Mental Health

The best plan for oppositional behavior in a school-aged child is prevention at younger ages! But here is the family coming to see us, struggling to get cooperation, and often increasingly embarrassed and angry.

Sometimes the dynamics leading to this behavior seem obvious: the parent tells their child to put away the toys they have pulled out in your waiting room, is ignored, and cleans them up themselves without a word. The child smugly fiddles with their cell phone, reinforced by removal of the task. Even without a defined reward, this still constitutes positive reinforcement as it increases the likelihood of the same future behavior of ignoring a parental directive.

Preventing this “mild” oppositionality at a younger age may come from the parent jollying the child through the clean up, participating with them in a game-like way counting the toys or making it a race, or even using only one request before grasping the child’s hand and “assisting” them in picking up a toy while praising cooperation but these tactics become less appropriate with age.

Other factors that may have led to school-aged child refusal include yelling at them, shaming, comparing them with a more compliant sibling, threatening a punishment that is never carried out, or deferring a consequence to the other caregiver. Of course, no child would want to please a caregiver with this kind of interaction by obeying them. By school age, children have a greater need to exert autonomy and avoid humiliation and may do this by getting angry, talking back, insulting the parent, or leaving the scene. This is especially likely if peers or siblings are present and the child wants to show that they can’t be bossed around.
 

Practical advice

So what can we advise when habits of refusal have already been established? Keeping in mind the major school-age psychosocial tasks of developing autonomy and self-esteem, the parent may need to overdo opportunities for this child to have choices and experience respect. When the child has a generalized oppositional stance, the parent may feel that it is difficult to identify opportunities to do this. The key in that case is to set up for cooperation and focus on small positive or neutral bits of behavior to reinforce. For example, requesting that the child do something they want to do anyways, such as come for a snack or turn on the TV, can be met with a brief but sincere “thanks” or “thanks for hopping on that.”

Sarcasm is counterproductive at all times, as it is insulting. Asking the child’s opinion regularly then listening and reflecting, rephrasing what they said, and even checking to see if the parent “got it right” do not require that the parent agrees. Any disagreement that the parent feels is needed can be withheld for a few minutes to indicate respect for the child’s opinion. For a child to learn to make “good choices” of behavior comes also from noticing how “not so good choices” worked out, a reflection the parent can try to elicit nonjudgmentally. Rebuilding the relationship can be done over time with respectful communication and assuring daily times of showing interest in the child, fooling around together, or playing a game.

While giving more choices respects autonomy, the options must really be acceptable to the parent. They may allow the child to choose some aspects of family activities – a skate park, or a certain eatery, or parts of the outing could be optional. Sometimes the order of upcoming events can provide a choice even if attendance is required. Sometimes the dress code can be flexible (flip flops, okay sure!), or a friend (preferably a well-behaved one!) could be invited along.
 

Pitfalls to avoid

Avoiding humiliation may be obvious, such as not complementing a singing performance or insistence on the child self-reporting bad behavior. For some families the parents may need to avoid their own embarrassing habits of “bad jokes” or outlandish clothes as a reasonable accommodation. Other kinds of humiliation to avoid may be specific to the child’s weaknesses, such as insisting that a clumsy child play on a team or a shy child speak to strangers. While it may be valuable for the child to work on those weaknesses, this should be done in private, if possible, or even with a coach who is not the parent if the relationship is strained.

Sensitive or anxious children are more prone to embarrassment and may then react with oppositional responses. They often do better with notice or coaching for upcoming events that may be in a category that has upset them in the past; for example, a visit from an overly affectionate aunt. Children may gain respect for their parents by being given a task that serves as an early escape route for these situations (Oh, would you please run out to the car and get my sweater?) although progressively tolerating undesirable situations is also important practice. A kindly debrief later with praise for progress also builds skills.
 

Reinforcing behaviors and revisiting consequences

Gaining more privileges as the reward for cooperation and responsibility is the natural sequence with development but oppositional children may need a chart, ideally negotiated as a family, to be clear about this cause-effect plan and what is expected for them to earn more freedom. Another benefit of a chart is that it is an objective translator of rules that can literally be pointed to rather than a parent-child conversation that could become an argument. Parents need to make expectations clear and follow through on promised increased privileges or consequences to be seen as fair. Having regular routines for chores, not just for activities, reduces refusal as well. Such concrete steps are especially important for children with ADHD who are often easily distracted from parental requests even if they meant to follow them and have a weak sense of timing. I have seen some wise parents give their distracted or impulsive child “a minute to decide if that is their final choice” before levying a consequence.

“When-then” statements can be useful both for coaching appropriate behavior in advance, debriefs, and alerting to consequences when needed. For example: “When you ask your aunt a question right away when you meet her then her hugs will be shorter” is coaching. “When you come home an hour late then you will have an hour earlier curfew the next week” is a graded consequence.
 

The cell phone issue

I can’t omit mentioning the specific situation of a child on a cell phone or tablet ignoring or refusing requests. While having possession of such a device may be seen as a safety measure (How can he reach me?) and social coinage (All my friends have one!), they are distracting and addicting and now the most common reason I see for oppositional interactions. This has been discussed elsewhere, so let me just say that a device is a privilege and should not “belong” to a child. Delaying the age of “lending” the device, establishing rules for use to certain situations and durations, and removing it for defined periods if it is interfering with cooperation are basic principles, even though enforcing them may result in upsets. Parents may need to change their own device use to be able to address oppositional behavior in their child.

Strategies for building better behavior

How important is it for the parent to verbalize what they are doing to instruct or accommodate their school-aged child? In the presence of others, the fewer words highlighting that an intervention is underway the better. Sometimes having a secret signal to prompt or praise, even a wink, can be helpful without being humiliating. These should be decided on together in private and practiced at first in nonstressful situations. Comments of appreciation or praise are appropriate then and are often reinforcing but should be very specific; for example, “I’m glad you got ready right away when it was time to leave” rather than general or backwards praise “Ready on time today, huh?” For some, especially younger or special-needs children, marks, points, tickets, tokens, or little prizes may be beneficial reinforcers, especially when trying to establish new patterns of interaction. Praise should fairly quickly replace more concrete rewards, though, by weaning, first by intermittent delivery or spacing further apart.

When counseling about oppositional behavior in school-aged children eliciting specific examples is key to determining whether parents are overly rigid or lax, have realistic expectations for their individual child’s temperament, skills, and past experiences (for example, traumas). As Ross Greene, PhD, points out,¹ assisting families in understanding the gaps in skills that bring out opposition and categorizing behaviors into the rare “must-do’s,” and the many “just drop it’s,” in order to focus on understanding and building strategies and cooperation for situations that are important but not critical (Plan B) may require regular counseling by a mental health professional to help a child develop adaptive behavior and facilitate family harmony.

Reference

1. Greene RW. The Explosive Child: A New Approach for Understanding and Parenting Easily Frustrated, Chronically Inflexible Children, Sixth Edition, (New York: Harper Paperbacks, 2021).

Dr. Howard is assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS (www.CHADIS.com). She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to MDedge News. Email her at pdnews@mdedge.com.

The best plan for oppositional behavior in a school-aged child is prevention at younger ages! But here is the family coming to see us, struggling to get cooperation, and often increasingly embarrassed and angry.

Sometimes the dynamics leading to this behavior seem obvious: the parent tells their child to put away the toys they have pulled out in your waiting room, is ignored, and cleans them up themselves without a word. The child smugly fiddles with their cell phone, reinforced by removal of the task. Even without a defined reward, this still constitutes positive reinforcement as it increases the likelihood of the same future behavior of ignoring a parental directive.

Preventing this “mild” oppositionality at a younger age may come from the parent jollying the child through the clean up, participating with them in a game-like way counting the toys or making it a race, or even using only one request before grasping the child’s hand and “assisting” them in picking up a toy while praising cooperation but these tactics become less appropriate with age.

Other factors that may have led to school-aged child refusal include yelling at them, shaming, comparing them with a more compliant sibling, threatening a punishment that is never carried out, or deferring a consequence to the other caregiver. Of course, no child would want to please a caregiver with this kind of interaction by obeying them. By school age, children have a greater need to exert autonomy and avoid humiliation and may do this by getting angry, talking back, insulting the parent, or leaving the scene. This is especially likely if peers or siblings are present and the child wants to show that they can’t be bossed around.
 

Practical advice

So what can we advise when habits of refusal have already been established? Keeping in mind the major school-age psychosocial tasks of developing autonomy and self-esteem, the parent may need to overdo opportunities for this child to have choices and experience respect. When the child has a generalized oppositional stance, the parent may feel that it is difficult to identify opportunities to do this. The key in that case is to set up for cooperation and focus on small positive or neutral bits of behavior to reinforce. For example, requesting that the child do something they want to do anyways, such as come for a snack or turn on the TV, can be met with a brief but sincere “thanks” or “thanks for hopping on that.”

Sarcasm is counterproductive at all times, as it is insulting. Asking the child’s opinion regularly then listening and reflecting, rephrasing what they said, and even checking to see if the parent “got it right” do not require that the parent agrees. Any disagreement that the parent feels is needed can be withheld for a few minutes to indicate respect for the child’s opinion. For a child to learn to make “good choices” of behavior comes also from noticing how “not so good choices” worked out, a reflection the parent can try to elicit nonjudgmentally. Rebuilding the relationship can be done over time with respectful communication and assuring daily times of showing interest in the child, fooling around together, or playing a game.

While giving more choices respects autonomy, the options must really be acceptable to the parent. They may allow the child to choose some aspects of family activities – a skate park, or a certain eatery, or parts of the outing could be optional. Sometimes the order of upcoming events can provide a choice even if attendance is required. Sometimes the dress code can be flexible (flip flops, okay sure!), or a friend (preferably a well-behaved one!) could be invited along.
 

Pitfalls to avoid

Avoiding humiliation may be obvious, such as not complementing a singing performance or insistence on the child self-reporting bad behavior. For some families the parents may need to avoid their own embarrassing habits of “bad jokes” or outlandish clothes as a reasonable accommodation. Other kinds of humiliation to avoid may be specific to the child’s weaknesses, such as insisting that a clumsy child play on a team or a shy child speak to strangers. While it may be valuable for the child to work on those weaknesses, this should be done in private, if possible, or even with a coach who is not the parent if the relationship is strained.

Sensitive or anxious children are more prone to embarrassment and may then react with oppositional responses. They often do better with notice or coaching for upcoming events that may be in a category that has upset them in the past; for example, a visit from an overly affectionate aunt. Children may gain respect for their parents by being given a task that serves as an early escape route for these situations (Oh, would you please run out to the car and get my sweater?) although progressively tolerating undesirable situations is also important practice. A kindly debrief later with praise for progress also builds skills.
 

Reinforcing behaviors and revisiting consequences

Gaining more privileges as the reward for cooperation and responsibility is the natural sequence with development but oppositional children may need a chart, ideally negotiated as a family, to be clear about this cause-effect plan and what is expected for them to earn more freedom. Another benefit of a chart is that it is an objective translator of rules that can literally be pointed to rather than a parent-child conversation that could become an argument. Parents need to make expectations clear and follow through on promised increased privileges or consequences to be seen as fair. Having regular routines for chores, not just for activities, reduces refusal as well. Such concrete steps are especially important for children with ADHD who are often easily distracted from parental requests even if they meant to follow them and have a weak sense of timing. I have seen some wise parents give their distracted or impulsive child “a minute to decide if that is their final choice” before levying a consequence.

“When-then” statements can be useful both for coaching appropriate behavior in advance, debriefs, and alerting to consequences when needed. For example: “When you ask your aunt a question right away when you meet her then her hugs will be shorter” is coaching. “When you come home an hour late then you will have an hour earlier curfew the next week” is a graded consequence.
 

The cell phone issue

I can’t omit mentioning the specific situation of a child on a cell phone or tablet ignoring or refusing requests. While having possession of such a device may be seen as a safety measure (How can he reach me?) and social coinage (All my friends have one!), they are distracting and addicting and now the most common reason I see for oppositional interactions. This has been discussed elsewhere, so let me just say that a device is a privilege and should not “belong” to a child. Delaying the age of “lending” the device, establishing rules for use to certain situations and durations, and removing it for defined periods if it is interfering with cooperation are basic principles, even though enforcing them may result in upsets. Parents may need to change their own device use to be able to address oppositional behavior in their child.

Strategies for building better behavior

How important is it for the parent to verbalize what they are doing to instruct or accommodate their school-aged child? In the presence of others, the fewer words highlighting that an intervention is underway the better. Sometimes having a secret signal to prompt or praise, even a wink, can be helpful without being humiliating. These should be decided on together in private and practiced at first in nonstressful situations. Comments of appreciation or praise are appropriate then and are often reinforcing but should be very specific; for example, “I’m glad you got ready right away when it was time to leave” rather than general or backwards praise “Ready on time today, huh?” For some, especially younger or special-needs children, marks, points, tickets, tokens, or little prizes may be beneficial reinforcers, especially when trying to establish new patterns of interaction. Praise should fairly quickly replace more concrete rewards, though, by weaning, first by intermittent delivery or spacing further apart.

When counseling about oppositional behavior in school-aged children eliciting specific examples is key to determining whether parents are overly rigid or lax, have realistic expectations for their individual child’s temperament, skills, and past experiences (for example, traumas). As Ross Greene, PhD, points out,¹ assisting families in understanding the gaps in skills that bring out opposition and categorizing behaviors into the rare “must-do’s,” and the many “just drop it’s,” in order to focus on understanding and building strategies and cooperation for situations that are important but not critical (Plan B) may require regular counseling by a mental health professional to help a child develop adaptive behavior and facilitate family harmony.

Reference

1. Greene RW. The Explosive Child: A New Approach for Understanding and Parenting Easily Frustrated, Chronically Inflexible Children, Sixth Edition, (New York: Harper Paperbacks, 2021).

Dr. Howard is assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS (www.CHADIS.com). She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to MDedge News. Email her at pdnews@mdedge.com.

The best plan for oppositional behavior in a school-aged child is prevention at younger ages! But here is the family coming to see us, struggling to get cooperation, and often increasingly embarrassed and angry.

Sometimes the dynamics leading to this behavior seem obvious: the parent tells their child to put away the toys they have pulled out in your waiting room, is ignored, and cleans them up themselves without a word. The child smugly fiddles with their cell phone, reinforced by removal of the task. Even without a defined reward, this still constitutes positive reinforcement as it increases the likelihood of the same future behavior of ignoring a parental directive.

Preventing this “mild” oppositionality at a younger age may come from the parent jollying the child through the clean up, participating with them in a game-like way counting the toys or making it a race, or even using only one request before grasping the child’s hand and “assisting” them in picking up a toy while praising cooperation but these tactics become less appropriate with age.

Other factors that may have led to school-aged child refusal include yelling at them, shaming, comparing them with a more compliant sibling, threatening a punishment that is never carried out, or deferring a consequence to the other caregiver. Of course, no child would want to please a caregiver with this kind of interaction by obeying them. By school age, children have a greater need to exert autonomy and avoid humiliation and may do this by getting angry, talking back, insulting the parent, or leaving the scene. This is especially likely if peers or siblings are present and the child wants to show that they can’t be bossed around.
 

Practical advice

So what can we advise when habits of refusal have already been established? Keeping in mind the major school-age psychosocial tasks of developing autonomy and self-esteem, the parent may need to overdo opportunities for this child to have choices and experience respect. When the child has a generalized oppositional stance, the parent may feel that it is difficult to identify opportunities to do this. The key in that case is to set up for cooperation and focus on small positive or neutral bits of behavior to reinforce. For example, requesting that the child do something they want to do anyways, such as come for a snack or turn on the TV, can be met with a brief but sincere “thanks” or “thanks for hopping on that.”

Sarcasm is counterproductive at all times, as it is insulting. Asking the child’s opinion regularly then listening and reflecting, rephrasing what they said, and even checking to see if the parent “got it right” do not require that the parent agrees. Any disagreement that the parent feels is needed can be withheld for a few minutes to indicate respect for the child’s opinion. For a child to learn to make “good choices” of behavior comes also from noticing how “not so good choices” worked out, a reflection the parent can try to elicit nonjudgmentally. Rebuilding the relationship can be done over time with respectful communication and assuring daily times of showing interest in the child, fooling around together, or playing a game.

While giving more choices respects autonomy, the options must really be acceptable to the parent. They may allow the child to choose some aspects of family activities – a skate park, or a certain eatery, or parts of the outing could be optional. Sometimes the order of upcoming events can provide a choice even if attendance is required. Sometimes the dress code can be flexible (flip flops, okay sure!), or a friend (preferably a well-behaved one!) could be invited along.
 

Pitfalls to avoid

Avoiding humiliation may be obvious, such as not complementing a singing performance or insistence on the child self-reporting bad behavior. For some families the parents may need to avoid their own embarrassing habits of “bad jokes” or outlandish clothes as a reasonable accommodation. Other kinds of humiliation to avoid may be specific to the child’s weaknesses, such as insisting that a clumsy child play on a team or a shy child speak to strangers. While it may be valuable for the child to work on those weaknesses, this should be done in private, if possible, or even with a coach who is not the parent if the relationship is strained.

Sensitive or anxious children are more prone to embarrassment and may then react with oppositional responses. They often do better with notice or coaching for upcoming events that may be in a category that has upset them in the past; for example, a visit from an overly affectionate aunt. Children may gain respect for their parents by being given a task that serves as an early escape route for these situations (Oh, would you please run out to the car and get my sweater?) although progressively tolerating undesirable situations is also important practice. A kindly debrief later with praise for progress also builds skills.
 

