficulties with organization and task completion.
• Caregiver training may assist families in developing specific behavioral management skills that support adherence. This training can be as straightforward as instructing caregivers on the use of positive reinforcement when teaching their children to swallow pills. It may also encompass structured behavioral interventions aimed at training caregivers to utilize rewards and consequences in order to maximize medication adherence.⁷⁴

Continue to: Clinician interventions

Clinician interventions. Clinicians can use decision aids to help inform families about treatment options, promote shared decision making, and decrease uncertainty about the treatment plan⁷⁵ (see Related Resources). Early titration of ADHD medications and early first contact (within months of starting medication treatment) between caregivers and clinicians, whether via in-person visit, telephone, or email, have also been related to improved adherence.²⁸ Furthermore, clinicians can improve adherence by prescribing a simplified medication regimen (ie, long-acting formulations that provide full-day coverage). To address the negative impact of high out-of-pocket ADHD medication costs on adherence, clinicians can also prescribe generic preparations and/or “preferred” medications options on an individual patient’s formulary.

Because clinician knowledge and expertise in ADHD care has been linked to improved patient medication adherence,⁶⁸ clinicians are encouraged to use the American Academy of Pediatrics (AAP) guideline for diagnosis and treatment of ADHD, which includes a supplemental process of care algorithm (last published in 2011,¹⁰ with an updated guideline anticipated in 2019), as well as the AAP/National Institute for Children’s Health Quality (NICHQ) ADHD Toolkit,⁷⁶ which includes items helpful for ADHD diagnosis and treatment. The Society for Developmental and Behavioral Pediatrics is also developing a clinical practice guideline for the diagnosis and treatment of complex ADHD (ie, ADHD complicated by coexisting mental health, developmental, and/or psychosocial conditions or issues), with publication anticipated in 2019. Primary care providers can also improve their expertise in ADHD care by pursuing additional mental health–related trainings (such as those conducted by the REACH Institute).⁷⁷

Because receiving ADHD care from a specialist has been shown to improve medication initiation and adherence,^62,69 other strategies to address the short supply of child psychiatrists include offering incentives to medical students to pursue a career in child psychiatry (eg, loan forgiveness). Telepsychiatry and co-location of mental health specialists and primary care providers are additional innovative ways in which ADHD specialty care can be delivered to more patients.⁶⁴

Finally, providing culturally-sensitive care can strengthen the clinician-caregiver relationship and promote adherence to treatment. For example, clinicians can partner with local groups to increase their understanding of how different racial/ethnic groups perceive ADHD and its treatment.⁶⁴

Peer support models. Peers are credible role models who have a valued role in facilitating the use of mental health services by empowering families and enhancing service satisfaction.⁷⁸ In several communities in the United States, peer models using family advocates have been introduced.⁷⁹ Family advocates are typically caregivers of children who have special needs or have been involved in the mental health system. Their perspective—as peers and first-hand consumers of the health care and/or mental health system—can make them powerful and effective coaches to families of children with ADHD. By helping families to navigate ADHD care systems successfully, family advocates can play an important role in enhancing ADHD medication adherence, although further investigation is needed. In addition, the stigma around ADHD medication use, which adversely impacts adherence, can be mitigated if caregivers participate in organized ADHD-related support groups (eg, Children and Adults with ADHD [CHADD]).

Continue to: Health disparity-reducing interventions

Health disparity-reducing interventions. Successful health disparity-reducing interventions—such as those developed to enhance care of other chronic disorders including asthma and diabetes—can be applied to improve ADHD care. These interventions, which include medical-legal partnerships (eg, between clinicians, social workers, legal advocates, and community partners) in primary care centers, have been shown to improve health insurance coverage and therefore health care access.^80,81 Although some hardships linked to nonadherence (eg, low socioeconomic status) may not be amenable to health care–related interventions, screening for these hardships can identify children who are most at risk for poor adherence. This would alert clinicians to proactively identify barriers to adherence and implement mitigation strategies. This might include developing more streamlined, easier-to-follow management plans for these patients, such as those that can be delivered through pharmacist-physician collaborative programs⁸² and school-based therapy programs.^83-85

Bottom Line

Suboptimal adherence to medications for attention-deficit/hyperactivity disorder (ADHD) can be addressed through patient/family education, behavioral strategies, clinician interventions, peer support models, and health disparity-reducing interventions. By improving ADHD treatment adherence, these interventions have the potential to maximize long-term outcomes.

Related Resources

• Cohen Children’s Medical Center Northwell Health. The ADHD Medication Guide. www.ADHDMedicationGuide.com. Revised December 31, 2017.
• Cincinnati Children’s Hospital Medical Center. Decision aids to facilitate shared decision making in practice. www.cincinnatichildrens.org/service/j/anderson-center/ evidence-based-care/decision-aids.
• CHADD. Children and Adults with attention-deficit/ hyperactivity disorder. www.chadd.org.

Drug Brand Name

Methylphenidate • Concerta, Ritalin

Attention-deficit/hyperactivity disorder (ADHD) is the most common childhood neurodevelopmental disorder, affecting 8% to 12% of school-aged children in the United States^1-3 with significant impairments that often persist into adulthood.^4-8 Current guidelines recommend stimulant medication and/or behavioral therapies as first-line treatments for ADHD.^9,10 There is a wealth of evidence on the efficacy of stimulants in ADHD, with the most significant effects noted on core ADHD symptoms.^11,12 Additional evidence links stimulants to decreased long-term negative outcomes, including reduced school absences and grade retention,¹³ as well as modestly but significantly improved reading and math scores.¹⁴ Other studies have reported that individuals with ADHD who receive medication have decreased criminality,^15,16 motor vehicle accidents,^17,18 injuries,¹⁹ substance abuse,^20-22 and risk for subsequent and concurrent depression.²³ Therefore, the evidence suggests that consistent medication treatment helps improve outcomes for individuals with ADHD.

