Depression

For the last 30 years, the Center for Women’s Mental Health at Massachusetts General Hospital (MGH) has had as part of its mission, the conveying of accurate information about the reproductive safety of psychiatric medications. There has been a spectrum of medicines developed across psychiatric indications over the last several decades, and many studies over those decades have attempted to delineate the reproductive safety of these agents.

With the development of new antidepressants and second-generation antipsychotics has come an appreciation of the utility of these agents across a wide range of psychiatric disease states and psychiatric symptoms. More and more data demonstrate the efficacy of these medicines for mood and anxiety disorders; these agents are also used for a broad array of symptoms from insomnia, irritability, and symptoms of posttraumatic stress disorder (PTSD) just as examples — even absent formal approval by the US Food and Drug Administration (FDA) for these specific indications. With the growing use of medicines, including new antidepressants like selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors, and second-generation atypical antipsychotics, there has been a greater interest and appreciation of the need to provide women with the best information about reproductive safety of these medicines as well.

When I began working in reproductive psychiatry, the FDA was using the pregnancy labeling categories introduced in 1979. The categories were simple, but also oversimplified in terms of incompletely conveying information about reproductive safety. For instance, category labels of B and C under the old labeling system could be nebulous, containing sparse information (in the case of category B) or animal data and some conflicting human data (in the case of category C) that may not have translated into relevant or easily interpretable safety information for patients and clinicians.

It was on that basis the current Pregnancy and Lactation Labeling (PLLR) Final Rule was published in 2014, which was a shift from categorical labeling to more descriptive labeling, including updated actual information on the package insert about available reproductive safety data, animal data, and data on lactation.

Even following the publication of the PLLR, there has still been an acknowledgment in the field that our assessment tools for postmarketing reproductive safety surveillance are incomplete. A recent 2-day FDA workshop hosted by the Duke-Margolis Center for Health Policy on optimizing the use of postapproval pregnancy safety studies sought to discuss the many questions that still surround this issue. Based on presentations at this workshop, a framework emerged for the future of assessing the reproductive safety of medications, which included an effort to develop the most effective model using tools such as pregnancy registries and harnessing “big data,” whether through electronic health records or large administrative databases from public and private insurers. Together, these various sources of information can provide signals of potential concern, prompting the need for a more rigorous look at the reproductive safety of a medication, or provide reassurance if data fail to indicate the absence of a signal of risk.

FDA’s new commitments under the latest reauthorization of the Prescription Drug User Fee Act (PDUFA VII) include pregnancy-specific postmarketing safety requirements as well as the creation of a framework for how data from pregnancy-specific postmarketing studies can be used. The agency is also conducting demonstration projects, including one for assessing the performance of pregnancy registries for the potential to detect safety signals for medications early in pregnancy. FDA is expanding its Sentinel Initiative to help accomplish these aims, and is implementing an Active Risk Identification and Analysis (ARIA) system to conduct active safety surveillance of medications used during pregnancy.

Pregnancy registries have now been available for decades, and some have been more successful than others across different classes of medicines, with the most rigorous registries including prospective follow-up of women across pregnancies and careful documentation of malformations (at best with original source data and with a blinded dysmorphologist). Still, with all of its rigor, even the best-intentioned efforts with respect to pregnancy registries have limitations. As I mentioned in my testimony during the public comment portion of the workshop, the sheer volume of pregnancy data from administrative databases we now have access to is attractive, but the quality of these data needs to be good enough to ascertain a signal of risk if they are to be used as a basis for reproductive safety determination.

The flip side of using data from large administrative databases is using carefully collected data from pregnancy registries. With a pregnancy registry, accrual of a substantial number of participants can also take a considerable period of time, and initial risk estimates of outcomes can have typically large confidence intervals, which can make it difficult to discern whether a drug is safe for women of reproductive age.

Another key issue is a lack of participation from manufacturers with respect to commitment to collection of high-quality reproductive safety data. History has shown that many medication manufacturers, unless required to have a dedicated registry as part of a postmarketing requirement or commitment, will invest sparse resources to track data on safety of fetal drug exposure. Participation is typically voluntary and varies from company to company unless, as noted previously, there is a postmarketing requirement or commitment tied to the approval of a medication. Just as a recent concrete example, the manufacturer of a new medication recently approved by the FDA for the treatment of postpartum depression (which will include presumably sexually active women well into the first postpartum year) has no plan to support the collection of reproductive safety data on this new medication because it is not required to, based on current FDA guidelines and the absence of a postmarketing requirement to do so.
 

Looking ahead

While the PLLR was a huge step forward in the field from the old pregnancy category system that could misinform women contemplating pregnancy, it also sets the stage for the next iteration of a system that allows us to generate information more quickly about the reproductive safety of medications. In psychiatry, as many as 10% of women use SSRIs during pregnancy. With drugs like atypical antipsychotics being used across disease states — in schizophrenia, bipolar disorder, depression, anxiety, insomnia, and PTSD — and where new classes of medicine are becoming available, like with ketamine or steroids, we need to have a system by which we can more quickly ascertain reproductive safety information. This information informs treatment decisions during a critical life event of deciding to try to become pregnant or during an actual pregnancy.

In my mind, it is reassuring when a registry has even as few as 50-60 cases of fetal exposure without an increase in the risk for malformation, because it can mean we are not seeing a repeat of the past with medications like thalidomide and sodium valproate. However, patients and clinicians are starved for better data. Risk assessment is also different from clinician to clinician and patient to patient. We want to empower patients to make decisions that work for them based on more rapidly accumulating information and help inform their decisions.

To come out on the “other side” of the PLLR, we will need to find a way to accelerate our ability to identify signals of risk or information that is reassuring (or not reassuring) so that clinicians and patients are not left waiting for the next paper to come out, which can be confusing when study results frequently conflict. I believe we have an obligation today to do this better, because the areas of reproductive toxicology and pharmacovigilance are growing incredibly quickly, and clinicians and patients are seeing these volumes of data being published without the ability to integrate that information in a systematic way.

Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital (MGH) in Boston, which provides information resources and conducts clinical care and research in reproductive mental health. He has been a consultant to manufacturers of psychiatric medications. Full disclosure information for Dr. Cohen is available at womensmentalhealth.org. Email Dr. Cohen at obnews@mdedge.com.

For the last 30 years, the Center for Women’s Mental Health at Massachusetts General Hospital (MGH) has had as part of its mission, the conveying of accurate information about the reproductive safety of psychiatric medications. There has been a spectrum of medicines developed across psychiatric indications over the last several decades, and many studies over those decades have attempted to delineate the reproductive safety of these agents.

With the development of new antidepressants and second-generation antipsychotics has come an appreciation of the utility of these agents across a wide range of psychiatric disease states and psychiatric symptoms. More and more data demonstrate the efficacy of these medicines for mood and anxiety disorders; these agents are also used for a broad array of symptoms from insomnia, irritability, and symptoms of posttraumatic stress disorder (PTSD) just as examples — even absent formal approval by the US Food and Drug Administration (FDA) for these specific indications. With the growing use of medicines, including new antidepressants like selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors, and second-generation atypical antipsychotics, there has been a greater interest and appreciation of the need to provide women with the best information about reproductive safety of these medicines as well.

When I began working in reproductive psychiatry, the FDA was using the pregnancy labeling categories introduced in 1979. The categories were simple, but also oversimplified in terms of incompletely conveying information about reproductive safety. For instance, category labels of B and C under the old labeling system could be nebulous, containing sparse information (in the case of category B) or animal data and some conflicting human data (in the case of category C) that may not have translated into relevant or easily interpretable safety information for patients and clinicians.

It was on that basis the current Pregnancy and Lactation Labeling (PLLR) Final Rule was published in 2014, which was a shift from categorical labeling to more descriptive labeling, including updated actual information on the package insert about available reproductive safety data, animal data, and data on lactation.

Even following the publication of the PLLR, there has still been an acknowledgment in the field that our assessment tools for postmarketing reproductive safety surveillance are incomplete. A recent 2-day FDA workshop hosted by the Duke-Margolis Center for Health Policy on optimizing the use of postapproval pregnancy safety studies sought to discuss the many questions that still surround this issue. Based on presentations at this workshop, a framework emerged for the future of assessing the reproductive safety of medications, which included an effort to develop the most effective model using tools such as pregnancy registries and harnessing “big data,” whether through electronic health records or large administrative databases from public and private insurers. Together, these various sources of information can provide signals of potential concern, prompting the need for a more rigorous look at the reproductive safety of a medication, or provide reassurance if data fail to indicate the absence of a signal of risk.

FDA’s new commitments under the latest reauthorization of the Prescription Drug User Fee Act (PDUFA VII) include pregnancy-specific postmarketing safety requirements as well as the creation of a framework for how data from pregnancy-specific postmarketing studies can be used. The agency is also conducting demonstration projects, including one for assessing the performance of pregnancy registries for the potential to detect safety signals for medications early in pregnancy. FDA is expanding its Sentinel Initiative to help accomplish these aims, and is implementing an Active Risk Identification and Analysis (ARIA) system to conduct active safety surveillance of medications used during pregnancy.

Pregnancy registries have now been available for decades, and some have been more successful than others across different classes of medicines, with the most rigorous registries including prospective follow-up of women across pregnancies and careful documentation of malformations (at best with original source data and with a blinded dysmorphologist). Still, with all of its rigor, even the best-intentioned efforts with respect to pregnancy registries have limitations. As I mentioned in my testimony during the public comment portion of the workshop, the sheer volume of pregnancy data from administrative databases we now have access to is attractive, but the quality of these data needs to be good enough to ascertain a signal of risk if they are to be used as a basis for reproductive safety determination.

The flip side of using data from large administrative databases is using carefully collected data from pregnancy registries. With a pregnancy registry, accrual of a substantial number of participants can also take a considerable period of time, and initial risk estimates of outcomes can have typically large confidence intervals, which can make it difficult to discern whether a drug is safe for women of reproductive age.

Another key issue is a lack of participation from manufacturers with respect to commitment to collection of high-quality reproductive safety data. History has shown that many medication manufacturers, unless required to have a dedicated registry as part of a postmarketing requirement or commitment, will invest sparse resources to track data on safety of fetal drug exposure. Participation is typically voluntary and varies from company to company unless, as noted previously, there is a postmarketing requirement or commitment tied to the approval of a medication. Just as a recent concrete example, the manufacturer of a new medication recently approved by the FDA for the treatment of postpartum depression (which will include presumably sexually active women well into the first postpartum year) has no plan to support the collection of reproductive safety data on this new medication because it is not required to, based on current FDA guidelines and the absence of a postmarketing requirement to do so.
 

Looking ahead

While the PLLR was a huge step forward in the field from the old pregnancy category system that could misinform women contemplating pregnancy, it also sets the stage for the next iteration of a system that allows us to generate information more quickly about the reproductive safety of medications. In psychiatry, as many as 10% of women use SSRIs during pregnancy. With drugs like atypical antipsychotics being used across disease states — in schizophrenia, bipolar disorder, depression, anxiety, insomnia, and PTSD — and where new classes of medicine are becoming available, like with ketamine or steroids, we need to have a system by which we can more quickly ascertain reproductive safety information. This information informs treatment decisions during a critical life event of deciding to try to become pregnant or during an actual pregnancy.

In my mind, it is reassuring when a registry has even as few as 50-60 cases of fetal exposure without an increase in the risk for malformation, because it can mean we are not seeing a repeat of the past with medications like thalidomide and sodium valproate. However, patients and clinicians are starved for better data. Risk assessment is also different from clinician to clinician and patient to patient. We want to empower patients to make decisions that work for them based on more rapidly accumulating information and help inform their decisions.

To come out on the “other side” of the PLLR, we will need to find a way to accelerate our ability to identify signals of risk or information that is reassuring (or not reassuring) so that clinicians and patients are not left waiting for the next paper to come out, which can be confusing when study results frequently conflict. I believe we have an obligation today to do this better, because the areas of reproductive toxicology and pharmacovigilance are growing incredibly quickly, and clinicians and patients are seeing these volumes of data being published without the ability to integrate that information in a systematic way.

Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital (MGH) in Boston, which provides information resources and conducts clinical care and research in reproductive mental health. He has been a consultant to manufacturers of psychiatric medications. Full disclosure information for Dr. Cohen is available at womensmentalhealth.org. Email Dr. Cohen at obnews@mdedge.com.

For the last 30 years, the Center for Women’s Mental Health at Massachusetts General Hospital (MGH) has had as part of its mission, the conveying of accurate information about the reproductive safety of psychiatric medications. There has been a spectrum of medicines developed across psychiatric indications over the last several decades, and many studies over those decades have attempted to delineate the reproductive safety of these agents.

With the development of new antidepressants and second-generation antipsychotics has come an appreciation of the utility of these agents across a wide range of psychiatric disease states and psychiatric symptoms. More and more data demonstrate the efficacy of these medicines for mood and anxiety disorders; these agents are also used for a broad array of symptoms from insomnia, irritability, and symptoms of posttraumatic stress disorder (PTSD) just as examples — even absent formal approval by the US Food and Drug Administration (FDA) for these specific indications. With the growing use of medicines, including new antidepressants like selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors, and second-generation atypical antipsychotics, there has been a greater interest and appreciation of the need to provide women with the best information about reproductive safety of these medicines as well.

When I began working in reproductive psychiatry, the FDA was using the pregnancy labeling categories introduced in 1979. The categories were simple, but also oversimplified in terms of incompletely conveying information about reproductive safety. For instance, category labels of B and C under the old labeling system could be nebulous, containing sparse information (in the case of category B) or animal data and some conflicting human data (in the case of category C) that may not have translated into relevant or easily interpretable safety information for patients and clinicians.

It was on that basis the current Pregnancy and Lactation Labeling (PLLR) Final Rule was published in 2014, which was a shift from categorical labeling to more descriptive labeling, including updated actual information on the package insert about available reproductive safety data, animal data, and data on lactation.

Even following the publication of the PLLR, there has still been an acknowledgment in the field that our assessment tools for postmarketing reproductive safety surveillance are incomplete. A recent 2-day FDA workshop hosted by the Duke-Margolis Center for Health Policy on optimizing the use of postapproval pregnancy safety studies sought to discuss the many questions that still surround this issue. Based on presentations at this workshop, a framework emerged for the future of assessing the reproductive safety of medications, which included an effort to develop the most effective model using tools such as pregnancy registries and harnessing “big data,” whether through electronic health records or large administrative databases from public and private insurers. Together, these various sources of information can provide signals of potential concern, prompting the need for a more rigorous look at the reproductive safety of a medication, or provide reassurance if data fail to indicate the absence of a signal of risk.

FDA’s new commitments under the latest reauthorization of the Prescription Drug User Fee Act (PDUFA VII) include pregnancy-specific postmarketing safety requirements as well as the creation of a framework for how data from pregnancy-specific postmarketing studies can be used. The agency is also conducting demonstration projects, including one for assessing the performance of pregnancy registries for the potential to detect safety signals for medications early in pregnancy. FDA is expanding its Sentinel Initiative to help accomplish these aims, and is implementing an Active Risk Identification and Analysis (ARIA) system to conduct active safety surveillance of medications used during pregnancy.

Pregnancy registries have now been available for decades, and some have been more successful than others across different classes of medicines, with the most rigorous registries including prospective follow-up of women across pregnancies and careful documentation of malformations (at best with original source data and with a blinded dysmorphologist). Still, with all of its rigor, even the best-intentioned efforts with respect to pregnancy registries have limitations. As I mentioned in my testimony during the public comment portion of the workshop, the sheer volume of pregnancy data from administrative databases we now have access to is attractive, but the quality of these data needs to be good enough to ascertain a signal of risk if they are to be used as a basis for reproductive safety determination.

The flip side of using data from large administrative databases is using carefully collected data from pregnancy registries. With a pregnancy registry, accrual of a substantial number of participants can also take a considerable period of time, and initial risk estimates of outcomes can have typically large confidence intervals, which can make it difficult to discern whether a drug is safe for women of reproductive age.

Another key issue is a lack of participation from manufacturers with respect to commitment to collection of high-quality reproductive safety data. History has shown that many medication manufacturers, unless required to have a dedicated registry as part of a postmarketing requirement or commitment, will invest sparse resources to track data on safety of fetal drug exposure. Participation is typically voluntary and varies from company to company unless, as noted previously, there is a postmarketing requirement or commitment tied to the approval of a medication. Just as a recent concrete example, the manufacturer of a new medication recently approved by the FDA for the treatment of postpartum depression (which will include presumably sexually active women well into the first postpartum year) has no plan to support the collection of reproductive safety data on this new medication because it is not required to, based on current FDA guidelines and the absence of a postmarketing requirement to do so.
 

Looking ahead

While the PLLR was a huge step forward in the field from the old pregnancy category system that could misinform women contemplating pregnancy, it also sets the stage for the next iteration of a system that allows us to generate information more quickly about the reproductive safety of medications. In psychiatry, as many as 10% of women use SSRIs during pregnancy. With drugs like atypical antipsychotics being used across disease states — in schizophrenia, bipolar disorder, depression, anxiety, insomnia, and PTSD — and where new classes of medicine are becoming available, like with ketamine or steroids, we need to have a system by which we can more quickly ascertain reproductive safety information. This information informs treatment decisions during a critical life event of deciding to try to become pregnant or during an actual pregnancy.

In my mind, it is reassuring when a registry has even as few as 50-60 cases of fetal exposure without an increase in the risk for malformation, because it can mean we are not seeing a repeat of the past with medications like thalidomide and sodium valproate. However, patients and clinicians are starved for better data. Risk assessment is also different from clinician to clinician and patient to patient. We want to empower patients to make decisions that work for them based on more rapidly accumulating information and help inform their decisions.

To come out on the “other side” of the PLLR, we will need to find a way to accelerate our ability to identify signals of risk or information that is reassuring (or not reassuring) so that clinicians and patients are not left waiting for the next paper to come out, which can be confusing when study results frequently conflict. I believe we have an obligation today to do this better, because the areas of reproductive toxicology and pharmacovigilance are growing incredibly quickly, and clinicians and patients are seeing these volumes of data being published without the ability to integrate that information in a systematic way.

Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital (MGH) in Boston, which provides information resources and conducts clinical care and research in reproductive mental health. He has been a consultant to manufacturers of psychiatric medications. Full disclosure information for Dr. Cohen is available at womensmentalhealth.org. Email Dr. Cohen at obnews@mdedge.com.

More than one in three women worldwide (at least 40 million women) annually experience lasting health problems in the months or years following childbirth, according to a new study published in The Lancet Global Health.

Those problems include pain during sexual intercourse (35%), low back pain (32%), urinary incontinence (8% to 31%), anxiety (9% to 24%), anal incontinence (19%), depression (11% to 17%), fear of childbirth (6% to 15%), perineal pain (11%), and secondary infertility (11%).

Other problems included pelvic organ prolapse, posttraumatic stress disorder, thyroid dysfunction, mastitis, HIV seroconversion (when the body begins to produce detectable levels of HIV antibodies), nerve injury, and psychosis. 

The study says most women see a doctor 6  to 12 weeks after birth and then rarely talk to doctors about these nagging health problems. Many of the problems don’t show up until 6 or more weeks after birth.

“To comprehensively address these conditions, broader and more comprehensive health service opportunities are needed, which should extend beyond 6 weeks postpartum and embrace multidisciplinary models of care,” the study says. “This approach can ensure that these conditions are promptly identified and given the attention that they deserve.”

The study is part of a series organized by the United Nation’s Special Program on Human Reproduction, the World Health Organization, and the U.S. Agency for International Development. The authors said most of the data came from high-income nations. There was little data from low-income and middle-income countries except for postpartum depression, anxiety, and psychosis.

“Many postpartum conditions cause considerable suffering in women’s daily life long after birth, both emotionally and physically, and yet they are largely underappreciated, underrecognized, and underreported,” Pascale Allotey, MD, director of Sexual and Reproductive Health and Research at WHO, said in a statement.

“Throughout their lives, and beyond motherhood, women need access to a range of services from health-care providers who listen to their concerns and meet their needs — so they not only survive childbirth but can enjoy good health and quality of life.”
 

A version of this article appeared on WebMD.com.

More than one in three women worldwide (at least 40 million women) annually experience lasting health problems in the months or years following childbirth, according to a new study published in The Lancet Global Health.

Those problems include pain during sexual intercourse (35%), low back pain (32%), urinary incontinence (8% to 31%), anxiety (9% to 24%), anal incontinence (19%), depression (11% to 17%), fear of childbirth (6% to 15%), perineal pain (11%), and secondary infertility (11%).

Other problems included pelvic organ prolapse, posttraumatic stress disorder, thyroid dysfunction, mastitis, HIV seroconversion (when the body begins to produce detectable levels of HIV antibodies), nerve injury, and psychosis. 

The study says most women see a doctor 6  to 12 weeks after birth and then rarely talk to doctors about these nagging health problems. Many of the problems don’t show up until 6 or more weeks after birth.

“To comprehensively address these conditions, broader and more comprehensive health service opportunities are needed, which should extend beyond 6 weeks postpartum and embrace multidisciplinary models of care,” the study says. “This approach can ensure that these conditions are promptly identified and given the attention that they deserve.”

The study is part of a series organized by the United Nation’s Special Program on Human Reproduction, the World Health Organization, and the U.S. Agency for International Development. The authors said most of the data came from high-income nations. There was little data from low-income and middle-income countries except for postpartum depression, anxiety, and psychosis.

“Many postpartum conditions cause considerable suffering in women’s daily life long after birth, both emotionally and physically, and yet they are largely underappreciated, underrecognized, and underreported,” Pascale Allotey, MD, director of Sexual and Reproductive Health and Research at WHO, said in a statement.

“Throughout their lives, and beyond motherhood, women need access to a range of services from health-care providers who listen to their concerns and meet their needs — so they not only survive childbirth but can enjoy good health and quality of life.”
 

A version of this article appeared on WebMD.com.

More than one in three women worldwide (at least 40 million women) annually experience lasting health problems in the months or years following childbirth, according to a new study published in The Lancet Global Health.

Those problems include pain during sexual intercourse (35%), low back pain (32%), urinary incontinence (8% to 31%), anxiety (9% to 24%), anal incontinence (19%), depression (11% to 17%), fear of childbirth (6% to 15%), perineal pain (11%), and secondary infertility (11%).

Other problems included pelvic organ prolapse, posttraumatic stress disorder, thyroid dysfunction, mastitis, HIV seroconversion (when the body begins to produce detectable levels of HIV antibodies), nerve injury, and psychosis. 

The study says most women see a doctor 6  to 12 weeks after birth and then rarely talk to doctors about these nagging health problems. Many of the problems don’t show up until 6 or more weeks after birth.

“To comprehensively address these conditions, broader and more comprehensive health service opportunities are needed, which should extend beyond 6 weeks postpartum and embrace multidisciplinary models of care,” the study says. “This approach can ensure that these conditions are promptly identified and given the attention that they deserve.”

The study is part of a series organized by the United Nation’s Special Program on Human Reproduction, the World Health Organization, and the U.S. Agency for International Development. The authors said most of the data came from high-income nations. There was little data from low-income and middle-income countries except for postpartum depression, anxiety, and psychosis.

“Many postpartum conditions cause considerable suffering in women’s daily life long after birth, both emotionally and physically, and yet they are largely underappreciated, underrecognized, and underreported,” Pascale Allotey, MD, director of Sexual and Reproductive Health and Research at WHO, said in a statement.

“Throughout their lives, and beyond motherhood, women need access to a range of services from health-care providers who listen to their concerns and meet their needs — so they not only survive childbirth but can enjoy good health and quality of life.”
 

A version of this article appeared on WebMD.com.

Difficult ethical situations can arise when treating perinatal women who have serious mental illness (SMI). Clinicians must consider ethical issues related to administering antipsychotic medications, the safety of breastfeeding, and concerns for child welfare. They need to carefully weigh the risks and benefits of each decision when treating perinatal women who have SMI. Ethical guidelines can help clinicians best support families in these situations.

In this article, we describe 2 cases of women with psychotic disorders who requested to breastfeed after delivering their child during an inpatient psychiatric hospitalization. The course of their hospitalizations illustrated common ethical questions and facilitated the creation of a framework to assist with complex decision-making regarding breastfeeding on inpatient psychiatric units.