Reinforcing behaviors and revisiting consequences

Gaining more privileges as the reward for cooperation and responsibility is the natural sequence with development but oppositional children may need a chart, ideally negotiated as a family, to be clear about this cause-effect plan and what is expected for them to earn more freedom. Another benefit of a chart is that it is an objective translator of rules that can literally be pointed to rather than a parent-child conversation that could become an argument. Parents need to make expectations clear and follow through on promised increased privileges or consequences to be seen as fair. Having regular routines for chores, not just for activities, reduces refusal as well. Such concrete steps are especially important for children with ADHD who are often easily distracted from parental requests even if they meant to follow them and have a weak sense of timing. I have seen some wise parents give their distracted or impulsive child “a minute to decide if that is their final choice” before levying a consequence.

“When-then” statements can be useful both for coaching appropriate behavior in advance, debriefs, and alerting to consequences when needed. For example: “When you ask your aunt a question right away when you meet her then her hugs will be shorter” is coaching. “When you come home an hour late then you will have an hour earlier curfew the next week” is a graded consequence.
 

The cell phone issue

I can’t omit mentioning the specific situation of a child on a cell phone or tablet ignoring or refusing requests. While having possession of such a device may be seen as a safety measure (How can he reach me?) and social coinage (All my friends have one!), they are distracting and addicting and now the most common reason I see for oppositional interactions. This has been discussed elsewhere, so let me just say that a device is a privilege and should not “belong” to a child. Delaying the age of “lending” the device, establishing rules for use to certain situations and durations, and removing it for defined periods if it is interfering with cooperation are basic principles, even though enforcing them may result in upsets. Parents may need to change their own device use to be able to address oppositional behavior in their child.

Strategies for building better behavior

How important is it for the parent to verbalize what they are doing to instruct or accommodate their school-aged child? In the presence of others, the fewer words highlighting that an intervention is underway the better. Sometimes having a secret signal to prompt or praise, even a wink, can be helpful without being humiliating. These should be decided on together in private and practiced at first in nonstressful situations. Comments of appreciation or praise are appropriate then and are often reinforcing but should be very specific; for example, “I’m glad you got ready right away when it was time to leave” rather than general or backwards praise “Ready on time today, huh?” For some, especially younger or special-needs children, marks, points, tickets, tokens, or little prizes may be beneficial reinforcers, especially when trying to establish new patterns of interaction. Praise should fairly quickly replace more concrete rewards, though, by weaning, first by intermittent delivery or spacing further apart.

When counseling about oppositional behavior in school-aged children eliciting specific examples is key to determining whether parents are overly rigid or lax, have realistic expectations for their individual child’s temperament, skills, and past experiences (for example, traumas). As Ross Greene, PhD, points out,¹ assisting families in understanding the gaps in skills that bring out opposition and categorizing behaviors into the rare “must-do’s,” and the many “just drop it’s,” in order to focus on understanding and building strategies and cooperation for situations that are important but not critical (Plan B) may require regular counseling by a mental health professional to help a child develop adaptive behavior and facilitate family harmony.

Reference

1. Greene RW. The Explosive Child: A New Approach for Understanding and Parenting Easily Frustrated, Chronically Inflexible Children, Sixth Edition, (New York: Harper Paperbacks, 2021).

Dr. Howard is assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS (www.CHADIS.com). She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to MDedge News. Email her at pdnews@mdedge.com.

Veterans speak of losing their innocence and longing to regain it. They ask: “Why can’t I just go back to the way I was?”

Jonathan Shay, Achilles in Vietnam ¹

On July 17, 2023, several media outlets covering military and federal news carried a story about the US Department of Veterans Affairs (VA) plan to conduct a major survey of moral injury in veterans.² This is not the first such survey: There have been numerous previous studies conducted by both VA and non-VA investigators.³ Moral injury has been increasingly recognized as the signature wound of service members, especially those who fought in Operation Enduring Freedom and Operation Iraqi Freedom.⁴ This new VA survey can provide crucial information because we know so little about moral injury or how to help those with the condition.

At the time of this writing, there has been no official VA public statement about the study. At face value, this seemed to be strange, given that the groundbreaking research could improve the diagnosis and therapy of moral injury. According to a June 2023 VA Office of Research and Development internal announcement, the primary goal of the study is to determine the prevalence of moral injury among US veterans. The secondary goals of the study are to (1) compare those who develop moral injury and those who do not after exposure to similar traumas; and (2) conduct interviews about thoughts and experiences from 20 veterans who identify as having moral injury and 20 who do not but who have similar exposure to morally injurious events.

Data for the study will be collected through an extensive online survey from a nationally representative sample of 3000 post-9/11 war veterans. The sample will include at least 950 who served in a war zone and at least 400 who are aged 18 to 54 years. The respondents will be paid $20 for the 30 to 45 minutes survey. The collection and analysis of data are expected to take 3 or more years.

The modern version of moral injury is often associated with Jonathan Shay, MD, a VA psychiatrist.⁵ Shay wrote about the origin of moral injury found in Homer’s The Iliad and The Odyssey and how the poems offer ancient echoes of his therapy with modern-day combat veterans.¹

There is no universal agreement on the definition of moral injury. A working definition of moral injury used in the VA suggests that it describes the difficulties that people face after doing high-stakes actions that violate a sense of what is right and just or after being forced to experience others’ immoral actions.⁶

Two conditions are necessary for moral injury to occur. First, an individual acts or witnesses an action that contravenes their core ethical principles. Secondly, that occurrence is experienced as a breach of the person’s moral barrier. Military personnel killing civilians to protect their lives and those of their fellow troops is a tragic example of moral injury. The translation of this for health care professionals may be the inability to save severely wounded service members in the combat theater due to the exigencies of war.⁷

Experts in moral injury emphasize the importance of distinguishing the phenomenon from posttraumatic stress disorder (PTSD). Unlike many psychiatric disorders, both moral injury and PTSD have known etiologies: traumatic events. An individual may have 1 or both conditions, and each can manifest anger, guilt, shame, and loss of trust in others. One way that moral injury can be distinguished from PTSD is that it goes beyond the psychological to compromise the moral and often spiritual beliefs and values of the individual. One of the characteristics that makes us human is that we have a conscience to guide us in navigating the moral field of human life, but moral injury scrambles the internal compass that discerns right and wrong, good and bad. When an individual commits an action or witnesses the perpetration of an action that crosses their personal moral boundary, their integrity is shattered, and they may lose faith in their intrinsic worth. These beliefs prevent many service members from disclosing their distress, leading some commentators to refer to moral injury as a silent or invisible wound.⁸

The timing of the VA’s launching of a study of moral injury of this size and scope may reflect 3 recent developments: Not unexpected in VA matters, one is political, another is benefits, and the last pertains to health care.

First, August marks the second anniversary of the withdrawal of American troops from Afghanistan. Many Afghans who assisted US forces during the war were not evacuated. For some of the troops who served in the country, these events as well as the chaotic end to the long war were experienced as a contravening of an ethical code, resulting in moral injury.⁹

Second, many of those service members are now calling on the federal government to recognize and respond to the detrimental impact of the withdrawal, including the high prevalence of moral injury in troops who served in Afghanistan.¹⁰ Moral injury at this time is not considered a psychiatric diagnosis; hence, not eligible for VA benefits. However, many of the psychological manifestations of moral injury, such as depression and anxiety, are established service-connected disorders.

Third, several VA studies have demonstrated that moral injury either alone or combined with PTSD substantially elevates the risk of suicide.¹¹ Since preventing suicide is a major strategic priority for the VA, the importance of learning more about the epidemiology of moral injury is the necessary first step to developing therapeutic approaches. At a time when organized medicine is becoming increasingly technological and fragmented, launching this unprecedented survey demonstrates the VA’s commitment to delivering holistic and humanistic care of the service member: body, mind, and spirit.

This project also sends a strong message to those who lobby for shifting funding from the VA to community care or call for privatization. Veterans are different: They experience unique disorders borne of the battles they fought for our freedom. The VA has the specialized knowledge and skills in research and health care to develop the knowledge to ground innovative treatments for conditions like moral injury, PTSD, and traumatic brain injuries. VA chaplains and mental health professionals have pioneered assessment instruments and promising therapies for moral injury. Their distinctive expertise unrivaled in the civilian sector benefits not only veterans but also the wider community where there is a growing awareness of the devastating impact of moral injury, particularly on health care professionals.¹² And there may have been no other time in history when this broken, violent world was more in need of moral healing and peace.

Veterans speak of losing their innocence and longing to regain it. They ask: “Why can’t I just go back to the way I was?”

Jonathan Shay, Achilles in Vietnam ¹

On July 17, 2023, several media outlets covering military and federal news carried a story about the US Department of Veterans Affairs (VA) plan to conduct a major survey of moral injury in veterans.² This is not the first such survey: There have been numerous previous studies conducted by both VA and non-VA investigators.³ Moral injury has been increasingly recognized as the signature wound of service members, especially those who fought in Operation Enduring Freedom and Operation Iraqi Freedom.⁴ This new VA survey can provide crucial information because we know so little about moral injury or how to help those with the condition.

At the time of this writing, there has been no official VA public statement about the study. At face value, this seemed to be strange, given that the groundbreaking research could improve the diagnosis and therapy of moral injury. According to a June 2023 VA Office of Research and Development internal announcement, the primary goal of the study is to determine the prevalence of moral injury among US veterans. The secondary goals of the study are to (1) compare those who develop moral injury and those who do not after exposure to similar traumas; and (2) conduct interviews about thoughts and experiences from 20 veterans who identify as having moral injury and 20 who do not but who have similar exposure to morally injurious events.

Data for the study will be collected through an extensive online survey from a nationally representative sample of 3000 post-9/11 war veterans. The sample will include at least 950 who served in a war zone and at least 400 who are aged 18 to 54 years. The respondents will be paid $20 for the 30 to 45 minutes survey. The collection and analysis of data are expected to take 3 or more years.

The modern version of moral injury is often associated with Jonathan Shay, MD, a VA psychiatrist.⁵ Shay wrote about the origin of moral injury found in Homer’s The Iliad and The Odyssey and how the poems offer ancient echoes of his therapy with modern-day combat veterans.¹

There is no universal agreement on the definition of moral injury. A working definition of moral injury used in the VA suggests that it describes the difficulties that people face after doing high-stakes actions that violate a sense of what is right and just or after being forced to experience others’ immoral actions.⁶

Two conditions are necessary for moral injury to occur. First, an individual acts or witnesses an action that contravenes their core ethical principles. Secondly, that occurrence is experienced as a breach of the person’s moral barrier. Military personnel killing civilians to protect their lives and those of their fellow troops is a tragic example of moral injury. The translation of this for health care professionals may be the inability to save severely wounded service members in the combat theater due to the exigencies of war.⁷

Experts in moral injury emphasize the importance of distinguishing the phenomenon from posttraumatic stress disorder (PTSD). Unlike many psychiatric disorders, both moral injury and PTSD have known etiologies: traumatic events. An individual may have 1 or both conditions, and each can manifest anger, guilt, shame, and loss of trust in others. One way that moral injury can be distinguished from PTSD is that it goes beyond the psychological to compromise the moral and often spiritual beliefs and values of the individual. One of the characteristics that makes us human is that we have a conscience to guide us in navigating the moral field of human life, but moral injury scrambles the internal compass that discerns right and wrong, good and bad. When an individual commits an action or witnesses the perpetration of an action that crosses their personal moral boundary, their integrity is shattered, and they may lose faith in their intrinsic worth. These beliefs prevent many service members from disclosing their distress, leading some commentators to refer to moral injury as a silent or invisible wound.⁸

The timing of the VA’s launching of a study of moral injury of this size and scope may reflect 3 recent developments: Not unexpected in VA matters, one is political, another is benefits, and the last pertains to health care.

First, August marks the second anniversary of the withdrawal of American troops from Afghanistan. Many Afghans who assisted US forces during the war were not evacuated. For some of the troops who served in the country, these events as well as the chaotic end to the long war were experienced as a contravening of an ethical code, resulting in moral injury.⁹

Second, many of those service members are now calling on the federal government to recognize and respond to the detrimental impact of the withdrawal, including the high prevalence of moral injury in troops who served in Afghanistan.¹⁰ Moral injury at this time is not considered a psychiatric diagnosis; hence, not eligible for VA benefits. However, many of the psychological manifestations of moral injury, such as depression and anxiety, are established service-connected disorders.

Third, several VA studies have demonstrated that moral injury either alone or combined with PTSD substantially elevates the risk of suicide.¹¹ Since preventing suicide is a major strategic priority for the VA, the importance of learning more about the epidemiology of moral injury is the necessary first step to developing therapeutic approaches. At a time when organized medicine is becoming increasingly technological and fragmented, launching this unprecedented survey demonstrates the VA’s commitment to delivering holistic and humanistic care of the service member: body, mind, and spirit.

This project also sends a strong message to those who lobby for shifting funding from the VA to community care or call for privatization. Veterans are different: They experience unique disorders borne of the battles they fought for our freedom. The VA has the specialized knowledge and skills in research and health care to develop the knowledge to ground innovative treatments for conditions like moral injury, PTSD, and traumatic brain injuries. VA chaplains and mental health professionals have pioneered assessment instruments and promising therapies for moral injury. Their distinctive expertise unrivaled in the civilian sector benefits not only veterans but also the wider community where there is a growing awareness of the devastating impact of moral injury, particularly on health care professionals.¹² And there may have been no other time in history when this broken, violent world was more in need of moral healing and peace.

Veterans speak of losing their innocence and longing to regain it. They ask: “Why can’t I just go back to the way I was?”

Jonathan Shay, Achilles in Vietnam ¹

On July 17, 2023, several media outlets covering military and federal news carried a story about the US Department of Veterans Affairs (VA) plan to conduct a major survey of moral injury in veterans.² This is not the first such survey: There have been numerous previous studies conducted by both VA and non-VA investigators.³ Moral injury has been increasingly recognized as the signature wound of service members, especially those who fought in Operation Enduring Freedom and Operation Iraqi Freedom.⁴ This new VA survey can provide crucial information because we know so little about moral injury or how to help those with the condition.

At the time of this writing, there has been no official VA public statement about the study. At face value, this seemed to be strange, given that the groundbreaking research could improve the diagnosis and therapy of moral injury. According to a June 2023 VA Office of Research and Development internal announcement, the primary goal of the study is to determine the prevalence of moral injury among US veterans. The secondary goals of the study are to (1) compare those who develop moral injury and those who do not after exposure to similar traumas; and (2) conduct interviews about thoughts and experiences from 20 veterans who identify as having moral injury and 20 who do not but who have similar exposure to morally injurious events.

Data for the study will be collected through an extensive online survey from a nationally representative sample of 3000 post-9/11 war veterans. The sample will include at least 950 who served in a war zone and at least 400 who are aged 18 to 54 years. The respondents will be paid $20 for the 30 to 45 minutes survey. The collection and analysis of data are expected to take 3 or more years.

The modern version of moral injury is often associated with Jonathan Shay, MD, a VA psychiatrist.⁵ Shay wrote about the origin of moral injury found in Homer’s The Iliad and The Odyssey and how the poems offer ancient echoes of his therapy with modern-day combat veterans.¹

There is no universal agreement on the definition of moral injury. A working definition of moral injury used in the VA suggests that it describes the difficulties that people face after doing high-stakes actions that violate a sense of what is right and just or after being forced to experience others’ immoral actions.⁶

Two conditions are necessary for moral injury to occur. First, an individual acts or witnesses an action that contravenes their core ethical principles. Secondly, that occurrence is experienced as a breach of the person’s moral barrier. Military personnel killing civilians to protect their lives and those of their fellow troops is a tragic example of moral injury. The translation of this for health care professionals may be the inability to save severely wounded service members in the combat theater due to the exigencies of war.⁷

Experts in moral injury emphasize the importance of distinguishing the phenomenon from posttraumatic stress disorder (PTSD). Unlike many psychiatric disorders, both moral injury and PTSD have known etiologies: traumatic events. An individual may have 1 or both conditions, and each can manifest anger, guilt, shame, and loss of trust in others. One way that moral injury can be distinguished from PTSD is that it goes beyond the psychological to compromise the moral and often spiritual beliefs and values of the individual. One of the characteristics that makes us human is that we have a conscience to guide us in navigating the moral field of human life, but moral injury scrambles the internal compass that discerns right and wrong, good and bad. When an individual commits an action or witnesses the perpetration of an action that crosses their personal moral boundary, their integrity is shattered, and they may lose faith in their intrinsic worth. These beliefs prevent many service members from disclosing their distress, leading some commentators to refer to moral injury as a silent or invisible wound.⁸

The timing of the VA’s launching of a study of moral injury of this size and scope may reflect 3 recent developments: Not unexpected in VA matters, one is political, another is benefits, and the last pertains to health care.

First, August marks the second anniversary of the withdrawal of American troops from Afghanistan. Many Afghans who assisted US forces during the war were not evacuated. For some of the troops who served in the country, these events as well as the chaotic end to the long war were experienced as a contravening of an ethical code, resulting in moral injury.⁹

Second, many of those service members are now calling on the federal government to recognize and respond to the detrimental impact of the withdrawal, including the high prevalence of moral injury in troops who served in Afghanistan.¹⁰ Moral injury at this time is not considered a psychiatric diagnosis; hence, not eligible for VA benefits. However, many of the psychological manifestations of moral injury, such as depression and anxiety, are established service-connected disorders.