Adherence is defined as “the extent to which a person’s behavior (eg, taking medication) corresponds with agreed recommendations from a clinician.”²⁴ Unfortunately, pediatric ADHD medication adherence has been found to be poor (approximately 64%).^25-30 Nonadherence to ADHD medication has been linked to multiple factors, including caregiver/family and child/adolescent factors (Table 1), medication-related factors (Table 2), and health care/system factors (Table 3). Understanding and addressing these factors is essential to maximizing long-term outcomes. In this article, we review the factors associated with nonadherence to ADHD medication, and outline strategies to improve adherence.

Caregiver/family characteristics

Caregiver beliefs about ADHD and their attitudes toward treatment have been associated with the initiation of and adherence to ADHD medication. For example, caregivers who view a child’s difficulties as a medical disorder that requires a biologic intervention are more likely to accept and adhere to medication.³¹ Similarly, caregivers who perceive ADHD medication as safe, effective, and socially acceptable are more likely to be treatment-adherent.^32-35Other caregiver-related factors associated with improved ADHD medication adherence include:

• increased caregiver knowledge about ADHD³³
• receiving an ADHD diagnosis based on a thorough diagnostic process (ie, comprehensive psychological testing)³⁶
• satisfaction with information about medicine
• comfort with the treatment plan.³⁴

Socioeconomic status, family functioning, and caregiver mental health diagnoses (eg, ADHD, depression) have also been linked to ADHD medication adherence. Several studies, including the Multimodal Treatment Study of Children with ADHD,¹¹ a landmark study of stimulant medication for children with ADHD, have found an association between low income and decreased likelihood of receiving ADHD medication.^2,37-39 Further, Gau et al⁴⁰ found that negative caregiver-child relationships and family dysfunction were associated with poor medication adherence in children with ADHD.⁹ Prior studies have also shown that mothers of children with ADHD are more likely to have depression and/or anxiety,^41,42 and that caregivers with a history of mental health diagnoses are more accepting of initiating medication treatment for their children.⁴³ However, additional studies have found that caregiver mental health diagnoses decreased the likelihood of ADHD medication adherence.^40,44

Child characteristics

Child characteristics associated with decreased ADHD medication adherence include older age (eg, adolescents vs school-aged children),^{29,30,34,40,45-47} non-White race, Hispanic ethnicity,^29,33,48-51 female gender,^29,33,52 lower baseline ADHD symptom severity,^30,37 and child unwillingness to take medications.³⁴ However, prior studies have not been completely consistent about the relationship between child comorbid conditions (eg, oppositional defiant disorder [ODD], conduct disorder) and ADHD medication adherence. A few studies found that child comorbid conditions, especially ODD, mediate poor ADHD medication adherence, possibly secondary to an increased caregiver-child conflict.^30,53,54 However, other studies have reported that the presence of comorbid ODD, depression, and anxiety predicted increased adherence to ADHD medications.^37,46

Medication-related factors

Adverse effects of medications are the most commonly cited reason for ADHD medication nonadherence.^5,33,54-56 The adverse effects most often linked to nonadherence are reduced weight/appetite, increased aggressive behavior/irritability, and sleep difficulties.^54,57 Studies comparing methylphenidates and amphetamines, including 2 recent meta-analyses, suggest that amphetamines may be less well-tolerated on average, particularly with regard to emotional lability and irritability.^45,58,59 Therefore, clinicians might consider using methylphenidate-based preparations as first-line psychopharmacologic interventions in children with ADHD, as is consistent with the findings and conclusions drawn by a recent systematic review and meta-analysis of the comparative efficacy and tolerability of ADHD medications.⁶⁰

On the other hand, increased ADHD medication effectiveness has been associated with improved medication adherence.^5,34,54-56 Medication titration and dosing factors have also been shown to affect adherence. Specifically, adherence has been improved when ADHD medications are titrated in a systematic manner soon after starting treatment, and when families have an early first contact with a physician after starting medication (within 3 months).²⁸ In addition, use of a simplified dose regimen has been linked to better adherence: patients who are prescribed long-acting stimulants are more likely to adhere to treatment compared with patients who take short-acting formulations.^{26,40,49,61-63} It is possible that long-acting stimulants increase adherence because they produce more even and sustained effects on ADHD symptoms throughout the day, compared with short-acting formulations.⁶⁴ Furthermore, the inconvenience of taking multiple doses throughout the day, as well as the potential social stigma of mid-school day dosing, may negatively impact adherence to short-acting formulations.¹⁰

Continue to: Health care/system factors

Several studies have investigated the influence of health services factors on ADHD medication adherence. Specifically, limited transportation services and lack of mental health providers in the community have been linked to decreased ADHD medication adherence.^47,65,66 Furthermore, limited insurance coverage and higher costs of ADHD medications, which lead to substantial out-of-pocket payments for families, have been associated with decreased likelihood of ADHD medication adherence.^29,67

Clinician-related factors also can affect ADHD medication adherence. For example, a clinician’s lack knowledge of ADHD care can negatively impact ADHD medication adherence.⁶⁸ Two studies have documented improved ADHD medication adherence when treatment is provided by specialists (eg, child psychiatrists) rather than by community primary care providers, possibly because specialists are more likely to provide close stimulant titration and monitoring (ie, ≥ 3 visits in the first 90 days) and use higher maximum doses.^62,69 Furthermore, ADHD medication initiation and adherence are increased when patients have a strong working alliance with their clinician and trust the health care system,^31,34,35 as well as when there is a match between the caregiver’s and clinician’s perception of the cause, course, and best treatment practices for a child’s ADHD.⁶⁵

Strategies to improve medication adherence

A number of strategies to improve ADHD medication adherence can be derived from our knowledge of the factors that influence adherence.

Patient/family education. Unanswered questions about ADHD diagnosis, etiology, and medication adverse effects can negatively impact the ADHD treatment process. Therefore, patient/family education regarding ADHD and its management is necessary to improve medication adherence, because it helps families attain the knowledge, confidence, and motivation to manage their child’s condition.