CASE 1

Ms. C, age 41, is multigravida with a psychiatric history of chronic, severe schizoaffective disorder and lives in supportive housing. When Ms. C presents to the hospital in search of a rape kit, clinicians discover she is 22 weeks pregnant but has not received any prenatal care. Psychiatry is consulted because she is found to be intermittently agitated and endorses grandiose delusions. Ms. C requires involuntary hospitalization for decompensated psychosis because she refuses prenatal and psychiatric care. Because it has reassuring reproductive safety data,¹ olanzapine 5 mg/d is started. However, Ms. C experiences minimal improvement from a maximum dose of 20 mg/d. After 13 weeks on the psychiatry unit, she is transferred to obstetrics service for preeclampsia with severe features. Ms. C requires an urgent cesarean delivery at 37 weeks. Her baby boy is transferred to the neonatal intensive care unit (NICU) for transient tachypnea. After delivery and in consultation with psychiatry, the pediatrics team calls Child Protective Services (CPS) due to concern for neglect driven by Ms. C’s psychiatric condition. Ms. C visits the child with medical unit staff supervision in the NICU without consulting with the psychiatry service or CPS. On postpartum Day 2, Ms. C is transferred back to psychiatry for persistent psychosis.

On postpartum Day 3, Ms. C starts to produce breastmilk and requests to breastfeed. At this time, the multidisciplinary team determines she is not able to visit her child in the NICU due to psychiatric instability. No plan is developed to facilitate hand expression or pumping of breastmilk while Ms. C is on the psychiatric unit. The clinical teams discuss whether the benefits of breastfeeding and/or pumping breastmilk would outweigh the risks. CPS determines that Ms. C is unable to retain custody and places the child in kinship foster care while awaiting clinical improvement from her.

CASE 2

Ms. S, age 32, has a history of schizophrenia. She lives with her husband and parents. She is pregnant for the first time and has been receiving consistent prenatal care. Ms. S is brought to the hospital by her husband for bizarre behavior and paranoia after self-discontinuing risperidone 2 mg twice daily due to concern about the medication’s influence on her pregnancy. An ultrasound confirms she is 37 weeks pregnant. Psychiatry is consulted because Ms. S is internally preoccupied, delusional, and endorses auditory hallucinations. She requires involuntary hospitalization for decompensated psychosis. During admission, Ms. S experiences improvement of her psychiatric symptoms while receiving risperidone 2 mg twice daily, which she takes consistently after receiving extensive psychoeducation regarding its safety profile during pregnancy and lactation.

After 2 weeks on the psychiatry unit, Ms. S’s care team transfers her to the obstetrics service with one-to-one supervision. At 39 weeks gestation, she has a vaginal delivery without complications. Because there are no concerns about infant harm, obstetrics, pediatrics, and psychiatry coordinate care so the baby can room in with Ms. S, her husband, and a staff supervisor to facilitate bonding. Ms. S starts to lactate, wishes to breastfeed, and meets with lactation, pediatric, obstetric, and psychiatric specialists to discuss the risks and benefits of breastfeeding and pumping breastmilk. She pursues direct breastfeeding until the baby is discharged home with the husband at postpartum Day 2. CPS is not called because there are no concerns for parental abuse or neglect at the infant’s discharge.

On postpartum Day 2, the obstetrics service transfers Ms. S back to the psychiatric unit for further treatment of her paranoia. She wishes to pump breastmilk while hospitalized, so the treatment team supplies a breast pump, facilitates the storage of breastmilk, and coordinates supervision during pumping to reduce the ligature risk. Ms. S’s husband visits daily to transport the milk and feed the infant breastmilk and formula to meet its nutritional needs. Ms. S maintains psychiatric stability while breast pumping, and the team helps transition her to breastfeeding during visitation with her husband and infant until she is discharged home at 2 weeks postpartum.

Continue to: Approaching care with a relational ethics framework

A relational ethics framework was constructed to evaluate whether to support breastfeeding for both patients during their psychiatric hospitalizations. A relational ethics perspective is defined as “a moral responsibility within a context of human relations” [that] “recognizes the human interdependency and reciprocity within which personal autonomy is embedded.”² This framework values connectedness and commonality between various and even conflicting parties. In the setting of a clinician-patient relationship, health care decisions are made with consideration of the patient’s traditional beliefs, values, and principles rather than the application of impartial moral principles. For these complex cases, this framework was chosen to determine the safest possible outcome for both mother and child.

Risks/benefits of breastfeeding by patients who have SMI

There are several methods of breastfeeding, including direct breastfeeding and other ways of expressing breastmilk such as pumping or hand expression.³ Unlike other forms of feeding using breastmilk, direct breastfeeding has been extensively studied, has well-established medical and psychological benefits for newborns and mothers, and enhances long-term bonding.⁴ Compared with their counterparts who do not breastfeed, mothers who breastfeed have lower rates of unintended pregnancy, cardiovascular disease, postpartum bleeding, osteoporosis, and breast and ovarian cancer.⁵ Among its key psychological benefits, breastfeeding is associated with an increase in maternal self-efficacy and, in some research, has been shown to be associated with a decreased risk of postpartum depression and stress.Additionally, breastfed infants experience lower rates of childhood infection and obesity, and improved nutrition, cognitive development, and immune function.⁶ The American Academy of Pediatrics recognizes these benefits and recommends that women exclusively breastfeed for 6 months postpartum and continue to breastfeed for 2 years or beyond if mutually desired by the mother and child.⁷ Absolute contraindications to breastfeeding must be ruled out (eg, infant classic galactosemia; maternal use of illicit substances such as cocaine, opioids, or phencyclidine; maternal HIV infection, etc).

The risks of breastfeeding by patients who have SMI must also be considered. In severe situations, the infant can be exposed to a mother’s agitation secondary to psychosis.^8,9 The transmission of antipsychotic medication through breastmilk and associated adverse effects (eg, sedation, poor feeding, and extrapyramidal symptoms) are also potential risks and varies among different antipsychotic medications.^1,10 Therefore, when prescribing an antipsychotic for a patient with SMI who breastfeeds, it is crucial to consider the medication’s safety profile as well as other factors, such as the relative infant dose (the weight-adjusted [ie, mg/kg] percentage of the maternal dosage ingested by a fully breastfed infant) and the molecular characteristics of the medication.^10-12 Neonates should be routinely monitored for adverse effects, medication toxicity, and withdrawal symptoms, and care should be coordinated with the infant’s pediatrician. Certain antipsychotic medications, such as aripiprazole, may impact breastmilk production through the dopamine agonist’s interference of the prolactin reflex and anticholinergic properties.^11,13 For a patient with SMI, perhaps the most significant risk involves the time and resources needed for breastfeeding, which can interfere with sleep and psychiatric treatment and possibly further exacerbate psychiatric symptoms.^14-16 Additionally, breastfeeding difficulties or disruption can increase the risk of psychiatric symptoms and psychological distress.¹⁷ In Ms. C’s case, there was a delay in the baby latching as well as multiple medical and psychiatric factors that hindered the milk-ejection reflex to properly initiate; both of these factors rendered breastfeeding particularly difficult while Ms. C was on the inpatient psychiatry unit.¹⁷ In comparison, Ms. S was able to bond with her infant shortly after delivery, which facilitated the milk-ejection reflex and lactation.

Patients who wish to directly breastfeed but struggle to do so while tending to their acute psychiatric condition can benefit from expression of breastmilk that can be provided to the infant or discarded to facilitate breastfeeding in the future.¹⁸ While expression of breastmilk may not be as advantageous for infant health as direct breastfeeding due to the potential changes in breastmilk composition from collecting, storing, and heating, this option can be more protective than formula feeding and facilitate future breastfeeding.¹⁹ In these clinical scenarios, it is standard care to provide a hospital-grade breast pump to the patient, much like a continuous positive airway pressure machine is provided to patients with obstructive sleep apnea.²⁰ However, there is often considerable difficulty obtaining proper breastfeeding equipment and a lack of services devoted to perinatal care in general inpatient settings. Barriers to direct breastfeeding and pumping of breastmilk are highlighted in the Table.²¹

Limitations on breastfeeding on an inpatient unit

The limitations in care and restrictions placed on breastfeeding are more optimally addressed in a mother and baby unit (MBU). MBUs are specialized inpatient psychiatric units designed for mothers experiencing severe perinatal psychiatric difficulties. Unlike general psychiatric units, MBUs allow for joint, full-time admission of mothers and their infants. These units also include multidisciplinary staff who specialize in treating perinatal mental health issues as well as infant care and child development.²² Admission into an MBU is considered best practice for new mothers requiring treatment, particularly in the United Kingdom, Australia, and France, as it is well-recognized that the separation of mother and baby can be psychologically harmful.²³ In the UK, most patients admitted to an MBU showed significant improvement of their psychiatric symptoms and reported overall high satisfaction with care.^24,25 Patients who experience postpartum psychosis prefer MBUs over general psychiatric units because the latter often lack specialized perinatal support, appropriate visitor arrangements, and adequate time with their infant.^26-28

Continue to: The resistance to adopting MBUs in the United States...

The resistance to adopting MBUs in the United States has posed significant barriers in care for perinatal patients and has been attributed to financial barriers, medicolegal risk, staffing, and safety concerns.²⁹ Though currently there are no MBUs in the US, other specialized units have been created. A partial day hospitalization program created in 2000 in Rhode Island for mothers and infants revolutionized the psychiatric care experience for new mothers.³⁰ Since then, other institutions have significantly expanded their services to include perinatal psychiatry inpatient units, yet unlike MBUs, these units typically do not provide overnight rooming-in with infants.³¹ They have the necessary resources and facilities to accommodate the mother’s needs and maximize positive mother-infant interaction, while actively integrating the infant into the mother’s treatment. Breast pumping is treated as a necessary medical procedure and patients can easily access hospital-grade breast pumps with staff supervision. At one such perinatal psychiatric inpatient unit, high rates of treatment satisfaction and significant improvements in symptoms of depression, anxiety, active suicidal ideation, and overall functioning were observed at discharge.³² Therefore, it is crucial to incorporate strategies in general psychiatry units to improve perinatal care, acknowledging that most patients will not have access to these specialized units.²¹

A framework to approaching the relational ethics decisions

An interdisciplinary team used a relational ethics perspective to carefully analyze the risks and benefits of these complex cases. In Figure 1, we propose a framework for the relational ethics decisions of breastfeeding on general inpatient psychiatric units. In creating this framework, we considered principles of autonomy, beneficence, and nonmaleficence, along with the medical and logistical barriers to breastfeeding.

In Ms. C’s case, the team determined that the risks—which included disrupting the mother’s psychiatric treatment, exposing her to psychological harm due to increasing attachment before remanding the child to CPS custody, and risks to the child due to potential unpredictable agitation driven by the treatment-refractory psychosis of the mother as well as that of other psychiatric patients—outweighed the benefits of breastfeeding. We instead recommended breast pumping as an alternative once Ms. C’s psychiatric stability improved. We presented Ms. C with the option of breast pumping on postpartum Day 5. During a 1-day period in which she showed improved behavioral control, she was counseled on the risks and benefits of breastfeeding and exclusive pumping and was notified that the team would help her with the necessary resources, including consultation with a lactation specialist and breast pump. Despite lactation consultant support, Ms. C had low milk production and difficulty with hand expression, which was very discouraging to her. She produced 1 ounce of milk that was shared with the newborn while in the NICU. Because Ms. C’s psychiatric symptoms continued to be severe, with lability and aggression, and because pumping was triggering distress, the multidisciplinary team determined the best course of care would be to focus on her psychiatric recovery rather than on pumping breastmilk. To reduce milk production and minimize discomfort secondary to breast engorgement, the lactation consultant recommended cold compresses, pain management, and compression of breasts. Ultimately, the mother-infant dyad was unable to reap the benefits of breastfeeding (via pumping or direct breastfeeding) due to the mother’s underlying psychiatric illness, although the staffing, psychosocial support, and logistical limitations contributed to this outcome.³³

In Ms. S’s case, the treatment team determined that there were no medical or psychiatric contraindications to breastfeeding, and she was counseled on the risks and benefits of direct breastfeeding and pumping. The treatment team determined it was safe for Ms. S to directly breastfeed as there were no concerns for infant harm post­delivery with constant supervision while on the obstetrics floor. The patient opted to directly breastfeed, which was successful with the guidance of a lactation specialist. When she was transferred to the psychiatric unit on postpartum Day 2, her child was discharged home with the husband. The patient was then encouraged to pump while the psychiatrists monitored her symptoms closely and facilitated increased staff and resources. Transportation of breastmilk was made possible by the family, and on postpartum Day 5, as the patient maintained psychiatric stability, the team discussed with Ms. S and her husband the prospect of direct breastfeeding. The treatment team arranged for separate visitation hours to minimize the possibility of exposing the infant to aggression from other patients on the unit and advocated with hospital leadership to approve of infant visitation on the unit.

Impact of involvement of Child Protective Services

The involvement of CPS also added complexity to Ms. C’s case. Without proper legal guidance, mothers with psychosis who lose custody can find it difficult to navigate the legal system and maintain contact with their children.³⁴ As the prevalence of custody loss in mothers with psychosis is high (approximately 50% according to research published in the last 10 years), effective interventions to reunite the mother and child must be promoted (Figure 2).^35-39 Ultimately, the goal of psychiatric hospitalization for perinatal women who have SMI is psychiatric stabilization. The preemptive involvement of psychiatry is crucial because it can allow for early postpartum planning and can provide an opportunity to address feeding options and custody concerns with the patient, social supports and services, and various medical teams. In Ms. C’s case, she visited her baby in the NICU on postpartum Day 2 without consultation with psychiatry or CPS, which posed risks to the patient, infant, and staff. It is vital that various clinicians collaborate with each other and the patient, working towards the goal of optimizing the patient’s mental health to allow for parenting rights in the future and maximizing a sustainable attachment between the parent and child. In Ms. S’s case, the husband was able to facilitate caring for the baby while the mother was hospitalized and played an integral role in the feeding process via pumped breastmilk and transport of the infant for direct breastfeeding.

Continue to: The differences in these 2 cases...

The differences in these 2 cases show the extreme importance of social support to benefit both the mother and child, and the need for more comprehensive social services for women who do not have a social safety net.

Bottom Line

These complex cases highlight an ethical decision-making approach to breastfeeding in perinatal women who have serious mental illness. Collaborative care and shared decision-making, which highlight the interests of the mother and baby, are crucial when assessing the risks and benefits of breastfeeding and pumping breastmilk. Our relational ethics framework can be used to better evaluate and implement breastfeeding options on general psychiatric units.

Related Resources

• Tillman B, Sloan N, Westmoreland P. How COVID-19 affects peripartum women’s mental health. Current Psychiatry. 2021;20(6):18-22. doi:10.12788/cp.0129
• Koch J, Preinitz J. Antidepressants for patients who are breastfeeding: what to consider. Current Psychiatry. 2023;22(5):20-23,48. doi:10.12788/cp.0355

Drug Brand Names

Aripiprazole • Abilify
Olanzapine • Zyprexa
Risperidone • Risperdal

Difficult ethical situations can arise when treating perinatal women who have serious mental illness (SMI). Clinicians must consider ethical issues related to administering antipsychotic medications, the safety of breastfeeding, and concerns for child welfare. They need to carefully weigh the risks and benefits of each decision when treating perinatal women who have SMI. Ethical guidelines can help clinicians best support families in these situations.

In this article, we describe 2 cases of women with psychotic disorders who requested to breastfeed after delivering their child during an inpatient psychiatric hospitalization. The course of their hospitalizations illustrated common ethical questions and facilitated the creation of a framework to assist with complex decision-making regarding breastfeeding on inpatient psychiatric units.

CASE 1

Ms. C, age 41, is multigravida with a psychiatric history of chronic, severe schizoaffective disorder and lives in supportive housing. When Ms. C presents to the hospital in search of a rape kit, clinicians discover she is 22 weeks pregnant but has not received any prenatal care. Psychiatry is consulted because she is found to be intermittently agitated and endorses grandiose delusions. Ms. C requires involuntary hospitalization for decompensated psychosis because she refuses prenatal and psychiatric care. Because it has reassuring reproductive safety data,¹ olanzapine 5 mg/d is started. However, Ms. C experiences minimal improvement from a maximum dose of 20 mg/d. After 13 weeks on the psychiatry unit, she is transferred to obstetrics service for preeclampsia with severe features. Ms. C requires an urgent cesarean delivery at 37 weeks. Her baby boy is transferred to the neonatal intensive care unit (NICU) for transient tachypnea. After delivery and in consultation with psychiatry, the pediatrics team calls Child Protective Services (CPS) due to concern for neglect driven by Ms. C’s psychiatric condition. Ms. C visits the child with medical unit staff supervision in the NICU without consulting with the psychiatry service or CPS. On postpartum Day 2, Ms. C is transferred back to psychiatry for persistent psychosis.

On postpartum Day 3, Ms. C starts to produce breastmilk and requests to breastfeed. At this time, the multidisciplinary team determines she is not able to visit her child in the NICU due to psychiatric instability. No plan is developed to facilitate hand expression or pumping of breastmilk while Ms. C is on the psychiatric unit. The clinical teams discuss whether the benefits of breastfeeding and/or pumping breastmilk would outweigh the risks. CPS determines that Ms. C is unable to retain custody and places the child in kinship foster care while awaiting clinical improvement from her.

CASE 2

Ms. S, age 32, has a history of schizophrenia. She lives with her husband and parents. She is pregnant for the first time and has been receiving consistent prenatal care. Ms. S is brought to the hospital by her husband for bizarre behavior and paranoia after self-discontinuing risperidone 2 mg twice daily due to concern about the medication’s influence on her pregnancy. An ultrasound confirms she is 37 weeks pregnant. Psychiatry is consulted because Ms. S is internally preoccupied, delusional, and endorses auditory hallucinations. She requires involuntary hospitalization for decompensated psychosis. During admission, Ms. S experiences improvement of her psychiatric symptoms while receiving risperidone 2 mg twice daily, which she takes consistently after receiving extensive psychoeducation regarding its safety profile during pregnancy and lactation.

After 2 weeks on the psychiatry unit, Ms. S’s care team transfers her to the obstetrics service with one-to-one supervision. At 39 weeks gestation, she has a vaginal delivery without complications. Because there are no concerns about infant harm, obstetrics, pediatrics, and psychiatry coordinate care so the baby can room in with Ms. S, her husband, and a staff supervisor to facilitate bonding. Ms. S starts to lactate, wishes to breastfeed, and meets with lactation, pediatric, obstetric, and psychiatric specialists to discuss the risks and benefits of breastfeeding and pumping breastmilk. She pursues direct breastfeeding until the baby is discharged home with the husband at postpartum Day 2. CPS is not called because there are no concerns for parental abuse or neglect at the infant’s discharge.

On postpartum Day 2, the obstetrics service transfers Ms. S back to the psychiatric unit for further treatment of her paranoia. She wishes to pump breastmilk while hospitalized, so the treatment team supplies a breast pump, facilitates the storage of breastmilk, and coordinates supervision during pumping to reduce the ligature risk. Ms. S’s husband visits daily to transport the milk and feed the infant breastmilk and formula to meet its nutritional needs. Ms. S maintains psychiatric stability while breast pumping, and the team helps transition her to breastfeeding during visitation with her husband and infant until she is discharged home at 2 weeks postpartum.

Continue to: Approaching care with a relational ethics framework

A relational ethics framework was constructed to evaluate whether to support breastfeeding for both patients during their psychiatric hospitalizations. A relational ethics perspective is defined as “a moral responsibility within a context of human relations” [that] “recognizes the human interdependency and reciprocity within which personal autonomy is embedded.”² This framework values connectedness and commonality between various and even conflicting parties. In the setting of a clinician-patient relationship, health care decisions are made with consideration of the patient’s traditional beliefs, values, and principles rather than the application of impartial moral principles. For these complex cases, this framework was chosen to determine the safest possible outcome for both mother and child.

Risks/benefits of breastfeeding by patients who have SMI

There are several methods of breastfeeding, including direct breastfeeding and other ways of expressing breastmilk such as pumping or hand expression.³ Unlike other forms of feeding using breastmilk, direct breastfeeding has been extensively studied, has well-established medical and psychological benefits for newborns and mothers, and enhances long-term bonding.⁴ Compared with their counterparts who do not breastfeed, mothers who breastfeed have lower rates of unintended pregnancy, cardiovascular disease, postpartum bleeding, osteoporosis, and breast and ovarian cancer.⁵ Among its key psychological benefits, breastfeeding is associated with an increase in maternal self-efficacy and, in some research, has been shown to be associated with a decreased risk of postpartum depression and stress.Additionally, breastfed infants experience lower rates of childhood infection and obesity, and improved nutrition, cognitive development, and immune function.⁶ The American Academy of Pediatrics recognizes these benefits and recommends that women exclusively breastfeed for 6 months postpartum and continue to breastfeed for 2 years or beyond if mutually desired by the mother and child.⁷ Absolute contraindications to breastfeeding must be ruled out (eg, infant classic galactosemia; maternal use of illicit substances such as cocaine, opioids, or phencyclidine; maternal HIV infection, etc).

The risks of breastfeeding by patients who have SMI must also be considered. In severe situations, the infant can be exposed to a mother’s agitation secondary to psychosis.^8,9 The transmission of antipsychotic medication through breastmilk and associated adverse effects (eg, sedation, poor feeding, and extrapyramidal symptoms) are also potential risks and varies among different antipsychotic medications.^1,10 Therefore, when prescribing an antipsychotic for a patient with SMI who breastfeeds, it is crucial to consider the medication’s safety profile as well as other factors, such as the relative infant dose (the weight-adjusted [ie, mg/kg] percentage of the maternal dosage ingested by a fully breastfed infant) and the molecular characteristics of the medication.^10-12 Neonates should be routinely monitored for adverse effects, medication toxicity, and withdrawal symptoms, and care should be coordinated with the infant’s pediatrician. Certain antipsychotic medications, such as aripiprazole, may impact breastmilk production through the dopamine agonist’s interference of the prolactin reflex and anticholinergic properties.^11,13 For a patient with SMI, perhaps the most significant risk involves the time and resources needed for breastfeeding, which can interfere with sleep and psychiatric treatment and possibly further exacerbate psychiatric symptoms.^14-16 Additionally, breastfeeding difficulties or disruption can increase the risk of psychiatric symptoms and psychological distress.¹⁷ In Ms. C’s case, there was a delay in the baby latching as well as multiple medical and psychiatric factors that hindered the milk-ejection reflex to properly initiate; both of these factors rendered breastfeeding particularly difficult while Ms. C was on the inpatient psychiatry unit.¹⁷ In comparison, Ms. S was able to bond with her infant shortly after delivery, which facilitated the milk-ejection reflex and lactation.

Patients who wish to directly breastfeed but struggle to do so while tending to their acute psychiatric condition can benefit from expression of breastmilk that can be provided to the infant or discarded to facilitate breastfeeding in the future.¹⁸ While expression of breastmilk may not be as advantageous for infant health as direct breastfeeding due to the potential changes in breastmilk composition from collecting, storing, and heating, this option can be more protective than formula feeding and facilitate future breastfeeding.¹⁹ In these clinical scenarios, it is standard care to provide a hospital-grade breast pump to the patient, much like a continuous positive airway pressure machine is provided to patients with obstructive sleep apnea.²⁰ However, there is often considerable difficulty obtaining proper breastfeeding equipment and a lack of services devoted to perinatal care in general inpatient settings. Barriers to direct breastfeeding and pumping of breastmilk are highlighted in the Table.²¹

Limitations on breastfeeding on an inpatient unit

The limitations in care and restrictions placed on breastfeeding are more optimally addressed in a mother and baby unit (MBU). MBUs are specialized inpatient psychiatric units designed for mothers experiencing severe perinatal psychiatric difficulties. Unlike general psychiatric units, MBUs allow for joint, full-time admission of mothers and their infants. These units also include multidisciplinary staff who specialize in treating perinatal mental health issues as well as infant care and child development.²² Admission into an MBU is considered best practice for new mothers requiring treatment, particularly in the United Kingdom, Australia, and France, as it is well-recognized that the separation of mother and baby can be psychologically harmful.²³ In the UK, most patients admitted to an MBU showed significant improvement of their psychiatric symptoms and reported overall high satisfaction with care.^24,25 Patients who experience postpartum psychosis prefer MBUs over general psychiatric units because the latter often lack specialized perinatal support, appropriate visitor arrangements, and adequate time with their infant.^26-28

Continue to: The resistance to adopting MBUs in the United States...