Third, several VA studies have demonstrated that moral injury either alone or combined with PTSD substantially elevates the risk of suicide.¹¹ Since preventing suicide is a major strategic priority for the VA, the importance of learning more about the epidemiology of moral injury is the necessary first step to developing therapeutic approaches. At a time when organized medicine is becoming increasingly technological and fragmented, launching this unprecedented survey demonstrates the VA’s commitment to delivering holistic and humanistic care of the service member: body, mind, and spirit.

This project also sends a strong message to those who lobby for shifting funding from the VA to community care or call for privatization. Veterans are different: They experience unique disorders borne of the battles they fought for our freedom. The VA has the specialized knowledge and skills in research and health care to develop the knowledge to ground innovative treatments for conditions like moral injury, PTSD, and traumatic brain injuries. VA chaplains and mental health professionals have pioneered assessment instruments and promising therapies for moral injury. Their distinctive expertise unrivaled in the civilian sector benefits not only veterans but also the wider community where there is a growing awareness of the devastating impact of moral injury, particularly on health care professionals.¹² And there may have been no other time in history when this broken, violent world was more in need of moral healing and peace.

New research calls into question the established method of assessing patient response to antidepressant treatment and expands the concepts of “responder” and “nonresponder.” 

Investigators assessed more than 800 patients with major depressive disorder (MDD) attending a partial hospital program. The patients completed questionnaires about depressive symptoms as well as functioning and broader measures of quality of life (QoL).

Brown University

Although fewer than 40% were classified as treatment responders on the basis of depressive symptoms, as measured by the Remission from Depression Questionnaire (RDQ), two-thirds met criteria as responders on the Patient Global Rating of Improvement (PGI) scale, which takes into consideration broader domains of life satisfaction.

“The treatments we’re offering patients may be doing a better job than we think in treating depression, because many patients say they feel significantly better, even if their depression symptoms haven’t been diminished by the arbitrary threshold of 50% or greater improvement,” study investigator Mark Zimmerman, MD, professor of psychiatry and human behavior, Brown University, Providence, R.I., told this news organization.

“Many of these patients – even if they have ongoing depressive symptoms – nevertheless say treatment has been very or extremely helpful, which is picked by other emphasizes in outcome, such as functioning, quality of life, coping abilities, and positive mental health,” added Dr. Zimmerman, director of the outpatient division at the Partial Hospital Program, Rhode Island Hospital.

The study was published online in the Annals of Clinical Psychiatry.

What’s the best tool?

“Almost all studies of depression treatment rely on measures of symptom severity to evaluate outcome – which is understandable, because a diagnosis of MDD requires a minimum number of symptoms for a sustained period of time,” said Dr. Zimmerman.

However, while important, symptom reduction is only one component of depression treatment. Improving overall function, QoL, and ability to deal with life’s stressors are equally important, he said.

Dr. Zimmerman emphasized he’s an “advocate, supporter, and practitioner of measurement-based care.” This approach, he said, “increases efficiency of the visit and directs me to the areas I should be inquiring about and the areas that need less time for inquiry.”

Measurement tools also enable numerical documentation of how a patient is doing and helps them understand and recognize their improvement.

The question is which tool captures improvements most effectively. Several surveys show that patients value improved functioning and QoL as primary treatment goals, which “is different from the emphasis of symptom improvement found in research,” said Dr. Zimmerman.

A multidimensional questionnaire that assesses functioning, QoL, and coping ability as well as symptoms is more likely to reflect patients’ treatment goals than simply measuring symptoms, he said.

Dr. Zimmerman and his coauthor reported on findings from the Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) Project, which “examined the concordance between patients’ global rating of improvement from treatment and responder status, based on a depression symptoms severity scale.”
 

Doing better than we think

The study was conducted in Rhode Island Hospital’s department of psychiatry partial hospital program, where 844 patients with MDD (65.2% women; mean [SD] age, 36.8 [13.9] years) completed the RDQ – a self-report measure that “assesses constructs that patients consider to be relevant for assessing treatment outcome.” This questionnaire assesses symptom and nonsymptom domains that people consider important when evaluating treatment effectiveness.

To the original 41-item questionnaire, the researchers added 19 items. The final 60-item questionnaire included the following:

• 14 depressive symptoms.
• 11 nondepressive symptoms.
• 5 coping ability/stress tolerance items (for instance, “I had trouble handling pressure”).
• 12 positive mental health items (for instance, “I saw myself as a person of value”).
• 10 functioning items (for instance, “I was socially withdrawn”).
• 8 general well-being/life satisfaction items (for instance, “I was engaging in life rather than hiding from it”).

Patients were divided into three groups:

• Symptom responders (whose scores on the RDQ depressive symptom subscale improved by ≥ 50% from admission to discharge).
• PGI responders, who weren’t symptom responders – that is, who reported global improvement but didn’t improve ≥ 50% on the depression symptom subscale.
• Nonresponders (that is, patients who didn’t respond on the PGI and the depressive symptom subscale).

The researchers compared the three groups on the four symptom domains of the RDQ. Patients also completed the PGI on discharge, and the researchers compared these responses to responses to the RDQ.

Only 38.7% were responders on the depressive symptoms subscale, while 67.4% were PGI responders.

Most patients (91.4%) who were responders on the depressive symptom subscale were also PGI responders, while 32% were PGI responders but not responders on the depressive symptom subscale.

Although 29.2% were nonresponders on both measures, 70.8% were responders on one scale or the other.

As far as the nonsymptom domains, response rates varied between 30% (life satisfaction) to 33.1% (positive mental health).

“If you’re using a measurement tool in practice, I’d recommend one that goes beyond symptom improvement and also captures broader domains,” Dr. Zimmerman said.
 

‘Better enough’

Commenting on the study, Philip Muskin, MD, professor of psychiatry, Columbia University Medical Center, New York, said the use of symptom-driven rating scales to measure depression response originated in mandates of the U.S. Food and Drug Administration to determine whether a drug being tested in a clinical trial is superior to placebo.

Columbia University Medical Center

“But there has been, for a long time, the question of whether these people are really better,” said Dr. Muskin, who was not involved with the current study. “Symptomatically, they may show improvement, but do they actually perceive themselves as better?”

Some patients might report, “I’m about 75% myself, but not back to 100%.” Dr. Muskin doesn’t “take these to be hard-and-fast numbers, but patients can tell you how they perceive themselves. This study suggests that if you’re wedded to [symptom measurement] scales, you may not realize that patients are actually getting better. And who decides if a patient is better, or better enough? The patient decides that.”

He added that some patients won’t achieve complete remission. “Even if I can’t get the person to be 100% better, I’m glad if I can help them become ‘better enough’ to function in life, do things, go to work, and improve in quality-of-life domains.”

The study received no outside funding. Dr. Zimmerman and his coauthor and Dr. Muskin report no relevant financial relationships.

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

New research calls into question the established method of assessing patient response to antidepressant treatment and expands the concepts of “responder” and “nonresponder.” 

Investigators assessed more than 800 patients with major depressive disorder (MDD) attending a partial hospital program. The patients completed questionnaires about depressive symptoms as well as functioning and broader measures of quality of life (QoL).

Brown University

Although fewer than 40% were classified as treatment responders on the basis of depressive symptoms, as measured by the Remission from Depression Questionnaire (RDQ), two-thirds met criteria as responders on the Patient Global Rating of Improvement (PGI) scale, which takes into consideration broader domains of life satisfaction.

“The treatments we’re offering patients may be doing a better job than we think in treating depression, because many patients say they feel significantly better, even if their depression symptoms haven’t been diminished by the arbitrary threshold of 50% or greater improvement,” study investigator Mark Zimmerman, MD, professor of psychiatry and human behavior, Brown University, Providence, R.I., told this news organization.

“Many of these patients – even if they have ongoing depressive symptoms – nevertheless say treatment has been very or extremely helpful, which is picked by other emphasizes in outcome, such as functioning, quality of life, coping abilities, and positive mental health,” added Dr. Zimmerman, director of the outpatient division at the Partial Hospital Program, Rhode Island Hospital.

The study was published online in the Annals of Clinical Psychiatry.

What’s the best tool?

“Almost all studies of depression treatment rely on measures of symptom severity to evaluate outcome – which is understandable, because a diagnosis of MDD requires a minimum number of symptoms for a sustained period of time,” said Dr. Zimmerman.

However, while important, symptom reduction is only one component of depression treatment. Improving overall function, QoL, and ability to deal with life’s stressors are equally important, he said.

Dr. Zimmerman emphasized he’s an “advocate, supporter, and practitioner of measurement-based care.” This approach, he said, “increases efficiency of the visit and directs me to the areas I should be inquiring about and the areas that need less time for inquiry.”

Measurement tools also enable numerical documentation of how a patient is doing and helps them understand and recognize their improvement.

The question is which tool captures improvements most effectively. Several surveys show that patients value improved functioning and QoL as primary treatment goals, which “is different from the emphasis of symptom improvement found in research,” said Dr. Zimmerman.

A multidimensional questionnaire that assesses functioning, QoL, and coping ability as well as symptoms is more likely to reflect patients’ treatment goals than simply measuring symptoms, he said.

Dr. Zimmerman and his coauthor reported on findings from the Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) Project, which “examined the concordance between patients’ global rating of improvement from treatment and responder status, based on a depression symptoms severity scale.”
 

Doing better than we think

The study was conducted in Rhode Island Hospital’s department of psychiatry partial hospital program, where 844 patients with MDD (65.2% women; mean [SD] age, 36.8 [13.9] years) completed the RDQ – a self-report measure that “assesses constructs that patients consider to be relevant for assessing treatment outcome.” This questionnaire assesses symptom and nonsymptom domains that people consider important when evaluating treatment effectiveness.

To the original 41-item questionnaire, the researchers added 19 items. The final 60-item questionnaire included the following:

• 14 depressive symptoms.
• 11 nondepressive symptoms.
• 5 coping ability/stress tolerance items (for instance, “I had trouble handling pressure”).
• 12 positive mental health items (for instance, “I saw myself as a person of value”).
• 10 functioning items (for instance, “I was socially withdrawn”).
• 8 general well-being/life satisfaction items (for instance, “I was engaging in life rather than hiding from it”).

Patients were divided into three groups:

• Symptom responders (whose scores on the RDQ depressive symptom subscale improved by ≥ 50% from admission to discharge).
• PGI responders, who weren’t symptom responders – that is, who reported global improvement but didn’t improve ≥ 50% on the depression symptom subscale.
• Nonresponders (that is, patients who didn’t respond on the PGI and the depressive symptom subscale).

The researchers compared the three groups on the four symptom domains of the RDQ. Patients also completed the PGI on discharge, and the researchers compared these responses to responses to the RDQ.

Only 38.7% were responders on the depressive symptoms subscale, while 67.4% were PGI responders.

Most patients (91.4%) who were responders on the depressive symptom subscale were also PGI responders, while 32% were PGI responders but not responders on the depressive symptom subscale.

Although 29.2% were nonresponders on both measures, 70.8% were responders on one scale or the other.

As far as the nonsymptom domains, response rates varied between 30% (life satisfaction) to 33.1% (positive mental health).

“If you’re using a measurement tool in practice, I’d recommend one that goes beyond symptom improvement and also captures broader domains,” Dr. Zimmerman said.
 

‘Better enough’

Commenting on the study, Philip Muskin, MD, professor of psychiatry, Columbia University Medical Center, New York, said the use of symptom-driven rating scales to measure depression response originated in mandates of the U.S. Food and Drug Administration to determine whether a drug being tested in a clinical trial is superior to placebo.

Columbia University Medical Center

“But there has been, for a long time, the question of whether these people are really better,” said Dr. Muskin, who was not involved with the current study. “Symptomatically, they may show improvement, but do they actually perceive themselves as better?”

Some patients might report, “I’m about 75% myself, but not back to 100%.” Dr. Muskin doesn’t “take these to be hard-and-fast numbers, but patients can tell you how they perceive themselves. This study suggests that if you’re wedded to [symptom measurement] scales, you may not realize that patients are actually getting better. And who decides if a patient is better, or better enough? The patient decides that.”

He added that some patients won’t achieve complete remission. “Even if I can’t get the person to be 100% better, I’m glad if I can help them become ‘better enough’ to function in life, do things, go to work, and improve in quality-of-life domains.”

The study received no outside funding. Dr. Zimmerman and his coauthor and Dr. Muskin report no relevant financial relationships.

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

New research calls into question the established method of assessing patient response to antidepressant treatment and expands the concepts of “responder” and “nonresponder.” 

Investigators assessed more than 800 patients with major depressive disorder (MDD) attending a partial hospital program. The patients completed questionnaires about depressive symptoms as well as functioning and broader measures of quality of life (QoL).

Brown University

Although fewer than 40% were classified as treatment responders on the basis of depressive symptoms, as measured by the Remission from Depression Questionnaire (RDQ), two-thirds met criteria as responders on the Patient Global Rating of Improvement (PGI) scale, which takes into consideration broader domains of life satisfaction.

“The treatments we’re offering patients may be doing a better job than we think in treating depression, because many patients say they feel significantly better, even if their depression symptoms haven’t been diminished by the arbitrary threshold of 50% or greater improvement,” study investigator Mark Zimmerman, MD, professor of psychiatry and human behavior, Brown University, Providence, R.I., told this news organization.

“Many of these patients – even if they have ongoing depressive symptoms – nevertheless say treatment has been very or extremely helpful, which is picked by other emphasizes in outcome, such as functioning, quality of life, coping abilities, and positive mental health,” added Dr. Zimmerman, director of the outpatient division at the Partial Hospital Program, Rhode Island Hospital.

The study was published online in the Annals of Clinical Psychiatry.

What’s the best tool?

“Almost all studies of depression treatment rely on measures of symptom severity to evaluate outcome – which is understandable, because a diagnosis of MDD requires a minimum number of symptoms for a sustained period of time,” said Dr. Zimmerman.

However, while important, symptom reduction is only one component of depression treatment. Improving overall function, QoL, and ability to deal with life’s stressors are equally important, he said.

Dr. Zimmerman emphasized he’s an “advocate, supporter, and practitioner of measurement-based care.” This approach, he said, “increases efficiency of the visit and directs me to the areas I should be inquiring about and the areas that need less time for inquiry.”

Measurement tools also enable numerical documentation of how a patient is doing and helps them understand and recognize their improvement.

The question is which tool captures improvements most effectively. Several surveys show that patients value improved functioning and QoL as primary treatment goals, which “is different from the emphasis of symptom improvement found in research,” said Dr. Zimmerman.

A multidimensional questionnaire that assesses functioning, QoL, and coping ability as well as symptoms is more likely to reflect patients’ treatment goals than simply measuring symptoms, he said.

Dr. Zimmerman and his coauthor reported on findings from the Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) Project, which “examined the concordance between patients’ global rating of improvement from treatment and responder status, based on a depression symptoms severity scale.”
 

Doing better than we think

The study was conducted in Rhode Island Hospital’s department of psychiatry partial hospital program, where 844 patients with MDD (65.2% women; mean [SD] age, 36.8 [13.9] years) completed the RDQ – a self-report measure that “assesses constructs that patients consider to be relevant for assessing treatment outcome.” This questionnaire assesses symptom and nonsymptom domains that people consider important when evaluating treatment effectiveness.

To the original 41-item questionnaire, the researchers added 19 items. The final 60-item questionnaire included the following:

• 14 depressive symptoms.
• 11 nondepressive symptoms.
• 5 coping ability/stress tolerance items (for instance, “I had trouble handling pressure”).
• 12 positive mental health items (for instance, “I saw myself as a person of value”).
• 10 functioning items (for instance, “I was socially withdrawn”).
• 8 general well-being/life satisfaction items (for instance, “I was engaging in life rather than hiding from it”).

Patients were divided into three groups:

• Symptom responders (whose scores on the RDQ depressive symptom subscale improved by ≥ 50% from admission to discharge).
• PGI responders, who weren’t symptom responders – that is, who reported global improvement but didn’t improve ≥ 50% on the depression symptom subscale.
• Nonresponders (that is, patients who didn’t respond on the PGI and the depressive symptom subscale).

The researchers compared the three groups on the four symptom domains of the RDQ. Patients also completed the PGI on discharge, and the researchers compared these responses to responses to the RDQ.

Only 38.7% were responders on the depressive symptoms subscale, while 67.4% were PGI responders.

Most patients (91.4%) who were responders on the depressive symptom subscale were also PGI responders, while 32% were PGI responders but not responders on the depressive symptom subscale.

Although 29.2% were nonresponders on both measures, 70.8% were responders on one scale or the other.

As far as the nonsymptom domains, response rates varied between 30% (life satisfaction) to 33.1% (positive mental health).

“If you’re using a measurement tool in practice, I’d recommend one that goes beyond symptom improvement and also captures broader domains,” Dr. Zimmerman said.
 

‘Better enough’

Commenting on the study, Philip Muskin, MD, professor of psychiatry, Columbia University Medical Center, New York, said the use of symptom-driven rating scales to measure depression response originated in mandates of the U.S. Food and Drug Administration to determine whether a drug being tested in a clinical trial is superior to placebo.

Columbia University Medical Center

“But there has been, for a long time, the question of whether these people are really better,” said Dr. Muskin, who was not involved with the current study. “Symptomatically, they may show improvement, but do they actually perceive themselves as better?”

Some patients might report, “I’m about 75% myself, but not back to 100%.” Dr. Muskin doesn’t “take these to be hard-and-fast numbers, but patients can tell you how they perceive themselves. This study suggests that if you’re wedded to [symptom measurement] scales, you may not realize that patients are actually getting better. And who decides if a patient is better, or better enough? The patient decides that.”