Clinicians have an important role in educating patients about⁷⁰:

• the medications they are taking
• why they are taking them
• what the medications look like
• the time of medication administration
• the potential adverse effects
• what to do if adverse effects occur
• what regular testing/monitoring is necessary.

Clinicians can provide appropriate psychoeducation by sharing written materials and trusted websites with families (see Related Resources).

Behavioral strategies. Behavioral interventions have been among the most effective strategies for improving medication adherence in other chronic conditions.⁷¹ Behavioral strategies are likely to be particularly important for families of children with ADHD and comorbid conditions such as ODD because these families experience considerable caregiver-child conflict.⁷² Moreover, parents of children with ADHD are at higher risk for having ADHD and depression themselves,⁷³ both of which may interfere with a parent’s ability to obtain and administer medications consistently. Thus, for these families, using a combination of psychoeducation and behavioral strategies will be necessary to affect change in attitude and behavior. Behavioral strategies that can be used to improve medication adherence include:

• Technology-based interventions can reduce the impact of environmental barriers to adherence. For example, pharmacy automatic prescription renewal systems can reduce the likelihood of families failing to obtain ADHD medication refills. Pill reminder boxes, smartphone alerts, and setting various alarms can effectively prompt caregivers/patients to administer medication. In particular, these methods can be crucial in families for which multiple members have ADHD and its attendant difficulties with organization and task completion.
• Caregiver training may assist families in developing specific behavioral management skills that support adherence. This training can be as straightforward as instructing caregivers on the use of positive reinforcement when teaching their children to swallow pills. It may also encompass structured behavioral interventions aimed at training caregivers to utilize rewards and consequences in order to maximize medication adherence.⁷⁴

Continue to: Clinician interventions

Clinician interventions. Clinicians can use decision aids to help inform families about treatment options, promote shared decision making, and decrease uncertainty about the treatment plan⁷⁵ (see Related Resources). Early titration of ADHD medications and early first contact (within months of starting medication treatment) between caregivers and clinicians, whether via in-person visit, telephone, or email, have also been related to improved adherence.²⁸ Furthermore, clinicians can improve adherence by prescribing a simplified medication regimen (ie, long-acting formulations that provide full-day coverage). To address the negative impact of high out-of-pocket ADHD medication costs on adherence, clinicians can also prescribe generic preparations and/or “preferred” medications options on an individual patient’s formulary.

Because clinician knowledge and expertise in ADHD care has been linked to improved patient medication adherence,⁶⁸ clinicians are encouraged to use the American Academy of Pediatrics (AAP) guideline for diagnosis and treatment of ADHD, which includes a supplemental process of care algorithm (last published in 2011,¹⁰ with an updated guideline anticipated in 2019), as well as the AAP/National Institute for Children’s Health Quality (NICHQ) ADHD Toolkit,⁷⁶ which includes items helpful for ADHD diagnosis and treatment. The Society for Developmental and Behavioral Pediatrics is also developing a clinical practice guideline for the diagnosis and treatment of complex ADHD (ie, ADHD complicated by coexisting mental health, developmental, and/or psychosocial conditions or issues), with publication anticipated in 2019. Primary care providers can also improve their expertise in ADHD care by pursuing additional mental health–related trainings (such as those conducted by the REACH Institute).⁷⁷

Because receiving ADHD care from a specialist has been shown to improve medication initiation and adherence,^62,69 other strategies to address the short supply of child psychiatrists include offering incentives to medical students to pursue a career in child psychiatry (eg, loan forgiveness). Telepsychiatry and co-location of mental health specialists and primary care providers are additional innovative ways in which ADHD specialty care can be delivered to more patients.⁶⁴

Finally, providing culturally-sensitive care can strengthen the clinician-caregiver relationship and promote adherence to treatment. For example, clinicians can partner with local groups to increase their understanding of how different racial/ethnic groups perceive ADHD and its treatment.⁶⁴

Peer support models. Peers are credible role models who have a valued role in facilitating the use of mental health services by empowering families and enhancing service satisfaction.⁷⁸ In several communities in the United States, peer models using family advocates have been introduced.⁷⁹ Family advocates are typically caregivers of children who have special needs or have been involved in the mental health system. Their perspective—as peers and first-hand consumers of the health care and/or mental health system—can make them powerful and effective coaches to families of children with ADHD. By helping families to navigate ADHD care systems successfully, family advocates can play an important role in enhancing ADHD medication adherence, although further investigation is needed. In addition, the stigma around ADHD medication use, which adversely impacts adherence, can be mitigated if caregivers participate in organized ADHD-related support groups (eg, Children and Adults with ADHD [CHADD]).

Continue to: Health disparity-reducing interventions

Health disparity-reducing interventions. Successful health disparity-reducing interventions—such as those developed to enhance care of other chronic disorders including asthma and diabetes—can be applied to improve ADHD care. These interventions, which include medical-legal partnerships (eg, between clinicians, social workers, legal advocates, and community partners) in primary care centers, have been shown to improve health insurance coverage and therefore health care access.^80,81 Although some hardships linked to nonadherence (eg, low socioeconomic status) may not be amenable to health care–related interventions, screening for these hardships can identify children who are most at risk for poor adherence. This would alert clinicians to proactively identify barriers to adherence and implement mitigation strategies. This might include developing more streamlined, easier-to-follow management plans for these patients, such as those that can be delivered through pharmacist-physician collaborative programs⁸² and school-based therapy programs.^83-85

Bottom Line

Suboptimal adherence to medications for attention-deficit/hyperactivity disorder (ADHD) can be addressed through patient/family education, behavioral strategies, clinician interventions, peer support models, and health disparity-reducing interventions. By improving ADHD treatment adherence, these interventions have the potential to maximize long-term outcomes.

Related Resources

• Cohen Children’s Medical Center Northwell Health. The ADHD Medication Guide. www.ADHDMedicationGuide.com. Revised December 31, 2017.
• Cincinnati Children’s Hospital Medical Center. Decision aids to facilitate shared decision making in practice. www.cincinnatichildrens.org/service/j/anderson-center/ evidence-based-care/decision-aids.
• CHADD. Children and Adults with attention-deficit/ hyperactivity disorder. www.chadd.org.