The resistance to adopting MBUs in the United States has posed significant barriers in care for perinatal patients and has been attributed to financial barriers, medicolegal risk, staffing, and safety concerns.²⁹ Though currently there are no MBUs in the US, other specialized units have been created. A partial day hospitalization program created in 2000 in Rhode Island for mothers and infants revolutionized the psychiatric care experience for new mothers.³⁰ Since then, other institutions have significantly expanded their services to include perinatal psychiatry inpatient units, yet unlike MBUs, these units typically do not provide overnight rooming-in with infants.³¹ They have the necessary resources and facilities to accommodate the mother’s needs and maximize positive mother-infant interaction, while actively integrating the infant into the mother’s treatment. Breast pumping is treated as a necessary medical procedure and patients can easily access hospital-grade breast pumps with staff supervision. At one such perinatal psychiatric inpatient unit, high rates of treatment satisfaction and significant improvements in symptoms of depression, anxiety, active suicidal ideation, and overall functioning were observed at discharge.³² Therefore, it is crucial to incorporate strategies in general psychiatry units to improve perinatal care, acknowledging that most patients will not have access to these specialized units.²¹

A framework to approaching the relational ethics decisions

An interdisciplinary team used a relational ethics perspective to carefully analyze the risks and benefits of these complex cases. In Figure 1, we propose a framework for the relational ethics decisions of breastfeeding on general inpatient psychiatric units. In creating this framework, we considered principles of autonomy, beneficence, and nonmaleficence, along with the medical and logistical barriers to breastfeeding.

In Ms. C’s case, the team determined that the risks—which included disrupting the mother’s psychiatric treatment, exposing her to psychological harm due to increasing attachment before remanding the child to CPS custody, and risks to the child due to potential unpredictable agitation driven by the treatment-refractory psychosis of the mother as well as that of other psychiatric patients—outweighed the benefits of breastfeeding. We instead recommended breast pumping as an alternative once Ms. C’s psychiatric stability improved. We presented Ms. C with the option of breast pumping on postpartum Day 5. During a 1-day period in which she showed improved behavioral control, she was counseled on the risks and benefits of breastfeeding and exclusive pumping and was notified that the team would help her with the necessary resources, including consultation with a lactation specialist and breast pump. Despite lactation consultant support, Ms. C had low milk production and difficulty with hand expression, which was very discouraging to her. She produced 1 ounce of milk that was shared with the newborn while in the NICU. Because Ms. C’s psychiatric symptoms continued to be severe, with lability and aggression, and because pumping was triggering distress, the multidisciplinary team determined the best course of care would be to focus on her psychiatric recovery rather than on pumping breastmilk. To reduce milk production and minimize discomfort secondary to breast engorgement, the lactation consultant recommended cold compresses, pain management, and compression of breasts. Ultimately, the mother-infant dyad was unable to reap the benefits of breastfeeding (via pumping or direct breastfeeding) due to the mother’s underlying psychiatric illness, although the staffing, psychosocial support, and logistical limitations contributed to this outcome.³³

In Ms. S’s case, the treatment team determined that there were no medical or psychiatric contraindications to breastfeeding, and she was counseled on the risks and benefits of direct breastfeeding and pumping. The treatment team determined it was safe for Ms. S to directly breastfeed as there were no concerns for infant harm post­delivery with constant supervision while on the obstetrics floor. The patient opted to directly breastfeed, which was successful with the guidance of a lactation specialist. When she was transferred to the psychiatric unit on postpartum Day 2, her child was discharged home with the husband. The patient was then encouraged to pump while the psychiatrists monitored her symptoms closely and facilitated increased staff and resources. Transportation of breastmilk was made possible by the family, and on postpartum Day 5, as the patient maintained psychiatric stability, the team discussed with Ms. S and her husband the prospect of direct breastfeeding. The treatment team arranged for separate visitation hours to minimize the possibility of exposing the infant to aggression from other patients on the unit and advocated with hospital leadership to approve of infant visitation on the unit.

Impact of involvement of Child Protective Services

The involvement of CPS also added complexity to Ms. C’s case. Without proper legal guidance, mothers with psychosis who lose custody can find it difficult to navigate the legal system and maintain contact with their children.³⁴ As the prevalence of custody loss in mothers with psychosis is high (approximately 50% according to research published in the last 10 years), effective interventions to reunite the mother and child must be promoted (Figure 2).^35-39 Ultimately, the goal of psychiatric hospitalization for perinatal women who have SMI is psychiatric stabilization. The preemptive involvement of psychiatry is crucial because it can allow for early postpartum planning and can provide an opportunity to address feeding options and custody concerns with the patient, social supports and services, and various medical teams. In Ms. C’s case, she visited her baby in the NICU on postpartum Day 2 without consultation with psychiatry or CPS, which posed risks to the patient, infant, and staff. It is vital that various clinicians collaborate with each other and the patient, working towards the goal of optimizing the patient’s mental health to allow for parenting rights in the future and maximizing a sustainable attachment between the parent and child. In Ms. S’s case, the husband was able to facilitate caring for the baby while the mother was hospitalized and played an integral role in the feeding process via pumped breastmilk and transport of the infant for direct breastfeeding.

Continue to: The differences in these 2 cases...

The differences in these 2 cases show the extreme importance of social support to benefit both the mother and child, and the need for more comprehensive social services for women who do not have a social safety net.

Bottom Line

These complex cases highlight an ethical decision-making approach to breastfeeding in perinatal women who have serious mental illness. Collaborative care and shared decision-making, which highlight the interests of the mother and baby, are crucial when assessing the risks and benefits of breastfeeding and pumping breastmilk. Our relational ethics framework can be used to better evaluate and implement breastfeeding options on general psychiatric units.

Related Resources

• Tillman B, Sloan N, Westmoreland P. How COVID-19 affects peripartum women’s mental health. Current Psychiatry. 2021;20(6):18-22. doi:10.12788/cp.0129
• Koch J, Preinitz J. Antidepressants for patients who are breastfeeding: what to consider. Current Psychiatry. 2023;22(5):20-23,48. doi:10.12788/cp.0355

Drug Brand Names

Aripiprazole • Abilify
Olanzapine • Zyprexa
Risperidone • Risperdal

Difficult ethical situations can arise when treating perinatal women who have serious mental illness (SMI). Clinicians must consider ethical issues related to administering antipsychotic medications, the safety of breastfeeding, and concerns for child welfare. They need to carefully weigh the risks and benefits of each decision when treating perinatal women who have SMI. Ethical guidelines can help clinicians best support families in these situations.

In this article, we describe 2 cases of women with psychotic disorders who requested to breastfeed after delivering their child during an inpatient psychiatric hospitalization. The course of their hospitalizations illustrated common ethical questions and facilitated the creation of a framework to assist with complex decision-making regarding breastfeeding on inpatient psychiatric units.

CASE 1

Ms. C, age 41, is multigravida with a psychiatric history of chronic, severe schizoaffective disorder and lives in supportive housing. When Ms. C presents to the hospital in search of a rape kit, clinicians discover she is 22 weeks pregnant but has not received any prenatal care. Psychiatry is consulted because she is found to be intermittently agitated and endorses grandiose delusions. Ms. C requires involuntary hospitalization for decompensated psychosis because she refuses prenatal and psychiatric care. Because it has reassuring reproductive safety data,¹ olanzapine 5 mg/d is started. However, Ms. C experiences minimal improvement from a maximum dose of 20 mg/d. After 13 weeks on the psychiatry unit, she is transferred to obstetrics service for preeclampsia with severe features. Ms. C requires an urgent cesarean delivery at 37 weeks. Her baby boy is transferred to the neonatal intensive care unit (NICU) for transient tachypnea. After delivery and in consultation with psychiatry, the pediatrics team calls Child Protective Services (CPS) due to concern for neglect driven by Ms. C’s psychiatric condition. Ms. C visits the child with medical unit staff supervision in the NICU without consulting with the psychiatry service or CPS. On postpartum Day 2, Ms. C is transferred back to psychiatry for persistent psychosis.

On postpartum Day 3, Ms. C starts to produce breastmilk and requests to breastfeed. At this time, the multidisciplinary team determines she is not able to visit her child in the NICU due to psychiatric instability. No plan is developed to facilitate hand expression or pumping of breastmilk while Ms. C is on the psychiatric unit. The clinical teams discuss whether the benefits of breastfeeding and/or pumping breastmilk would outweigh the risks. CPS determines that Ms. C is unable to retain custody and places the child in kinship foster care while awaiting clinical improvement from her.

CASE 2

Ms. S, age 32, has a history of schizophrenia. She lives with her husband and parents. She is pregnant for the first time and has been receiving consistent prenatal care. Ms. S is brought to the hospital by her husband for bizarre behavior and paranoia after self-discontinuing risperidone 2 mg twice daily due to concern about the medication’s influence on her pregnancy. An ultrasound confirms she is 37 weeks pregnant. Psychiatry is consulted because Ms. S is internally preoccupied, delusional, and endorses auditory hallucinations. She requires involuntary hospitalization for decompensated psychosis. During admission, Ms. S experiences improvement of her psychiatric symptoms while receiving risperidone 2 mg twice daily, which she takes consistently after receiving extensive psychoeducation regarding its safety profile during pregnancy and lactation.

After 2 weeks on the psychiatry unit, Ms. S’s care team transfers her to the obstetrics service with one-to-one supervision. At 39 weeks gestation, she has a vaginal delivery without complications. Because there are no concerns about infant harm, obstetrics, pediatrics, and psychiatry coordinate care so the baby can room in with Ms. S, her husband, and a staff supervisor to facilitate bonding. Ms. S starts to lactate, wishes to breastfeed, and meets with lactation, pediatric, obstetric, and psychiatric specialists to discuss the risks and benefits of breastfeeding and pumping breastmilk. She pursues direct breastfeeding until the baby is discharged home with the husband at postpartum Day 2. CPS is not called because there are no concerns for parental abuse or neglect at the infant’s discharge.

On postpartum Day 2, the obstetrics service transfers Ms. S back to the psychiatric unit for further treatment of her paranoia. She wishes to pump breastmilk while hospitalized, so the treatment team supplies a breast pump, facilitates the storage of breastmilk, and coordinates supervision during pumping to reduce the ligature risk. Ms. S’s husband visits daily to transport the milk and feed the infant breastmilk and formula to meet its nutritional needs. Ms. S maintains psychiatric stability while breast pumping, and the team helps transition her to breastfeeding during visitation with her husband and infant until she is discharged home at 2 weeks postpartum.

Continue to: Approaching care with a relational ethics framework

A relational ethics framework was constructed to evaluate whether to support breastfeeding for both patients during their psychiatric hospitalizations. A relational ethics perspective is defined as “a moral responsibility within a context of human relations” [that] “recognizes the human interdependency and reciprocity within which personal autonomy is embedded.”² This framework values connectedness and commonality between various and even conflicting parties. In the setting of a clinician-patient relationship, health care decisions are made with consideration of the patient’s traditional beliefs, values, and principles rather than the application of impartial moral principles. For these complex cases, this framework was chosen to determine the safest possible outcome for both mother and child.

Risks/benefits of breastfeeding by patients who have SMI

There are several methods of breastfeeding, including direct breastfeeding and other ways of expressing breastmilk such as pumping or hand expression.³ Unlike other forms of feeding using breastmilk, direct breastfeeding has been extensively studied, has well-established medical and psychological benefits for newborns and mothers, and enhances long-term bonding.⁴ Compared with their counterparts who do not breastfeed, mothers who breastfeed have lower rates of unintended pregnancy, cardiovascular disease, postpartum bleeding, osteoporosis, and breast and ovarian cancer.⁵ Among its key psychological benefits, breastfeeding is associated with an increase in maternal self-efficacy and, in some research, has been shown to be associated with a decreased risk of postpartum depression and stress.Additionally, breastfed infants experience lower rates of childhood infection and obesity, and improved nutrition, cognitive development, and immune function.⁶ The American Academy of Pediatrics recognizes these benefits and recommends that women exclusively breastfeed for 6 months postpartum and continue to breastfeed for 2 years or beyond if mutually desired by the mother and child.⁷ Absolute contraindications to breastfeeding must be ruled out (eg, infant classic galactosemia; maternal use of illicit substances such as cocaine, opioids, or phencyclidine; maternal HIV infection, etc).

The risks of breastfeeding by patients who have SMI must also be considered. In severe situations, the infant can be exposed to a mother’s agitation secondary to psychosis.^8,9 The transmission of antipsychotic medication through breastmilk and associated adverse effects (eg, sedation, poor feeding, and extrapyramidal symptoms) are also potential risks and varies among different antipsychotic medications.^1,10 Therefore, when prescribing an antipsychotic for a patient with SMI who breastfeeds, it is crucial to consider the medication’s safety profile as well as other factors, such as the relative infant dose (the weight-adjusted [ie, mg/kg] percentage of the maternal dosage ingested by a fully breastfed infant) and the molecular characteristics of the medication.^10-12 Neonates should be routinely monitored for adverse effects, medication toxicity, and withdrawal symptoms, and care should be coordinated with the infant’s pediatrician. Certain antipsychotic medications, such as aripiprazole, may impact breastmilk production through the dopamine agonist’s interference of the prolactin reflex and anticholinergic properties.^11,13 For a patient with SMI, perhaps the most significant risk involves the time and resources needed for breastfeeding, which can interfere with sleep and psychiatric treatment and possibly further exacerbate psychiatric symptoms.^14-16 Additionally, breastfeeding difficulties or disruption can increase the risk of psychiatric symptoms and psychological distress.¹⁷ In Ms. C’s case, there was a delay in the baby latching as well as multiple medical and psychiatric factors that hindered the milk-ejection reflex to properly initiate; both of these factors rendered breastfeeding particularly difficult while Ms. C was on the inpatient psychiatry unit.¹⁷ In comparison, Ms. S was able to bond with her infant shortly after delivery, which facilitated the milk-ejection reflex and lactation.

Patients who wish to directly breastfeed but struggle to do so while tending to their acute psychiatric condition can benefit from expression of breastmilk that can be provided to the infant or discarded to facilitate breastfeeding in the future.¹⁸ While expression of breastmilk may not be as advantageous for infant health as direct breastfeeding due to the potential changes in breastmilk composition from collecting, storing, and heating, this option can be more protective than formula feeding and facilitate future breastfeeding.¹⁹ In these clinical scenarios, it is standard care to provide a hospital-grade breast pump to the patient, much like a continuous positive airway pressure machine is provided to patients with obstructive sleep apnea.²⁰ However, there is often considerable difficulty obtaining proper breastfeeding equipment and a lack of services devoted to perinatal care in general inpatient settings. Barriers to direct breastfeeding and pumping of breastmilk are highlighted in the Table.²¹

Limitations on breastfeeding on an inpatient unit

The limitations in care and restrictions placed on breastfeeding are more optimally addressed in a mother and baby unit (MBU). MBUs are specialized inpatient psychiatric units designed for mothers experiencing severe perinatal psychiatric difficulties. Unlike general psychiatric units, MBUs allow for joint, full-time admission of mothers and their infants. These units also include multidisciplinary staff who specialize in treating perinatal mental health issues as well as infant care and child development.²² Admission into an MBU is considered best practice for new mothers requiring treatment, particularly in the United Kingdom, Australia, and France, as it is well-recognized that the separation of mother and baby can be psychologically harmful.²³ In the UK, most patients admitted to an MBU showed significant improvement of their psychiatric symptoms and reported overall high satisfaction with care.^24,25 Patients who experience postpartum psychosis prefer MBUs over general psychiatric units because the latter often lack specialized perinatal support, appropriate visitor arrangements, and adequate time with their infant.^26-28

Continue to: The resistance to adopting MBUs in the United States...

The resistance to adopting MBUs in the United States has posed significant barriers in care for perinatal patients and has been attributed to financial barriers, medicolegal risk, staffing, and safety concerns.²⁹ Though currently there are no MBUs in the US, other specialized units have been created. A partial day hospitalization program created in 2000 in Rhode Island for mothers and infants revolutionized the psychiatric care experience for new mothers.³⁰ Since then, other institutions have significantly expanded their services to include perinatal psychiatry inpatient units, yet unlike MBUs, these units typically do not provide overnight rooming-in with infants.³¹ They have the necessary resources and facilities to accommodate the mother’s needs and maximize positive mother-infant interaction, while actively integrating the infant into the mother’s treatment. Breast pumping is treated as a necessary medical procedure and patients can easily access hospital-grade breast pumps with staff supervision. At one such perinatal psychiatric inpatient unit, high rates of treatment satisfaction and significant improvements in symptoms of depression, anxiety, active suicidal ideation, and overall functioning were observed at discharge.³² Therefore, it is crucial to incorporate strategies in general psychiatry units to improve perinatal care, acknowledging that most patients will not have access to these specialized units.²¹

A framework to approaching the relational ethics decisions

An interdisciplinary team used a relational ethics perspective to carefully analyze the risks and benefits of these complex cases. In Figure 1, we propose a framework for the relational ethics decisions of breastfeeding on general inpatient psychiatric units. In creating this framework, we considered principles of autonomy, beneficence, and nonmaleficence, along with the medical and logistical barriers to breastfeeding.

In Ms. C’s case, the team determined that the risks—which included disrupting the mother’s psychiatric treatment, exposing her to psychological harm due to increasing attachment before remanding the child to CPS custody, and risks to the child due to potential unpredictable agitation driven by the treatment-refractory psychosis of the mother as well as that of other psychiatric patients—outweighed the benefits of breastfeeding. We instead recommended breast pumping as an alternative once Ms. C’s psychiatric stability improved. We presented Ms. C with the option of breast pumping on postpartum Day 5. During a 1-day period in which she showed improved behavioral control, she was counseled on the risks and benefits of breastfeeding and exclusive pumping and was notified that the team would help her with the necessary resources, including consultation with a lactation specialist and breast pump. Despite lactation consultant support, Ms. C had low milk production and difficulty with hand expression, which was very discouraging to her. She produced 1 ounce of milk that was shared with the newborn while in the NICU. Because Ms. C’s psychiatric symptoms continued to be severe, with lability and aggression, and because pumping was triggering distress, the multidisciplinary team determined the best course of care would be to focus on her psychiatric recovery rather than on pumping breastmilk. To reduce milk production and minimize discomfort secondary to breast engorgement, the lactation consultant recommended cold compresses, pain management, and compression of breasts. Ultimately, the mother-infant dyad was unable to reap the benefits of breastfeeding (via pumping or direct breastfeeding) due to the mother’s underlying psychiatric illness, although the staffing, psychosocial support, and logistical limitations contributed to this outcome.³³

In Ms. S’s case, the treatment team determined that there were no medical or psychiatric contraindications to breastfeeding, and she was counseled on the risks and benefits of direct breastfeeding and pumping. The treatment team determined it was safe for Ms. S to directly breastfeed as there were no concerns for infant harm post­delivery with constant supervision while on the obstetrics floor. The patient opted to directly breastfeed, which was successful with the guidance of a lactation specialist. When she was transferred to the psychiatric unit on postpartum Day 2, her child was discharged home with the husband. The patient was then encouraged to pump while the psychiatrists monitored her symptoms closely and facilitated increased staff and resources. Transportation of breastmilk was made possible by the family, and on postpartum Day 5, as the patient maintained psychiatric stability, the team discussed with Ms. S and her husband the prospect of direct breastfeeding. The treatment team arranged for separate visitation hours to minimize the possibility of exposing the infant to aggression from other patients on the unit and advocated with hospital leadership to approve of infant visitation on the unit.

Impact of involvement of Child Protective Services

The involvement of CPS also added complexity to Ms. C’s case. Without proper legal guidance, mothers with psychosis who lose custody can find it difficult to navigate the legal system and maintain contact with their children.³⁴ As the prevalence of custody loss in mothers with psychosis is high (approximately 50% according to research published in the last 10 years), effective interventions to reunite the mother and child must be promoted (Figure 2).^35-39 Ultimately, the goal of psychiatric hospitalization for perinatal women who have SMI is psychiatric stabilization. The preemptive involvement of psychiatry is crucial because it can allow for early postpartum planning and can provide an opportunity to address feeding options and custody concerns with the patient, social supports and services, and various medical teams. In Ms. C’s case, she visited her baby in the NICU on postpartum Day 2 without consultation with psychiatry or CPS, which posed risks to the patient, infant, and staff. It is vital that various clinicians collaborate with each other and the patient, working towards the goal of optimizing the patient’s mental health to allow for parenting rights in the future and maximizing a sustainable attachment between the parent and child. In Ms. S’s case, the husband was able to facilitate caring for the baby while the mother was hospitalized and played an integral role in the feeding process via pumped breastmilk and transport of the infant for direct breastfeeding.

Continue to: The differences in these 2 cases...

The differences in these 2 cases show the extreme importance of social support to benefit both the mother and child, and the need for more comprehensive social services for women who do not have a social safety net.

Bottom Line

These complex cases highlight an ethical decision-making approach to breastfeeding in perinatal women who have serious mental illness. Collaborative care and shared decision-making, which highlight the interests of the mother and baby, are crucial when assessing the risks and benefits of breastfeeding and pumping breastmilk. Our relational ethics framework can be used to better evaluate and implement breastfeeding options on general psychiatric units.

Related Resources

• Tillman B, Sloan N, Westmoreland P. How COVID-19 affects peripartum women’s mental health. Current Psychiatry. 2021;20(6):18-22. doi:10.12788/cp.0129
• Koch J, Preinitz J. Antidepressants for patients who are breastfeeding: what to consider. Current Psychiatry. 2023;22(5):20-23,48. doi:10.12788/cp.0355

Drug Brand Names

Aripiprazole • Abilify
Olanzapine • Zyprexa
Risperidone • Risperdal

TOPLINE: 

Excessive television-watching is tied to an increased risk for dementia, Parkinson’s disease (PD), and depression, whereas a limited amount of daily computer use that is not work-related is linked to a lower risk for dementia.

METHODOLOGY:

• Investigators analyzed data on 473,184 people aged 39-72 years from the UK Biobank who were enrolled from 2006 to 2010 and followed until a diagnosis of dementia, PD, depression, death, or study end (2018 for Wales residents; 2021 for residents of England and Scotland).
• Participants reported on the number of hours they spent outside of work exercising, watching television, and using the computer.
• MRI was conducted to determine participants’ brain volume.

TAKEAWAY: 

• During the study, 6096 people developed dementia, 3000 developed PD, 23,600 developed depression, 1200 developed dementia and depression, and 486 developed PD and depression.
• Compared with those who watched TV for under 1 hour per day, those who reported watching 4 or more hours per day had a 28% higher risk for dementia (adjusted hazard ratio [aHR], 1.28; 95% CI, 1.17-1.39), a 35% higher risk for depression, (aHR, 1.35; 95% CI, 1.29-1.40) and a 16% greater risk for PD (aHR, 1.16; 95% CI, 1.03-1.29).
• However, moderate computer use outside of work seemed somewhat protective. Participants who used the computer for 30-60 minutes per day had lower risks for dementia (aHR, 0.68; 95% CI, 0.64-0.72), PD, (aHR, 0.86; 95% CI, 0.79-0.93), and depression (aHR, 0.85; 95% CI, 0.83-0.88) compared with those who reported the lowest levels of computer usage.
• Replacing 30 minutes per day of computer time with an equal amount of structured exercise was associated with decreased risk for dementia (aHR, 0.74; 95% CI, 0.85-0.95) and PD (aHR, 0.84; 95% CI, 0.78-0.90).

IN PRACTICE:

The association between extended periods of TV use and higher risk for PD and dementia could be explained by a lack of activity, the authors note. They add that sedentary behavior is, “associated with biomarkers of low-grade inflammation and changes in inflammation markers that could initiate and or worsen neuroinflammation and contribute to neurodegeneration.”

SOURCE:

Hanzhang Wu, PhD, of Tianjin University of Traditional Medicine in Tianjin, China, led the study, which was published online in the International Journal of Behavioral Nutrition and Physical Activity.