He added that some patients won’t achieve complete remission. “Even if I can’t get the person to be 100% better, I’m glad if I can help them become ‘better enough’ to function in life, do things, go to work, and improve in quality-of-life domains.”

The study received no outside funding. Dr. Zimmerman and his coauthor and Dr. Muskin report no relevant financial relationships.

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

TOPLINE:

Even after accounting for sociodemographic factors, intellectual disabilities, and psychiatric diagnoses, autism is associated with an 83% increased risk of self-harm among females and a 47% increased risk among males.

METHODOLOGY:

Evidence shows those with autism have over threefold greater odds than their counterparts without the disorder of self-injurious behavior, suicidal ideation, suicide attempt, or suicide death, but reasons for these elevated risks are unclear.

Using various linked databases in the province of Ontario, researchers identified all individuals with an autism diagnosis from April 1, 1988, to March 31, 2018, and matched each on age and sex to four nonautistic individuals for the comparison group.

Investigators created two cohorts to separately evaluate outcomes of self-harm events leading to emergency health care and suicide death with the accrual period for both cohorts beginning at a person’s 10th birthday.

The self-harm cohort included 379,630 individuals while the suicide cohort included 334,690 individuals.

TAKEAWAY:

Over 15 years, autistic females showed the highest cumulative self-harm events, followed by autistic males, nonautistic females, and nonautistic males; over 25 years, autistic males had the highest cumulative incidence of suicide death, followed by autistic females, nonautistic males, and nonautistic females.

Autism had independent associations with self-harm events (females: relative rate, 1.83 [95% confidence interval, 1.61-2.08]; males: RR, 1.47 [95% CI, 1.28-1.69]) even after accounting for sociodemographic factors (varied directions of associations), intellectual disabilities (associated with increased risks), and psychiatric diagnoses including mood and anxiety, psychotic, addiction, and personality disorders (associated with increased risks).

For both females and males, final models showed autism per se was not significantly associated with suicide death, but certain correlates were linked to risk. Among both sexes, intellectual disabilities were associated with reduced risks and psychiatric diagnoses were associated with increased risks.

As a substantial proportion (28.4%) of the suicide cohort did not have data on self-harm, researchers were unable to examine the association of self-harm with suicide death.

IN PRACTICE:

That psychiatric diagnoses increased suicide risks among people with autism suggests supports to reduce such risks “should consider multifactorial mechanisms, with a particular focus on the prevention and timely treatment of psychiatric illnesses,” write the authors.

SOURCE:

The study was conducted by Meng-Chuan Lai, MD, PhD, Centre for Addiction and Mental Health, Toronto, and colleagues. It was published online in JAMA Network Open.

LIMITATIONS:

The autism cohort didn’t capture those diagnosed in private practices or with subtle presentations not yet diagnosed. Misclassification of autistic people in the nonautistic cohort may have resulted in underestimation of suicide-related outcomes. The administrative data don’t reliably identify diagnoses associated with suicide risks such as attention-deficit/hyperactivity disorder or subcategories of mood disorders, and don’t contain information about risk and protective mechanisms of suicide behaviors such as family history.

DISCLOSURES:

The study received support from ICES, an independent nonprofit research institute; the Innovation Fund of the Alternative Funding Plan for the Academic Health Sciences Centres of Ontario; the Academic Scholars Award from the Department of Psychiatry, University of Toronto; and the Canadian Institutes of Health Research Sex and Gender Science Chair. Dr. Lai reported receiving personal fees from SAGE Publications as an editorial honorarium outside the submitted work. One coauthor reported receiving honoraria from the BMJ Group, Archives of Diseases in Childhood.

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

TOPLINE:

Even after accounting for sociodemographic factors, intellectual disabilities, and psychiatric diagnoses, autism is associated with an 83% increased risk of self-harm among females and a 47% increased risk among males.

METHODOLOGY:

Evidence shows those with autism have over threefold greater odds than their counterparts without the disorder of self-injurious behavior, suicidal ideation, suicide attempt, or suicide death, but reasons for these elevated risks are unclear.

Using various linked databases in the province of Ontario, researchers identified all individuals with an autism diagnosis from April 1, 1988, to March 31, 2018, and matched each on age and sex to four nonautistic individuals for the comparison group.

Investigators created two cohorts to separately evaluate outcomes of self-harm events leading to emergency health care and suicide death with the accrual period for both cohorts beginning at a person’s 10th birthday.

The self-harm cohort included 379,630 individuals while the suicide cohort included 334,690 individuals.

TAKEAWAY:

Over 15 years, autistic females showed the highest cumulative self-harm events, followed by autistic males, nonautistic females, and nonautistic males; over 25 years, autistic males had the highest cumulative incidence of suicide death, followed by autistic females, nonautistic males, and nonautistic females.

Autism had independent associations with self-harm events (females: relative rate, 1.83 [95% confidence interval, 1.61-2.08]; males: RR, 1.47 [95% CI, 1.28-1.69]) even after accounting for sociodemographic factors (varied directions of associations), intellectual disabilities (associated with increased risks), and psychiatric diagnoses including mood and anxiety, psychotic, addiction, and personality disorders (associated with increased risks).

For both females and males, final models showed autism per se was not significantly associated with suicide death, but certain correlates were linked to risk. Among both sexes, intellectual disabilities were associated with reduced risks and psychiatric diagnoses were associated with increased risks.

As a substantial proportion (28.4%) of the suicide cohort did not have data on self-harm, researchers were unable to examine the association of self-harm with suicide death.

IN PRACTICE:

That psychiatric diagnoses increased suicide risks among people with autism suggests supports to reduce such risks “should consider multifactorial mechanisms, with a particular focus on the prevention and timely treatment of psychiatric illnesses,” write the authors.

SOURCE:

The study was conducted by Meng-Chuan Lai, MD, PhD, Centre for Addiction and Mental Health, Toronto, and colleagues. It was published online in JAMA Network Open.

LIMITATIONS:

The autism cohort didn’t capture those diagnosed in private practices or with subtle presentations not yet diagnosed. Misclassification of autistic people in the nonautistic cohort may have resulted in underestimation of suicide-related outcomes. The administrative data don’t reliably identify diagnoses associated with suicide risks such as attention-deficit/hyperactivity disorder or subcategories of mood disorders, and don’t contain information about risk and protective mechanisms of suicide behaviors such as family history.

DISCLOSURES:

The study received support from ICES, an independent nonprofit research institute; the Innovation Fund of the Alternative Funding Plan for the Academic Health Sciences Centres of Ontario; the Academic Scholars Award from the Department of Psychiatry, University of Toronto; and the Canadian Institutes of Health Research Sex and Gender Science Chair. Dr. Lai reported receiving personal fees from SAGE Publications as an editorial honorarium outside the submitted work. One coauthor reported receiving honoraria from the BMJ Group, Archives of Diseases in Childhood.

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

TOPLINE:

Even after accounting for sociodemographic factors, intellectual disabilities, and psychiatric diagnoses, autism is associated with an 83% increased risk of self-harm among females and a 47% increased risk among males.

METHODOLOGY:

Evidence shows those with autism have over threefold greater odds than their counterparts without the disorder of self-injurious behavior, suicidal ideation, suicide attempt, or suicide death, but reasons for these elevated risks are unclear.

Using various linked databases in the province of Ontario, researchers identified all individuals with an autism diagnosis from April 1, 1988, to March 31, 2018, and matched each on age and sex to four nonautistic individuals for the comparison group.

Investigators created two cohorts to separately evaluate outcomes of self-harm events leading to emergency health care and suicide death with the accrual period for both cohorts beginning at a person’s 10th birthday.

The self-harm cohort included 379,630 individuals while the suicide cohort included 334,690 individuals.

TAKEAWAY:

Over 15 years, autistic females showed the highest cumulative self-harm events, followed by autistic males, nonautistic females, and nonautistic males; over 25 years, autistic males had the highest cumulative incidence of suicide death, followed by autistic females, nonautistic males, and nonautistic females.

Autism had independent associations with self-harm events (females: relative rate, 1.83 [95% confidence interval, 1.61-2.08]; males: RR, 1.47 [95% CI, 1.28-1.69]) even after accounting for sociodemographic factors (varied directions of associations), intellectual disabilities (associated with increased risks), and psychiatric diagnoses including mood and anxiety, psychotic, addiction, and personality disorders (associated with increased risks).

For both females and males, final models showed autism per se was not significantly associated with suicide death, but certain correlates were linked to risk. Among both sexes, intellectual disabilities were associated with reduced risks and psychiatric diagnoses were associated with increased risks.

As a substantial proportion (28.4%) of the suicide cohort did not have data on self-harm, researchers were unable to examine the association of self-harm with suicide death.

IN PRACTICE:

That psychiatric diagnoses increased suicide risks among people with autism suggests supports to reduce such risks “should consider multifactorial mechanisms, with a particular focus on the prevention and timely treatment of psychiatric illnesses,” write the authors.

SOURCE:

The study was conducted by Meng-Chuan Lai, MD, PhD, Centre for Addiction and Mental Health, Toronto, and colleagues. It was published online in JAMA Network Open.

LIMITATIONS:

The autism cohort didn’t capture those diagnosed in private practices or with subtle presentations not yet diagnosed. Misclassification of autistic people in the nonautistic cohort may have resulted in underestimation of suicide-related outcomes. The administrative data don’t reliably identify diagnoses associated with suicide risks such as attention-deficit/hyperactivity disorder or subcategories of mood disorders, and don’t contain information about risk and protective mechanisms of suicide behaviors such as family history.

DISCLOSURES:

The study received support from ICES, an independent nonprofit research institute; the Innovation Fund of the Alternative Funding Plan for the Academic Health Sciences Centres of Ontario; the Academic Scholars Award from the Department of Psychiatry, University of Toronto; and the Canadian Institutes of Health Research Sex and Gender Science Chair. Dr. Lai reported receiving personal fees from SAGE Publications as an editorial honorarium outside the submitted work. One coauthor reported receiving honoraria from the BMJ Group, Archives of Diseases in Childhood.

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

One of the most controversial issues today is whether a physician should be permitted, or even obligated, to assist patients with a terminal or incurable illness to end their life – a process known as medical assistance in dying (MAID) or physician-assisted suicide (PAS.)

Until recently, this contentious issue applied only to patients with physical illnesses who want to end their suffering and who seek out a physician willing to assist with that objective. In the United States and other countries, this is the patient population who may be able to avail themselves of this option.

However, newly proposed legislation in Canada – which has the largest number of physician-assisted deaths worldwide – would expand the indication for MAID to include serious mental illness. Originally set to be passed in March 2023, the law has been deferred for final decision until March 2024.

A recent commentary by psychiatrist Dinah Miller, MD, explored the ethics of this proposed legislation for mental health professionals. “To offer the option of death facilitated by the very person who is trying to get [patients with serious mental illness] better seems so counter to everything I have learned and contradicts our role as psychiatrists who work so hard to prevent suicide,” Dr. Miller wrote. “As psychiatrists, do we offer hope to our most vulnerable patients, or do we offer death? Do we rail against suicide, or do we facilitate it?”

Dr. Miller’s piece garnered a huge amount of reader response that included many laudatory comments: a “nuanced and open-ended inquiry here,” “timely and honest,” and “beautifully written.” One reader thanked the author for “this thoughtful, questioning, and open reflection on what it means to be a psychiatrist facing a thorny and deeply personal practice and philosophical question.”
 

Cognitive distortion or objective reality?

Many readers were opposed to any type of physician involvement in hastening a patient’s death, regardless of whether the condition is medical or psychiatric. “Let others who wish to die make their own arrangement without the aid of the medical profession,” one reader wrote.

But others felt that for those with terminal physical illnesses or intractable pain, it is justified for medical professionals to either facilitate death or, at the very least, withhold life-prolonging treatments.

A critical-care physician described responding to families’ accusations that withdrawal of life-sustaining measures means “playing God.” On the contrary, the physician wrote, “there is a limit to our abilities; and withdrawing those life-prolonging interventions allows nature or God or whatever to play a role and take its course.”

Another U.S. reader pointed out that “multiple polls in this country have shown that the majority of the general public, physicians in general and psychiatrists in particular, support the option of MAID for the terminally ill. They do not find it at variance with their calling as physicians.”

“I and many of my elderly friends don’t fear death but fear prolonged dementia with its dependency and lack of quality of life,” one reader wrote. “We would be much more at peace if we could put in our advanced directive that we request MAID once some point of dependency has been reached.”

Another wrote that in the event of entering a state of “degrading dependency and hardship on the family, please let me go peacefully, without burdening others, into that good night [of death].”

Many felt that not only physical illness but also the prospect of cognitive degeneration – specifically dementia – also justifies assisting patient death.
 

“Enormous suffering”

One Canadian reader noted that provisions for advance consent are now in place in Canada for those facing the prospect of neurodegenerative disease and who are still mentally competent to make such decisions.

But therein lies the rub – the concept of an advanced directive goes to the question of decisional capacity. Dr. Miller noted that “depression distorts cognition and leads many patients to believe that they would be better off dead and that their loves ones would be better off without them.”

The concept of “cognitive distortion” implies that the illness itself may impede the decisional capacity required for an advanced directive or a decision made in the moment, in the absence of such a directive. Dr. Miller asked, “How do we determine whether patients with serious mental illness are competent to make such a decision or whether it is mental illness that is driving their perception of a future without hope?”

One reader attested to this from personal experience. “As both a physician and a sufferer of severe, often profound depression for 50 years, I can confidently say that ... the pursuit of death is the result of an impaired mental state, which simultaneously prevents a rational decision.”

Another agreed. “As a psychiatrist, I treated suicidal patients almost every day of my 27-year career. I believe in making every effort to prevent the suicide of a healthy depressed person and I do not support MAID for psychiatric conditions. But I do support MAID for the terminally ill.”

Other readers disagreed. In the words of one commentator, “I think that if we are going to help mentally ill people, we have to consider their choices. The stress imposed by a severe/intractable mental illness is as bad as any other devastating medical illness. If no one is going to hold their hand in life (as support services are limited and psychiatric treatments often fail), allow a medical professional to hold their hand through their final moments.”

A psychiatrist described very ill patients with treatment-resistant bipolar disorder who had not only received medications, including ketamine, but had also received electroconvulsive therapy and still did not respond.

“Their suffering is enormous and the truth is that there is no improvement for more than a few days or weeks and later they return to their hell. Appreciating that they would be better off dead for themselves and their families is not always a cognitive distortion but an objective evaluation of their reality.”

However, as another reader pointed out, an issue with the argument presented here is that it presupposes that MAID requires “clinical justification.” But in Canada, “MAID ... is understood as an expression of personal autonomy. Rooted in liberal political philosophy of individualism ... approval for death need not be based on a clinical assessment.” Instead, “death is seen as a ‘right’ that the state must therefore provide.”
 

Another form of eugenics?

Dr. Miller raised the ethical implications of racial and socioeconomic factors playing a role in the consideration of MAID for those with psychiatric illness.

“Might those who are poor, who have less access to expensive treatment options and social support, be more likely to request facilitated death?” she asks. “Do we risk facilitating a patient’s demise when other options are unavailable because of a lack of access to treatment or when social and financial struggles exacerbate a person’s hopelessness? Should we worry that psychiatric euthanasia will turn into a form of eugenics where those who can’t contribute are made to feel that they should bow out?”

Several readers agreed. “Looking at the disproportionate burden of illness, rates of imprisonment, and application of the death penalty indicates to me that race and socioeconomic status will be an immediate factor in how, where, and with whom MAID for mental illness would be practice in much, if not all, of the U.S.,” wrote one physician.

A Canadian reader expressed similar concerns. “I’ve seen a handful of people, including someone I considered a good friend, opt for MAID because it was easier than living as a disabled person in poverty without adequate mental health care.”

Another Canadian clinician noted that offering people good care can make all the difference. “As a Canadian mental health clinician who served youth with severe mental illness for over 20 years through our socialized medical network, I can attest to the difference good care usually makes in shifting clients from despair and a commitment to death to embracing life once again. Let’s not, as clinicians, embrace easing a government/state-sanctioned pathway to death.”

Some readers believe that these types of issues can’t be solved with a blanket approach, noting that each case is different. “Real life is always more complicated than academic discussions. Having served on a hospital ethics committee, I know that each case is unique,” one reader noted.

Another reader added, “I think all we can do as physicians is to let people decide for themselves and participate only if our conscience allows.”
 

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

One of the most controversial issues today is whether a physician should be permitted, or even obligated, to assist patients with a terminal or incurable illness to end their life – a process known as medical assistance in dying (MAID) or physician-assisted suicide (PAS.)

Until recently, this contentious issue applied only to patients with physical illnesses who want to end their suffering and who seek out a physician willing to assist with that objective. In the United States and other countries, this is the patient population who may be able to avail themselves of this option.

However, newly proposed legislation in Canada – which has the largest number of physician-assisted deaths worldwide – would expand the indication for MAID to include serious mental illness. Originally set to be passed in March 2023, the law has been deferred for final decision until March 2024.

A recent commentary by psychiatrist Dinah Miller, MD, explored the ethics of this proposed legislation for mental health professionals. “To offer the option of death facilitated by the very person who is trying to get [patients with serious mental illness] better seems so counter to everything I have learned and contradicts our role as psychiatrists who work so hard to prevent suicide,” Dr. Miller wrote. “As psychiatrists, do we offer hope to our most vulnerable patients, or do we offer death? Do we rail against suicide, or do we facilitate it?”