Drug Brand Name

Methylphenidate • Concerta, Ritalin

For many people, artificial intelligence (AI) brings to mind some form of humanoid robot that speaks and acts like a human. However, AI is much more than merely robotics and machines. Professor John McCarthy of Stanford University, who first coined the term “artificial intelligence” in the early 1950s, defined it as “the science and engineering of making intelligent machines, especially intelligent computer programs”; he defined intelligence as “the computational part of the ability to achieve goals.^”1 Artificial intelligence also is commonly defined as the development of computer systems able to perform tasks that normally require human intelligence.² English Mathematician Alan Turing is considered one of the forefathers of AI research, and devised the first test to determine if a computer program was intelligent (Box 1³). Today, AI has established itself as an integral part of medicine and psychiatry.

Box 1

The semantics of AI

Two subsets of AI are machine learning and deep learning.^4,5 Machine learning is defined as a set of methods that can automatically detect patterns in data and then use the uncovered pattern to predict future data.⁴ Deep learning is a form of machine learning that enables computers to learn from experience and understand the world in terms of a hierarchy of concepts.⁵

Machine learning can be supervised, semi-supervised, or unsupervised. The majority of practical machine learning uses supervised learning, where all data are labeled and an algorithm is used to learn the mapping function from the input to the output. In unsupervised learning, all data are unlabeled and the algorithm models the underlying structure of the data by itself. Semi-supervised learning is a mixture of both.⁶

Many researchers also categorize AI into 2 types: general or “strong” AI, and narrow or “weak” AI. Strong AI is defined as computers that can think on a level at least equal to humans and are able to experience emotions and even consciousness.⁷ Weak AI includes adding “thinking-like” features to computers to make them more useful tools. Almost all AI technologies available today are considered to be weak AI.

AI in medicine

AI is being developed for a broad range of applications in medicine. This includes informatics approaches, including learning in health management systems such as electronic health records, and actively guiding physicians in their treatment decisions.⁸

AI has been applied to assist administrative workflows that reach beyond automated non-patient care activities such as chart documentation and placing orders. One example is the Judy Reitz Capacity Command Center, which was designed and built with GE Healthcare Partners.⁹ It combines AI technology in the form of systems engineering and predictive analytics to better manage multiple workflows in different administrative settings, including patient safety, volume, flow, and access to care.⁹

In April 2018, Intel Corporation surveyed 200 health-care decision makers in the United States regarding their use of AI in practice and their attitudes toward it.¹⁰ Overall, 37% of respondents reported using AI and 54% expected to increase their use of AI in the next 5 years. Clinical use of AI (77%) was more common than administrative use (41%) or financial use (26 %).¹⁰

Continue to: Box 2

Box 2^11-19 describes studies that evaluated the clinical use of AI in specialties other than psychiatry.

Box 2

How can AI be used in psychiatry?

Artificially intelligent technologies have been used in psychiatry for several decades. One of the earliest examples is ELIZA, a computer program published by Professor Joseph Weizenbaum of the Massachusetts Institute of Technology in 1966.²⁰ ELIZA consisted of a language analyzer and a script or a set of rules to improvise around a certain theme; the script DOCTOR was used to simulate a Rogerian psychotherapist.²⁰

The application of AI in psychiatry has come a long way since the pioneering work of Weizenbaum. A recent study examined AI’s ability to distinguish between an individual who had suicidal ideation vs a control group. Machine-learning algorithms were used to evaluate functional MRI scans of 34 participants (17 who had suicidal ideation and 17 controls) to identify certain neural signatures of concepts related to life and death.²¹ The machine-learning algorithms were able to distinguish between these 2 groups with 91% accuracy. They also were able to distinguish between individuals who attempted suicide and those who did not with 94% accuracy.²¹

A study from the University of Cincinnati looked at using machine learning and natural language processing to distinguish genuine suicide notes from “fake” suicide notes that had been written by a healthy control group.²² Sixty-six notes were evaluated and categorized by 11 mental health professionals (psychiatrists, social workers, and emergency medicine physicians) and 31 PGY-3 residents. The accuracy of their results was compared with that of 9 machine-learning algorithms.²² The best machine-learning algorithm accurately classified the notes 78% of the time, compared with 63% of the time for the mental health professionals and 49% of the time for the residents.²²

Researchers at Vanderbilt University examined using machine learning to predict suicide risk.²³ They developed algorithms to scan electronic health records of 5,167 adults, 3,250 of whom had attempted suicide. In a review of the patients’ data from 1 week to 2 years before the attempt, the algorithms looked for certain predictors of suicide attempts, including recurrent depression, psychotic disorder, and substance use. The algorithm was 80% accurate at predicting whether a patient would attempt suicide within the next 2 years, and 84% accurate at predicting an attempt within the next week.²³

Continue to: In a prospective study...

In a prospective study, researchers at Cincinnati Children’s Hospital used a machine-learning algorithm to evaluate 379 patients who were categorized into 3 groups: suicidal, mentally ill but not suicidal, or controls.²⁴ All participants completed a standardized behavioral rating scale and participated in a semi-structured interview. Based on the participants’ linguistic and acoustic characteristics, the algorithm was able to classify them into the 3 groups with 85% accuracy.²⁴

Many studies have looked at using language analysis to predicting the risk of psychosis in at-risk individuals. In one study, researchers evaluated individuals known to be at high risk for developing psychosis, some of whom eventually did develop psychosis.²⁵ Participants were asked to retell a story and to answer questions about that story. Researchers fed the transcripts of these interviews into a language analysis program that looked at semantic coherence, syntactic complexity, and other factors. The algorithm was able to predict the future occurrence of psychosis with 82% accuracy. Participants who converted to psychosis had decreased semantic coherence and reduced syntactic complexity.²⁵