LIMITATIONS: 

Screen behaviors were assessed using self-report measures, which is subject to recall bias. Also, there may have been variables confounding the findings for which investigators did not account. 

DISCLOSURES:

The study was funded by the National Natural Science Foundation of China, the Tianjin Major Public Health Science and Technology Project, the National Health Commission of China, the Food Science and Technology Foundation of Chinese Institute of Food Science and Technology, the China Cohort Consortium, and the Chinese Nutrition Society Nutrition Research Foundation–DSM Research Fund, China. There were no disclosures reported.

Eve Bender has no relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE: 

Excessive television-watching is tied to an increased risk for dementia, Parkinson’s disease (PD), and depression, whereas a limited amount of daily computer use that is not work-related is linked to a lower risk for dementia.

METHODOLOGY:

• Investigators analyzed data on 473,184 people aged 39-72 years from the UK Biobank who were enrolled from 2006 to 2010 and followed until a diagnosis of dementia, PD, depression, death, or study end (2018 for Wales residents; 2021 for residents of England and Scotland).
• Participants reported on the number of hours they spent outside of work exercising, watching television, and using the computer.
• MRI was conducted to determine participants’ brain volume.

TAKEAWAY: 

• During the study, 6096 people developed dementia, 3000 developed PD, 23,600 developed depression, 1200 developed dementia and depression, and 486 developed PD and depression.
• Compared with those who watched TV for under 1 hour per day, those who reported watching 4 or more hours per day had a 28% higher risk for dementia (adjusted hazard ratio [aHR], 1.28; 95% CI, 1.17-1.39), a 35% higher risk for depression, (aHR, 1.35; 95% CI, 1.29-1.40) and a 16% greater risk for PD (aHR, 1.16; 95% CI, 1.03-1.29).
• However, moderate computer use outside of work seemed somewhat protective. Participants who used the computer for 30-60 minutes per day had lower risks for dementia (aHR, 0.68; 95% CI, 0.64-0.72), PD, (aHR, 0.86; 95% CI, 0.79-0.93), and depression (aHR, 0.85; 95% CI, 0.83-0.88) compared with those who reported the lowest levels of computer usage.
• Replacing 30 minutes per day of computer time with an equal amount of structured exercise was associated with decreased risk for dementia (aHR, 0.74; 95% CI, 0.85-0.95) and PD (aHR, 0.84; 95% CI, 0.78-0.90).

IN PRACTICE:

The association between extended periods of TV use and higher risk for PD and dementia could be explained by a lack of activity, the authors note. They add that sedentary behavior is, “associated with biomarkers of low-grade inflammation and changes in inflammation markers that could initiate and or worsen neuroinflammation and contribute to neurodegeneration.”

SOURCE:

Hanzhang Wu, PhD, of Tianjin University of Traditional Medicine in Tianjin, China, led the study, which was published online in the International Journal of Behavioral Nutrition and Physical Activity.

LIMITATIONS: 

Screen behaviors were assessed using self-report measures, which is subject to recall bias. Also, there may have been variables confounding the findings for which investigators did not account. 

DISCLOSURES:

The study was funded by the National Natural Science Foundation of China, the Tianjin Major Public Health Science and Technology Project, the National Health Commission of China, the Food Science and Technology Foundation of Chinese Institute of Food Science and Technology, the China Cohort Consortium, and the Chinese Nutrition Society Nutrition Research Foundation–DSM Research Fund, China. There were no disclosures reported.

Eve Bender has no relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE: 

Excessive television-watching is tied to an increased risk for dementia, Parkinson’s disease (PD), and depression, whereas a limited amount of daily computer use that is not work-related is linked to a lower risk for dementia.

METHODOLOGY:

• Investigators analyzed data on 473,184 people aged 39-72 years from the UK Biobank who were enrolled from 2006 to 2010 and followed until a diagnosis of dementia, PD, depression, death, or study end (2018 for Wales residents; 2021 for residents of England and Scotland).
• Participants reported on the number of hours they spent outside of work exercising, watching television, and using the computer.
• MRI was conducted to determine participants’ brain volume.

TAKEAWAY: 

• During the study, 6096 people developed dementia, 3000 developed PD, 23,600 developed depression, 1200 developed dementia and depression, and 486 developed PD and depression.
• Compared with those who watched TV for under 1 hour per day, those who reported watching 4 or more hours per day had a 28% higher risk for dementia (adjusted hazard ratio [aHR], 1.28; 95% CI, 1.17-1.39), a 35% higher risk for depression, (aHR, 1.35; 95% CI, 1.29-1.40) and a 16% greater risk for PD (aHR, 1.16; 95% CI, 1.03-1.29).
• However, moderate computer use outside of work seemed somewhat protective. Participants who used the computer for 30-60 minutes per day had lower risks for dementia (aHR, 0.68; 95% CI, 0.64-0.72), PD, (aHR, 0.86; 95% CI, 0.79-0.93), and depression (aHR, 0.85; 95% CI, 0.83-0.88) compared with those who reported the lowest levels of computer usage.
• Replacing 30 minutes per day of computer time with an equal amount of structured exercise was associated with decreased risk for dementia (aHR, 0.74; 95% CI, 0.85-0.95) and PD (aHR, 0.84; 95% CI, 0.78-0.90).

IN PRACTICE:

The association between extended periods of TV use and higher risk for PD and dementia could be explained by a lack of activity, the authors note. They add that sedentary behavior is, “associated with biomarkers of low-grade inflammation and changes in inflammation markers that could initiate and or worsen neuroinflammation and contribute to neurodegeneration.”

SOURCE:

Hanzhang Wu, PhD, of Tianjin University of Traditional Medicine in Tianjin, China, led the study, which was published online in the International Journal of Behavioral Nutrition and Physical Activity.

LIMITATIONS: 

Screen behaviors were assessed using self-report measures, which is subject to recall bias. Also, there may have been variables confounding the findings for which investigators did not account. 

DISCLOSURES:

The study was funded by the National Natural Science Foundation of China, the Tianjin Major Public Health Science and Technology Project, the National Health Commission of China, the Food Science and Technology Foundation of Chinese Institute of Food Science and Technology, the China Cohort Consortium, and the Chinese Nutrition Society Nutrition Research Foundation–DSM Research Fund, China. There were no disclosures reported.

Eve Bender has no relevant financial relationships.

A version of this article appeared on Medscape.com.

Some call the drug “ecstasy” or “molly.” Researchers are calling it a potential tool to help treat loneliness.

As public health experts sound the alarm on a rising loneliness epidemic in the United States and across the globe, early research is finding that MDMA could increase social connectedness and reduce defensiveness in some people — effects that some say could, in combination with therapy, help combat loneliness. 

In the latest study, MDMA “led to a robust increase in feelings of connection” among people socializing in a controlled setting. Participants were dosed with either MDMA or a placebo and asked to chat with a stranger. Afterward, those who took MDMA said their companion was more responsive and attentive, and that they had plenty in common. The drug also “increased participants’ ratings of liking their partners, feeling connected and finding the conversation enjoyable and meaningful.” 

The study was small — just 18 participants — but its results “have implications for MDMA-assisted therapy,” the authors wrote. “This feeling of connectedness could help patients feel safe and trusting, thereby facilitating deeper emotional exploration.” 

MDMA “really does seem to make people want to interact more with other people,” says Harriet de Wit, PhD, a neuropharmacologist at the University of Chicago and one of the study’s authors. The results echo those of earlier research using psychedelics like LSD or psilocybin. 

It’s important to note that any intervention involving MDMA or psychedelics would be a drug-assisted therapy — that is, used in conjunction with the appropriate therapy and in a therapeutic setting. MDMA-assisted therapy has already drawn popular and scientific attention, as it recently cleared clinical trials for treating posttraumatic stress disorder (PTSD) and may be nearing approval by the US Food and Drug Administration (FDA). 

According to Friederike Holze, PhD, psychopharmacologist at the University of Basel, in Switzerland, “there could be a place” for MDMA and psychedelics in treating chronic loneliness, but only under professional supervision. 

There would have to be clear guidelines too, says Joshua Woolley, MD, PhD, a psychiatrist at the University of California, San Francisco. 

MDMA and psychedelics “induce this plastic state, a state where people can change. They feel open, they feel like things are possible,” Dr. Woolley says. Then, with therapy, “you can help them change.”

Loneliness Can Impact Our Health

On top of the mental health ramifications, the physiologic effects of loneliness could have grave consequences over time. In observational studies, loneliness has been linked to higher risks for cancer and heart disease, and shorter lifespan. One third  of Americans over 45 say they are chronically lonely. 

Chronic loneliness changes how we think and behave, research shows. It makes us fear contact with others and see them in a more negative light, as more threatening and less trustworthy. Lonely people prefer to stand farther apart  from strangers and avoid touch. 

This is where MDMA-assisted therapies could potentially help, by easing these defensive tendencies, according to Dr. Woolley.

MDMA, Psychedelics, and Social Behavior

MDMA, or 3,4-methylenedioxymethamphetamine, is a hybrid  between a stimulant and a psychedelic. In Dr. de Wit’s earlier experiments, volunteers given MDMA engaged more in communal activities, chatting, and playing games. They used more positive words during social encounters than those who had received a placebo. And after MDMA, people felt less rejected if they were slighted in Cyberball  — a virtual ball-tossing game commonly used to measure the effects of social exclusion.

MDMA has been shown to reduce people’s response to other’s negative emotions, diminishing activation of the amygdala (the brain’s fear center) while looking at pictures of angry faces. 

This could be helpful. “If you perceive a person’s natural expression as being a little bit angry, if that disappears, then you might be more inclined to interact,” de Wit says. 

However, there may be downsides, too. If a drug makes people more trusting and willing to connect, they could be taken advantage of. This is why, Dr. Woolley says, “psychedelics have been used in cults.” 

MDMA may also make the experience of touch more pleasant. In a series of experiments in 2019, researchers gently stroked volunteers ’ arms with a goat-hair brush, mimicking the comforting gestures one may receive from a loved one. At the same time, the scientists monitored the volunteers’ facial muscles. People on MDMA perceived gentle touch as more pleasant than those on placebo, and their smile muscles activated more.

MDMA and psychedelics boost social behaviors in animals, too — suggesting that their effects on relationships have a biological basis. Rats on MDMA are more likely to lie next to each other, and mice become more resilient to social stress. Even octopuses become more outgoing after a dose of MDMA, choosing to spend more time with other octopuses instead of a new toy. Classic psychedelics show similar effects — LSD, for example, makes mice more social. 

Psychedelics can induce a sense of a “dissolution of the self-other boundary,” Dr. Woolley says. People who take them often say it’s “helped them feel more connected to themselves and other people.” LSD, first synthesized in 1938, may help increase empathy in some people. 

Psilocybin, a compound found in over 200 species of mushrooms and used for centuries in Mesoamerican rituals, also seems to boost empathy, with effects persisting for at least seven days. In Cyberball, the online ball-throwing game, people who took psilocybin felt less socially rejected, an outcome reflected in their brain activation patterns in one study — the areas responsible for social-pain processing appeared to dim after a dose. 

Making It Legal and Putting It to Use

In 2020, Oregon became the first state to establish a regulatory framework for psilocybin for therapeutic use, and  Colorado  followed suit in 2022. Such therapeutic applications of psilocybin could help fight loneliness as well, Dr. Woolley believes, because a “ common symptom of depression is that people feel socially withdrawn and lack motivation, ” he says. As mentioned above, MDMA-assisted therapy is also nearing FDA approval for PTSD. 

What remain unclear are the exact mechanisms at play. 

“MDMA releases oxytocin, and it does that through serotonin receptors,” Dr. de Wit says. Serotonin activates 5-HT1A receptors in the hypothalamus, releasing oxytocin into the bloodstream. In Dr. de Wit’s recent experiments, the more people felt connected after taking MDMA, the more oxytocin was found circulating in their bodies. (Another drug, methamphetamine, also upped the levels of oxytocin but did not increase feelings of connectedness.) 

“It’s likely that both something in the serotonin system independent of oxytocin, and oxytocin itself, contribute,” Dr. de Wit says. Dopamine, a neurotransmitter responsible for motivation, appears to increase as well. 

The empathy-boosting effects of LSD also seem to be at least partly driven by oxytocin, experiments published in 2021 revealed. Studies in mice, meanwhile, suggest that glutamate, a chemical messenger in the brain, may be behind some of LSD’s prosocial effects. 

Scientists are fairly certain which receptors these drugs bind to and which neurotransmitters they affect. “How that gets translated into these higher-order things like empathy and feeling connected to the world, we don’t totally understand,” Dr. Woolley says.

Challenges and the Future

Although MDMA and psychedelics are largely considered safe when taken in a legal, medically controlled setting, there is reason to be cautious.

“They have relatively low impact on the body, like heart rate increase or blood pressure increase. But they might leave some disturbing psychological effects,” says Dr. Holze. Scientists routinely screen experiment volunteers for their risk for psychiatric disorders. 

Although risk for addiction is low with both MDMA and psychedelics, there is always some risk for misuse. MDMA “ can produce feelings of well-being, and then people might use it repeatedly, ” Dr. de Wit says. “ That doesn ’ t seem to be a problem for really a lot of people, but it could easily happen. ”  

Still, possibilities remain for MDMA in the fight against loneliness. 

“[People] feel open, they feel like things are possible, they feel like they’re unstuck,” Dr. Woolley says. “You can harness that in psychotherapy.”

A version of this article appeared on Medscape.com.

Some call the drug “ecstasy” or “molly.” Researchers are calling it a potential tool to help treat loneliness.

As public health experts sound the alarm on a rising loneliness epidemic in the United States and across the globe, early research is finding that MDMA could increase social connectedness and reduce defensiveness in some people — effects that some say could, in combination with therapy, help combat loneliness. 

In the latest study, MDMA “led to a robust increase in feelings of connection” among people socializing in a controlled setting. Participants were dosed with either MDMA or a placebo and asked to chat with a stranger. Afterward, those who took MDMA said their companion was more responsive and attentive, and that they had plenty in common. The drug also “increased participants’ ratings of liking their partners, feeling connected and finding the conversation enjoyable and meaningful.” 

The study was small — just 18 participants — but its results “have implications for MDMA-assisted therapy,” the authors wrote. “This feeling of connectedness could help patients feel safe and trusting, thereby facilitating deeper emotional exploration.” 

MDMA “really does seem to make people want to interact more with other people,” says Harriet de Wit, PhD, a neuropharmacologist at the University of Chicago and one of the study’s authors. The results echo those of earlier research using psychedelics like LSD or psilocybin. 

It’s important to note that any intervention involving MDMA or psychedelics would be a drug-assisted therapy — that is, used in conjunction with the appropriate therapy and in a therapeutic setting. MDMA-assisted therapy has already drawn popular and scientific attention, as it recently cleared clinical trials for treating posttraumatic stress disorder (PTSD) and may be nearing approval by the US Food and Drug Administration (FDA). 

According to Friederike Holze, PhD, psychopharmacologist at the University of Basel, in Switzerland, “there could be a place” for MDMA and psychedelics in treating chronic loneliness, but only under professional supervision. 

There would have to be clear guidelines too, says Joshua Woolley, MD, PhD, a psychiatrist at the University of California, San Francisco. 

MDMA and psychedelics “induce this plastic state, a state where people can change. They feel open, they feel like things are possible,” Dr. Woolley says. Then, with therapy, “you can help them change.”

Loneliness Can Impact Our Health

On top of the mental health ramifications, the physiologic effects of loneliness could have grave consequences over time. In observational studies, loneliness has been linked to higher risks for cancer and heart disease, and shorter lifespan. One third  of Americans over 45 say they are chronically lonely. 

Chronic loneliness changes how we think and behave, research shows. It makes us fear contact with others and see them in a more negative light, as more threatening and less trustworthy. Lonely people prefer to stand farther apart  from strangers and avoid touch. 

This is where MDMA-assisted therapies could potentially help, by easing these defensive tendencies, according to Dr. Woolley.

MDMA, Psychedelics, and Social Behavior

MDMA, or 3,4-methylenedioxymethamphetamine, is a hybrid  between a stimulant and a psychedelic. In Dr. de Wit’s earlier experiments, volunteers given MDMA engaged more in communal activities, chatting, and playing games. They used more positive words during social encounters than those who had received a placebo. And after MDMA, people felt less rejected if they were slighted in Cyberball  — a virtual ball-tossing game commonly used to measure the effects of social exclusion.

MDMA has been shown to reduce people’s response to other’s negative emotions, diminishing activation of the amygdala (the brain’s fear center) while looking at pictures of angry faces. 

This could be helpful. “If you perceive a person’s natural expression as being a little bit angry, if that disappears, then you might be more inclined to interact,” de Wit says. 

However, there may be downsides, too. If a drug makes people more trusting and willing to connect, they could be taken advantage of. This is why, Dr. Woolley says, “psychedelics have been used in cults.” 

MDMA may also make the experience of touch more pleasant. In a series of experiments in 2019, researchers gently stroked volunteers ’ arms with a goat-hair brush, mimicking the comforting gestures one may receive from a loved one. At the same time, the scientists monitored the volunteers’ facial muscles. People on MDMA perceived gentle touch as more pleasant than those on placebo, and their smile muscles activated more.

MDMA and psychedelics boost social behaviors in animals, too — suggesting that their effects on relationships have a biological basis. Rats on MDMA are more likely to lie next to each other, and mice become more resilient to social stress. Even octopuses become more outgoing after a dose of MDMA, choosing to spend more time with other octopuses instead of a new toy. Classic psychedelics show similar effects — LSD, for example, makes mice more social. 

Psychedelics can induce a sense of a “dissolution of the self-other boundary,” Dr. Woolley says. People who take them often say it’s “helped them feel more connected to themselves and other people.” LSD, first synthesized in 1938, may help increase empathy in some people. 

Psilocybin, a compound found in over 200 species of mushrooms and used for centuries in Mesoamerican rituals, also seems to boost empathy, with effects persisting for at least seven days. In Cyberball, the online ball-throwing game, people who took psilocybin felt less socially rejected, an outcome reflected in their brain activation patterns in one study — the areas responsible for social-pain processing appeared to dim after a dose. 

Making It Legal and Putting It to Use

In 2020, Oregon became the first state to establish a regulatory framework for psilocybin for therapeutic use, and  Colorado  followed suit in 2022. Such therapeutic applications of psilocybin could help fight loneliness as well, Dr. Woolley believes, because a “ common symptom of depression is that people feel socially withdrawn and lack motivation, ” he says. As mentioned above, MDMA-assisted therapy is also nearing FDA approval for PTSD. 

What remain unclear are the exact mechanisms at play. 

“MDMA releases oxytocin, and it does that through serotonin receptors,” Dr. de Wit says. Serotonin activates 5-HT1A receptors in the hypothalamus, releasing oxytocin into the bloodstream. In Dr. de Wit’s recent experiments, the more people felt connected after taking MDMA, the more oxytocin was found circulating in their bodies. (Another drug, methamphetamine, also upped the levels of oxytocin but did not increase feelings of connectedness.) 

“It’s likely that both something in the serotonin system independent of oxytocin, and oxytocin itself, contribute,” Dr. de Wit says. Dopamine, a neurotransmitter responsible for motivation, appears to increase as well. 

The empathy-boosting effects of LSD also seem to be at least partly driven by oxytocin, experiments published in 2021 revealed. Studies in mice, meanwhile, suggest that glutamate, a chemical messenger in the brain, may be behind some of LSD’s prosocial effects. 

Scientists are fairly certain which receptors these drugs bind to and which neurotransmitters they affect. “How that gets translated into these higher-order things like empathy and feeling connected to the world, we don’t totally understand,” Dr. Woolley says.

Challenges and the Future

Although MDMA and psychedelics are largely considered safe when taken in a legal, medically controlled setting, there is reason to be cautious.

“They have relatively low impact on the body, like heart rate increase or blood pressure increase. But they might leave some disturbing psychological effects,” says Dr. Holze. Scientists routinely screen experiment volunteers for their risk for psychiatric disorders. 

Although risk for addiction is low with both MDMA and psychedelics, there is always some risk for misuse. MDMA “ can produce feelings of well-being, and then people might use it repeatedly, ” Dr. de Wit says. “ That doesn ’ t seem to be a problem for really a lot of people, but it could easily happen. ”  

Still, possibilities remain for MDMA in the fight against loneliness. 

“[People] feel open, they feel like things are possible, they feel like they’re unstuck,” Dr. Woolley says. “You can harness that in psychotherapy.”

A version of this article appeared on Medscape.com.

Some call the drug “ecstasy” or “molly.” Researchers are calling it a potential tool to help treat loneliness.

As public health experts sound the alarm on a rising loneliness epidemic in the United States and across the globe, early research is finding that MDMA could increase social connectedness and reduce defensiveness in some people — effects that some say could, in combination with therapy, help combat loneliness. 

In the latest study, MDMA “led to a robust increase in feelings of connection” among people socializing in a controlled setting. Participants were dosed with either MDMA or a placebo and asked to chat with a stranger. Afterward, those who took MDMA said their companion was more responsive and attentive, and that they had plenty in common. The drug also “increased participants’ ratings of liking their partners, feeling connected and finding the conversation enjoyable and meaningful.” 

The study was small — just 18 participants — but its results “have implications for MDMA-assisted therapy,” the authors wrote. “This feeling of connectedness could help patients feel safe and trusting, thereby facilitating deeper emotional exploration.” 

MDMA “really does seem to make people want to interact more with other people,” says Harriet de Wit, PhD, a neuropharmacologist at the University of Chicago and one of the study’s authors. The results echo those of earlier research using psychedelics like LSD or psilocybin. 

It’s important to note that any intervention involving MDMA or psychedelics would be a drug-assisted therapy — that is, used in conjunction with the appropriate therapy and in a therapeutic setting. MDMA-assisted therapy has already drawn popular and scientific attention, as it recently cleared clinical trials for treating posttraumatic stress disorder (PTSD) and may be nearing approval by the US Food and Drug Administration (FDA). 

According to Friederike Holze, PhD, psychopharmacologist at the University of Basel, in Switzerland, “there could be a place” for MDMA and psychedelics in treating chronic loneliness, but only under professional supervision. 

There would have to be clear guidelines too, says Joshua Woolley, MD, PhD, a psychiatrist at the University of California, San Francisco. 

MDMA and psychedelics “induce this plastic state, a state where people can change. They feel open, they feel like things are possible,” Dr. Woolley says. Then, with therapy, “you can help them change.”

Loneliness Can Impact Our Health

On top of the mental health ramifications, the physiologic effects of loneliness could have grave consequences over time. In observational studies, loneliness has been linked to higher risks for cancer and heart disease, and shorter lifespan. One third  of Americans over 45 say they are chronically lonely. 

Chronic loneliness changes how we think and behave, research shows. It makes us fear contact with others and see them in a more negative light, as more threatening and less trustworthy. Lonely people prefer to stand farther apart  from strangers and avoid touch. 

This is where MDMA-assisted therapies could potentially help, by easing these defensive tendencies, according to Dr. Woolley.

MDMA, Psychedelics, and Social Behavior

MDMA, or 3,4-methylenedioxymethamphetamine, is a hybrid  between a stimulant and a psychedelic. In Dr. de Wit’s earlier experiments, volunteers given MDMA engaged more in communal activities, chatting, and playing games. They used more positive words during social encounters than those who had received a placebo. And after MDMA, people felt less rejected if they were slighted in Cyberball  — a virtual ball-tossing game commonly used to measure the effects of social exclusion.

MDMA has been shown to reduce people’s response to other’s negative emotions, diminishing activation of the amygdala (the brain’s fear center) while looking at pictures of angry faces. 

This could be helpful. “If you perceive a person’s natural expression as being a little bit angry, if that disappears, then you might be more inclined to interact,” de Wit says. 

However, there may be downsides, too. If a drug makes people more trusting and willing to connect, they could be taken advantage of. This is why, Dr. Woolley says, “psychedelics have been used in cults.” 

MDMA may also make the experience of touch more pleasant. In a series of experiments in 2019, researchers gently stroked volunteers ’ arms with a goat-hair brush, mimicking the comforting gestures one may receive from a loved one. At the same time, the scientists monitored the volunteers’ facial muscles. People on MDMA perceived gentle touch as more pleasant than those on placebo, and their smile muscles activated more.