Dr. Miller’s piece garnered a huge amount of reader response that included many laudatory comments: a “nuanced and open-ended inquiry here,” “timely and honest,” and “beautifully written.” One reader thanked the author for “this thoughtful, questioning, and open reflection on what it means to be a psychiatrist facing a thorny and deeply personal practice and philosophical question.”
 

Cognitive distortion or objective reality?

Many readers were opposed to any type of physician involvement in hastening a patient’s death, regardless of whether the condition is medical or psychiatric. “Let others who wish to die make their own arrangement without the aid of the medical profession,” one reader wrote.

But others felt that for those with terminal physical illnesses or intractable pain, it is justified for medical professionals to either facilitate death or, at the very least, withhold life-prolonging treatments.

A critical-care physician described responding to families’ accusations that withdrawal of life-sustaining measures means “playing God.” On the contrary, the physician wrote, “there is a limit to our abilities; and withdrawing those life-prolonging interventions allows nature or God or whatever to play a role and take its course.”

Another U.S. reader pointed out that “multiple polls in this country have shown that the majority of the general public, physicians in general and psychiatrists in particular, support the option of MAID for the terminally ill. They do not find it at variance with their calling as physicians.”

“I and many of my elderly friends don’t fear death but fear prolonged dementia with its dependency and lack of quality of life,” one reader wrote. “We would be much more at peace if we could put in our advanced directive that we request MAID once some point of dependency has been reached.”

Another wrote that in the event of entering a state of “degrading dependency and hardship on the family, please let me go peacefully, without burdening others, into that good night [of death].”

Many felt that not only physical illness but also the prospect of cognitive degeneration – specifically dementia – also justifies assisting patient death.
 

“Enormous suffering”

One Canadian reader noted that provisions for advance consent are now in place in Canada for those facing the prospect of neurodegenerative disease and who are still mentally competent to make such decisions.

But therein lies the rub – the concept of an advanced directive goes to the question of decisional capacity. Dr. Miller noted that “depression distorts cognition and leads many patients to believe that they would be better off dead and that their loves ones would be better off without them.”

The concept of “cognitive distortion” implies that the illness itself may impede the decisional capacity required for an advanced directive or a decision made in the moment, in the absence of such a directive. Dr. Miller asked, “How do we determine whether patients with serious mental illness are competent to make such a decision or whether it is mental illness that is driving their perception of a future without hope?”

One reader attested to this from personal experience. “As both a physician and a sufferer of severe, often profound depression for 50 years, I can confidently say that ... the pursuit of death is the result of an impaired mental state, which simultaneously prevents a rational decision.”

Another agreed. “As a psychiatrist, I treated suicidal patients almost every day of my 27-year career. I believe in making every effort to prevent the suicide of a healthy depressed person and I do not support MAID for psychiatric conditions. But I do support MAID for the terminally ill.”

Other readers disagreed. In the words of one commentator, “I think that if we are going to help mentally ill people, we have to consider their choices. The stress imposed by a severe/intractable mental illness is as bad as any other devastating medical illness. If no one is going to hold their hand in life (as support services are limited and psychiatric treatments often fail), allow a medical professional to hold their hand through their final moments.”

A psychiatrist described very ill patients with treatment-resistant bipolar disorder who had not only received medications, including ketamine, but had also received electroconvulsive therapy and still did not respond.

“Their suffering is enormous and the truth is that there is no improvement for more than a few days or weeks and later they return to their hell. Appreciating that they would be better off dead for themselves and their families is not always a cognitive distortion but an objective evaluation of their reality.”

However, as another reader pointed out, an issue with the argument presented here is that it presupposes that MAID requires “clinical justification.” But in Canada, “MAID ... is understood as an expression of personal autonomy. Rooted in liberal political philosophy of individualism ... approval for death need not be based on a clinical assessment.” Instead, “death is seen as a ‘right’ that the state must therefore provide.”
 

Another form of eugenics?

Dr. Miller raised the ethical implications of racial and socioeconomic factors playing a role in the consideration of MAID for those with psychiatric illness.

“Might those who are poor, who have less access to expensive treatment options and social support, be more likely to request facilitated death?” she asks. “Do we risk facilitating a patient’s demise when other options are unavailable because of a lack of access to treatment or when social and financial struggles exacerbate a person’s hopelessness? Should we worry that psychiatric euthanasia will turn into a form of eugenics where those who can’t contribute are made to feel that they should bow out?”

Several readers agreed. “Looking at the disproportionate burden of illness, rates of imprisonment, and application of the death penalty indicates to me that race and socioeconomic status will be an immediate factor in how, where, and with whom MAID for mental illness would be practice in much, if not all, of the U.S.,” wrote one physician.

A Canadian reader expressed similar concerns. “I’ve seen a handful of people, including someone I considered a good friend, opt for MAID because it was easier than living as a disabled person in poverty without adequate mental health care.”

Another Canadian clinician noted that offering people good care can make all the difference. “As a Canadian mental health clinician who served youth with severe mental illness for over 20 years through our socialized medical network, I can attest to the difference good care usually makes in shifting clients from despair and a commitment to death to embracing life once again. Let’s not, as clinicians, embrace easing a government/state-sanctioned pathway to death.”

Some readers believe that these types of issues can’t be solved with a blanket approach, noting that each case is different. “Real life is always more complicated than academic discussions. Having served on a hospital ethics committee, I know that each case is unique,” one reader noted.

Another reader added, “I think all we can do as physicians is to let people decide for themselves and participate only if our conscience allows.”
 

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

One of the most controversial issues today is whether a physician should be permitted, or even obligated, to assist patients with a terminal or incurable illness to end their life – a process known as medical assistance in dying (MAID) or physician-assisted suicide (PAS.)

Until recently, this contentious issue applied only to patients with physical illnesses who want to end their suffering and who seek out a physician willing to assist with that objective. In the United States and other countries, this is the patient population who may be able to avail themselves of this option.

However, newly proposed legislation in Canada – which has the largest number of physician-assisted deaths worldwide – would expand the indication for MAID to include serious mental illness. Originally set to be passed in March 2023, the law has been deferred for final decision until March 2024.

A recent commentary by psychiatrist Dinah Miller, MD, explored the ethics of this proposed legislation for mental health professionals. “To offer the option of death facilitated by the very person who is trying to get [patients with serious mental illness] better seems so counter to everything I have learned and contradicts our role as psychiatrists who work so hard to prevent suicide,” Dr. Miller wrote. “As psychiatrists, do we offer hope to our most vulnerable patients, or do we offer death? Do we rail against suicide, or do we facilitate it?”

Dr. Miller’s piece garnered a huge amount of reader response that included many laudatory comments: a “nuanced and open-ended inquiry here,” “timely and honest,” and “beautifully written.” One reader thanked the author for “this thoughtful, questioning, and open reflection on what it means to be a psychiatrist facing a thorny and deeply personal practice and philosophical question.”
 

Cognitive distortion or objective reality?

Many readers were opposed to any type of physician involvement in hastening a patient’s death, regardless of whether the condition is medical or psychiatric. “Let others who wish to die make their own arrangement without the aid of the medical profession,” one reader wrote.

But others felt that for those with terminal physical illnesses or intractable pain, it is justified for medical professionals to either facilitate death or, at the very least, withhold life-prolonging treatments.

A critical-care physician described responding to families’ accusations that withdrawal of life-sustaining measures means “playing God.” On the contrary, the physician wrote, “there is a limit to our abilities; and withdrawing those life-prolonging interventions allows nature or God or whatever to play a role and take its course.”

Another U.S. reader pointed out that “multiple polls in this country have shown that the majority of the general public, physicians in general and psychiatrists in particular, support the option of MAID for the terminally ill. They do not find it at variance with their calling as physicians.”

“I and many of my elderly friends don’t fear death but fear prolonged dementia with its dependency and lack of quality of life,” one reader wrote. “We would be much more at peace if we could put in our advanced directive that we request MAID once some point of dependency has been reached.”

Another wrote that in the event of entering a state of “degrading dependency and hardship on the family, please let me go peacefully, without burdening others, into that good night [of death].”

Many felt that not only physical illness but also the prospect of cognitive degeneration – specifically dementia – also justifies assisting patient death.
 

“Enormous suffering”

One Canadian reader noted that provisions for advance consent are now in place in Canada for those facing the prospect of neurodegenerative disease and who are still mentally competent to make such decisions.

But therein lies the rub – the concept of an advanced directive goes to the question of decisional capacity. Dr. Miller noted that “depression distorts cognition and leads many patients to believe that they would be better off dead and that their loves ones would be better off without them.”

The concept of “cognitive distortion” implies that the illness itself may impede the decisional capacity required for an advanced directive or a decision made in the moment, in the absence of such a directive. Dr. Miller asked, “How do we determine whether patients with serious mental illness are competent to make such a decision or whether it is mental illness that is driving their perception of a future without hope?”

One reader attested to this from personal experience. “As both a physician and a sufferer of severe, often profound depression for 50 years, I can confidently say that ... the pursuit of death is the result of an impaired mental state, which simultaneously prevents a rational decision.”

Another agreed. “As a psychiatrist, I treated suicidal patients almost every day of my 27-year career. I believe in making every effort to prevent the suicide of a healthy depressed person and I do not support MAID for psychiatric conditions. But I do support MAID for the terminally ill.”

Other readers disagreed. In the words of one commentator, “I think that if we are going to help mentally ill people, we have to consider their choices. The stress imposed by a severe/intractable mental illness is as bad as any other devastating medical illness. If no one is going to hold their hand in life (as support services are limited and psychiatric treatments often fail), allow a medical professional to hold their hand through their final moments.”

A psychiatrist described very ill patients with treatment-resistant bipolar disorder who had not only received medications, including ketamine, but had also received electroconvulsive therapy and still did not respond.

“Their suffering is enormous and the truth is that there is no improvement for more than a few days or weeks and later they return to their hell. Appreciating that they would be better off dead for themselves and their families is not always a cognitive distortion but an objective evaluation of their reality.”

However, as another reader pointed out, an issue with the argument presented here is that it presupposes that MAID requires “clinical justification.” But in Canada, “MAID ... is understood as an expression of personal autonomy. Rooted in liberal political philosophy of individualism ... approval for death need not be based on a clinical assessment.” Instead, “death is seen as a ‘right’ that the state must therefore provide.”
 

Another form of eugenics?

Dr. Miller raised the ethical implications of racial and socioeconomic factors playing a role in the consideration of MAID for those with psychiatric illness.

“Might those who are poor, who have less access to expensive treatment options and social support, be more likely to request facilitated death?” she asks. “Do we risk facilitating a patient’s demise when other options are unavailable because of a lack of access to treatment or when social and financial struggles exacerbate a person’s hopelessness? Should we worry that psychiatric euthanasia will turn into a form of eugenics where those who can’t contribute are made to feel that they should bow out?”

Several readers agreed. “Looking at the disproportionate burden of illness, rates of imprisonment, and application of the death penalty indicates to me that race and socioeconomic status will be an immediate factor in how, where, and with whom MAID for mental illness would be practice in much, if not all, of the U.S.,” wrote one physician.

A Canadian reader expressed similar concerns. “I’ve seen a handful of people, including someone I considered a good friend, opt for MAID because it was easier than living as a disabled person in poverty without adequate mental health care.”

Another Canadian clinician noted that offering people good care can make all the difference. “As a Canadian mental health clinician who served youth with severe mental illness for over 20 years through our socialized medical network, I can attest to the difference good care usually makes in shifting clients from despair and a commitment to death to embracing life once again. Let’s not, as clinicians, embrace easing a government/state-sanctioned pathway to death.”

Some readers believe that these types of issues can’t be solved with a blanket approach, noting that each case is different. “Real life is always more complicated than academic discussions. Having served on a hospital ethics committee, I know that each case is unique,” one reader noted.

Another reader added, “I think all we can do as physicians is to let people decide for themselves and participate only if our conscience allows.”
 

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

For the first time, the Food and Drug Administration approved a pill taken once daily for 14 days to help women manage the often strong, sometimes overpowering symptoms of postpartum depression.

Several experts in mental health and women’s health offered their views of this new treatment option for a condition that affects an estimated 1 in 8 women in the United States. What will it mean for easing symptoms such as hopelessness, crankiness, and lack of interest in bonding with the baby or, in the case of multiples, babies – and in some cases, thoughts of death or suicide?
 

A fast-acting option

“We don’t have many oral medications that are fast-acting antidepressants, so this is incredibly exciting,” said Sarah Oreck, MD, a psychiatrist in private practice in Los Angeles who specializes in reproductive psychiatry. The rapid response is likely because the medication targets the hormonal mechanism underlying postpartum depression, she added.

Zuranolone (Zurzuvae, Biogen/Sage) is different from most other antidepressants – it is designed to be taken for a shorter period. Also, Because zuranolone is a pill, it is more convenient to take than the other FDA-approved treatment, the IV infusion brexanolone (Zulresso, Sage).

“It’s obviously game changing to have something in pill form. The infusion has to be done at an infusion center to monitor people for any complications,” said Kimberly Yonkers, MD, a psychiatrist specializing in women’s health, a Distinguished Life Fellow of the American Psychiatric Association (APA), and the Katz Family Chair of Psychiatry at the University of Massachusetts Chan Medical School/UMass Memorial Medical Center in Worcester.

Women may experience improvement in postpartum depression in as soon as 3 days after starting the medication. In contrast, “typical antidepressants can take up to 2 weeks before patients notice a difference and 4 to 8 weeks to see a full response. A fast-acting pill that can be taken orally could be an ideal option for the 15% to 20% of women who experience postpartum depression,” said Priya Gopalan, MD, a psychiatrist with UPMC Western Psychiatric Hospital and Magee-Womens Hospital in Pittsburgh.

The medical community, and reproductive psychiatrists in particular, has always suspected differences in the biological underpinnings of postpartum depression and major depressive disorder, Dr. Oreck said. “We know that postpartum depression looks different from major depressive disorder and that hormonal shifts during pregnancy and postpartum are a huge risk factor for postpartum depression,” she said.

Although selective serotonin reuptake inhibitors (SSRIs) are helpful and currently the standard of care for treating moderate to severe postpartum depression in combination with therapy, Dr. Oreck added, early studies suggest that zuranolone may work faster and potentially be more effective than SSRIs in treating the condition.

Zuranolone is a version of a naturally occurring hormone called allopregnanolone, a metabolite of progesterone. Concentrations of allopregnanolone rise dramatically during pregnancy and then drop precipitously after childbirth. Zuranolone works through modulating GABA-A, a neurotransmitter implicated in the development of depression.

“It is encouraging that postpartum individuals may now have more options to manage a debilitating condition that affects them and their families,” said Christopher Zahn, MD, interim CEO and chief of clinical practice and health equity and quality for the American College of Obstetricians and Gynecologists (ACOG).

ACOG recommends women be screened for depression at least three times – during early pregnancy, later in pregnancy, and again after delivery. A decision to start this or any other medicine should be individualized and based on shared decision-making between a patient and doctor, Dr. Zahn added.

The cost of zuranolone is not yet known. Dr. Yonkers said cost of the infusion can serve as a cautionary tale for the manufacturer. Some reports put the infusion cost at $34,000. “Cost is going to be an important component to this. The previous intervention was priced so high that it was not affordable to many people and it was difficult to access.”
 

Beyond ‘baby blues’

The APA has changed the name from “postpartum depression” to “peripartum depression” because evidence suggests feelings and symptoms also can start late in pregnancy. “It means you don’t have to wait until somebody delivers to screen for depression. We have to recognize that depression can occur during pregnancy,” Dr. Yonkers said. “In fact it is not uncommon during the third trimester.”

No matter when it starts, the condition can be “very serious,” particularly if the person already experiences depression, including bipolar disorder, Dr. Yonkers added.

Postpartum depression “is more than just ‘baby blues.’ It is a potentially debilitating illness that causes feelings of intense sadness and worthlessness, making it difficult to care for and bond with your newborn,” Dr. Gopalan said.
 

Can be a medical emergency

Severe postpartum depression requires immediate attention and treatment.

“One of the things we have to be cautious about is for people with previous predisposition to hurt themselves,” Dr. Yonkers said. “It is therefore important to consider somebody’s medical and behavioral health history as well.

“For an individual with recurring depression or severe episodes of depression, this may not be sufficient, because they are just going to get these 14 days of therapy,” Dr. Yonkers said. “They may need ongoing antidepressants.

“It may not be the right pill for everybody,” Dr. Yonkers added. She recommended everyone be followed closely during and after treatment “to make sure they are responding and to monitor for relapse.”
 

The science that led to approval

The clinical trials showed early response in patients with severe postpartum depression. Researchers conducted two studies of women who developed a major depressive episode in the third trimester of pregnancy or within 4 weeks of delivery. They found women who took zuranolone once in the evening for 14 days “showed significantly more improvement in their symptoms compared to those in the placebo group.”

The antidepressant effect lasted at least 4 weeks after stopping the medication.

Drowsiness, dizziness, diarrhea, fatigue, nasopharyngitis, and urinary tract infection were the most common side effects. The label has a boxed warning noting that the medication can affect a person’s ability to drive and perform other potentially hazardous activities. Use of zuranolone may also cause suicidal thoughts and behavior, according to an FDA news release announcing the approval.
 

The start of more help for mothers?

Zuranolone is not a cure-all. As with most psychiatric prescriptions, the medication likely will work best in conjunction with behavioral health treatments such as psychotherapy, use of other medications, behavioral management, support groups, and self-care tools such as meditation, exercise, and yoga, Dr. Gopalan said.