A similar study looked at 34 at-risk youth in an attempt to predict who would develop psychosis based on speech pattern analysis.²⁶ The participants underwent baseline interviews and were assessed quarterly for 2.5 years. The algorithm was able to predict who would develop psychosis with 100% accuracy.²⁶

Challenges and limitations

The amount of research about applying machine learning to various fields of psychiatry continues to grow. With this increased interest, there have been reports of bias and human influence in the various stages of machine learning. Therefore, being aware of these challenges and engaging in practices to minimize their effects are necessary. Such practices include providing more details on data collection and processing, and constantly evaluating machine learning models for their relevance and utility to the research question proposed.²⁷

As is the case with most innovative, fast-growing technologies, AI has its fair share of criticisms and concerns. Critics have focused on the potential threat of privacy issues, medical errors, and ethical concerns. Researchers at the Stanford Center for Biomedical Ethics emphasize the importance of being aware of the different types of bias that humans and algorithm designs can introduce into health data.²⁸

Continue to: The Nuffield Council on Bioethics...

The Nuffield Council on Bioethics also emphasizes the importance of identifying the ethical issues raised by using AI in health care. Concerns include erroneous decisions made by AI and determining who is responsible for such errors, difficulty in validating the outputs of AI systems, and the potential for AI to be used for malicious purposes.²⁹

For clinicians who are considering implementing AI into their practice, it is vital to recognize where this technology belongs in a workflow and in the decision-making process. Jeffery Axt, a researcher on the clinical applications of AI, encourages clinicians to view using AI as a consulting tool to eliminate the element of fear associated with not having control over diagnostics and management.³⁰

What’s on the horizon

Research into using AI in psychiatry has drawn the attention of large companies. IBM is building an automated speech analysis application that uses machine learning to provide a real-time overview of a patient’s mental health.³¹ Social media platforms are also starting to incorporate AI technologies to scan posts for language and image patterns suggestive of suicidal thoughts or behavior.³²

“Chat bots”—AI that can conduct a conversation in natural language—are becoming popular as well. Woebot is a cognitive-behavioral therapy–based chat bot designed by a Stanford psychologist that can be accessed through Facebook Messenger. In a 2-week study, 70 young adults (age 18 to 28) with depression were randomly assigned to use Woebot or to read mental health e-books.³³ Participants who used Woebot experienced a significant reduction in depressive symptoms as measured by change in score on the Patient Health Questionnaire-9, while those assigned to the reading group did not.³³

Other researchers have focused on identifying patterns of inattention, hyperactivity, and impulsivity in children using AI technologies such as computer vision, machine learning, and data mining. For example, researchers at the University of Texas at Arlington and Yale University are analyzing data from watching children perform certain tasks involving attention, decision making, and emotion management.³⁴ There have been several advances in using AI to note abnormalities in a child’s gaze pattern that might suggest autism.³⁵

Continue to: A project at...

A project at the University of Southern California called SimSensei/Multisense uses software to track real-time behavior descriptors such as facial expressions, body postures, and acoustic features that can help identify psychological distress.³⁶ This software is combined with a virtual human platform that communicates with the patient as a therapist would.³⁶

The future of AI in health care appears to have great possibilities. Putting aside irrational fears of being replaced by computers one day, AI may someday be highly transformative, leading to vast improvements in patient care.

Bottom Line

Artificial intelligence (AI) —the development of computer systems able to perform tasks that normally require human intelligence—is being developed for use in a wide range of medical specialties. Potential uses in psychiatry include predicting a patient’s risk for suicide or psychosis. Privacy concerns, ethical issues, and the potential for medical errors are among the challenges of AI use in psychiatry.

Related Resources

• Durstewitz D, Koppe G, Meyer-Lindenberg A. Deep neural networks in psychiatry. Mol Psychiatry. 2019. doi:10.1038/s41380-019-0365-9.
• Kretzschmar K, Tyroll H, Pavarini G, et al; NeurOx Young People’s Advisory Group. Can your phone be your therapist? Young people’s ethical perspectives on the use of fully automated conversational agents (chatbots) in mental health support. Biomed Inform Insights. 2019;11:1178222619829083. doi: 10.1177/1178222619829083.

For many people, artificial intelligence (AI) brings to mind some form of humanoid robot that speaks and acts like a human. However, AI is much more than merely robotics and machines. Professor John McCarthy of Stanford University, who first coined the term “artificial intelligence” in the early 1950s, defined it as “the science and engineering of making intelligent machines, especially intelligent computer programs”; he defined intelligence as “the computational part of the ability to achieve goals.^”1 Artificial intelligence also is commonly defined as the development of computer systems able to perform tasks that normally require human intelligence.² English Mathematician Alan Turing is considered one of the forefathers of AI research, and devised the first test to determine if a computer program was intelligent (Box 1³). Today, AI has established itself as an integral part of medicine and psychiatry.

Box 1

The semantics of AI

Two subsets of AI are machine learning and deep learning.^4,5 Machine learning is defined as a set of methods that can automatically detect patterns in data and then use the uncovered pattern to predict future data.⁴ Deep learning is a form of machine learning that enables computers to learn from experience and understand the world in terms of a hierarchy of concepts.⁵

Machine learning can be supervised, semi-supervised, or unsupervised. The majority of practical machine learning uses supervised learning, where all data are labeled and an algorithm is used to learn the mapping function from the input to the output. In unsupervised learning, all data are unlabeled and the algorithm models the underlying structure of the data by itself. Semi-supervised learning is a mixture of both.⁶

Many researchers also categorize AI into 2 types: general or “strong” AI, and narrow or “weak” AI. Strong AI is defined as computers that can think on a level at least equal to humans and are able to experience emotions and even consciousness.⁷ Weak AI includes adding “thinking-like” features to computers to make them more useful tools. Almost all AI technologies available today are considered to be weak AI.