MDMA and psychedelics boost social behaviors in animals, too — suggesting that their effects on relationships have a biological basis. Rats on MDMA are more likely to lie next to each other, and mice become more resilient to social stress. Even octopuses become more outgoing after a dose of MDMA, choosing to spend more time with other octopuses instead of a new toy. Classic psychedelics show similar effects — LSD, for example, makes mice more social. 

Psychedelics can induce a sense of a “dissolution of the self-other boundary,” Dr. Woolley says. People who take them often say it’s “helped them feel more connected to themselves and other people.” LSD, first synthesized in 1938, may help increase empathy in some people. 

Psilocybin, a compound found in over 200 species of mushrooms and used for centuries in Mesoamerican rituals, also seems to boost empathy, with effects persisting for at least seven days. In Cyberball, the online ball-throwing game, people who took psilocybin felt less socially rejected, an outcome reflected in their brain activation patterns in one study — the areas responsible for social-pain processing appeared to dim after a dose. 

Making It Legal and Putting It to Use

In 2020, Oregon became the first state to establish a regulatory framework for psilocybin for therapeutic use, and  Colorado  followed suit in 2022. Such therapeutic applications of psilocybin could help fight loneliness as well, Dr. Woolley believes, because a “ common symptom of depression is that people feel socially withdrawn and lack motivation, ” he says. As mentioned above, MDMA-assisted therapy is also nearing FDA approval for PTSD. 

What remain unclear are the exact mechanisms at play. 

“MDMA releases oxytocin, and it does that through serotonin receptors,” Dr. de Wit says. Serotonin activates 5-HT1A receptors in the hypothalamus, releasing oxytocin into the bloodstream. In Dr. de Wit’s recent experiments, the more people felt connected after taking MDMA, the more oxytocin was found circulating in their bodies. (Another drug, methamphetamine, also upped the levels of oxytocin but did not increase feelings of connectedness.) 

“It’s likely that both something in the serotonin system independent of oxytocin, and oxytocin itself, contribute,” Dr. de Wit says. Dopamine, a neurotransmitter responsible for motivation, appears to increase as well. 

The empathy-boosting effects of LSD also seem to be at least partly driven by oxytocin, experiments published in 2021 revealed. Studies in mice, meanwhile, suggest that glutamate, a chemical messenger in the brain, may be behind some of LSD’s prosocial effects. 

Scientists are fairly certain which receptors these drugs bind to and which neurotransmitters they affect. “How that gets translated into these higher-order things like empathy and feeling connected to the world, we don’t totally understand,” Dr. Woolley says.

Challenges and the Future

Although MDMA and psychedelics are largely considered safe when taken in a legal, medically controlled setting, there is reason to be cautious.

“They have relatively low impact on the body, like heart rate increase or blood pressure increase. But they might leave some disturbing psychological effects,” says Dr. Holze. Scientists routinely screen experiment volunteers for their risk for psychiatric disorders. 

Although risk for addiction is low with both MDMA and psychedelics, there is always some risk for misuse. MDMA “ can produce feelings of well-being, and then people might use it repeatedly, ” Dr. de Wit says. “ That doesn ’ t seem to be a problem for really a lot of people, but it could easily happen. ”  

Still, possibilities remain for MDMA in the fight against loneliness. 

“[People] feel open, they feel like things are possible, they feel like they’re unstuck,” Dr. Woolley says. “You can harness that in psychotherapy.”

A version of this article appeared on Medscape.com.

TOPLINE: 

National survey data reveal an association between higher serum oleic acid levels and depression in adults, new research shows. 

METHODOLOGY:

Oleic acid is the most abundant fatty acid in plasma and has been associated with multiple neurologic diseases. However, the relationship between oleic acid and depression is unclear. 

This cross-sectional analyzed data on 4459 adults from the 2011-2014 National Health and Nutrition Examination Survey (NHANES).

Multivariable logistic regression models adjusting for demographics, health and lifestyle factors quantified the association between oleic acid levels and depression. Depression was assessed using the Patient Health Questionnaire-9 (PHQ-9) with depression defined as a score ≥ 10.

TAKEAWAY:

Serum oleic acid levels were positively associated with depression before and after multivariable adjustment.

After adjusting for all covariates, for every 1 mmol/L increase in serum oleic acid levels, the prevalence of depression increased by 40% (adjusted odds ratio [aOR], 1.40; 95% CI, 1.03-1.90). 

Adults in the top quartile of oleic acid (≥ 2.51 mmol/L) had a greater than twofold higher likelihood of depression (aOR, 2.22; 95% CI, 1.04-4.73) compared with peers in the lowest quartile (≤ 1.54 mmol/L). 

IN PRACTICE:

“A better understanding of the role of oleic acid in depression may lead to new preventive and therapeutic methods. Thus, carefully designed prospective studies are necessary to explore the positive effects of changing serum oleic acid levels through diet, medicine, or other measures on depression,” the authors write. 

SOURCE:

The study, with first author Jiahui Yin of Shandong University of Traditional Chinese Medicine in Jinan, China, was published online on November 16, 2023 in BMC Psychiatry .

LIMITATIONS: 

The cross-sectional study can’t prove causality. The findings may not apply to clinically diagnosed major depressive disorder. 

DISCLOSURES:

The study had no specific funding. The authors report no conflicts of interest.


A version of this article first appeared on Medscape.com.

TOPLINE: 

National survey data reveal an association between higher serum oleic acid levels and depression in adults, new research shows. 

METHODOLOGY:

Oleic acid is the most abundant fatty acid in plasma and has been associated with multiple neurologic diseases. However, the relationship between oleic acid and depression is unclear. 

This cross-sectional analyzed data on 4459 adults from the 2011-2014 National Health and Nutrition Examination Survey (NHANES).

Multivariable logistic regression models adjusting for demographics, health and lifestyle factors quantified the association between oleic acid levels and depression. Depression was assessed using the Patient Health Questionnaire-9 (PHQ-9) with depression defined as a score ≥ 10.

TAKEAWAY:

Serum oleic acid levels were positively associated with depression before and after multivariable adjustment.

After adjusting for all covariates, for every 1 mmol/L increase in serum oleic acid levels, the prevalence of depression increased by 40% (adjusted odds ratio [aOR], 1.40; 95% CI, 1.03-1.90). 

Adults in the top quartile of oleic acid (≥ 2.51 mmol/L) had a greater than twofold higher likelihood of depression (aOR, 2.22; 95% CI, 1.04-4.73) compared with peers in the lowest quartile (≤ 1.54 mmol/L). 

IN PRACTICE:

“A better understanding of the role of oleic acid in depression may lead to new preventive and therapeutic methods. Thus, carefully designed prospective studies are necessary to explore the positive effects of changing serum oleic acid levels through diet, medicine, or other measures on depression,” the authors write. 

SOURCE:

The study, with first author Jiahui Yin of Shandong University of Traditional Chinese Medicine in Jinan, China, was published online on November 16, 2023 in BMC Psychiatry .

LIMITATIONS: 

The cross-sectional study can’t prove causality. The findings may not apply to clinically diagnosed major depressive disorder. 

DISCLOSURES:

The study had no specific funding. The authors report no conflicts of interest.


A version of this article first appeared on Medscape.com.

TOPLINE: 

National survey data reveal an association between higher serum oleic acid levels and depression in adults, new research shows. 

METHODOLOGY:

Oleic acid is the most abundant fatty acid in plasma and has been associated with multiple neurologic diseases. However, the relationship between oleic acid and depression is unclear. 

This cross-sectional analyzed data on 4459 adults from the 2011-2014 National Health and Nutrition Examination Survey (NHANES).

Multivariable logistic regression models adjusting for demographics, health and lifestyle factors quantified the association between oleic acid levels and depression. Depression was assessed using the Patient Health Questionnaire-9 (PHQ-9) with depression defined as a score ≥ 10.

TAKEAWAY:

Serum oleic acid levels were positively associated with depression before and after multivariable adjustment.

After adjusting for all covariates, for every 1 mmol/L increase in serum oleic acid levels, the prevalence of depression increased by 40% (adjusted odds ratio [aOR], 1.40; 95% CI, 1.03-1.90). 

Adults in the top quartile of oleic acid (≥ 2.51 mmol/L) had a greater than twofold higher likelihood of depression (aOR, 2.22; 95% CI, 1.04-4.73) compared with peers in the lowest quartile (≤ 1.54 mmol/L). 

IN PRACTICE:

“A better understanding of the role of oleic acid in depression may lead to new preventive and therapeutic methods. Thus, carefully designed prospective studies are necessary to explore the positive effects of changing serum oleic acid levels through diet, medicine, or other measures on depression,” the authors write. 

SOURCE:

The study, with first author Jiahui Yin of Shandong University of Traditional Chinese Medicine in Jinan, China, was published online on November 16, 2023 in BMC Psychiatry .

LIMITATIONS: 

The cross-sectional study can’t prove causality. The findings may not apply to clinically diagnosed major depressive disorder. 

DISCLOSURES:

The study had no specific funding. The authors report no conflicts of interest.


A version of this article first appeared on Medscape.com.

TOPLINE:

A meta-analysis supports the use of mobile mental health apps, both as a standalone and added to conventional treatment, for adults with moderate to severe depression.

METHODOLOGY:

Mobile mental health apps have proliferated but data on their effectiveness in different patient populations is lacking.

To investigate, researchers conducted a systematic review and meta-analysis of 13 randomized clinical trials assessing treatment efficacy of mobile mental health apps in 1470 adults with moderate to severe depression.

The primary outcome was change in depression symptoms from pre- to post-treatment; secondary outcomes included patient-level factors associated with app efficacy.

TAKEAWAY: 

Mobile app interventions were associated with significantly reduced depressive symptoms vs both active and inactive control groups, with a medium effect size (standardized mean difference [SMD] 0.50).

App interventions delivered for < 8 weeks had a significantly greater effect size than those delivered for 8+ weeks (SMD 0.77 vs 0.43). Apps were more effective in patients not on medication or in therapy. Apps offering rewards or incentives also appeared to be more effective.

Interventions with in-app notifications were associated with significantly lower treatment outcomes (SMD 0.45) than interventions without (SMD 0.45 vs 0.71).

IN PRACTICE:

“The significant treatment efficacy of app-based interventions compared with active and inactive controls suggests the potential of mobile app interventions as an alternative to conventional psychotherapy, with further merits in accessibility, financial affordability, and safety from stigma,” the authors write.

SOURCE:

The study, with first author Hayoung Bae, BA, with Korea University School of Psychology, Seoul, South Korea, was published online November 20 in JAMA Network Open .

LIMITATIONS:

The findings are based on a small number of trials, with significant heterogeneity among the included trials. The analysis included only English-language publications. Using summary data for the subgroup analyses might have prevented a detailed understanding of the moderating associations of individual participant characteristics.

DISCLOSURES:

The study was supported by a grant from the National Research Foundation funded by the Korean government. The authors report no relevant financial relationships.

A version of this article first appeared on Medscape.com .

TOPLINE:

A meta-analysis supports the use of mobile mental health apps, both as a standalone and added to conventional treatment, for adults with moderate to severe depression.

METHODOLOGY:

Mobile mental health apps have proliferated but data on their effectiveness in different patient populations is lacking.

To investigate, researchers conducted a systematic review and meta-analysis of 13 randomized clinical trials assessing treatment efficacy of mobile mental health apps in 1470 adults with moderate to severe depression.

The primary outcome was change in depression symptoms from pre- to post-treatment; secondary outcomes included patient-level factors associated with app efficacy.

TAKEAWAY: 

Mobile app interventions were associated with significantly reduced depressive symptoms vs both active and inactive control groups, with a medium effect size (standardized mean difference [SMD] 0.50).

App interventions delivered for < 8 weeks had a significantly greater effect size than those delivered for 8+ weeks (SMD 0.77 vs 0.43). Apps were more effective in patients not on medication or in therapy. Apps offering rewards or incentives also appeared to be more effective.

Interventions with in-app notifications were associated with significantly lower treatment outcomes (SMD 0.45) than interventions without (SMD 0.45 vs 0.71).

IN PRACTICE:

“The significant treatment efficacy of app-based interventions compared with active and inactive controls suggests the potential of mobile app interventions as an alternative to conventional psychotherapy, with further merits in accessibility, financial affordability, and safety from stigma,” the authors write.

SOURCE:

The study, with first author Hayoung Bae, BA, with Korea University School of Psychology, Seoul, South Korea, was published online November 20 in JAMA Network Open .

LIMITATIONS:

The findings are based on a small number of trials, with significant heterogeneity among the included trials. The analysis included only English-language publications. Using summary data for the subgroup analyses might have prevented a detailed understanding of the moderating associations of individual participant characteristics.

DISCLOSURES:

The study was supported by a grant from the National Research Foundation funded by the Korean government. The authors report no relevant financial relationships.

A version of this article first appeared on Medscape.com .

TOPLINE:

A meta-analysis supports the use of mobile mental health apps, both as a standalone and added to conventional treatment, for adults with moderate to severe depression.

METHODOLOGY:

Mobile mental health apps have proliferated but data on their effectiveness in different patient populations is lacking.

To investigate, researchers conducted a systematic review and meta-analysis of 13 randomized clinical trials assessing treatment efficacy of mobile mental health apps in 1470 adults with moderate to severe depression.

The primary outcome was change in depression symptoms from pre- to post-treatment; secondary outcomes included patient-level factors associated with app efficacy.

TAKEAWAY: 

Mobile app interventions were associated with significantly reduced depressive symptoms vs both active and inactive control groups, with a medium effect size (standardized mean difference [SMD] 0.50).

App interventions delivered for < 8 weeks had a significantly greater effect size than those delivered for 8+ weeks (SMD 0.77 vs 0.43). Apps were more effective in patients not on medication or in therapy. Apps offering rewards or incentives also appeared to be more effective.

Interventions with in-app notifications were associated with significantly lower treatment outcomes (SMD 0.45) than interventions without (SMD 0.45 vs 0.71).

IN PRACTICE:

“The significant treatment efficacy of app-based interventions compared with active and inactive controls suggests the potential of mobile app interventions as an alternative to conventional psychotherapy, with further merits in accessibility, financial affordability, and safety from stigma,” the authors write.

SOURCE:

The study, with first author Hayoung Bae, BA, with Korea University School of Psychology, Seoul, South Korea, was published online November 20 in JAMA Network Open .

LIMITATIONS:

The findings are based on a small number of trials, with significant heterogeneity among the included trials. The analysis included only English-language publications. Using summary data for the subgroup analyses might have prevented a detailed understanding of the moderating associations of individual participant characteristics.

DISCLOSURES:

The study was supported by a grant from the National Research Foundation funded by the Korean government. The authors report no relevant financial relationships.

A version of this article first appeared on Medscape.com .

Ms. B, age 45, has a history of major depressive disorder (MDD) and migraines. She is admitted after presenting with anhedonia, hopelessness, and hypersomnia. These symptoms have become more severe over the last few weeks. Ms. B describes a past suicide attempt via overdose on doxylamine for which she required treatment in the intensive care unit. The only activity she enjoys is her weekly girls’ night, during which she drinks a few glasses of wine. Ms. B’s current medications are dextromethorphan/bupropion 45/105 mg twice daily and aripiprazole 5 mg/d, which she has taken for 3 months. She states she has “been on every antidepressant there is.”

When clinicians review Ms. B’s medication history, it is clear she has had adequate trials of selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), intranasal esketamine, multiple augmentation strategies, and electroconvulsive therapy (ECT). Ms. B seeks an alternative medication to improve her depressive symptoms.

Treatment-resistant depression (TRD) is commonly defined as depression that has not responded to ≥2 adequate trials of an antidepressant.¹ Some guidelines recommend monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants (TCAs) as second- or even third-line options for MDD,² while others recommend reserving them for patients with insufficient responses to alternative treatment modalities.^3,4 Although MAOIs and TCAs have been available since the 1950s, prescribing these medications has become less prevalent due to safety concerns, the availability of other pharmacologic options, and a lack of clinical training and comfort.^5,6 Most research notes that MAOIs are superior for treating atypical depression while TCAs are more effective for melancholic depression.^2-4 In a review of 20 studies, Thase et al⁷ found that 50% of TCA nonresponders benefited from an MAOI. In the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial, monotherapy with the MAOI tranylcypromine was associated with a lower remission rate than the TCA nortriptyline; many argue the dose of tranylcypromine was suboptimal, and few participants completed an adequate trial in the last level.^8,9 A more recent study by Kim et al¹⁰ found MAOIs to be “generally more effective” than TCAs for TRD, particularly in patients with fewer antidepressant trials; however, this was a small retrospective exploratory trial. A network meta-analysis found both classes to be “competitive” with SSRIs based on efficacy and tolerability, which leads to the question of whether these medications should be considered earlier in therapy.¹¹ Considering patient-specific factors and particular medication properties is an effective strategy when prescribing an MAOI or TCA.

Monoamine oxidase inhibitors

Four MAOIs are FDA-approved for treating MDD (Table 1^5,12-17): phenelzine, isocarboxazid, tranylcypromine, and selegiline. These medications irreversibly inhibit MAO, which exists as isomers A and B. MAO-A primarily metabolizes serotonin and norepinephrine, which is largely responsible for these medications’ antidepressant effects. Both isomers equally metabolize dopamine.^5,12,18 It is best to avoid using MAOIs in patients with cerebrovascular disease, hepatic disease, or pheochromocytoma. Patients with active substance use disorders (particularly sympathomimetics and hallucinogens) are at an increased risk for hypertensive crises and serotonin syndrome, respectively. The most common adverse effects are orthostatic hypotension (despite more well-known concerns regarding hypertension), alterations in sleep patterns (insomnia or hypersomnia, depending on the agent), gastrointestinal issues, and anticholinergic adverse effects such as dry mouth and constipation.^13,19-21

In one review and meta-analysis, phenelzine displayed the highest efficacy across all MAOIs.¹¹ It likely requires high doses to achieve adequate MAO inhibition.¹¹ A metabolite of phenelzine inhibits gamma-aminobutyric acid transaminase and may be helpful for patients with comorbid anxiety disorders or MDD with anxious distress.^18,21 Additional considerations include phenelzine’s propensity for orthostasis (with rapid titrations and higher doses), sedation, weight gain, sexual dysfunction, and a rare adverse effect of vitamin B6 deficiency.^{5,13,14,20-22}

Use of isocarboxazid in clinical practice is rare. Its adverse effects are similar to those of phenelzine but isocarboxazid is less studied. Tranylcypromine has a similar chemical structure to amphetamine. It can be stimulating at higher doses, potentially benefitting patients with comorbid attention-deficit/hyperactivity disorder (ADHD) or significant apathy.^13,23 Selegiline’s distinct quality is its availability as a transdermal patch, which may be useful for patients who struggle to take oral medications. At low doses (6 mg/24 h), the selegiline transdermal patch allows patients to disregard a dietary tyramine restriction because it avoids first-pass metabolism. It inhibits both MAO isomers in the brain but is only selective for MAO-B once concentrations are distributed to the liver. Higher doses require a tyramine-restricted diet because there is still some MAO-A inhibition in the gut. Selegiline is also stimulating because it is converted to amphetamine and methamphetamine.^{5,12,13,17,19,24}

Despite promising results from the use of MAOIs, physicians and patients may be reluctant to use these medications due to perceived limitations. One prominent barrier is the infamous “cheese reaction.” Tyramine, an amino acid found in certain food and beverages (Table 2^{5,13-18,25-28}), is broken down by MAO-A in the gut. When this enzyme is inhibited, higher concentrations of tyramine reach systemic circulation. Tyramine’s release of norepinephrine (which now cannot be broken down) can lead to a hypertensive crisis. Consequently, a tyramine-restricted diet is recommended for patients taking an MAOI. However, the common notion that cheese, wine, and beer must be avoided is false, because most of the dietary restrictions developed following the discovery of MAOIs are antiquated.^5,12,25-28 Patients who take an MAOI only need to slightly adjust their diet, as outlined in Table 2.^{5,13-18,25-28} A reasonable serving size of most foods and beverages containing tyramine is unlikely to elicit this “pressor” response. Of the 4 MAOIs FDA-approved for MDD, tranylcypromine appears to be the most sensitive to tyramine.²¹ Transient postdose hypertension (regardless of tyramine) may occur after taking an MAOI.²⁹ Encourage patients to monitor their blood pressure.

Continue to: Additional hurdles include...

Additional hurdles include the required washout period from serotonergic medications and interactions with sympathomimetics. MAOIs pose the highest risk of serotonin syndrome; however, this usually occurs if given concomitantly with other serotonergic agents. The standard recommendation is a 14-day washout period from SSRIs (5 weeks for fluoxetine and 3 weeks for vortioxetine), SNRIs, mirtazapine, and other antidepressants. It can be distressing for patients to be without medication during that period. Because some antidepressants have much shorter half-lives, waiting 5 half-lives (typically 5 to 7 days) for the discontinued medication to be excreted is feasible if patients are closely monitored.^{5,12,13,25,27,30} There are rare instances where a TCA may be combined with an MAOI (typically initiated within 1 to 2 days of each other), but never clomipramine or imipramine due to their potent serotonin reuptake inhibition.³¹ If switching to an alternative MAOI, waiting 7 to 14 days is recommended to allow adequate time for the inhibited enzyme to regenerate.^14-17,32 Taking medications that increase dopamine and norepinephrine (eg, stimulants or oral over-the-counter decongestants) with an MAOI is typically not recommended due to the risk of hypertensive crisis.^25,27 In severe TRD or comorbid ADHD, successful simultaneous use of methylphenidate or amphetamine—typically at low doses—with close blood pressure monitoring has been reported.³³ There have also been positive cases of the use of modafinil in combination with an MAOI; however, this should be done with caution.^34,35 Clinicians must use clinical judgment when considering a combination of medications that pose a higher risk.

Tricyclic antidepressants

TCAs work differently than MAOIs to increase monoamines. They inhibit presynaptic serotonin and norepinephrine transporters in the CNS to increase levels of these chemicals in the synaptic cleft. While all TCAs inhibit these transporters, they do so at varying levels (Table 3^36-51). Based on their chemical structure, TCAs can be categorized into secondary and tertiary amines. Tertiary amines are metabolized via demethylation into their derivatives (Table 3^36-51). Patients who have recently suffered a myocardial infarction (MI) should avoid tertiary amines. TCAs can reduce heart rate variability, which is already decreased after an MI, thus presenting the potential for cardiac arrhythmias. TCAs should also be avoided in patients with cardiac conduction abnormalities.^38-46,52 Patients with a prior baseline cardiac conduction defect, such as a bundle branch block, are at higher risk for further cardiac abnormalities. In those with a preexisting first-degree heart block, TCAs can still be used, but electrocardiogram monitoring is recommended.^52,53 TCAs have also been reported to decrease the seizure threshold.^38-46 They can be used with caution in patients who have a history of epilepsy or head trauma, or with concomitant medications that lower the seizure threshold.^38-46

Overdose risk is a concern with TCAs because ingestion of 10 to 20 mg/kg can lead to significant toxicity.⁵⁴ This is due to their blockage of voltage-gated sodium channels found in the CNS and heart, which contributes to overdose symptoms such as a widened QRS complex and seizures. Symptoms usually develop within 2 hours but may be delayed up to 6 hours.⁵⁵ Patients with a history of overdose must be carefully assessed before initiating a TCA. Prescribing a limited supply of these medications may be valuable. The use of TCAs has often been limited due to their adverse effects, most of which are associated with their respective affinities for alpha 1, muscarinic 1, and histamine 1 receptors. Inhibition of the alpha 1 receptor is associated with hypotension, muscarinic 1 with anticholinergic adverse effects, and histamine 1 with sedation and weight gain. Tertiary amines have a higher affinity for these receptors compared to secondary amines, leading to a more significant adverse effect profile.^36,50 Among TCAs, amitriptyline is the most likely to cause hypotension, whereas desipramine and nortriptyline are least likely. Amitriptyline and clomipramine are most likely to cause anticholinergic adverse effects, whereas desipramine and nortriptyline are the least likely. Amitriptyline, doxepin, and imipramine have the highest propensity for QTc prolongation.³⁶

Beyond treating MDD, TCAs have shown benefits for treating other disease states (Table 4^{38-46,49,56-61}).These differing indications may help psychiatrists determine the best TCA to prescribe for a given patient. Amitriptyline is the most studied TCA for MDD; however, nortriptyline is typically preferred due to its favorable tolerability profile.^4,62 Nortriptyline also has data supporting its use in ECT to prevent relapse.⁶³ Amitriptyline and nortriptyline have shown benefits in patients with neuro­pathic pain and for migraine prophylaxis.^56-60 Although frequently used for MDD, clomipramine is not FDA-approved for this indication, but is for obsessive-compulsive disorder.³⁹ Doxepin is FDA-approved for insomnia at lower doses and for MDD at higher doses.⁴⁰ Therefore, it may benefit patients with sleep difficulties secondary to depression. Desipramine has been used off-label to treat ADHD in children and has shown some benefits in adults.^64-66 Protriptyline, trimipramine, and amoxapine are infrequently used in clinical practice.