Dr. Oreck said she hopes this first pill approval will lead to more discoveries. “I hope this is the beginning of more innovation and development of novel treatments that can target women’s mental health issues specifically – female reproductive hormones impact mental health in unique ways and it’s exciting to finally see research and development dollars dedicated to them,” she said. “The FDA approval of this pill provides the potential to improve the lives of millions of Americans suffering from postpartum depression.”

Dr. Oreck, Dr. Yonkers, Dr. Gopalan, and Dr. Zahn have disclosed no relevant financial relationships.
 

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

For the first time, the Food and Drug Administration approved a pill taken once daily for 14 days to help women manage the often strong, sometimes overpowering symptoms of postpartum depression.

Several experts in mental health and women’s health offered their views of this new treatment option for a condition that affects an estimated 1 in 8 women in the United States. What will it mean for easing symptoms such as hopelessness, crankiness, and lack of interest in bonding with the baby or, in the case of multiples, babies – and in some cases, thoughts of death or suicide?
 

A fast-acting option

“We don’t have many oral medications that are fast-acting antidepressants, so this is incredibly exciting,” said Sarah Oreck, MD, a psychiatrist in private practice in Los Angeles who specializes in reproductive psychiatry. The rapid response is likely because the medication targets the hormonal mechanism underlying postpartum depression, she added.

Zuranolone (Zurzuvae, Biogen/Sage) is different from most other antidepressants – it is designed to be taken for a shorter period. Also, Because zuranolone is a pill, it is more convenient to take than the other FDA-approved treatment, the IV infusion brexanolone (Zulresso, Sage).

“It’s obviously game changing to have something in pill form. The infusion has to be done at an infusion center to monitor people for any complications,” said Kimberly Yonkers, MD, a psychiatrist specializing in women’s health, a Distinguished Life Fellow of the American Psychiatric Association (APA), and the Katz Family Chair of Psychiatry at the University of Massachusetts Chan Medical School/UMass Memorial Medical Center in Worcester.

Women may experience improvement in postpartum depression in as soon as 3 days after starting the medication. In contrast, “typical antidepressants can take up to 2 weeks before patients notice a difference and 4 to 8 weeks to see a full response. A fast-acting pill that can be taken orally could be an ideal option for the 15% to 20% of women who experience postpartum depression,” said Priya Gopalan, MD, a psychiatrist with UPMC Western Psychiatric Hospital and Magee-Womens Hospital in Pittsburgh.

The medical community, and reproductive psychiatrists in particular, has always suspected differences in the biological underpinnings of postpartum depression and major depressive disorder, Dr. Oreck said. “We know that postpartum depression looks different from major depressive disorder and that hormonal shifts during pregnancy and postpartum are a huge risk factor for postpartum depression,” she said.

Although selective serotonin reuptake inhibitors (SSRIs) are helpful and currently the standard of care for treating moderate to severe postpartum depression in combination with therapy, Dr. Oreck added, early studies suggest that zuranolone may work faster and potentially be more effective than SSRIs in treating the condition.

Zuranolone is a version of a naturally occurring hormone called allopregnanolone, a metabolite of progesterone. Concentrations of allopregnanolone rise dramatically during pregnancy and then drop precipitously after childbirth. Zuranolone works through modulating GABA-A, a neurotransmitter implicated in the development of depression.

“It is encouraging that postpartum individuals may now have more options to manage a debilitating condition that affects them and their families,” said Christopher Zahn, MD, interim CEO and chief of clinical practice and health equity and quality for the American College of Obstetricians and Gynecologists (ACOG).

ACOG recommends women be screened for depression at least three times – during early pregnancy, later in pregnancy, and again after delivery. A decision to start this or any other medicine should be individualized and based on shared decision-making between a patient and doctor, Dr. Zahn added.

The cost of zuranolone is not yet known. Dr. Yonkers said cost of the infusion can serve as a cautionary tale for the manufacturer. Some reports put the infusion cost at $34,000. “Cost is going to be an important component to this. The previous intervention was priced so high that it was not affordable to many people and it was difficult to access.”
 

Beyond ‘baby blues’

The APA has changed the name from “postpartum depression” to “peripartum depression” because evidence suggests feelings and symptoms also can start late in pregnancy. “It means you don’t have to wait until somebody delivers to screen for depression. We have to recognize that depression can occur during pregnancy,” Dr. Yonkers said. “In fact it is not uncommon during the third trimester.”

No matter when it starts, the condition can be “very serious,” particularly if the person already experiences depression, including bipolar disorder, Dr. Yonkers added.

Postpartum depression “is more than just ‘baby blues.’ It is a potentially debilitating illness that causes feelings of intense sadness and worthlessness, making it difficult to care for and bond with your newborn,” Dr. Gopalan said.
 

Can be a medical emergency

Severe postpartum depression requires immediate attention and treatment.

“One of the things we have to be cautious about is for people with previous predisposition to hurt themselves,” Dr. Yonkers said. “It is therefore important to consider somebody’s medical and behavioral health history as well.

“For an individual with recurring depression or severe episodes of depression, this may not be sufficient, because they are just going to get these 14 days of therapy,” Dr. Yonkers said. “They may need ongoing antidepressants.

“It may not be the right pill for everybody,” Dr. Yonkers added. She recommended everyone be followed closely during and after treatment “to make sure they are responding and to monitor for relapse.”
 

The science that led to approval

The clinical trials showed early response in patients with severe postpartum depression. Researchers conducted two studies of women who developed a major depressive episode in the third trimester of pregnancy or within 4 weeks of delivery. They found women who took zuranolone once in the evening for 14 days “showed significantly more improvement in their symptoms compared to those in the placebo group.”

The antidepressant effect lasted at least 4 weeks after stopping the medication.

Drowsiness, dizziness, diarrhea, fatigue, nasopharyngitis, and urinary tract infection were the most common side effects. The label has a boxed warning noting that the medication can affect a person’s ability to drive and perform other potentially hazardous activities. Use of zuranolone may also cause suicidal thoughts and behavior, according to an FDA news release announcing the approval.
 

The start of more help for mothers?

Zuranolone is not a cure-all. As with most psychiatric prescriptions, the medication likely will work best in conjunction with behavioral health treatments such as psychotherapy, use of other medications, behavioral management, support groups, and self-care tools such as meditation, exercise, and yoga, Dr. Gopalan said.

Dr. Oreck said she hopes this first pill approval will lead to more discoveries. “I hope this is the beginning of more innovation and development of novel treatments that can target women’s mental health issues specifically – female reproductive hormones impact mental health in unique ways and it’s exciting to finally see research and development dollars dedicated to them,” she said. “The FDA approval of this pill provides the potential to improve the lives of millions of Americans suffering from postpartum depression.”

Dr. Oreck, Dr. Yonkers, Dr. Gopalan, and Dr. Zahn have disclosed no relevant financial relationships.
 

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

For the first time, the Food and Drug Administration approved a pill taken once daily for 14 days to help women manage the often strong, sometimes overpowering symptoms of postpartum depression.

Several experts in mental health and women’s health offered their views of this new treatment option for a condition that affects an estimated 1 in 8 women in the United States. What will it mean for easing symptoms such as hopelessness, crankiness, and lack of interest in bonding with the baby or, in the case of multiples, babies – and in some cases, thoughts of death or suicide?
 

A fast-acting option

“We don’t have many oral medications that are fast-acting antidepressants, so this is incredibly exciting,” said Sarah Oreck, MD, a psychiatrist in private practice in Los Angeles who specializes in reproductive psychiatry. The rapid response is likely because the medication targets the hormonal mechanism underlying postpartum depression, she added.

Zuranolone (Zurzuvae, Biogen/Sage) is different from most other antidepressants – it is designed to be taken for a shorter period. Also, Because zuranolone is a pill, it is more convenient to take than the other FDA-approved treatment, the IV infusion brexanolone (Zulresso, Sage).

“It’s obviously game changing to have something in pill form. The infusion has to be done at an infusion center to monitor people for any complications,” said Kimberly Yonkers, MD, a psychiatrist specializing in women’s health, a Distinguished Life Fellow of the American Psychiatric Association (APA), and the Katz Family Chair of Psychiatry at the University of Massachusetts Chan Medical School/UMass Memorial Medical Center in Worcester.

Women may experience improvement in postpartum depression in as soon as 3 days after starting the medication. In contrast, “typical antidepressants can take up to 2 weeks before patients notice a difference and 4 to 8 weeks to see a full response. A fast-acting pill that can be taken orally could be an ideal option for the 15% to 20% of women who experience postpartum depression,” said Priya Gopalan, MD, a psychiatrist with UPMC Western Psychiatric Hospital and Magee-Womens Hospital in Pittsburgh.

The medical community, and reproductive psychiatrists in particular, has always suspected differences in the biological underpinnings of postpartum depression and major depressive disorder, Dr. Oreck said. “We know that postpartum depression looks different from major depressive disorder and that hormonal shifts during pregnancy and postpartum are a huge risk factor for postpartum depression,” she said.

Although selective serotonin reuptake inhibitors (SSRIs) are helpful and currently the standard of care for treating moderate to severe postpartum depression in combination with therapy, Dr. Oreck added, early studies suggest that zuranolone may work faster and potentially be more effective than SSRIs in treating the condition.

Zuranolone is a version of a naturally occurring hormone called allopregnanolone, a metabolite of progesterone. Concentrations of allopregnanolone rise dramatically during pregnancy and then drop precipitously after childbirth. Zuranolone works through modulating GABA-A, a neurotransmitter implicated in the development of depression.

“It is encouraging that postpartum individuals may now have more options to manage a debilitating condition that affects them and their families,” said Christopher Zahn, MD, interim CEO and chief of clinical practice and health equity and quality for the American College of Obstetricians and Gynecologists (ACOG).

ACOG recommends women be screened for depression at least three times – during early pregnancy, later in pregnancy, and again after delivery. A decision to start this or any other medicine should be individualized and based on shared decision-making between a patient and doctor, Dr. Zahn added.

The cost of zuranolone is not yet known. Dr. Yonkers said cost of the infusion can serve as a cautionary tale for the manufacturer. Some reports put the infusion cost at $34,000. “Cost is going to be an important component to this. The previous intervention was priced so high that it was not affordable to many people and it was difficult to access.”
 

Beyond ‘baby blues’

The APA has changed the name from “postpartum depression” to “peripartum depression” because evidence suggests feelings and symptoms also can start late in pregnancy. “It means you don’t have to wait until somebody delivers to screen for depression. We have to recognize that depression can occur during pregnancy,” Dr. Yonkers said. “In fact it is not uncommon during the third trimester.”

No matter when it starts, the condition can be “very serious,” particularly if the person already experiences depression, including bipolar disorder, Dr. Yonkers added.

Postpartum depression “is more than just ‘baby blues.’ It is a potentially debilitating illness that causes feelings of intense sadness and worthlessness, making it difficult to care for and bond with your newborn,” Dr. Gopalan said.
 

Can be a medical emergency

Severe postpartum depression requires immediate attention and treatment.

“One of the things we have to be cautious about is for people with previous predisposition to hurt themselves,” Dr. Yonkers said. “It is therefore important to consider somebody’s medical and behavioral health history as well.

“For an individual with recurring depression or severe episodes of depression, this may not be sufficient, because they are just going to get these 14 days of therapy,” Dr. Yonkers said. “They may need ongoing antidepressants.

“It may not be the right pill for everybody,” Dr. Yonkers added. She recommended everyone be followed closely during and after treatment “to make sure they are responding and to monitor for relapse.”
 

The science that led to approval

The clinical trials showed early response in patients with severe postpartum depression. Researchers conducted two studies of women who developed a major depressive episode in the third trimester of pregnancy or within 4 weeks of delivery. They found women who took zuranolone once in the evening for 14 days “showed significantly more improvement in their symptoms compared to those in the placebo group.”

The antidepressant effect lasted at least 4 weeks after stopping the medication.

Drowsiness, dizziness, diarrhea, fatigue, nasopharyngitis, and urinary tract infection were the most common side effects. The label has a boxed warning noting that the medication can affect a person’s ability to drive and perform other potentially hazardous activities. Use of zuranolone may also cause suicidal thoughts and behavior, according to an FDA news release announcing the approval.
 

The start of more help for mothers?

Zuranolone is not a cure-all. As with most psychiatric prescriptions, the medication likely will work best in conjunction with behavioral health treatments such as psychotherapy, use of other medications, behavioral management, support groups, and self-care tools such as meditation, exercise, and yoga, Dr. Gopalan said.

Dr. Oreck said she hopes this first pill approval will lead to more discoveries. “I hope this is the beginning of more innovation and development of novel treatments that can target women’s mental health issues specifically – female reproductive hormones impact mental health in unique ways and it’s exciting to finally see research and development dollars dedicated to them,” she said. “The FDA approval of this pill provides the potential to improve the lives of millions of Americans suffering from postpartum depression.”

Dr. Oreck, Dr. Yonkers, Dr. Gopalan, and Dr. Zahn have disclosed no relevant financial relationships.
 

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

Ancestry was a significant predictor of response to lithium by adults with bipolar disorder (BPD), based on data from 172 individuals.

Lithium remains the first-line treatment for BPD, but clinical improvement occurs in less than one-third of patients, and factors that might affect response, especially genetic factors, have not been well studied, wrote Ana M. Díaz-Zuluaga, MD, of University of Antioquia, Medellín, Colombia, and colleagues.

Previous genetic research identified four linked single nucleotide polymorphisms (SNPs) in a single locus on chromosome 21 that were associated with lithium response, but the study was limited to individuals with European and Asian ancestry, the researchers said.

In a study published in the Journal of Affective Disorders, the researchers identified 172 adults aged 18 and older with a diagnosis of BPD I or II based on the DSM-IV-TR criteria. Participants had been taking lithium continuously for at least 6 months. Lithium response was defined using the Retrospective Criteria of Long-Term Treatment Response in Research Subjects with BD, also known as the Alda scale. Total Alda scale scores of 7 or higher indicated a responder phenotype; scores less than 7 were considered nonresponders.

Ancestry was determined using DNA samples and the software Structure Version 2.2, and participants were classified as Amerindian, African, or European.

The overall response rate to lithium was 15.11% (26 of 172 patients). In a univariate analysis, no significant differences emerged between responders and nonresponders in demographics or clinical characteristics. However, patients responsive to lithium were significantly less likely of African ancestry, compared with nonresponders (0.1 vs. 0.2, P = .005) and more likely of European ancestry (0.5 vs. 0.3, P = .024), and had fewer depressive episodes (2 vs. 3.9, P = .002). The difference in responders vs. nonresponders of Amerindian ancestry was not statistically significant (0.4 vs. 0.5, P = .204).

The researchers then used machine learning based on Advanced Recursive Partitioning Approaches (ARPAs) to create classification trees with and without ancestry components for predicting response to lithium. “Variable importance analysis shows that the most important predictor is the probability of Amerindian ancestry component, followed by the Amerindian and European ancestral components individual variances, and then by the African and European ancestry components,” the researchers wrote.

Without the ancestry component, the sensitivity and specificity for predicting a treatment response to lithium were 50% and 94.5% respectively, with an area under the curve of 72.2%.

“However, when ancestral components are included in the model, the sensitivity and specificity are 93 % and 84 %, respectively,” with an AUC of 89.2%, the researchers said.

Clinical predictors of treatment response included disease duration, number of depressive episodes, total number of affective episodes, and number of manic episodes.

The findings were limited by several factors including the cross-sectional design and potential impact of other psychotropic drugs, the researchers noted. A replication of the study in an independent dataset is needed to validate the findings, they said.

However, the study is the first known to explore the effect of ancestry on bipolar patients’ response to lithium, and suggests that ancestry components have potential predictive value in the clinical setting that could support a more personalized approach to treatment, the researchers said.

The study was supported by PRISMA U.T., Colciencias, Invitación 990 del 3 de Agosto de 2017, Código 111577757629, Contrato 781 de 2017; Convocatoria Programática Ciencias de la Salud 2014-2015 CODI-UdeA, and Convocatoria N.727-2015 Doctorados Nacionales, Colciencias, 2015. The researchers had no financial conflicts to disclose.

Ancestry was a significant predictor of response to lithium by adults with bipolar disorder (BPD), based on data from 172 individuals.

Lithium remains the first-line treatment for BPD, but clinical improvement occurs in less than one-third of patients, and factors that might affect response, especially genetic factors, have not been well studied, wrote Ana M. Díaz-Zuluaga, MD, of University of Antioquia, Medellín, Colombia, and colleagues.

Previous genetic research identified four linked single nucleotide polymorphisms (SNPs) in a single locus on chromosome 21 that were associated with lithium response, but the study was limited to individuals with European and Asian ancestry, the researchers said.

In a study published in the Journal of Affective Disorders, the researchers identified 172 adults aged 18 and older with a diagnosis of BPD I or II based on the DSM-IV-TR criteria. Participants had been taking lithium continuously for at least 6 months. Lithium response was defined using the Retrospective Criteria of Long-Term Treatment Response in Research Subjects with BD, also known as the Alda scale. Total Alda scale scores of 7 or higher indicated a responder phenotype; scores less than 7 were considered nonresponders.

Ancestry was determined using DNA samples and the software Structure Version 2.2, and participants were classified as Amerindian, African, or European.

The overall response rate to lithium was 15.11% (26 of 172 patients). In a univariate analysis, no significant differences emerged between responders and nonresponders in demographics or clinical characteristics. However, patients responsive to lithium were significantly less likely of African ancestry, compared with nonresponders (0.1 vs. 0.2, P = .005) and more likely of European ancestry (0.5 vs. 0.3, P = .024), and had fewer depressive episodes (2 vs. 3.9, P = .002). The difference in responders vs. nonresponders of Amerindian ancestry was not statistically significant (0.4 vs. 0.5, P = .204).