AI in medicine

AI is being developed for a broad range of applications in medicine. This includes informatics approaches, including learning in health management systems such as electronic health records, and actively guiding physicians in their treatment decisions.⁸

AI has been applied to assist administrative workflows that reach beyond automated non-patient care activities such as chart documentation and placing orders. One example is the Judy Reitz Capacity Command Center, which was designed and built with GE Healthcare Partners.⁹ It combines AI technology in the form of systems engineering and predictive analytics to better manage multiple workflows in different administrative settings, including patient safety, volume, flow, and access to care.⁹

In April 2018, Intel Corporation surveyed 200 health-care decision makers in the United States regarding their use of AI in practice and their attitudes toward it.¹⁰ Overall, 37% of respondents reported using AI and 54% expected to increase their use of AI in the next 5 years. Clinical use of AI (77%) was more common than administrative use (41%) or financial use (26 %).¹⁰

Continue to: Box 2

Box 2^11-19 describes studies that evaluated the clinical use of AI in specialties other than psychiatry.

Box 2

How can AI be used in psychiatry?

Artificially intelligent technologies have been used in psychiatry for several decades. One of the earliest examples is ELIZA, a computer program published by Professor Joseph Weizenbaum of the Massachusetts Institute of Technology in 1966.²⁰ ELIZA consisted of a language analyzer and a script or a set of rules to improvise around a certain theme; the script DOCTOR was used to simulate a Rogerian psychotherapist.²⁰

The application of AI in psychiatry has come a long way since the pioneering work of Weizenbaum. A recent study examined AI’s ability to distinguish between an individual who had suicidal ideation vs a control group. Machine-learning algorithms were used to evaluate functional MRI scans of 34 participants (17 who had suicidal ideation and 17 controls) to identify certain neural signatures of concepts related to life and death.²¹ The machine-learning algorithms were able to distinguish between these 2 groups with 91% accuracy. They also were able to distinguish between individuals who attempted suicide and those who did not with 94% accuracy.²¹

A study from the University of Cincinnati looked at using machine learning and natural language processing to distinguish genuine suicide notes from “fake” suicide notes that had been written by a healthy control group.²² Sixty-six notes were evaluated and categorized by 11 mental health professionals (psychiatrists, social workers, and emergency medicine physicians) and 31 PGY-3 residents. The accuracy of their results was compared with that of 9 machine-learning algorithms.²² The best machine-learning algorithm accurately classified the notes 78% of the time, compared with 63% of the time for the mental health professionals and 49% of the time for the residents.²²

Researchers at Vanderbilt University examined using machine learning to predict suicide risk.²³ They developed algorithms to scan electronic health records of 5,167 adults, 3,250 of whom had attempted suicide. In a review of the patients’ data from 1 week to 2 years before the attempt, the algorithms looked for certain predictors of suicide attempts, including recurrent depression, psychotic disorder, and substance use. The algorithm was 80% accurate at predicting whether a patient would attempt suicide within the next 2 years, and 84% accurate at predicting an attempt within the next week.²³

Continue to: In a prospective study...

In a prospective study, researchers at Cincinnati Children’s Hospital used a machine-learning algorithm to evaluate 379 patients who were categorized into 3 groups: suicidal, mentally ill but not suicidal, or controls.²⁴ All participants completed a standardized behavioral rating scale and participated in a semi-structured interview. Based on the participants’ linguistic and acoustic characteristics, the algorithm was able to classify them into the 3 groups with 85% accuracy.²⁴

Many studies have looked at using language analysis to predicting the risk of psychosis in at-risk individuals. In one study, researchers evaluated individuals known to be at high risk for developing psychosis, some of whom eventually did develop psychosis.²⁵ Participants were asked to retell a story and to answer questions about that story. Researchers fed the transcripts of these interviews into a language analysis program that looked at semantic coherence, syntactic complexity, and other factors. The algorithm was able to predict the future occurrence of psychosis with 82% accuracy. Participants who converted to psychosis had decreased semantic coherence and reduced syntactic complexity.²⁵

A similar study looked at 34 at-risk youth in an attempt to predict who would develop psychosis based on speech pattern analysis.²⁶ The participants underwent baseline interviews and were assessed quarterly for 2.5 years. The algorithm was able to predict who would develop psychosis with 100% accuracy.²⁶

Challenges and limitations

The amount of research about applying machine learning to various fields of psychiatry continues to grow. With this increased interest, there have been reports of bias and human influence in the various stages of machine learning. Therefore, being aware of these challenges and engaging in practices to minimize their effects are necessary. Such practices include providing more details on data collection and processing, and constantly evaluating machine learning models for their relevance and utility to the research question proposed.²⁷

As is the case with most innovative, fast-growing technologies, AI has its fair share of criticisms and concerns. Critics have focused on the potential threat of privacy issues, medical errors, and ethical concerns. Researchers at the Stanford Center for Biomedical Ethics emphasize the importance of being aware of the different types of bias that humans and algorithm designs can introduce into health data.²⁸

Continue to: The Nuffield Council on Bioethics...

The Nuffield Council on Bioethics also emphasizes the importance of identifying the ethical issues raised by using AI in health care. Concerns include erroneous decisions made by AI and determining who is responsible for such errors, difficulty in validating the outputs of AI systems, and the potential for AI to be used for malicious purposes.²⁹

For clinicians who are considering implementing AI into their practice, it is vital to recognize where this technology belongs in a workflow and in the decision-making process. Jeffery Axt, a researcher on the clinical applications of AI, encourages clinicians to view using AI as a consulting tool to eliminate the element of fear associated with not having control over diagnostics and management.³⁰

What’s on the horizon

Research into using AI in psychiatry has drawn the attention of large companies. IBM is building an automated speech analysis application that uses machine learning to provide a real-time overview of a patient’s mental health.³¹ Social media platforms are also starting to incorporate AI technologies to scan posts for language and image patterns suggestive of suicidal thoughts or behavior.³²

“Chat bots”—AI that can conduct a conversation in natural language—are becoming popular as well. Woebot is a cognitive-behavioral therapy–based chat bot designed by a Stanford psychologist that can be accessed through Facebook Messenger. In a 2-week study, 70 young adults (age 18 to 28) with depression were randomly assigned to use Woebot or to read mental health e-books.³³ Participants who used Woebot experienced a significant reduction in depressive symptoms as measured by change in score on the Patient Health Questionnaire-9, while those assigned to the reading group did not.³³

Other researchers have focused on identifying patterns of inattention, hyperactivity, and impulsivity in children using AI technologies such as computer vision, machine learning, and data mining. For example, researchers at the University of Texas at Arlington and Yale University are analyzing data from watching children perform certain tasks involving attention, decision making, and emotion management.³⁴ There have been several advances in using AI to note abnormalities in a child’s gaze pattern that might suggest autism.³⁵

Continue to: A project at...