A unique feature of TCAs is the ability to monitor serum concentrations (Table 3^36-51).Guidelines recommend therapeutic drug monitoring (TDM) with amitriptyline, clomi­pramine, imipramine, and nortriptyline for routine use. TDM is still recommended for doxepin, desipramine, and trimipramine, but its utility is largely for treatment failure or resistance.³⁷ These plasma levels can be altered based on coadministered medications (Table 5^38-46) and should be closely monitored. Physicians should obtain a trough level after at least 5 half-lives and before the next dose is due, and use TDM as indicated to optimize dosing.

Continue to: CASE CONTINUED

CASE CONTINUED

Ms. B’s outpatient psychiatrist provides collateral information about her medical history and confirms her long-standing MDD with multiple medication trials, though she has never received an MAOI or TCA. Ms. B is adamant she does not want a medication-free period between treatments and refuses to adjust her diet, despite being educated on the few changes necessary. She has no contraindications for TCAs and may benefit from a TCA for her comorbid migraines. The care team expresses concern for TCA overdose to Ms. B and her family. Ms. B’s sister reassures the team they will have someone monitor and dispense her medications at home. They decide to discontinue her current psychiatric regimen, and Ms. B is started on nortriptyline 50 mg/d at night, with plans to titrate based on tolerability.

Related Resources

• Meyer JM. A concise guide to monoamine oxidase inhibitors. Current Psychiatry. 2017;16(12):14-16,18-23,47,A.
• Espejo GD. Treating major depressive disorder after limited response to an initial agent. Current Psychiatry. 2021;20(10):51-53. doi:10.12788/cp.0178
• American Association of Psychiatric Pharmacists (AAPP) MAOI Pharmacist Toolkit. https://aapp.org/guideline/maoi

Drug Brand Names

Amitriptyline • Elavil
Amphetamine • Adzenys, Dyanavel
Aripiprazole • Abilify
Clomipramine • Anafranil
Desipramine • Norpramin
Dextromethorphan/bupropion • Auvelity
Doxepin • Sinequan, Adapin
Esketamine • Spravato
Fluoxetine • Prozac
Imipramine • Tofranil
Isocarboxazid • Marplan
Methamphetamine • Desoxyn
Mirtazapine • Remeron
Modafinil • Provigil
Nortriptyline • Pamelor
Phenelzine • Nardil
Protriptyline • Vivactil
Selegiline • Emsam
Tranylcypromine • Parnate
Trimipramine • Surmontil
Vortioxetine • Trintellix

Ms. B, age 45, has a history of major depressive disorder (MDD) and migraines. She is admitted after presenting with anhedonia, hopelessness, and hypersomnia. These symptoms have become more severe over the last few weeks. Ms. B describes a past suicide attempt via overdose on doxylamine for which she required treatment in the intensive care unit. The only activity she enjoys is her weekly girls’ night, during which she drinks a few glasses of wine. Ms. B’s current medications are dextromethorphan/bupropion 45/105 mg twice daily and aripiprazole 5 mg/d, which she has taken for 3 months. She states she has “been on every antidepressant there is.”

When clinicians review Ms. B’s medication history, it is clear she has had adequate trials of selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), intranasal esketamine, multiple augmentation strategies, and electroconvulsive therapy (ECT). Ms. B seeks an alternative medication to improve her depressive symptoms.

Treatment-resistant depression (TRD) is commonly defined as depression that has not responded to ≥2 adequate trials of an antidepressant.¹ Some guidelines recommend monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants (TCAs) as second- or even third-line options for MDD,² while others recommend reserving them for patients with insufficient responses to alternative treatment modalities.^3,4 Although MAOIs and TCAs have been available since the 1950s, prescribing these medications has become less prevalent due to safety concerns, the availability of other pharmacologic options, and a lack of clinical training and comfort.^5,6 Most research notes that MAOIs are superior for treating atypical depression while TCAs are more effective for melancholic depression.^2-4 In a review of 20 studies, Thase et al⁷ found that 50% of TCA nonresponders benefited from an MAOI. In the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial, monotherapy with the MAOI tranylcypromine was associated with a lower remission rate than the TCA nortriptyline; many argue the dose of tranylcypromine was suboptimal, and few participants completed an adequate trial in the last level.^8,9 A more recent study by Kim et al¹⁰ found MAOIs to be “generally more effective” than TCAs for TRD, particularly in patients with fewer antidepressant trials; however, this was a small retrospective exploratory trial. A network meta-analysis found both classes to be “competitive” with SSRIs based on efficacy and tolerability, which leads to the question of whether these medications should be considered earlier in therapy.¹¹ Considering patient-specific factors and particular medication properties is an effective strategy when prescribing an MAOI or TCA.

Monoamine oxidase inhibitors

Four MAOIs are FDA-approved for treating MDD (Table 1^5,12-17): phenelzine, isocarboxazid, tranylcypromine, and selegiline. These medications irreversibly inhibit MAO, which exists as isomers A and B. MAO-A primarily metabolizes serotonin and norepinephrine, which is largely responsible for these medications’ antidepressant effects. Both isomers equally metabolize dopamine.^5,12,18 It is best to avoid using MAOIs in patients with cerebrovascular disease, hepatic disease, or pheochromocytoma. Patients with active substance use disorders (particularly sympathomimetics and hallucinogens) are at an increased risk for hypertensive crises and serotonin syndrome, respectively. The most common adverse effects are orthostatic hypotension (despite more well-known concerns regarding hypertension), alterations in sleep patterns (insomnia or hypersomnia, depending on the agent), gastrointestinal issues, and anticholinergic adverse effects such as dry mouth and constipation.^13,19-21

In one review and meta-analysis, phenelzine displayed the highest efficacy across all MAOIs.¹¹ It likely requires high doses to achieve adequate MAO inhibition.¹¹ A metabolite of phenelzine inhibits gamma-aminobutyric acid transaminase and may be helpful for patients with comorbid anxiety disorders or MDD with anxious distress.^18,21 Additional considerations include phenelzine’s propensity for orthostasis (with rapid titrations and higher doses), sedation, weight gain, sexual dysfunction, and a rare adverse effect of vitamin B6 deficiency.^{5,13,14,20-22}

Use of isocarboxazid in clinical practice is rare. Its adverse effects are similar to those of phenelzine but isocarboxazid is less studied. Tranylcypromine has a similar chemical structure to amphetamine. It can be stimulating at higher doses, potentially benefitting patients with comorbid attention-deficit/hyperactivity disorder (ADHD) or significant apathy.^13,23 Selegiline’s distinct quality is its availability as a transdermal patch, which may be useful for patients who struggle to take oral medications. At low doses (6 mg/24 h), the selegiline transdermal patch allows patients to disregard a dietary tyramine restriction because it avoids first-pass metabolism. It inhibits both MAO isomers in the brain but is only selective for MAO-B once concentrations are distributed to the liver. Higher doses require a tyramine-restricted diet because there is still some MAO-A inhibition in the gut. Selegiline is also stimulating because it is converted to amphetamine and methamphetamine.^{5,12,13,17,19,24}

Despite promising results from the use of MAOIs, physicians and patients may be reluctant to use these medications due to perceived limitations. One prominent barrier is the infamous “cheese reaction.” Tyramine, an amino acid found in certain food and beverages (Table 2^{5,13-18,25-28}), is broken down by MAO-A in the gut. When this enzyme is inhibited, higher concentrations of tyramine reach systemic circulation. Tyramine’s release of norepinephrine (which now cannot be broken down) can lead to a hypertensive crisis. Consequently, a tyramine-restricted diet is recommended for patients taking an MAOI. However, the common notion that cheese, wine, and beer must be avoided is false, because most of the dietary restrictions developed following the discovery of MAOIs are antiquated.^5,12,25-28 Patients who take an MAOI only need to slightly adjust their diet, as outlined in Table 2.^{5,13-18,25-28} A reasonable serving size of most foods and beverages containing tyramine is unlikely to elicit this “pressor” response. Of the 4 MAOIs FDA-approved for MDD, tranylcypromine appears to be the most sensitive to tyramine.²¹ Transient postdose hypertension (regardless of tyramine) may occur after taking an MAOI.²⁹ Encourage patients to monitor their blood pressure.

Continue to: Additional hurdles include...

Additional hurdles include the required washout period from serotonergic medications and interactions with sympathomimetics. MAOIs pose the highest risk of serotonin syndrome; however, this usually occurs if given concomitantly with other serotonergic agents. The standard recommendation is a 14-day washout period from SSRIs (5 weeks for fluoxetine and 3 weeks for vortioxetine), SNRIs, mirtazapine, and other antidepressants. It can be distressing for patients to be without medication during that period. Because some antidepressants have much shorter half-lives, waiting 5 half-lives (typically 5 to 7 days) for the discontinued medication to be excreted is feasible if patients are closely monitored.^{5,12,13,25,27,30} There are rare instances where a TCA may be combined with an MAOI (typically initiated within 1 to 2 days of each other), but never clomipramine or imipramine due to their potent serotonin reuptake inhibition.³¹ If switching to an alternative MAOI, waiting 7 to 14 days is recommended to allow adequate time for the inhibited enzyme to regenerate.^14-17,32 Taking medications that increase dopamine and norepinephrine (eg, stimulants or oral over-the-counter decongestants) with an MAOI is typically not recommended due to the risk of hypertensive crisis.^25,27 In severe TRD or comorbid ADHD, successful simultaneous use of methylphenidate or amphetamine—typically at low doses—with close blood pressure monitoring has been reported.³³ There have also been positive cases of the use of modafinil in combination with an MAOI; however, this should be done with caution.^34,35 Clinicians must use clinical judgment when considering a combination of medications that pose a higher risk.

Tricyclic antidepressants

TCAs work differently than MAOIs to increase monoamines. They inhibit presynaptic serotonin and norepinephrine transporters in the CNS to increase levels of these chemicals in the synaptic cleft. While all TCAs inhibit these transporters, they do so at varying levels (Table 3^36-51). Based on their chemical structure, TCAs can be categorized into secondary and tertiary amines. Tertiary amines are metabolized via demethylation into their derivatives (Table 3^36-51). Patients who have recently suffered a myocardial infarction (MI) should avoid tertiary amines. TCAs can reduce heart rate variability, which is already decreased after an MI, thus presenting the potential for cardiac arrhythmias. TCAs should also be avoided in patients with cardiac conduction abnormalities.^38-46,52 Patients with a prior baseline cardiac conduction defect, such as a bundle branch block, are at higher risk for further cardiac abnormalities. In those with a preexisting first-degree heart block, TCAs can still be used, but electrocardiogram monitoring is recommended.^52,53 TCAs have also been reported to decrease the seizure threshold.^38-46 They can be used with caution in patients who have a history of epilepsy or head trauma, or with concomitant medications that lower the seizure threshold.^38-46

Overdose risk is a concern with TCAs because ingestion of 10 to 20 mg/kg can lead to significant toxicity.⁵⁴ This is due to their blockage of voltage-gated sodium channels found in the CNS and heart, which contributes to overdose symptoms such as a widened QRS complex and seizures. Symptoms usually develop within 2 hours but may be delayed up to 6 hours.⁵⁵ Patients with a history of overdose must be carefully assessed before initiating a TCA. Prescribing a limited supply of these medications may be valuable. The use of TCAs has often been limited due to their adverse effects, most of which are associated with their respective affinities for alpha 1, muscarinic 1, and histamine 1 receptors. Inhibition of the alpha 1 receptor is associated with hypotension, muscarinic 1 with anticholinergic adverse effects, and histamine 1 with sedation and weight gain. Tertiary amines have a higher affinity for these receptors compared to secondary amines, leading to a more significant adverse effect profile.^36,50 Among TCAs, amitriptyline is the most likely to cause hypotension, whereas desipramine and nortriptyline are least likely. Amitriptyline and clomipramine are most likely to cause anticholinergic adverse effects, whereas desipramine and nortriptyline are the least likely. Amitriptyline, doxepin, and imipramine have the highest propensity for QTc prolongation.³⁶

Beyond treating MDD, TCAs have shown benefits for treating other disease states (Table 4^{38-46,49,56-61}).These differing indications may help psychiatrists determine the best TCA to prescribe for a given patient. Amitriptyline is the most studied TCA for MDD; however, nortriptyline is typically preferred due to its favorable tolerability profile.^4,62 Nortriptyline also has data supporting its use in ECT to prevent relapse.⁶³ Amitriptyline and nortriptyline have shown benefits in patients with neuro­pathic pain and for migraine prophylaxis.^56-60 Although frequently used for MDD, clomipramine is not FDA-approved for this indication, but is for obsessive-compulsive disorder.³⁹ Doxepin is FDA-approved for insomnia at lower doses and for MDD at higher doses.⁴⁰ Therefore, it may benefit patients with sleep difficulties secondary to depression. Desipramine has been used off-label to treat ADHD in children and has shown some benefits in adults.^64-66 Protriptyline, trimipramine, and amoxapine are infrequently used in clinical practice.

A unique feature of TCAs is the ability to monitor serum concentrations (Table 3^36-51).Guidelines recommend therapeutic drug monitoring (TDM) with amitriptyline, clomi­pramine, imipramine, and nortriptyline for routine use. TDM is still recommended for doxepin, desipramine, and trimipramine, but its utility is largely for treatment failure or resistance.³⁷ These plasma levels can be altered based on coadministered medications (Table 5^38-46) and should be closely monitored. Physicians should obtain a trough level after at least 5 half-lives and before the next dose is due, and use TDM as indicated to optimize dosing.

Continue to: CASE CONTINUED

CASE CONTINUED

Ms. B’s outpatient psychiatrist provides collateral information about her medical history and confirms her long-standing MDD with multiple medication trials, though she has never received an MAOI or TCA. Ms. B is adamant she does not want a medication-free period between treatments and refuses to adjust her diet, despite being educated on the few changes necessary. She has no contraindications for TCAs and may benefit from a TCA for her comorbid migraines. The care team expresses concern for TCA overdose to Ms. B and her family. Ms. B’s sister reassures the team they will have someone monitor and dispense her medications at home. They decide to discontinue her current psychiatric regimen, and Ms. B is started on nortriptyline 50 mg/d at night, with plans to titrate based on tolerability.

Related Resources

• Meyer JM. A concise guide to monoamine oxidase inhibitors. Current Psychiatry. 2017;16(12):14-16,18-23,47,A.
• Espejo GD. Treating major depressive disorder after limited response to an initial agent. Current Psychiatry. 2021;20(10):51-53. doi:10.12788/cp.0178
• American Association of Psychiatric Pharmacists (AAPP) MAOI Pharmacist Toolkit. https://aapp.org/guideline/maoi

Drug Brand Names

Amitriptyline • Elavil
Amphetamine • Adzenys, Dyanavel
Aripiprazole • Abilify
Clomipramine • Anafranil
Desipramine • Norpramin
Dextromethorphan/bupropion • Auvelity
Doxepin • Sinequan, Adapin
Esketamine • Spravato
Fluoxetine • Prozac
Imipramine • Tofranil
Isocarboxazid • Marplan
Methamphetamine • Desoxyn
Mirtazapine • Remeron
Modafinil • Provigil
Nortriptyline • Pamelor
Phenelzine • Nardil
Protriptyline • Vivactil
Selegiline • Emsam
Tranylcypromine • Parnate
Trimipramine • Surmontil
Vortioxetine • Trintellix

Ms. B, age 45, has a history of major depressive disorder (MDD) and migraines. She is admitted after presenting with anhedonia, hopelessness, and hypersomnia. These symptoms have become more severe over the last few weeks. Ms. B describes a past suicide attempt via overdose on doxylamine for which she required treatment in the intensive care unit. The only activity she enjoys is her weekly girls’ night, during which she drinks a few glasses of wine. Ms. B’s current medications are dextromethorphan/bupropion 45/105 mg twice daily and aripiprazole 5 mg/d, which she has taken for 3 months. She states she has “been on every antidepressant there is.”

When clinicians review Ms. B’s medication history, it is clear she has had adequate trials of selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), intranasal esketamine, multiple augmentation strategies, and electroconvulsive therapy (ECT). Ms. B seeks an alternative medication to improve her depressive symptoms.

Treatment-resistant depression (TRD) is commonly defined as depression that has not responded to ≥2 adequate trials of an antidepressant.¹ Some guidelines recommend monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants (TCAs) as second- or even third-line options for MDD,² while others recommend reserving them for patients with insufficient responses to alternative treatment modalities.^3,4 Although MAOIs and TCAs have been available since the 1950s, prescribing these medications has become less prevalent due to safety concerns, the availability of other pharmacologic options, and a lack of clinical training and comfort.^5,6 Most research notes that MAOIs are superior for treating atypical depression while TCAs are more effective for melancholic depression.^2-4 In a review of 20 studies, Thase et al⁷ found that 50% of TCA nonresponders benefited from an MAOI. In the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial, monotherapy with the MAOI tranylcypromine was associated with a lower remission rate than the TCA nortriptyline; many argue the dose of tranylcypromine was suboptimal, and few participants completed an adequate trial in the last level.^8,9 A more recent study by Kim et al¹⁰ found MAOIs to be “generally more effective” than TCAs for TRD, particularly in patients with fewer antidepressant trials; however, this was a small retrospective exploratory trial. A network meta-analysis found both classes to be “competitive” with SSRIs based on efficacy and tolerability, which leads to the question of whether these medications should be considered earlier in therapy.¹¹ Considering patient-specific factors and particular medication properties is an effective strategy when prescribing an MAOI or TCA.

Monoamine oxidase inhibitors

Four MAOIs are FDA-approved for treating MDD (Table 1^5,12-17): phenelzine, isocarboxazid, tranylcypromine, and selegiline. These medications irreversibly inhibit MAO, which exists as isomers A and B. MAO-A primarily metabolizes serotonin and norepinephrine, which is largely responsible for these medications’ antidepressant effects. Both isomers equally metabolize dopamine.^5,12,18 It is best to avoid using MAOIs in patients with cerebrovascular disease, hepatic disease, or pheochromocytoma. Patients with active substance use disorders (particularly sympathomimetics and hallucinogens) are at an increased risk for hypertensive crises and serotonin syndrome, respectively. The most common adverse effects are orthostatic hypotension (despite more well-known concerns regarding hypertension), alterations in sleep patterns (insomnia or hypersomnia, depending on the agent), gastrointestinal issues, and anticholinergic adverse effects such as dry mouth and constipation.^13,19-21

In one review and meta-analysis, phenelzine displayed the highest efficacy across all MAOIs.¹¹ It likely requires high doses to achieve adequate MAO inhibition.¹¹ A metabolite of phenelzine inhibits gamma-aminobutyric acid transaminase and may be helpful for patients with comorbid anxiety disorders or MDD with anxious distress.^18,21 Additional considerations include phenelzine’s propensity for orthostasis (with rapid titrations and higher doses), sedation, weight gain, sexual dysfunction, and a rare adverse effect of vitamin B6 deficiency.^{5,13,14,20-22}

Use of isocarboxazid in clinical practice is rare. Its adverse effects are similar to those of phenelzine but isocarboxazid is less studied. Tranylcypromine has a similar chemical structure to amphetamine. It can be stimulating at higher doses, potentially benefitting patients with comorbid attention-deficit/hyperactivity disorder (ADHD) or significant apathy.^13,23 Selegiline’s distinct quality is its availability as a transdermal patch, which may be useful for patients who struggle to take oral medications. At low doses (6 mg/24 h), the selegiline transdermal patch allows patients to disregard a dietary tyramine restriction because it avoids first-pass metabolism. It inhibits both MAO isomers in the brain but is only selective for MAO-B once concentrations are distributed to the liver. Higher doses require a tyramine-restricted diet because there is still some MAO-A inhibition in the gut. Selegiline is also stimulating because it is converted to amphetamine and methamphetamine.^{5,12,13,17,19,24}

Despite promising results from the use of MAOIs, physicians and patients may be reluctant to use these medications due to perceived limitations. One prominent barrier is the infamous “cheese reaction.” Tyramine, an amino acid found in certain food and beverages (Table 2^{5,13-18,25-28}), is broken down by MAO-A in the gut. When this enzyme is inhibited, higher concentrations of tyramine reach systemic circulation. Tyramine’s release of norepinephrine (which now cannot be broken down) can lead to a hypertensive crisis. Consequently, a tyramine-restricted diet is recommended for patients taking an MAOI. However, the common notion that cheese, wine, and beer must be avoided is false, because most of the dietary restrictions developed following the discovery of MAOIs are antiquated.^5,12,25-28 Patients who take an MAOI only need to slightly adjust their diet, as outlined in Table 2.^{5,13-18,25-28} A reasonable serving size of most foods and beverages containing tyramine is unlikely to elicit this “pressor” response. Of the 4 MAOIs FDA-approved for MDD, tranylcypromine appears to be the most sensitive to tyramine.²¹ Transient postdose hypertension (regardless of tyramine) may occur after taking an MAOI.²⁹ Encourage patients to monitor their blood pressure.

Continue to: Additional hurdles include...

Additional hurdles include the required washout period from serotonergic medications and interactions with sympathomimetics. MAOIs pose the highest risk of serotonin syndrome; however, this usually occurs if given concomitantly with other serotonergic agents. The standard recommendation is a 14-day washout period from SSRIs (5 weeks for fluoxetine and 3 weeks for vortioxetine), SNRIs, mirtazapine, and other antidepressants. It can be distressing for patients to be without medication during that period. Because some antidepressants have much shorter half-lives, waiting 5 half-lives (typically 5 to 7 days) for the discontinued medication to be excreted is feasible if patients are closely monitored.^{5,12,13,25,27,30} There are rare instances where a TCA may be combined with an MAOI (typically initiated within 1 to 2 days of each other), but never clomipramine or imipramine due to their potent serotonin reuptake inhibition.³¹ If switching to an alternative MAOI, waiting 7 to 14 days is recommended to allow adequate time for the inhibited enzyme to regenerate.^14-17,32 Taking medications that increase dopamine and norepinephrine (eg, stimulants or oral over-the-counter decongestants) with an MAOI is typically not recommended due to the risk of hypertensive crisis.^25,27 In severe TRD or comorbid ADHD, successful simultaneous use of methylphenidate or amphetamine—typically at low doses—with close blood pressure monitoring has been reported.³³ There have also been positive cases of the use of modafinil in combination with an MAOI; however, this should be done with caution.^34,35 Clinicians must use clinical judgment when considering a combination of medications that pose a higher risk.