The researchers then used machine learning based on Advanced Recursive Partitioning Approaches (ARPAs) to create classification trees with and without ancestry components for predicting response to lithium. “Variable importance analysis shows that the most important predictor is the probability of Amerindian ancestry component, followed by the Amerindian and European ancestral components individual variances, and then by the African and European ancestry components,” the researchers wrote.

Without the ancestry component, the sensitivity and specificity for predicting a treatment response to lithium were 50% and 94.5% respectively, with an area under the curve of 72.2%.

“However, when ancestral components are included in the model, the sensitivity and specificity are 93 % and 84 %, respectively,” with an AUC of 89.2%, the researchers said.

Clinical predictors of treatment response included disease duration, number of depressive episodes, total number of affective episodes, and number of manic episodes.

The findings were limited by several factors including the cross-sectional design and potential impact of other psychotropic drugs, the researchers noted. A replication of the study in an independent dataset is needed to validate the findings, they said.

However, the study is the first known to explore the effect of ancestry on bipolar patients’ response to lithium, and suggests that ancestry components have potential predictive value in the clinical setting that could support a more personalized approach to treatment, the researchers said.

The study was supported by PRISMA U.T., Colciencias, Invitación 990 del 3 de Agosto de 2017, Código 111577757629, Contrato 781 de 2017; Convocatoria Programática Ciencias de la Salud 2014-2015 CODI-UdeA, and Convocatoria N.727-2015 Doctorados Nacionales, Colciencias, 2015. The researchers had no financial conflicts to disclose.

Ancestry was a significant predictor of response to lithium by adults with bipolar disorder (BPD), based on data from 172 individuals.

Lithium remains the first-line treatment for BPD, but clinical improvement occurs in less than one-third of patients, and factors that might affect response, especially genetic factors, have not been well studied, wrote Ana M. Díaz-Zuluaga, MD, of University of Antioquia, Medellín, Colombia, and colleagues.

Previous genetic research identified four linked single nucleotide polymorphisms (SNPs) in a single locus on chromosome 21 that were associated with lithium response, but the study was limited to individuals with European and Asian ancestry, the researchers said.

In a study published in the Journal of Affective Disorders, the researchers identified 172 adults aged 18 and older with a diagnosis of BPD I or II based on the DSM-IV-TR criteria. Participants had been taking lithium continuously for at least 6 months. Lithium response was defined using the Retrospective Criteria of Long-Term Treatment Response in Research Subjects with BD, also known as the Alda scale. Total Alda scale scores of 7 or higher indicated a responder phenotype; scores less than 7 were considered nonresponders.

Ancestry was determined using DNA samples and the software Structure Version 2.2, and participants were classified as Amerindian, African, or European.

The overall response rate to lithium was 15.11% (26 of 172 patients). In a univariate analysis, no significant differences emerged between responders and nonresponders in demographics or clinical characteristics. However, patients responsive to lithium were significantly less likely of African ancestry, compared with nonresponders (0.1 vs. 0.2, P = .005) and more likely of European ancestry (0.5 vs. 0.3, P = .024), and had fewer depressive episodes (2 vs. 3.9, P = .002). The difference in responders vs. nonresponders of Amerindian ancestry was not statistically significant (0.4 vs. 0.5, P = .204).

The researchers then used machine learning based on Advanced Recursive Partitioning Approaches (ARPAs) to create classification trees with and without ancestry components for predicting response to lithium. “Variable importance analysis shows that the most important predictor is the probability of Amerindian ancestry component, followed by the Amerindian and European ancestral components individual variances, and then by the African and European ancestry components,” the researchers wrote.

Without the ancestry component, the sensitivity and specificity for predicting a treatment response to lithium were 50% and 94.5% respectively, with an area under the curve of 72.2%.

“However, when ancestral components are included in the model, the sensitivity and specificity are 93 % and 84 %, respectively,” with an AUC of 89.2%, the researchers said.

Clinical predictors of treatment response included disease duration, number of depressive episodes, total number of affective episodes, and number of manic episodes.

The findings were limited by several factors including the cross-sectional design and potential impact of other psychotropic drugs, the researchers noted. A replication of the study in an independent dataset is needed to validate the findings, they said.

However, the study is the first known to explore the effect of ancestry on bipolar patients’ response to lithium, and suggests that ancestry components have potential predictive value in the clinical setting that could support a more personalized approach to treatment, the researchers said.

The study was supported by PRISMA U.T., Colciencias, Invitación 990 del 3 de Agosto de 2017, Código 111577757629, Contrato 781 de 2017; Convocatoria Programática Ciencias de la Salud 2014-2015 CODI-UdeA, and Convocatoria N.727-2015 Doctorados Nacionales, Colciencias, 2015. The researchers had no financial conflicts to disclose.

Aggressive marketing of OxyContin in the mid-1990s not only fueled the opioid crisis but also the spread of infectious diseases associated with injection drug use, a new analysis shows.

The uptick in rates of infectious diseases, namely, hepatitis and infective endocarditis, occurred after 2010, when OxyContin maker Purdue Pharma reformulated OxyContin to make it harder to crush and snort. This led many people who were already addicted to the powerful pain pills to move on to injecting heroin or fentanyl, which fueled the spread of infectious disease.

“Our results suggest that the mortality and morbidity consequences of OxyContin marketing continue to be salient more than 25 years later,” write Julia Dennett, PhD, and Gregg Gonsalves, PhD, with Yale University School of Public Health, New Haven, Conn.

Their study was published online in Health Affairs.
 

Long-term effects revealed

Until now, the long-term effects of widespread OxyContin marketing with regard to complications of injection drug use were unknown.

Dr. Dennett and Dr. Gonsalves evaluated the effects of OxyContin marketing on the long-term trajectories of various injection drug use–related outcomes. Using a difference-in-difference analysis, they compared states with high vs. low exposure to OxyContin marketing before and after the 2010 reformulation of the drug.

Before 2010, rates of infections associated with injection drug use and overdose deaths were similar in high- and low-marketing states, they found.

Those rates diverged after the 2010 reformulation, with more infections related to injection drug use in states exposed to more marketing.

Specifically, from 2010 until 2020, high-exposure states saw, on average, an additional 0.85 acute hepatitis B cases, 0.83 hepatitis C cases, and 0.62 cases of death from infective endocarditis per 100,000 residents.

High-exposure states also had 5.3 more deaths per 100,000 residents from synthetic opioid overdose.

“Prior to 2010, among these states, there were generally no statistically significant differences in these outcomes. After 2010, you saw them diverge dramatically,” Dr. Dennett said in a news release.

Dr. Dennett and Dr. Gonsalves say their findings support the view that the opioid epidemic is creating a converging public health crisis, as it is fueling a surge in infectious diseases, particularly hepatitis, infective endocarditis, and HIV.

“This study highlights a critical need for actions to address the spread of viral and bacterial infections and overdose associated with injection drug use, both in the states that were subject to Purdue’s promotional campaign and across the U.S. more broadly,” they add.

Purdue Pharma did not provide a comment on the study.

Funding for the study was provided by the National Institute on Drug Abuse. Disclosures for Dr. Dennett and Dr. Gonsalves were not available.

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

Aggressive marketing of OxyContin in the mid-1990s not only fueled the opioid crisis but also the spread of infectious diseases associated with injection drug use, a new analysis shows.

The uptick in rates of infectious diseases, namely, hepatitis and infective endocarditis, occurred after 2010, when OxyContin maker Purdue Pharma reformulated OxyContin to make it harder to crush and snort. This led many people who were already addicted to the powerful pain pills to move on to injecting heroin or fentanyl, which fueled the spread of infectious disease.

“Our results suggest that the mortality and morbidity consequences of OxyContin marketing continue to be salient more than 25 years later,” write Julia Dennett, PhD, and Gregg Gonsalves, PhD, with Yale University School of Public Health, New Haven, Conn.

Their study was published online in Health Affairs.
 

Long-term effects revealed

Until now, the long-term effects of widespread OxyContin marketing with regard to complications of injection drug use were unknown.

Dr. Dennett and Dr. Gonsalves evaluated the effects of OxyContin marketing on the long-term trajectories of various injection drug use–related outcomes. Using a difference-in-difference analysis, they compared states with high vs. low exposure to OxyContin marketing before and after the 2010 reformulation of the drug.

Before 2010, rates of infections associated with injection drug use and overdose deaths were similar in high- and low-marketing states, they found.

Those rates diverged after the 2010 reformulation, with more infections related to injection drug use in states exposed to more marketing.

Specifically, from 2010 until 2020, high-exposure states saw, on average, an additional 0.85 acute hepatitis B cases, 0.83 hepatitis C cases, and 0.62 cases of death from infective endocarditis per 100,000 residents.

High-exposure states also had 5.3 more deaths per 100,000 residents from synthetic opioid overdose.

“Prior to 2010, among these states, there were generally no statistically significant differences in these outcomes. After 2010, you saw them diverge dramatically,” Dr. Dennett said in a news release.

Dr. Dennett and Dr. Gonsalves say their findings support the view that the opioid epidemic is creating a converging public health crisis, as it is fueling a surge in infectious diseases, particularly hepatitis, infective endocarditis, and HIV.

“This study highlights a critical need for actions to address the spread of viral and bacterial infections and overdose associated with injection drug use, both in the states that were subject to Purdue’s promotional campaign and across the U.S. more broadly,” they add.

Purdue Pharma did not provide a comment on the study.

Funding for the study was provided by the National Institute on Drug Abuse. Disclosures for Dr. Dennett and Dr. Gonsalves were not available.

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

Aggressive marketing of OxyContin in the mid-1990s not only fueled the opioid crisis but also the spread of infectious diseases associated with injection drug use, a new analysis shows.

The uptick in rates of infectious diseases, namely, hepatitis and infective endocarditis, occurred after 2010, when OxyContin maker Purdue Pharma reformulated OxyContin to make it harder to crush and snort. This led many people who were already addicted to the powerful pain pills to move on to injecting heroin or fentanyl, which fueled the spread of infectious disease.

“Our results suggest that the mortality and morbidity consequences of OxyContin marketing continue to be salient more than 25 years later,” write Julia Dennett, PhD, and Gregg Gonsalves, PhD, with Yale University School of Public Health, New Haven, Conn.

Their study was published online in Health Affairs.
 

Long-term effects revealed

Until now, the long-term effects of widespread OxyContin marketing with regard to complications of injection drug use were unknown.

Dr. Dennett and Dr. Gonsalves evaluated the effects of OxyContin marketing on the long-term trajectories of various injection drug use–related outcomes. Using a difference-in-difference analysis, they compared states with high vs. low exposure to OxyContin marketing before and after the 2010 reformulation of the drug.

Before 2010, rates of infections associated with injection drug use and overdose deaths were similar in high- and low-marketing states, they found.

Those rates diverged after the 2010 reformulation, with more infections related to injection drug use in states exposed to more marketing.

Specifically, from 2010 until 2020, high-exposure states saw, on average, an additional 0.85 acute hepatitis B cases, 0.83 hepatitis C cases, and 0.62 cases of death from infective endocarditis per 100,000 residents.

High-exposure states also had 5.3 more deaths per 100,000 residents from synthetic opioid overdose.

“Prior to 2010, among these states, there were generally no statistically significant differences in these outcomes. After 2010, you saw them diverge dramatically,” Dr. Dennett said in a news release.

Dr. Dennett and Dr. Gonsalves say their findings support the view that the opioid epidemic is creating a converging public health crisis, as it is fueling a surge in infectious diseases, particularly hepatitis, infective endocarditis, and HIV.

“This study highlights a critical need for actions to address the spread of viral and bacterial infections and overdose associated with injection drug use, both in the states that were subject to Purdue’s promotional campaign and across the U.S. more broadly,” they add.

Purdue Pharma did not provide a comment on the study.

Funding for the study was provided by the National Institute on Drug Abuse. Disclosures for Dr. Dennett and Dr. Gonsalves were not available.

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

The Food and Drug Administration has approved the first oral agent specifically for postpartum depression, a condition that affects an estimated one in seven mothers in the United States.

The pill, zuranolone (Zurzuvae), is a neuroactive steroid that acts on GABAA receptors in the brain responsible for regulating mood, arousal, behavior, and cognition, according to Biogen, which, along with Sage Therapeutics, developed the product. The recommended dose for Zurzuvae is 50 mg taken once daily for 14 days, in the evening with a fatty meal, according to the FDA.

Olivier Le Moal/Getty Images

Postpartum depression often goes undiagnosed and untreated. Many mothers are hesitant to reveal their symptoms to family and clinicians, fearing they’ll be judged on their parenting. A 2017 study found that suicide accounted for roughly 5% of perinatal deaths among women in Canada, with most of those deaths occurring in the first 3 months in the year after giving birth.

“Postpartum depression is a serious and potentially life-threatening condition in which women experience sadness, guilt, worthlessness – even, in severe cases, thoughts of harming themselves or their child. And, because postpartum depression can disrupt the maternal-infant bond, it can also have consequences for the child’s physical and emotional development,” Tiffany R. Farchione, MD, director of the division of psychiatry at the FDA’s Center for Drug Evaluation and Research, said in a statement about the approval. “Having access to an oral medication will be a beneficial option for many of these women coping with extreme, and sometimes life-threatening, feelings.”

The other approved therapy for postpartum depression is the intravenous agent brexanolone (Zulresso; Sage). But the product requires prolonged infusions in hospital settings and costs $34,000.

FDA approval of Zurzuvae was based in part on data reported in a 2023 study in the American Journal of Psychiatry, which showed that the drug led to significantly greater improvement in depressive symptoms at 15 days compared with the placebo group. Improvements were observed on day 3, the earliest assessment, and were sustained at all subsequent visits during the treatment and follow-up period (through day 42).

Patients with anxiety who received the active drug experienced improvement in related symptoms compared with the patients who received a placebo.

The most common adverse events reported in the trial were somnolence and headaches. Weight gain, sexual dysfunction, withdrawal symptoms, and increased suicidal ideation or behavior were not observed.

The packaging for Zurzuvae will include a boxed warning noting that the drug can affect a user’s ability to drive and perform other potentially hazardous activities, possibly without their knowledge of the impairment, the FDA said. As a result, people who use Zurzuvae should not drive or operate heavy machinery for at least 12 hours after taking the pill.

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

The Food and Drug Administration has approved the first oral agent specifically for postpartum depression, a condition that affects an estimated one in seven mothers in the United States.

The pill, zuranolone (Zurzuvae), is a neuroactive steroid that acts on GABAA receptors in the brain responsible for regulating mood, arousal, behavior, and cognition, according to Biogen, which, along with Sage Therapeutics, developed the product. The recommended dose for Zurzuvae is 50 mg taken once daily for 14 days, in the evening with a fatty meal, according to the FDA.

Olivier Le Moal/Getty Images

Postpartum depression often goes undiagnosed and untreated. Many mothers are hesitant to reveal their symptoms to family and clinicians, fearing they’ll be judged on their parenting. A 2017 study found that suicide accounted for roughly 5% of perinatal deaths among women in Canada, with most of those deaths occurring in the first 3 months in the year after giving birth.

“Postpartum depression is a serious and potentially life-threatening condition in which women experience sadness, guilt, worthlessness – even, in severe cases, thoughts of harming themselves or their child. And, because postpartum depression can disrupt the maternal-infant bond, it can also have consequences for the child’s physical and emotional development,” Tiffany R. Farchione, MD, director of the division of psychiatry at the FDA’s Center for Drug Evaluation and Research, said in a statement about the approval. “Having access to an oral medication will be a beneficial option for many of these women coping with extreme, and sometimes life-threatening, feelings.”

The other approved therapy for postpartum depression is the intravenous agent brexanolone (Zulresso; Sage). But the product requires prolonged infusions in hospital settings and costs $34,000.

FDA approval of Zurzuvae was based in part on data reported in a 2023 study in the American Journal of Psychiatry, which showed that the drug led to significantly greater improvement in depressive symptoms at 15 days compared with the placebo group. Improvements were observed on day 3, the earliest assessment, and were sustained at all subsequent visits during the treatment and follow-up period (through day 42).

Patients with anxiety who received the active drug experienced improvement in related symptoms compared with the patients who received a placebo.

The most common adverse events reported in the trial were somnolence and headaches. Weight gain, sexual dysfunction, withdrawal symptoms, and increased suicidal ideation or behavior were not observed.

The packaging for Zurzuvae will include a boxed warning noting that the drug can affect a user’s ability to drive and perform other potentially hazardous activities, possibly without their knowledge of the impairment, the FDA said. As a result, people who use Zurzuvae should not drive or operate heavy machinery for at least 12 hours after taking the pill.

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

The Food and Drug Administration has approved the first oral agent specifically for postpartum depression, a condition that affects an estimated one in seven mothers in the United States.

The pill, zuranolone (Zurzuvae), is a neuroactive steroid that acts on GABAA receptors in the brain responsible for regulating mood, arousal, behavior, and cognition, according to Biogen, which, along with Sage Therapeutics, developed the product. The recommended dose for Zurzuvae is 50 mg taken once daily for 14 days, in the evening with a fatty meal, according to the FDA.

Olivier Le Moal/Getty Images

Postpartum depression often goes undiagnosed and untreated. Many mothers are hesitant to reveal their symptoms to family and clinicians, fearing they’ll be judged on their parenting. A 2017 study found that suicide accounted for roughly 5% of perinatal deaths among women in Canada, with most of those deaths occurring in the first 3 months in the year after giving birth.