A project at the University of Southern California called SimSensei/Multisense uses software to track real-time behavior descriptors such as facial expressions, body postures, and acoustic features that can help identify psychological distress.³⁶ This software is combined with a virtual human platform that communicates with the patient as a therapist would.³⁶

The future of AI in health care appears to have great possibilities. Putting aside irrational fears of being replaced by computers one day, AI may someday be highly transformative, leading to vast improvements in patient care.

Bottom Line

Artificial intelligence (AI) —the development of computer systems able to perform tasks that normally require human intelligence—is being developed for use in a wide range of medical specialties. Potential uses in psychiatry include predicting a patient’s risk for suicide or psychosis. Privacy concerns, ethical issues, and the potential for medical errors are among the challenges of AI use in psychiatry.

Related Resources

• Durstewitz D, Koppe G, Meyer-Lindenberg A. Deep neural networks in psychiatry. Mol Psychiatry. 2019. doi:10.1038/s41380-019-0365-9.
• Kretzschmar K, Tyroll H, Pavarini G, et al; NeurOx Young People’s Advisory Group. Can your phone be your therapist? Young people’s ethical perspectives on the use of fully automated conversational agents (chatbots) in mental health support. Biomed Inform Insights. 2019;11:1178222619829083. doi: 10.1177/1178222619829083.

For many people, artificial intelligence (AI) brings to mind some form of humanoid robot that speaks and acts like a human. However, AI is much more than merely robotics and machines. Professor John McCarthy of Stanford University, who first coined the term “artificial intelligence” in the early 1950s, defined it as “the science and engineering of making intelligent machines, especially intelligent computer programs”; he defined intelligence as “the computational part of the ability to achieve goals.^”1 Artificial intelligence also is commonly defined as the development of computer systems able to perform tasks that normally require human intelligence.² English Mathematician Alan Turing is considered one of the forefathers of AI research, and devised the first test to determine if a computer program was intelligent (Box 1³). Today, AI has established itself as an integral part of medicine and psychiatry.

Box 1

The semantics of AI

Two subsets of AI are machine learning and deep learning.^4,5 Machine learning is defined as a set of methods that can automatically detect patterns in data and then use the uncovered pattern to predict future data.⁴ Deep learning is a form of machine learning that enables computers to learn from experience and understand the world in terms of a hierarchy of concepts.⁵

Machine learning can be supervised, semi-supervised, or unsupervised. The majority of practical machine learning uses supervised learning, where all data are labeled and an algorithm is used to learn the mapping function from the input to the output. In unsupervised learning, all data are unlabeled and the algorithm models the underlying structure of the data by itself. Semi-supervised learning is a mixture of both.⁶

Many researchers also categorize AI into 2 types: general or “strong” AI, and narrow or “weak” AI. Strong AI is defined as computers that can think on a level at least equal to humans and are able to experience emotions and even consciousness.⁷ Weak AI includes adding “thinking-like” features to computers to make them more useful tools. Almost all AI technologies available today are considered to be weak AI.

AI in medicine

AI is being developed for a broad range of applications in medicine. This includes informatics approaches, including learning in health management systems such as electronic health records, and actively guiding physicians in their treatment decisions.⁸

AI has been applied to assist administrative workflows that reach beyond automated non-patient care activities such as chart documentation and placing orders. One example is the Judy Reitz Capacity Command Center, which was designed and built with GE Healthcare Partners.⁹ It combines AI technology in the form of systems engineering and predictive analytics to better manage multiple workflows in different administrative settings, including patient safety, volume, flow, and access to care.⁹

In April 2018, Intel Corporation surveyed 200 health-care decision makers in the United States regarding their use of AI in practice and their attitudes toward it.¹⁰ Overall, 37% of respondents reported using AI and 54% expected to increase their use of AI in the next 5 years. Clinical use of AI (77%) was more common than administrative use (41%) or financial use (26 %).¹⁰

Continue to: Box 2

Box 2^11-19 describes studies that evaluated the clinical use of AI in specialties other than psychiatry.

Box 2

How can AI be used in psychiatry?

Artificially intelligent technologies have been used in psychiatry for several decades. One of the earliest examples is ELIZA, a computer program published by Professor Joseph Weizenbaum of the Massachusetts Institute of Technology in 1966.²⁰ ELIZA consisted of a language analyzer and a script or a set of rules to improvise around a certain theme; the script DOCTOR was used to simulate a Rogerian psychotherapist.²⁰

The application of AI in psychiatry has come a long way since the pioneering work of Weizenbaum. A recent study examined AI’s ability to distinguish between an individual who had suicidal ideation vs a control group. Machine-learning algorithms were used to evaluate functional MRI scans of 34 participants (17 who had suicidal ideation and 17 controls) to identify certain neural signatures of concepts related to life and death.²¹ The machine-learning algorithms were able to distinguish between these 2 groups with 91% accuracy. They also were able to distinguish between individuals who attempted suicide and those who did not with 94% accuracy.²¹

A study from the University of Cincinnati looked at using machine learning and natural language processing to distinguish genuine suicide notes from “fake” suicide notes that had been written by a healthy control group.²² Sixty-six notes were evaluated and categorized by 11 mental health professionals (psychiatrists, social workers, and emergency medicine physicians) and 31 PGY-3 residents. The accuracy of their results was compared with that of 9 machine-learning algorithms.²² The best machine-learning algorithm accurately classified the notes 78% of the time, compared with 63% of the time for the mental health professionals and 49% of the time for the residents.²²

Researchers at Vanderbilt University examined using machine learning to predict suicide risk.²³ They developed algorithms to scan electronic health records of 5,167 adults, 3,250 of whom had attempted suicide. In a review of the patients’ data from 1 week to 2 years before the attempt, the algorithms looked for certain predictors of suicide attempts, including recurrent depression, psychotic disorder, and substance use. The algorithm was 80% accurate at predicting whether a patient would attempt suicide within the next 2 years, and 84% accurate at predicting an attempt within the next week.²³

Continue to: In a prospective study...