Tricyclic antidepressants

TCAs work differently than MAOIs to increase monoamines. They inhibit presynaptic serotonin and norepinephrine transporters in the CNS to increase levels of these chemicals in the synaptic cleft. While all TCAs inhibit these transporters, they do so at varying levels (Table 3^36-51). Based on their chemical structure, TCAs can be categorized into secondary and tertiary amines. Tertiary amines are metabolized via demethylation into their derivatives (Table 3^36-51). Patients who have recently suffered a myocardial infarction (MI) should avoid tertiary amines. TCAs can reduce heart rate variability, which is already decreased after an MI, thus presenting the potential for cardiac arrhythmias. TCAs should also be avoided in patients with cardiac conduction abnormalities.^38-46,52 Patients with a prior baseline cardiac conduction defect, such as a bundle branch block, are at higher risk for further cardiac abnormalities. In those with a preexisting first-degree heart block, TCAs can still be used, but electrocardiogram monitoring is recommended.^52,53 TCAs have also been reported to decrease the seizure threshold.^38-46 They can be used with caution in patients who have a history of epilepsy or head trauma, or with concomitant medications that lower the seizure threshold.^38-46

Overdose risk is a concern with TCAs because ingestion of 10 to 20 mg/kg can lead to significant toxicity.⁵⁴ This is due to their blockage of voltage-gated sodium channels found in the CNS and heart, which contributes to overdose symptoms such as a widened QRS complex and seizures. Symptoms usually develop within 2 hours but may be delayed up to 6 hours.⁵⁵ Patients with a history of overdose must be carefully assessed before initiating a TCA. Prescribing a limited supply of these medications may be valuable. The use of TCAs has often been limited due to their adverse effects, most of which are associated with their respective affinities for alpha 1, muscarinic 1, and histamine 1 receptors. Inhibition of the alpha 1 receptor is associated with hypotension, muscarinic 1 with anticholinergic adverse effects, and histamine 1 with sedation and weight gain. Tertiary amines have a higher affinity for these receptors compared to secondary amines, leading to a more significant adverse effect profile.^36,50 Among TCAs, amitriptyline is the most likely to cause hypotension, whereas desipramine and nortriptyline are least likely. Amitriptyline and clomipramine are most likely to cause anticholinergic adverse effects, whereas desipramine and nortriptyline are the least likely. Amitriptyline, doxepin, and imipramine have the highest propensity for QTc prolongation.³⁶

Beyond treating MDD, TCAs have shown benefits for treating other disease states (Table 4^{38-46,49,56-61}).These differing indications may help psychiatrists determine the best TCA to prescribe for a given patient. Amitriptyline is the most studied TCA for MDD; however, nortriptyline is typically preferred due to its favorable tolerability profile.^4,62 Nortriptyline also has data supporting its use in ECT to prevent relapse.⁶³ Amitriptyline and nortriptyline have shown benefits in patients with neuro­pathic pain and for migraine prophylaxis.^56-60 Although frequently used for MDD, clomipramine is not FDA-approved for this indication, but is for obsessive-compulsive disorder.³⁹ Doxepin is FDA-approved for insomnia at lower doses and for MDD at higher doses.⁴⁰ Therefore, it may benefit patients with sleep difficulties secondary to depression. Desipramine has been used off-label to treat ADHD in children and has shown some benefits in adults.^64-66 Protriptyline, trimipramine, and amoxapine are infrequently used in clinical practice.

A unique feature of TCAs is the ability to monitor serum concentrations (Table 3^36-51).Guidelines recommend therapeutic drug monitoring (TDM) with amitriptyline, clomi­pramine, imipramine, and nortriptyline for routine use. TDM is still recommended for doxepin, desipramine, and trimipramine, but its utility is largely for treatment failure or resistance.³⁷ These plasma levels can be altered based on coadministered medications (Table 5^38-46) and should be closely monitored. Physicians should obtain a trough level after at least 5 half-lives and before the next dose is due, and use TDM as indicated to optimize dosing.

Continue to: CASE CONTINUED

CASE CONTINUED

Ms. B’s outpatient psychiatrist provides collateral information about her medical history and confirms her long-standing MDD with multiple medication trials, though she has never received an MAOI or TCA. Ms. B is adamant she does not want a medication-free period between treatments and refuses to adjust her diet, despite being educated on the few changes necessary. She has no contraindications for TCAs and may benefit from a TCA for her comorbid migraines. The care team expresses concern for TCA overdose to Ms. B and her family. Ms. B’s sister reassures the team they will have someone monitor and dispense her medications at home. They decide to discontinue her current psychiatric regimen, and Ms. B is started on nortriptyline 50 mg/d at night, with plans to titrate based on tolerability.

Related Resources

• Meyer JM. A concise guide to monoamine oxidase inhibitors. Current Psychiatry. 2017;16(12):14-16,18-23,47,A.
• Espejo GD. Treating major depressive disorder after limited response to an initial agent. Current Psychiatry. 2021;20(10):51-53. doi:10.12788/cp.0178
• American Association of Psychiatric Pharmacists (AAPP) MAOI Pharmacist Toolkit. https://aapp.org/guideline/maoi

Drug Brand Names

Amitriptyline • Elavil
Amphetamine • Adzenys, Dyanavel
Aripiprazole • Abilify
Clomipramine • Anafranil
Desipramine • Norpramin
Dextromethorphan/bupropion • Auvelity
Doxepin • Sinequan, Adapin
Esketamine • Spravato
Fluoxetine • Prozac
Imipramine • Tofranil
Isocarboxazid • Marplan
Methamphetamine • Desoxyn
Mirtazapine • Remeron
Modafinil • Provigil
Nortriptyline • Pamelor
Phenelzine • Nardil
Protriptyline • Vivactil
Selegiline • Emsam
Tranylcypromine • Parnate
Trimipramine • Surmontil
Vortioxetine • Trintellix

CASE Thoughts of harming baby

Ms. A, age 37, is G4P2, 4 months postpartum, and breastfeeding. She has major depressive disorder (MDD) with peripartum onset, posttraumatic stress disorder, and mild intellectual disability. For years she has been stable on fluoxetine 40 mg/d and prazosin 2 mg/d. Despite recent titration of her medications, at her most recent outpatient appointment Ms. A reports having a depressed mood with frequent crying, insomnia, a lack of desire to bond with her baby, and feelings of shame. She also says she has had auditory hallucinations and thoughts of harming her baby. Ms. A’s outpatient physician makes an urgent request for her to be evaluated at the psychiatric emergency department (ED).

HISTORY Depression and possible auditory hallucinations

Ms. A developed MDD following the birth of her first child, for which her care team initiated fluoxetine at 20 mg/d and titrated it to 40 mg/d,which was effective. At that time, her outpatient physician documented potential psychotic features, including vague descriptions of derogatory auditory hallucinations. However, it was unclear if these auditory hallucinations were more representative of a distressing inner monologue without the quality of an external voice. The team determined that Ms. A was not at acute risk for harm to herself or her baby and was appropriate for outpatient care. Because the nature of these possible auditory hallucinations was mild, nondistressing, and nonthreatening, the treatment team did not initiate an antipsychotic and Ms. A was not hospitalized. She has no history of hypomanic/manic episodes and has never met criteria for a psychotic disorder.

EVALUATION Distressing thoughts and discontinued medications

During the evaluation by psychiatric emergency services, Ms. A reports that 2 weeks after giving birth she experienced a worsening of her depressive symptoms. She says she began hearing voices telling her to harm herself and her baby and describes frequent distressing thoughts, such as stabbing her baby with a knife and running over her baby with a car. Ms. A says she repeatedly wakes up at night to check on her baby’s breathing, overfeeds her baby due to a fear of inadequate nutrition, and notes intermittent feelings of confusion. Afraid of being alone with her infant, Ms. A asks her partner and mother to move in with her. Additionally, she says 2 weeks ago she discontinued all her medications at the suggestion of her partner, who recommended herbal supplements. Ms. A’s initial routine laboratory results are unremarkable and her urine drug screen is negative for all substances.

[polldaddy:13041928]

The authors’ observations

Approximately 85% of birthing parents experience some form of postpartum mood disturbance; 10% to 15% develop more significant symptoms of anxiety or depression.³ The etiology of postpartum illness is multifactorial, and includes psychiatric personal/family history, insomnia, acute and chronic psychosocial stressors, and rapid hormone fluctuations.¹ As a result, the postpartum period represents a vulnerable time for birthing parents, particularly those with previously established psychiatric illness.

Ms. A’s initial presentation was concerning for a possible diagnosis of postpartum psychosis vs obsessive-compulsive disorder (OCD) with postpartum onset; other differential diagnoses included MDD with peripartum onset and psychotic features (Table^1-6). Ms. A’s subjective clinical history was significant for critical pertinent findings of both OCD with postpartum onset (ie, egodystonic intrusive thoughts, checking behaviors, feelings of shame, and seeking reassurance) and postpartum psychosis (ie, command auditory hallucinations and waxing/waning confusion), which added to diagnostic complexity.

Although postpartum psychosis is rare (1 to 2 cases per 1,000 women),⁵ it is considered a psychiatric emergency because it has significant potential for infanticide, morbidity, and mortality. Most symptoms develop within the first 2 weeks of the postpartum period.² There are many risk factors for the development of postpartum psychosis; however, in first-time pregnancies, a previous diagnosis of BD I is the single most important risk factor.¹ Approximately 20% to 30% of women with BD experience postpartum psychosis.⁴

For many patients (approximately 56.7%, according to 1 meta-analysis⁷), postpartum psychosis denotes an episode of BD, representing a more severe form of illness with increased risk of recurrence. Most manic or mixed mood episodes reoccur within the first year removed from the perinatal period. In contrast, for some patients (approximately 43.5% according to the same meta-analysis), the episode denotes “isolated postpartum psychosis.”⁷ Isolated postpartum psychosis is a psychotic episode that occurs only in the postpartum period with no recurrence of psychosis or recurrence of psychosis exclusive to postpartum periods. If treated, this type of postpartum psychosis has a more favorable prognosis than postpartum psychosis in a patient with BD.⁷ As such, a BD diagnosis should not be established at the onset of a patient’s first postpartum psychosis presentation. Regardless of type, all presentations of postpartum psychosis are considered a psychiatry emergency.

Continue to: The prevalence of OCD...

The prevalence of OCD with postpartum onset varies. One study estimated it occurs in 2.43% of cases.⁴ However, the true prevalence is likely underreported due to feelings of guilt or shame associated with intrusive thoughts, and fear of stigmatization and separation from the baby. Approximately 70.6% of women experiencing OCD with postpartum onset have a comorbid depressive disorder.⁴

Ms. A’s presentation to the psychiatric ED carried with it diagnostic complexity and uncertainty. Her initial presentation was concerning for elements of both postpartum psychosis and OCD with postpartum onset. After her evaluation in the psychiatric ED, there remained a lack of clear and convincing evidence for a diagnosis of OCD with postpartum onset, which eliminated the possibility of discharging Ms. A with robust safety planning and reinitiation of a selective serotonin reuptake inhibitor.

Additionally, because auditory hallucinations are atypical in OCD, the treatment team remained concerned for a diagnosis of postpartum psychosis, which would warrant hospitalization. With assistance from the institution’s reproductive psychiatrists, the treatment team discussed the importance of inpatient hospitalization for risk mitigation, close observation, and thorough evaluation for greater diagnostic clarity and certainty.

TREATMENT Involuntary hospitalization

The treatment team counsels Ms. A and her partner on her differential diagnoses, including the elevated acute risk of harm to herself and her baby if she has postpartum psychosis, as well as the need for continued observation and evaluation. When alone with a clinician, Ms. A says she understands and agrees to voluntary hospitalization. However, following a subsequent risk-benefit discussion with her partner, they both grew increasingly concerned about her separation from the baby and reinitiating her medications. Amid these concerns, the treatment team notices that Ms. A attempts to minimize her symptoms. Ms. A changes her mind and no longer consents to hospitalization. She is placed on a psychiatric hold for involuntary hospitalization on the psychiatric inpatient unit.

On the inpatient unit, the inpatient clinicians and a reproductive psychiatrist continue to evaluate Ms. A. Though her diagnosis remains unclear, Ms. A agrees to start a trial of quetiapine 100 mg/d titrated to 150 mg/d to manage her potential postpartum psychosis, depressed mood, insomnia (off-label), anxiety (off-label), and OCD (off-label). Lithium is deferred because Ms. A is breastfeeding.

[polldaddy:13041932]

Continue to: The authors' observations

Due to an elevated acute risk of suicide and infanticide, postpartum psychosis represents a psychiatric emergency and often requires hospitalization. The Figure outlines steps in evaluating a patient with concerns for postpartum psychosis in a psychiatric emergency service setting. Due to the waxing and waning nature of symptoms, patients may appear psychiatrically stable at any time but remain at an overall elevated acute risk of harm to self and/or their baby.

If a patient is being considered for discharge based on yes answers to all questions in Step 2 of the Figure, the emergency psychiatric clinician must initiate appropriate psychotropic medications and complete robust safety planning with the patient and a trusted adult who will provide direct supervision. Safety planning may include (but is not limited to) strict return precautions, education on concerning symptoms and behaviors, psychotropic education and agreement of compliance, and detailed instructions on outpatient follow-up within 1 week. Ideally—and as was the case for Ms. A—a reproductive psychiatrist should be consulted in the emergency setting for shared decision-making on admission vs discharge, medication management, and outpatient follow-up considerations.

Because postpartum psychosis carries significant risks and hospitalization generally results in separating the patient from their baby, initiating psychotropics should not be delayed. Clinicians must consider the patient’s psychiatric history, allergies, and breastfeeding status.

Based on current evidence, first-line treatment for postpartum psychosis includes a mood stabilizer, an antipsychotic, and possibly a benzodiazepine.⁶ Thus, an appropriate initial treatment regimen would be a benzodiazepine (particularly lorazepam due to its relatively shorter half-life) and an antipsychotic (eg, haloperidol, olanzapine, or quetiapine) for acute psychosis, plus lithium for mood stabilization.^1,5

If the postpartum psychosis represents an episode of BD, use of a long-term mood stabilizer may be required. In contrast, for isolated postpartum psychosis, clinicians may consider initiating psychotropics only in the immediate postpartum period, with an eventual slow taper. In future pregnancies, psychotropics may be reintroduced postpartum, which will avoid peripartum fetal exposure.⁸ If the patient is breastfeeding, lithium may be deferred in an acute care setting. For patients with evidence of catatonia, severe suicidality, refusal of oral intake with compromised nutrition, severe agitation, or treatment resistance, electro­convulsive therapy remains a safe and effective treatment option.⁶ Additionally, the safety of continued breastfeeding in acute psychosis must be considered, with the potential for recommending discontinuation, which would decrease sleep disruptions at night and increase the ability of others to feed the baby. Comprehensive care requires nonpharmacologic interventions, including psychoeducation for the patient and their family, individual psychotherapy, and expansion of psychosocial supports.

Continue to: Patients who have experienced...

Patients who have experienced an episode of postpartum psychosis are predisposed to another episode in future pregnancies.¹ Current research recommends prophylaxis of recurrence with lithium monotherapy.^1,2,5,6 Similar to other psychotropics in reproductive psychiatry, maintenance therapy on lithium requires a thorough “risk vs risk” discussion with the patient. The risk of lithium use while pregnant and/or breastfeeding must be weighed against the risks associated with postpartum psychosis (ie, infanticide, suicide, poor peripartum care, or poor infant bonding).

OUTCOME Improved mood

After 7 days of inpatient treatment with quetiapine, Ms. A demonstrates improvement in the targeted depressive symptoms (including improved motivation/energy and insomnia, decreased feelings of guilt, and denial of ongoing suicidal ideation). Additionally, the thoughts of harming her baby are less frequent, and command auditory hallucinations resolve. Upon discharge, Ms. A and her partner meet with inpatient clinicians for continued counseling, safety planning, and plans for outpatient follow-up with the institution’s reproductive psychiatrist.

The authors’ observations

Many aspects of Ms. A’s initial presentation in the psychiatric ED were challenging. Given the presence of symptoms of both psychosis and OCD, a diagnosis was difficult to ascertain in the emergency setting. Since command auditory hallucinations are atypical in patients with postpartum OCD, the treatment team maintained high suspicion for postpartum psychosis, which represented an emergency requiring inpatient care.

Hospitalization separated Ms. A from her baby, for whom she was the primary caregiver. Additional considerations for inpatient admission and psychotropic initiation were necessary, because Ms. A was breastfeeding. Although Ms. A’s partner was able to provide full-time childcare, the patient ultimately did not agree to hospitalization and required an emergency hold for involuntary admission, which was an additional barrier to care. Furthermore, her partner held unfavorable beliefs regarding psychotropic medications and Ms. A’s need for hospital admission, which required ongoing patient and partner education in the emergency, inpatient, and outpatient settings. Moreover, if Ms. A’s symptoms were ultimately attributable to postpartum OCD, the patient’s involuntary hospitalization might have increased the risk of stigmatization of mental illness and treatment with psychotropics.

Bottom Line

The peripartum period is a vulnerable time for patients, particularly those with previously diagnosed psychiatric illnesses. Postpartum psychosis is the most severe form of postpartum psychiatric illness and often represents an episode of bipolar disorder. Due to an elevated acute risk of suicide and infanticide, postpartum psychosis is a psychiatric emergency and warrants inpatient hospitalization for immediate intervention.

Related Resources

• Sharma V. Does your patient have postpartum OCD? Current Psychiatry. 2019;18(5):9-10.
• Hatters Friedman S, Prakash C, Nagel-Yang S. Postpartum psychosis: protecting mother and infant. Current Psychiatry. 2019;18(4):12-21.

Drug Brand Names

Fluoxetine • Prozac
Haloperidol • Haldol
Lithium • Eskalith, Lithobid
Lorazepam • Ativan
Olanzapine • Zyprexa
Prazosin • Minipress
Quetiapine • Seroquel
Sertraline • Zoloft
Valproic acid • Depakene

CASE Thoughts of harming baby

Ms. A, age 37, is G4P2, 4 months postpartum, and breastfeeding. She has major depressive disorder (MDD) with peripartum onset, posttraumatic stress disorder, and mild intellectual disability. For years she has been stable on fluoxetine 40 mg/d and prazosin 2 mg/d. Despite recent titration of her medications, at her most recent outpatient appointment Ms. A reports having a depressed mood with frequent crying, insomnia, a lack of desire to bond with her baby, and feelings of shame. She also says she has had auditory hallucinations and thoughts of harming her baby. Ms. A’s outpatient physician makes an urgent request for her to be evaluated at the psychiatric emergency department (ED).

HISTORY Depression and possible auditory hallucinations

Ms. A developed MDD following the birth of her first child, for which her care team initiated fluoxetine at 20 mg/d and titrated it to 40 mg/d,which was effective. At that time, her outpatient physician documented potential psychotic features, including vague descriptions of derogatory auditory hallucinations. However, it was unclear if these auditory hallucinations were more representative of a distressing inner monologue without the quality of an external voice. The team determined that Ms. A was not at acute risk for harm to herself or her baby and was appropriate for outpatient care. Because the nature of these possible auditory hallucinations was mild, nondistressing, and nonthreatening, the treatment team did not initiate an antipsychotic and Ms. A was not hospitalized. She has no history of hypomanic/manic episodes and has never met criteria for a psychotic disorder.

EVALUATION Distressing thoughts and discontinued medications

During the evaluation by psychiatric emergency services, Ms. A reports that 2 weeks after giving birth she experienced a worsening of her depressive symptoms. She says she began hearing voices telling her to harm herself and her baby and describes frequent distressing thoughts, such as stabbing her baby with a knife and running over her baby with a car. Ms. A says she repeatedly wakes up at night to check on her baby’s breathing, overfeeds her baby due to a fear of inadequate nutrition, and notes intermittent feelings of confusion. Afraid of being alone with her infant, Ms. A asks her partner and mother to move in with her. Additionally, she says 2 weeks ago she discontinued all her medications at the suggestion of her partner, who recommended herbal supplements. Ms. A’s initial routine laboratory results are unremarkable and her urine drug screen is negative for all substances.

[polldaddy:13041928]

The authors’ observations

Approximately 85% of birthing parents experience some form of postpartum mood disturbance; 10% to 15% develop more significant symptoms of anxiety or depression.³ The etiology of postpartum illness is multifactorial, and includes psychiatric personal/family history, insomnia, acute and chronic psychosocial stressors, and rapid hormone fluctuations.¹ As a result, the postpartum period represents a vulnerable time for birthing parents, particularly those with previously established psychiatric illness.

Ms. A’s initial presentation was concerning for a possible diagnosis of postpartum psychosis vs obsessive-compulsive disorder (OCD) with postpartum onset; other differential diagnoses included MDD with peripartum onset and psychotic features (Table^1-6). Ms. A’s subjective clinical history was significant for critical pertinent findings of both OCD with postpartum onset (ie, egodystonic intrusive thoughts, checking behaviors, feelings of shame, and seeking reassurance) and postpartum psychosis (ie, command auditory hallucinations and waxing/waning confusion), which added to diagnostic complexity.

Although postpartum psychosis is rare (1 to 2 cases per 1,000 women),⁵ it is considered a psychiatric emergency because it has significant potential for infanticide, morbidity, and mortality. Most symptoms develop within the first 2 weeks of the postpartum period.² There are many risk factors for the development of postpartum psychosis; however, in first-time pregnancies, a previous diagnosis of BD I is the single most important risk factor.¹ Approximately 20% to 30% of women with BD experience postpartum psychosis.⁴

For many patients (approximately 56.7%, according to 1 meta-analysis⁷), postpartum psychosis denotes an episode of BD, representing a more severe form of illness with increased risk of recurrence. Most manic or mixed mood episodes reoccur within the first year removed from the perinatal period. In contrast, for some patients (approximately 43.5% according to the same meta-analysis), the episode denotes “isolated postpartum psychosis.”⁷ Isolated postpartum psychosis is a psychotic episode that occurs only in the postpartum period with no recurrence of psychosis or recurrence of psychosis exclusive to postpartum periods. If treated, this type of postpartum psychosis has a more favorable prognosis than postpartum psychosis in a patient with BD.⁷ As such, a BD diagnosis should not be established at the onset of a patient’s first postpartum psychosis presentation. Regardless of type, all presentations of postpartum psychosis are considered a psychiatry emergency.

Continue to: The prevalence of OCD...

The prevalence of OCD with postpartum onset varies. One study estimated it occurs in 2.43% of cases.⁴ However, the true prevalence is likely underreported due to feelings of guilt or shame associated with intrusive thoughts, and fear of stigmatization and separation from the baby. Approximately 70.6% of women experiencing OCD with postpartum onset have a comorbid depressive disorder.⁴

Ms. A’s presentation to the psychiatric ED carried with it diagnostic complexity and uncertainty. Her initial presentation was concerning for elements of both postpartum psychosis and OCD with postpartum onset. After her evaluation in the psychiatric ED, there remained a lack of clear and convincing evidence for a diagnosis of OCD with postpartum onset, which eliminated the possibility of discharging Ms. A with robust safety planning and reinitiation of a selective serotonin reuptake inhibitor.

Additionally, because auditory hallucinations are atypical in OCD, the treatment team remained concerned for a diagnosis of postpartum psychosis, which would warrant hospitalization. With assistance from the institution’s reproductive psychiatrists, the treatment team discussed the importance of inpatient hospitalization for risk mitigation, close observation, and thorough evaluation for greater diagnostic clarity and certainty.

TREATMENT Involuntary hospitalization

The treatment team counsels Ms. A and her partner on her differential diagnoses, including the elevated acute risk of harm to herself and her baby if she has postpartum psychosis, as well as the need for continued observation and evaluation. When alone with a clinician, Ms. A says she understands and agrees to voluntary hospitalization. However, following a subsequent risk-benefit discussion with her partner, they both grew increasingly concerned about her separation from the baby and reinitiating her medications. Amid these concerns, the treatment team notices that Ms. A attempts to minimize her symptoms. Ms. A changes her mind and no longer consents to hospitalization. She is placed on a psychiatric hold for involuntary hospitalization on the psychiatric inpatient unit.

On the inpatient unit, the inpatient clinicians and a reproductive psychiatrist continue to evaluate Ms. A. Though her diagnosis remains unclear, Ms. A agrees to start a trial of quetiapine 100 mg/d titrated to 150 mg/d to manage her potential postpartum psychosis, depressed mood, insomnia (off-label), anxiety (off-label), and OCD (off-label). Lithium is deferred because Ms. A is breastfeeding.

[polldaddy:13041932]

Continue to: The authors' observations

Due to an elevated acute risk of suicide and infanticide, postpartum psychosis represents a psychiatric emergency and often requires hospitalization. The Figure outlines steps in evaluating a patient with concerns for postpartum psychosis in a psychiatric emergency service setting. Due to the waxing and waning nature of symptoms, patients may appear psychiatrically stable at any time but remain at an overall elevated acute risk of harm to self and/or their baby.

If a patient is being considered for discharge based on yes answers to all questions in Step 2 of the Figure, the emergency psychiatric clinician must initiate appropriate psychotropic medications and complete robust safety planning with the patient and a trusted adult who will provide direct supervision. Safety planning may include (but is not limited to) strict return precautions, education on concerning symptoms and behaviors, psychotropic education and agreement of compliance, and detailed instructions on outpatient follow-up within 1 week. Ideally—and as was the case for Ms. A—a reproductive psychiatrist should be consulted in the emergency setting for shared decision-making on admission vs discharge, medication management, and outpatient follow-up considerations.