“Postpartum depression is a serious and potentially life-threatening condition in which women experience sadness, guilt, worthlessness – even, in severe cases, thoughts of harming themselves or their child. And, because postpartum depression can disrupt the maternal-infant bond, it can also have consequences for the child’s physical and emotional development,” Tiffany R. Farchione, MD, director of the division of psychiatry at the FDA’s Center for Drug Evaluation and Research, said in a statement about the approval. “Having access to an oral medication will be a beneficial option for many of these women coping with extreme, and sometimes life-threatening, feelings.”

The other approved therapy for postpartum depression is the intravenous agent brexanolone (Zulresso; Sage). But the product requires prolonged infusions in hospital settings and costs $34,000.

FDA approval of Zurzuvae was based in part on data reported in a 2023 study in the American Journal of Psychiatry, which showed that the drug led to significantly greater improvement in depressive symptoms at 15 days compared with the placebo group. Improvements were observed on day 3, the earliest assessment, and were sustained at all subsequent visits during the treatment and follow-up period (through day 42).

Patients with anxiety who received the active drug experienced improvement in related symptoms compared with the patients who received a placebo.

The most common adverse events reported in the trial were somnolence and headaches. Weight gain, sexual dysfunction, withdrawal symptoms, and increased suicidal ideation or behavior were not observed.

The packaging for Zurzuvae will include a boxed warning noting that the drug can affect a user’s ability to drive and perform other potentially hazardous activities, possibly without their knowledge of the impairment, the FDA said. As a result, people who use Zurzuvae should not drive or operate heavy machinery for at least 12 hours after taking the pill.

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

Bipolar disorder (BD) is linked to a sixfold increased risk of early death from external causes and a twofold increased risk of dying prematurely from somatic disease than the general population, a new study shows.

In addition, patients with BD are three times more likely to die prematurely of all causes, compared with the general population, with alcohol-related diseases contributing to more premature deaths than cardiovascular disease (CVD), diabetes, and cancer.

The study results emphasize the need for personalized approaches to risk prediction and prevention of premature cause-specific mortality over the life-course of individuals with BD, lead investigator Tapio Paljärvi, PhD, an epidemiologist at Niuvanniemi Hospital in Kuopio, Finland, told this news organization.

The findings were published online in BMJ Mental Health.
 

Alcohol a major contributor to early death

A number of studies have established that those with BD have twice the risk of dying prematurely, compared with those without the disorder.

To learn more about the factors contributing to early death in this patient population, the investigators analyzed data from nationwide Finnish medical and insurance registries. They identified and tracked the health of 47,000 patients, aged 15-64 years, with BD between 2004 and 2018.

The average age at the beginning of the monitoring period was 38 years, and 57% of the cohort were women.

To determine the excess deaths directly attributable to BD, the researchers compared the ratio of deaths observed over the monitoring period in those with BD to the number expected to die in the general population, also known as the standard mortality ratio.

Of the group with BD, 3,300 died during the monitoring period. The average age at death was 50, and almost two-thirds (65%, or 2,137) of those who died were men.

Investigators grouped excess deaths in BD patients into two categories – somatic and external.

Of those with BD who died from somatic or disease-related causes, alcohol caused the highest rate of death (29%). The second-leading cause was heart disease and stroke (27%), followed by cancer (22%), respiratory diseases (4%), and diabetes (2%).

Among the 595 patients with BD who died because of alcohol consumption, liver disease was the leading cause of death (48%). The second cause was accidental alcohol poisoning (28%), followed by alcohol dependence (10%).

The leading cause of death from external causes in BD patients was suicide (58%, or 740), nearly half of which (48%) were from an overdose with prescribed psychotropic medications.

Overall, 64%, or 2,104, of the deaths in BD patients from any cause were considered excess deaths, that is, the number of deaths above those expected for those without BD of comparable age and sex.

Most of the excess deaths from somatic illness were either from alcohol-related causes (40%) – a rate three times higher than that of the general population – CVD (26%), or cancer (10%).
 

High suicide rate

When the team examined excess deaths from external causes, they found that 61% (651) were attributable to suicide, a rate eight times higher than that of the general population.

“In terms of absolute numbers, somatic causes of death represented the majority of all deaths in BD, as also reported in previous research,” Dr. Paljärvi said.

“However, this finding reflects the fact that in many high-income countries most of the deaths are due to somatic causes; with CVD, cancers, and diseases of the nervous system as the leading causes of death in the older age groups,” he added.

Dr. Paljärvi advised that clinicians treating patients with BD balance therapeutic response with potentially serious long-term medication side effects, to prevent premature deaths.

A stronger emphasis on identifying and treating comorbid substance abuse is also warranted, he noted.

Dr. Paljärvi noted that the underlying causes of the excess somatic mortality in people with BD are not fully understood, but may result from the “complex interaction between various established risk factors, including tobacco use, alcohol abuse, physical inactivity, unhealthy diet, obesity, hypertension, etc.”

Regarding the generalizability of the findings, he said many previous studies have been based only on inpatient data and noted that the current study included individuals from various sources including inpatient and outpatient registries as well as social insurance registries.

“While the reported excess all-cause mortality rates are strikingly similar across populations globally, there is a paucity of more detailed cause-specific analyses of excess mortality in BD,” said Dr. Paljärvi, adding that these findings should be replicated in other countries, including the United States.
 

Chronic inflammation

Commenting on the findings, Benjamin Goldstein, MD, PhD, professor of psychiatry and pharmacology at the University of Toronto, noted that there are clear disparities in access to, and quality of care among, patients with BD and other serious mental illnesses.

“Taking heart disease as an example, disparities exist at virtually every point of contact, ranging from the point of preventive care to the time it takes to be assessed in the ER, to the likelihood of receiving cardiac catheterization, to the quality of postdischarge care,” said Dr. Goldstein.

He also noted that CVD occurs in patients with BD, on average, 10-15 years earlier than the general population. However, he added, “there is important evidence that when people with BD receive the same standard of care as those without BD their cardiovascular outcomes are similar.”

Dr. Goldstein also noted that inflammation, which is a driver of cardiovascular risk, is elevated among patients with BD, particularly during mania and depression.

“Given that the average person with BD has some degree of mood symptoms about 40% of the time, chronically elevated inflammation likely contributes in part to the excess risk of heart disease in bipolar disorder,” he said.

Dr. Goldstein’s team’s research focuses on microvessels. “We have found that microvessel function in both the heart and the brain, determined by MRI, is reduced among teens with BD,” he said.

His team has also found that endothelial function in fingertip microvessels, an indicator of future heart disease risk, varies according to mood states.

“Collectively, these findings suggest the microvascular problems may explain, in part, the extra risk of heart disease beyond traditional risk factors in BD,” he added.

The study was funded by a Wellcome Trust Senior Clinical Research Fellowship and by the Oxford Health Biomedical Research Centre. Dr. Paljärvi and Dr. Goldstein report no relevant financial relationships.

A version of this article appeared on Medscape.com.

Bipolar disorder (BD) is linked to a sixfold increased risk of early death from external causes and a twofold increased risk of dying prematurely from somatic disease than the general population, a new study shows.

In addition, patients with BD are three times more likely to die prematurely of all causes, compared with the general population, with alcohol-related diseases contributing to more premature deaths than cardiovascular disease (CVD), diabetes, and cancer.

The study results emphasize the need for personalized approaches to risk prediction and prevention of premature cause-specific mortality over the life-course of individuals with BD, lead investigator Tapio Paljärvi, PhD, an epidemiologist at Niuvanniemi Hospital in Kuopio, Finland, told this news organization.

The findings were published online in BMJ Mental Health.
 

Alcohol a major contributor to early death

A number of studies have established that those with BD have twice the risk of dying prematurely, compared with those without the disorder.

To learn more about the factors contributing to early death in this patient population, the investigators analyzed data from nationwide Finnish medical and insurance registries. They identified and tracked the health of 47,000 patients, aged 15-64 years, with BD between 2004 and 2018.

The average age at the beginning of the monitoring period was 38 years, and 57% of the cohort were women.

To determine the excess deaths directly attributable to BD, the researchers compared the ratio of deaths observed over the monitoring period in those with BD to the number expected to die in the general population, also known as the standard mortality ratio.

Of the group with BD, 3,300 died during the monitoring period. The average age at death was 50, and almost two-thirds (65%, or 2,137) of those who died were men.

Investigators grouped excess deaths in BD patients into two categories – somatic and external.

Of those with BD who died from somatic or disease-related causes, alcohol caused the highest rate of death (29%). The second-leading cause was heart disease and stroke (27%), followed by cancer (22%), respiratory diseases (4%), and diabetes (2%).

Among the 595 patients with BD who died because of alcohol consumption, liver disease was the leading cause of death (48%). The second cause was accidental alcohol poisoning (28%), followed by alcohol dependence (10%).

The leading cause of death from external causes in BD patients was suicide (58%, or 740), nearly half of which (48%) were from an overdose with prescribed psychotropic medications.

Overall, 64%, or 2,104, of the deaths in BD patients from any cause were considered excess deaths, that is, the number of deaths above those expected for those without BD of comparable age and sex.

Most of the excess deaths from somatic illness were either from alcohol-related causes (40%) – a rate three times higher than that of the general population – CVD (26%), or cancer (10%).
 

High suicide rate

When the team examined excess deaths from external causes, they found that 61% (651) were attributable to suicide, a rate eight times higher than that of the general population.

“In terms of absolute numbers, somatic causes of death represented the majority of all deaths in BD, as also reported in previous research,” Dr. Paljärvi said.

“However, this finding reflects the fact that in many high-income countries most of the deaths are due to somatic causes; with CVD, cancers, and diseases of the nervous system as the leading causes of death in the older age groups,” he added.

Dr. Paljärvi advised that clinicians treating patients with BD balance therapeutic response with potentially serious long-term medication side effects, to prevent premature deaths.

A stronger emphasis on identifying and treating comorbid substance abuse is also warranted, he noted.

Dr. Paljärvi noted that the underlying causes of the excess somatic mortality in people with BD are not fully understood, but may result from the “complex interaction between various established risk factors, including tobacco use, alcohol abuse, physical inactivity, unhealthy diet, obesity, hypertension, etc.”

Regarding the generalizability of the findings, he said many previous studies have been based only on inpatient data and noted that the current study included individuals from various sources including inpatient and outpatient registries as well as social insurance registries.

“While the reported excess all-cause mortality rates are strikingly similar across populations globally, there is a paucity of more detailed cause-specific analyses of excess mortality in BD,” said Dr. Paljärvi, adding that these findings should be replicated in other countries, including the United States.
 

Chronic inflammation

Commenting on the findings, Benjamin Goldstein, MD, PhD, professor of psychiatry and pharmacology at the University of Toronto, noted that there are clear disparities in access to, and quality of care among, patients with BD and other serious mental illnesses.

“Taking heart disease as an example, disparities exist at virtually every point of contact, ranging from the point of preventive care to the time it takes to be assessed in the ER, to the likelihood of receiving cardiac catheterization, to the quality of postdischarge care,” said Dr. Goldstein.

He also noted that CVD occurs in patients with BD, on average, 10-15 years earlier than the general population. However, he added, “there is important evidence that when people with BD receive the same standard of care as those without BD their cardiovascular outcomes are similar.”

Dr. Goldstein also noted that inflammation, which is a driver of cardiovascular risk, is elevated among patients with BD, particularly during mania and depression.

“Given that the average person with BD has some degree of mood symptoms about 40% of the time, chronically elevated inflammation likely contributes in part to the excess risk of heart disease in bipolar disorder,” he said.

Dr. Goldstein’s team’s research focuses on microvessels. “We have found that microvessel function in both the heart and the brain, determined by MRI, is reduced among teens with BD,” he said.

His team has also found that endothelial function in fingertip microvessels, an indicator of future heart disease risk, varies according to mood states.

“Collectively, these findings suggest the microvascular problems may explain, in part, the extra risk of heart disease beyond traditional risk factors in BD,” he added.

The study was funded by a Wellcome Trust Senior Clinical Research Fellowship and by the Oxford Health Biomedical Research Centre. Dr. Paljärvi and Dr. Goldstein report no relevant financial relationships.

A version of this article appeared on Medscape.com.

Bipolar disorder (BD) is linked to a sixfold increased risk of early death from external causes and a twofold increased risk of dying prematurely from somatic disease than the general population, a new study shows.

In addition, patients with BD are three times more likely to die prematurely of all causes, compared with the general population, with alcohol-related diseases contributing to more premature deaths than cardiovascular disease (CVD), diabetes, and cancer.

The study results emphasize the need for personalized approaches to risk prediction and prevention of premature cause-specific mortality over the life-course of individuals with BD, lead investigator Tapio Paljärvi, PhD, an epidemiologist at Niuvanniemi Hospital in Kuopio, Finland, told this news organization.

The findings were published online in BMJ Mental Health.
 

Alcohol a major contributor to early death

A number of studies have established that those with BD have twice the risk of dying prematurely, compared with those without the disorder.

To learn more about the factors contributing to early death in this patient population, the investigators analyzed data from nationwide Finnish medical and insurance registries. They identified and tracked the health of 47,000 patients, aged 15-64 years, with BD between 2004 and 2018.

The average age at the beginning of the monitoring period was 38 years, and 57% of the cohort were women.

To determine the excess deaths directly attributable to BD, the researchers compared the ratio of deaths observed over the monitoring period in those with BD to the number expected to die in the general population, also known as the standard mortality ratio.

Of the group with BD, 3,300 died during the monitoring period. The average age at death was 50, and almost two-thirds (65%, or 2,137) of those who died were men.

Investigators grouped excess deaths in BD patients into two categories – somatic and external.

Of those with BD who died from somatic or disease-related causes, alcohol caused the highest rate of death (29%). The second-leading cause was heart disease and stroke (27%), followed by cancer (22%), respiratory diseases (4%), and diabetes (2%).

Among the 595 patients with BD who died because of alcohol consumption, liver disease was the leading cause of death (48%). The second cause was accidental alcohol poisoning (28%), followed by alcohol dependence (10%).

The leading cause of death from external causes in BD patients was suicide (58%, or 740), nearly half of which (48%) were from an overdose with prescribed psychotropic medications.

Overall, 64%, or 2,104, of the deaths in BD patients from any cause were considered excess deaths, that is, the number of deaths above those expected for those without BD of comparable age and sex.

Most of the excess deaths from somatic illness were either from alcohol-related causes (40%) – a rate three times higher than that of the general population – CVD (26%), or cancer (10%).
 

High suicide rate

When the team examined excess deaths from external causes, they found that 61% (651) were attributable to suicide, a rate eight times higher than that of the general population.

“In terms of absolute numbers, somatic causes of death represented the majority of all deaths in BD, as also reported in previous research,” Dr. Paljärvi said.

“However, this finding reflects the fact that in many high-income countries most of the deaths are due to somatic causes; with CVD, cancers, and diseases of the nervous system as the leading causes of death in the older age groups,” he added.

Dr. Paljärvi advised that clinicians treating patients with BD balance therapeutic response with potentially serious long-term medication side effects, to prevent premature deaths.

A stronger emphasis on identifying and treating comorbid substance abuse is also warranted, he noted.

Dr. Paljärvi noted that the underlying causes of the excess somatic mortality in people with BD are not fully understood, but may result from the “complex interaction between various established risk factors, including tobacco use, alcohol abuse, physical inactivity, unhealthy diet, obesity, hypertension, etc.”

Regarding the generalizability of the findings, he said many previous studies have been based only on inpatient data and noted that the current study included individuals from various sources including inpatient and outpatient registries as well as social insurance registries.

“While the reported excess all-cause mortality rates are strikingly similar across populations globally, there is a paucity of more detailed cause-specific analyses of excess mortality in BD,” said Dr. Paljärvi, adding that these findings should be replicated in other countries, including the United States.
 

Chronic inflammation

Commenting on the findings, Benjamin Goldstein, MD, PhD, professor of psychiatry and pharmacology at the University of Toronto, noted that there are clear disparities in access to, and quality of care among, patients with BD and other serious mental illnesses.

“Taking heart disease as an example, disparities exist at virtually every point of contact, ranging from the point of preventive care to the time it takes to be assessed in the ER, to the likelihood of receiving cardiac catheterization, to the quality of postdischarge care,” said Dr. Goldstein.

He also noted that CVD occurs in patients with BD, on average, 10-15 years earlier than the general population. However, he added, “there is important evidence that when people with BD receive the same standard of care as those without BD their cardiovascular outcomes are similar.”

Dr. Goldstein also noted that inflammation, which is a driver of cardiovascular risk, is elevated among patients with BD, particularly during mania and depression.

“Given that the average person with BD has some degree of mood symptoms about 40% of the time, chronically elevated inflammation likely contributes in part to the excess risk of heart disease in bipolar disorder,” he said.

Dr. Goldstein’s team’s research focuses on microvessels. “We have found that microvessel function in both the heart and the brain, determined by MRI, is reduced among teens with BD,” he said.

His team has also found that endothelial function in fingertip microvessels, an indicator of future heart disease risk, varies according to mood states.

“Collectively, these findings suggest the microvascular problems may explain, in part, the extra risk of heart disease beyond traditional risk factors in BD,” he added.

The study was funded by a Wellcome Trust Senior Clinical Research Fellowship and by the Oxford Health Biomedical Research Centre. Dr. Paljärvi and Dr. Goldstein report no relevant financial relationships.

A version of this article appeared on Medscape.com.