In a prospective study, researchers at Cincinnati Children’s Hospital used a machine-learning algorithm to evaluate 379 patients who were categorized into 3 groups: suicidal, mentally ill but not suicidal, or controls.²⁴ All participants completed a standardized behavioral rating scale and participated in a semi-structured interview. Based on the participants’ linguistic and acoustic characteristics, the algorithm was able to classify them into the 3 groups with 85% accuracy.²⁴

Many studies have looked at using language analysis to predicting the risk of psychosis in at-risk individuals. In one study, researchers evaluated individuals known to be at high risk for developing psychosis, some of whom eventually did develop psychosis.²⁵ Participants were asked to retell a story and to answer questions about that story. Researchers fed the transcripts of these interviews into a language analysis program that looked at semantic coherence, syntactic complexity, and other factors. The algorithm was able to predict the future occurrence of psychosis with 82% accuracy. Participants who converted to psychosis had decreased semantic coherence and reduced syntactic complexity.²⁵

A similar study looked at 34 at-risk youth in an attempt to predict who would develop psychosis based on speech pattern analysis.²⁶ The participants underwent baseline interviews and were assessed quarterly for 2.5 years. The algorithm was able to predict who would develop psychosis with 100% accuracy.²⁶

Challenges and limitations

The amount of research about applying machine learning to various fields of psychiatry continues to grow. With this increased interest, there have been reports of bias and human influence in the various stages of machine learning. Therefore, being aware of these challenges and engaging in practices to minimize their effects are necessary. Such practices include providing more details on data collection and processing, and constantly evaluating machine learning models for their relevance and utility to the research question proposed.²⁷

As is the case with most innovative, fast-growing technologies, AI has its fair share of criticisms and concerns. Critics have focused on the potential threat of privacy issues, medical errors, and ethical concerns. Researchers at the Stanford Center for Biomedical Ethics emphasize the importance of being aware of the different types of bias that humans and algorithm designs can introduce into health data.²⁸

Continue to: The Nuffield Council on Bioethics...

The Nuffield Council on Bioethics also emphasizes the importance of identifying the ethical issues raised by using AI in health care. Concerns include erroneous decisions made by AI and determining who is responsible for such errors, difficulty in validating the outputs of AI systems, and the potential for AI to be used for malicious purposes.²⁹

For clinicians who are considering implementing AI into their practice, it is vital to recognize where this technology belongs in a workflow and in the decision-making process. Jeffery Axt, a researcher on the clinical applications of AI, encourages clinicians to view using AI as a consulting tool to eliminate the element of fear associated with not having control over diagnostics and management.³⁰

What’s on the horizon

Research into using AI in psychiatry has drawn the attention of large companies. IBM is building an automated speech analysis application that uses machine learning to provide a real-time overview of a patient’s mental health.³¹ Social media platforms are also starting to incorporate AI technologies to scan posts for language and image patterns suggestive of suicidal thoughts or behavior.³²

“Chat bots”—AI that can conduct a conversation in natural language—are becoming popular as well. Woebot is a cognitive-behavioral therapy–based chat bot designed by a Stanford psychologist that can be accessed through Facebook Messenger. In a 2-week study, 70 young adults (age 18 to 28) with depression were randomly assigned to use Woebot or to read mental health e-books.³³ Participants who used Woebot experienced a significant reduction in depressive symptoms as measured by change in score on the Patient Health Questionnaire-9, while those assigned to the reading group did not.³³

Other researchers have focused on identifying patterns of inattention, hyperactivity, and impulsivity in children using AI technologies such as computer vision, machine learning, and data mining. For example, researchers at the University of Texas at Arlington and Yale University are analyzing data from watching children perform certain tasks involving attention, decision making, and emotion management.³⁴ There have been several advances in using AI to note abnormalities in a child’s gaze pattern that might suggest autism.³⁵

Continue to: A project at...

A project at the University of Southern California called SimSensei/Multisense uses software to track real-time behavior descriptors such as facial expressions, body postures, and acoustic features that can help identify psychological distress.³⁶ This software is combined with a virtual human platform that communicates with the patient as a therapist would.³⁶

The future of AI in health care appears to have great possibilities. Putting aside irrational fears of being replaced by computers one day, AI may someday be highly transformative, leading to vast improvements in patient care.

Bottom Line

Artificial intelligence (AI) —the development of computer systems able to perform tasks that normally require human intelligence—is being developed for use in a wide range of medical specialties. Potential uses in psychiatry include predicting a patient’s risk for suicide or psychosis. Privacy concerns, ethical issues, and the potential for medical errors are among the challenges of AI use in psychiatry.

Related Resources

• Durstewitz D, Koppe G, Meyer-Lindenberg A. Deep neural networks in psychiatry. Mol Psychiatry. 2019. doi:10.1038/s41380-019-0365-9.
• Kretzschmar K, Tyroll H, Pavarini G, et al; NeurOx Young People’s Advisory Group. Can your phone be your therapist? Young people’s ethical perspectives on the use of fully automated conversational agents (chatbots) in mental health support. Biomed Inform Insights. 2019;11:1178222619829083. doi: 10.1177/1178222619829083.