Because postpartum psychosis carries significant risks and hospitalization generally results in separating the patient from their baby, initiating psychotropics should not be delayed. Clinicians must consider the patient’s psychiatric history, allergies, and breastfeeding status.

Based on current evidence, first-line treatment for postpartum psychosis includes a mood stabilizer, an antipsychotic, and possibly a benzodiazepine.⁶ Thus, an appropriate initial treatment regimen would be a benzodiazepine (particularly lorazepam due to its relatively shorter half-life) and an antipsychotic (eg, haloperidol, olanzapine, or quetiapine) for acute psychosis, plus lithium for mood stabilization.^1,5

If the postpartum psychosis represents an episode of BD, use of a long-term mood stabilizer may be required. In contrast, for isolated postpartum psychosis, clinicians may consider initiating psychotropics only in the immediate postpartum period, with an eventual slow taper. In future pregnancies, psychotropics may be reintroduced postpartum, which will avoid peripartum fetal exposure.⁸ If the patient is breastfeeding, lithium may be deferred in an acute care setting. For patients with evidence of catatonia, severe suicidality, refusal of oral intake with compromised nutrition, severe agitation, or treatment resistance, electro­convulsive therapy remains a safe and effective treatment option.⁶ Additionally, the safety of continued breastfeeding in acute psychosis must be considered, with the potential for recommending discontinuation, which would decrease sleep disruptions at night and increase the ability of others to feed the baby. Comprehensive care requires nonpharmacologic interventions, including psychoeducation for the patient and their family, individual psychotherapy, and expansion of psychosocial supports.

Continue to: Patients who have experienced...

Patients who have experienced an episode of postpartum psychosis are predisposed to another episode in future pregnancies.¹ Current research recommends prophylaxis of recurrence with lithium monotherapy.^1,2,5,6 Similar to other psychotropics in reproductive psychiatry, maintenance therapy on lithium requires a thorough “risk vs risk” discussion with the patient. The risk of lithium use while pregnant and/or breastfeeding must be weighed against the risks associated with postpartum psychosis (ie, infanticide, suicide, poor peripartum care, or poor infant bonding).

OUTCOME Improved mood

After 7 days of inpatient treatment with quetiapine, Ms. A demonstrates improvement in the targeted depressive symptoms (including improved motivation/energy and insomnia, decreased feelings of guilt, and denial of ongoing suicidal ideation). Additionally, the thoughts of harming her baby are less frequent, and command auditory hallucinations resolve. Upon discharge, Ms. A and her partner meet with inpatient clinicians for continued counseling, safety planning, and plans for outpatient follow-up with the institution’s reproductive psychiatrist.

The authors’ observations

Many aspects of Ms. A’s initial presentation in the psychiatric ED were challenging. Given the presence of symptoms of both psychosis and OCD, a diagnosis was difficult to ascertain in the emergency setting. Since command auditory hallucinations are atypical in patients with postpartum OCD, the treatment team maintained high suspicion for postpartum psychosis, which represented an emergency requiring inpatient care.

Hospitalization separated Ms. A from her baby, for whom she was the primary caregiver. Additional considerations for inpatient admission and psychotropic initiation were necessary, because Ms. A was breastfeeding. Although Ms. A’s partner was able to provide full-time childcare, the patient ultimately did not agree to hospitalization and required an emergency hold for involuntary admission, which was an additional barrier to care. Furthermore, her partner held unfavorable beliefs regarding psychotropic medications and Ms. A’s need for hospital admission, which required ongoing patient and partner education in the emergency, inpatient, and outpatient settings. Moreover, if Ms. A’s symptoms were ultimately attributable to postpartum OCD, the patient’s involuntary hospitalization might have increased the risk of stigmatization of mental illness and treatment with psychotropics.

Bottom Line

The peripartum period is a vulnerable time for patients, particularly those with previously diagnosed psychiatric illnesses. Postpartum psychosis is the most severe form of postpartum psychiatric illness and often represents an episode of bipolar disorder. Due to an elevated acute risk of suicide and infanticide, postpartum psychosis is a psychiatric emergency and warrants inpatient hospitalization for immediate intervention.

Related Resources

• Sharma V. Does your patient have postpartum OCD? Current Psychiatry. 2019;18(5):9-10.
• Hatters Friedman S, Prakash C, Nagel-Yang S. Postpartum psychosis: protecting mother and infant. Current Psychiatry. 2019;18(4):12-21.

Drug Brand Names

Fluoxetine • Prozac
Haloperidol • Haldol
Lithium • Eskalith, Lithobid
Lorazepam • Ativan
Olanzapine • Zyprexa
Prazosin • Minipress
Quetiapine • Seroquel
Sertraline • Zoloft
Valproic acid • Depakene

CASE Thoughts of harming baby

Ms. A, age 37, is G4P2, 4 months postpartum, and breastfeeding. She has major depressive disorder (MDD) with peripartum onset, posttraumatic stress disorder, and mild intellectual disability. For years she has been stable on fluoxetine 40 mg/d and prazosin 2 mg/d. Despite recent titration of her medications, at her most recent outpatient appointment Ms. A reports having a depressed mood with frequent crying, insomnia, a lack of desire to bond with her baby, and feelings of shame. She also says she has had auditory hallucinations and thoughts of harming her baby. Ms. A’s outpatient physician makes an urgent request for her to be evaluated at the psychiatric emergency department (ED).

HISTORY Depression and possible auditory hallucinations

Ms. A developed MDD following the birth of her first child, for which her care team initiated fluoxetine at 20 mg/d and titrated it to 40 mg/d,which was effective. At that time, her outpatient physician documented potential psychotic features, including vague descriptions of derogatory auditory hallucinations. However, it was unclear if these auditory hallucinations were more representative of a distressing inner monologue without the quality of an external voice. The team determined that Ms. A was not at acute risk for harm to herself or her baby and was appropriate for outpatient care. Because the nature of these possible auditory hallucinations was mild, nondistressing, and nonthreatening, the treatment team did not initiate an antipsychotic and Ms. A was not hospitalized. She has no history of hypomanic/manic episodes and has never met criteria for a psychotic disorder.

EVALUATION Distressing thoughts and discontinued medications

During the evaluation by psychiatric emergency services, Ms. A reports that 2 weeks after giving birth she experienced a worsening of her depressive symptoms. She says she began hearing voices telling her to harm herself and her baby and describes frequent distressing thoughts, such as stabbing her baby with a knife and running over her baby with a car. Ms. A says she repeatedly wakes up at night to check on her baby’s breathing, overfeeds her baby due to a fear of inadequate nutrition, and notes intermittent feelings of confusion. Afraid of being alone with her infant, Ms. A asks her partner and mother to move in with her. Additionally, she says 2 weeks ago she discontinued all her medications at the suggestion of her partner, who recommended herbal supplements. Ms. A’s initial routine laboratory results are unremarkable and her urine drug screen is negative for all substances.

[polldaddy:13041928]

The authors’ observations

Approximately 85% of birthing parents experience some form of postpartum mood disturbance; 10% to 15% develop more significant symptoms of anxiety or depression.³ The etiology of postpartum illness is multifactorial, and includes psychiatric personal/family history, insomnia, acute and chronic psychosocial stressors, and rapid hormone fluctuations.¹ As a result, the postpartum period represents a vulnerable time for birthing parents, particularly those with previously established psychiatric illness.

Ms. A’s initial presentation was concerning for a possible diagnosis of postpartum psychosis vs obsessive-compulsive disorder (OCD) with postpartum onset; other differential diagnoses included MDD with peripartum onset and psychotic features (Table^1-6). Ms. A’s subjective clinical history was significant for critical pertinent findings of both OCD with postpartum onset (ie, egodystonic intrusive thoughts, checking behaviors, feelings of shame, and seeking reassurance) and postpartum psychosis (ie, command auditory hallucinations and waxing/waning confusion), which added to diagnostic complexity.

Although postpartum psychosis is rare (1 to 2 cases per 1,000 women),⁵ it is considered a psychiatric emergency because it has significant potential for infanticide, morbidity, and mortality. Most symptoms develop within the first 2 weeks of the postpartum period.² There are many risk factors for the development of postpartum psychosis; however, in first-time pregnancies, a previous diagnosis of BD I is the single most important risk factor.¹ Approximately 20% to 30% of women with BD experience postpartum psychosis.⁴

For many patients (approximately 56.7%, according to 1 meta-analysis⁷), postpartum psychosis denotes an episode of BD, representing a more severe form of illness with increased risk of recurrence. Most manic or mixed mood episodes reoccur within the first year removed from the perinatal period. In contrast, for some patients (approximately 43.5% according to the same meta-analysis), the episode denotes “isolated postpartum psychosis.”⁷ Isolated postpartum psychosis is a psychotic episode that occurs only in the postpartum period with no recurrence of psychosis or recurrence of psychosis exclusive to postpartum periods. If treated, this type of postpartum psychosis has a more favorable prognosis than postpartum psychosis in a patient with BD.⁷ As such, a BD diagnosis should not be established at the onset of a patient’s first postpartum psychosis presentation. Regardless of type, all presentations of postpartum psychosis are considered a psychiatry emergency.

Continue to: The prevalence of OCD...

The prevalence of OCD with postpartum onset varies. One study estimated it occurs in 2.43% of cases.⁴ However, the true prevalence is likely underreported due to feelings of guilt or shame associated with intrusive thoughts, and fear of stigmatization and separation from the baby. Approximately 70.6% of women experiencing OCD with postpartum onset have a comorbid depressive disorder.⁴

Ms. A’s presentation to the psychiatric ED carried with it diagnostic complexity and uncertainty. Her initial presentation was concerning for elements of both postpartum psychosis and OCD with postpartum onset. After her evaluation in the psychiatric ED, there remained a lack of clear and convincing evidence for a diagnosis of OCD with postpartum onset, which eliminated the possibility of discharging Ms. A with robust safety planning and reinitiation of a selective serotonin reuptake inhibitor.

Additionally, because auditory hallucinations are atypical in OCD, the treatment team remained concerned for a diagnosis of postpartum psychosis, which would warrant hospitalization. With assistance from the institution’s reproductive psychiatrists, the treatment team discussed the importance of inpatient hospitalization for risk mitigation, close observation, and thorough evaluation for greater diagnostic clarity and certainty.

TREATMENT Involuntary hospitalization

The treatment team counsels Ms. A and her partner on her differential diagnoses, including the elevated acute risk of harm to herself and her baby if she has postpartum psychosis, as well as the need for continued observation and evaluation. When alone with a clinician, Ms. A says she understands and agrees to voluntary hospitalization. However, following a subsequent risk-benefit discussion with her partner, they both grew increasingly concerned about her separation from the baby and reinitiating her medications. Amid these concerns, the treatment team notices that Ms. A attempts to minimize her symptoms. Ms. A changes her mind and no longer consents to hospitalization. She is placed on a psychiatric hold for involuntary hospitalization on the psychiatric inpatient unit.

On the inpatient unit, the inpatient clinicians and a reproductive psychiatrist continue to evaluate Ms. A. Though her diagnosis remains unclear, Ms. A agrees to start a trial of quetiapine 100 mg/d titrated to 150 mg/d to manage her potential postpartum psychosis, depressed mood, insomnia (off-label), anxiety (off-label), and OCD (off-label). Lithium is deferred because Ms. A is breastfeeding.

[polldaddy:13041932]

Continue to: The authors' observations

Due to an elevated acute risk of suicide and infanticide, postpartum psychosis represents a psychiatric emergency and often requires hospitalization. The Figure outlines steps in evaluating a patient with concerns for postpartum psychosis in a psychiatric emergency service setting. Due to the waxing and waning nature of symptoms, patients may appear psychiatrically stable at any time but remain at an overall elevated acute risk of harm to self and/or their baby.

If a patient is being considered for discharge based on yes answers to all questions in Step 2 of the Figure, the emergency psychiatric clinician must initiate appropriate psychotropic medications and complete robust safety planning with the patient and a trusted adult who will provide direct supervision. Safety planning may include (but is not limited to) strict return precautions, education on concerning symptoms and behaviors, psychotropic education and agreement of compliance, and detailed instructions on outpatient follow-up within 1 week. Ideally—and as was the case for Ms. A—a reproductive psychiatrist should be consulted in the emergency setting for shared decision-making on admission vs discharge, medication management, and outpatient follow-up considerations.

Because postpartum psychosis carries significant risks and hospitalization generally results in separating the patient from their baby, initiating psychotropics should not be delayed. Clinicians must consider the patient’s psychiatric history, allergies, and breastfeeding status.

Based on current evidence, first-line treatment for postpartum psychosis includes a mood stabilizer, an antipsychotic, and possibly a benzodiazepine.⁶ Thus, an appropriate initial treatment regimen would be a benzodiazepine (particularly lorazepam due to its relatively shorter half-life) and an antipsychotic (eg, haloperidol, olanzapine, or quetiapine) for acute psychosis, plus lithium for mood stabilization.^1,5

If the postpartum psychosis represents an episode of BD, use of a long-term mood stabilizer may be required. In contrast, for isolated postpartum psychosis, clinicians may consider initiating psychotropics only in the immediate postpartum period, with an eventual slow taper. In future pregnancies, psychotropics may be reintroduced postpartum, which will avoid peripartum fetal exposure.⁸ If the patient is breastfeeding, lithium may be deferred in an acute care setting. For patients with evidence of catatonia, severe suicidality, refusal of oral intake with compromised nutrition, severe agitation, or treatment resistance, electro­convulsive therapy remains a safe and effective treatment option.⁶ Additionally, the safety of continued breastfeeding in acute psychosis must be considered, with the potential for recommending discontinuation, which would decrease sleep disruptions at night and increase the ability of others to feed the baby. Comprehensive care requires nonpharmacologic interventions, including psychoeducation for the patient and their family, individual psychotherapy, and expansion of psychosocial supports.

Continue to: Patients who have experienced...

Patients who have experienced an episode of postpartum psychosis are predisposed to another episode in future pregnancies.¹ Current research recommends prophylaxis of recurrence with lithium monotherapy.^1,2,5,6 Similar to other psychotropics in reproductive psychiatry, maintenance therapy on lithium requires a thorough “risk vs risk” discussion with the patient. The risk of lithium use while pregnant and/or breastfeeding must be weighed against the risks associated with postpartum psychosis (ie, infanticide, suicide, poor peripartum care, or poor infant bonding).

OUTCOME Improved mood

After 7 days of inpatient treatment with quetiapine, Ms. A demonstrates improvement in the targeted depressive symptoms (including improved motivation/energy and insomnia, decreased feelings of guilt, and denial of ongoing suicidal ideation). Additionally, the thoughts of harming her baby are less frequent, and command auditory hallucinations resolve. Upon discharge, Ms. A and her partner meet with inpatient clinicians for continued counseling, safety planning, and plans for outpatient follow-up with the institution’s reproductive psychiatrist.

The authors’ observations

Many aspects of Ms. A’s initial presentation in the psychiatric ED were challenging. Given the presence of symptoms of both psychosis and OCD, a diagnosis was difficult to ascertain in the emergency setting. Since command auditory hallucinations are atypical in patients with postpartum OCD, the treatment team maintained high suspicion for postpartum psychosis, which represented an emergency requiring inpatient care.

Hospitalization separated Ms. A from her baby, for whom she was the primary caregiver. Additional considerations for inpatient admission and psychotropic initiation were necessary, because Ms. A was breastfeeding. Although Ms. A’s partner was able to provide full-time childcare, the patient ultimately did not agree to hospitalization and required an emergency hold for involuntary admission, which was an additional barrier to care. Furthermore, her partner held unfavorable beliefs regarding psychotropic medications and Ms. A’s need for hospital admission, which required ongoing patient and partner education in the emergency, inpatient, and outpatient settings. Moreover, if Ms. A’s symptoms were ultimately attributable to postpartum OCD, the patient’s involuntary hospitalization might have increased the risk of stigmatization of mental illness and treatment with psychotropics.

Bottom Line

The peripartum period is a vulnerable time for patients, particularly those with previously diagnosed psychiatric illnesses. Postpartum psychosis is the most severe form of postpartum psychiatric illness and often represents an episode of bipolar disorder. Due to an elevated acute risk of suicide and infanticide, postpartum psychosis is a psychiatric emergency and warrants inpatient hospitalization for immediate intervention.

Related Resources

• Sharma V. Does your patient have postpartum OCD? Current Psychiatry. 2019;18(5):9-10.
• Hatters Friedman S, Prakash C, Nagel-Yang S. Postpartum psychosis: protecting mother and infant. Current Psychiatry. 2019;18(4):12-21.

Drug Brand Names

Fluoxetine • Prozac
Haloperidol • Haldol
Lithium • Eskalith, Lithobid
Lorazepam • Ativan
Olanzapine • Zyprexa
Prazosin • Minipress
Quetiapine • Seroquel
Sertraline • Zoloft
Valproic acid • Depakene

Perinatal psychiatry focuses on the evaluation, diagnosis, and treatment of mental health disorders during the preconception, pregnancy, and postpartum periods. Mood disorders, anxiety disorders, and posttraumatic stress disorder are the most common mental health conditions that arise during the perinatal period.¹ Mediating factors include hormone fluctuations, sleep deprivation, trauma exposure, financial stress, having a history of psychiatric illness, and factors related to newborn care.

During the perinatal period, a comprehensive psychiatric interview is crucial. Effective screening and identification of maternal mental health conditions necessitate more than merely checking off boxes on a questionnaire. It requires compassionate, informed, and individualized conversations between physicians and their patients.

In addition to asking about pertinent positive and negative psychiatric symptoms, the following screening questions could be asked during a structured interview to identify perinatal issues during pregnancy and the postpartum period.

During pregnancy

• How do you feel about your pregnancy?
• Was this pregnancy planned or unplanned, desired or not?
• Was fertility treatment needed or used?
• Did you think about stopping the pregnancy? If so, was your decision influenced by laws that restrict abortion in your state?
• Do you feel connected to the fetus?
• Do you have a room or crib at home for the baby? A car seat? Clothing? Baby supplies?
• Are you planning on breastfeeding?
• Do you have thoughts on future desired fertility and/or contraception?
• Who is your support system at home?
• How is your relationship with the baby’s father?
• How is the baby’s father’s mental well-being?
• Have you been subject to any abuse, intimate partner violence, or neglect?
• Are your other children being taken care of properly? What is the plan for them during delivery days at the hospital?

During the postpartum period

• Was your baby born prematurely?
• Did you have a vaginal or cesarean delivery?
• Did you encounter any delivery complications?
• Did you see the baby after the delivery?
• Do you feel connected to or able to bond with the baby?
• Do you have access to maternity leave from work?
• Have you had scary or upsetting thoughts about hurting your baby?
• Do you have any concerns about your treatment plan, such as medication use?
• In case of an emergency, are you aware of perinatal psychiatry resources in your area or the national maternal mental health hotline (833-852-6262)?

The American College of Obstetricians and Gynecologists clinical practice guidelines recommend that clinicians conduct depression and anxiety screening at least once during the perinatal period by using a standardized, validated tool.² Psychiatry residents should receive adequate guidance and education about perinatal psychiatric evaluation, risk assessment, and treatment counseling. Early detection of mental health symptoms allows for early referral, close surveillance during episodes of vulnerability, and better access to mental health care during the perinatal period.

Perinatal psychiatry focuses on the evaluation, diagnosis, and treatment of mental health disorders during the preconception, pregnancy, and postpartum periods. Mood disorders, anxiety disorders, and posttraumatic stress disorder are the most common mental health conditions that arise during the perinatal period.¹ Mediating factors include hormone fluctuations, sleep deprivation, trauma exposure, financial stress, having a history of psychiatric illness, and factors related to newborn care.

During the perinatal period, a comprehensive psychiatric interview is crucial. Effective screening and identification of maternal mental health conditions necessitate more than merely checking off boxes on a questionnaire. It requires compassionate, informed, and individualized conversations between physicians and their patients.

In addition to asking about pertinent positive and negative psychiatric symptoms, the following screening questions could be asked during a structured interview to identify perinatal issues during pregnancy and the postpartum period.

During pregnancy

• How do you feel about your pregnancy?
• Was this pregnancy planned or unplanned, desired or not?
• Was fertility treatment needed or used?
• Did you think about stopping the pregnancy? If so, was your decision influenced by laws that restrict abortion in your state?
• Do you feel connected to the fetus?
• Do you have a room or crib at home for the baby? A car seat? Clothing? Baby supplies?
• Are you planning on breastfeeding?
• Do you have thoughts on future desired fertility and/or contraception?
• Who is your support system at home?
• How is your relationship with the baby’s father?
• How is the baby’s father’s mental well-being?
• Have you been subject to any abuse, intimate partner violence, or neglect?
• Are your other children being taken care of properly? What is the plan for them during delivery days at the hospital?

During the postpartum period

• Was your baby born prematurely?
• Did you have a vaginal or cesarean delivery?
• Did you encounter any delivery complications?
• Did you see the baby after the delivery?
• Do you feel connected to or able to bond with the baby?
• Do you have access to maternity leave from work?
• Have you had scary or upsetting thoughts about hurting your baby?
• Do you have any concerns about your treatment plan, such as medication use?
• In case of an emergency, are you aware of perinatal psychiatry resources in your area or the national maternal mental health hotline (833-852-6262)?

The American College of Obstetricians and Gynecologists clinical practice guidelines recommend that clinicians conduct depression and anxiety screening at least once during the perinatal period by using a standardized, validated tool.² Psychiatry residents should receive adequate guidance and education about perinatal psychiatric evaluation, risk assessment, and treatment counseling. Early detection of mental health symptoms allows for early referral, close surveillance during episodes of vulnerability, and better access to mental health care during the perinatal period.

Perinatal psychiatry focuses on the evaluation, diagnosis, and treatment of mental health disorders during the preconception, pregnancy, and postpartum periods. Mood disorders, anxiety disorders, and posttraumatic stress disorder are the most common mental health conditions that arise during the perinatal period.¹ Mediating factors include hormone fluctuations, sleep deprivation, trauma exposure, financial stress, having a history of psychiatric illness, and factors related to newborn care.

During the perinatal period, a comprehensive psychiatric interview is crucial. Effective screening and identification of maternal mental health conditions necessitate more than merely checking off boxes on a questionnaire. It requires compassionate, informed, and individualized conversations between physicians and their patients.

In addition to asking about pertinent positive and negative psychiatric symptoms, the following screening questions could be asked during a structured interview to identify perinatal issues during pregnancy and the postpartum period.

During pregnancy

• How do you feel about your pregnancy?
• Was this pregnancy planned or unplanned, desired or not?
• Was fertility treatment needed or used?
• Did you think about stopping the pregnancy? If so, was your decision influenced by laws that restrict abortion in your state?
• Do you feel connected to the fetus?
• Do you have a room or crib at home for the baby? A car seat? Clothing? Baby supplies?
• Are you planning on breastfeeding?
• Do you have thoughts on future desired fertility and/or contraception?
• Who is your support system at home?
• How is your relationship with the baby’s father?
• How is the baby’s father’s mental well-being?
• Have you been subject to any abuse, intimate partner violence, or neglect?
• Are your other children being taken care of properly? What is the plan for them during delivery days at the hospital?

During the postpartum period

• Was your baby born prematurely?
• Did you have a vaginal or cesarean delivery?
• Did you encounter any delivery complications?
• Did you see the baby after the delivery?
• Do you feel connected to or able to bond with the baby?
• Do you have access to maternity leave from work?
• Have you had scary or upsetting thoughts about hurting your baby?
• Do you have any concerns about your treatment plan, such as medication use?
• In case of an emergency, are you aware of perinatal psychiatry resources in your area or the national maternal mental health hotline (833-852-6262)?

The American College of Obstetricians and Gynecologists clinical practice guidelines recommend that clinicians conduct depression and anxiety screening at least once during the perinatal period by using a standardized, validated tool.² Psychiatry residents should receive adequate guidance and education about perinatal psychiatric evaluation, risk assessment, and treatment counseling. Early detection of mental health symptoms allows for early referral, close surveillance during episodes of vulnerability, and better access to mental health care during the perinatal period.