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Family-oriented care in adult psychiatric residency
The Group for the Advancement of Psychiatry’s Committee on the Family published an updated curriculum in October 2021 on family-oriented care. The first curriculum, published in 2006, was nominated as the American Association of Directors of Psychiatric Residency Training model curriculum for family-oriented care. The updated curriculum, produced by the GAP family committee and guests, is shorter and more focused.
The following is a summary of the introduction and the highlights.
Introduction
Use of family systems–based techniques in the diagnosis and care of patients is a key evidence-based tool for psychiatric disorders. However, it is not a current Accreditation Council for Graduate Medical Education Training training requirement, and it is possible to complete psychiatry residency without exposure to this key framework.
Here, we highlight the importance of considering patients through a “family systems” lens and the incorporation of multiple individuals from an individual patient’s identified system in their care.
Current medicine curricula emphasize patient autonomy, one of the core pillars of ethics. Autonomy is the cornerstone of the everyday practice within medicine of communicating all risks, benefits, and alternatives of a proposed treatment to a patient making decisions about desired paths forward. This prevents paternalistic care in which the doctor “knows best” and makes decisions for the patient. Unfortunately, the emphasis of this pillar has morphed over time into the idea that the individual patient is the only person to whom this information should be provided or from whom information should be obtained.
Extensive research proves conclusively that family support, education, and psychoeducation improve both patient and family functioning in medical and psychiatric illness. as well as overlook the opportunity to use the structure and support system around a patient to strengthen their care and improve treatment outcomes.
The network and family dynamics around a patient can be critical to providing accurate information on medication adherence and symptoms, supporting recovery, and handling emergencies. Markedly improved patient outcomes occur when family members are seen as allies and offered support, assessment, and psychoeducation. In fact, the American Psychiatric Association’s Practice Guidelines on the treatment of schizophrenia (2020), major depressive disorder (2010), and bipolar disorder (2002) include the expectation that patients’ family members will be involved in the assessment and treatment of patients. Yet, training in how to incorporate these practices is often minimal or nonexistent during residency.
A family systems orientation is distinguished by its view of the family as a transactional system. Stressful events and problems of an individual member affect the whole family as a functional unit, with ripple effects for all members and their relationships. In turn, the family response – how the family handles problems – contributes significantly to positive adaptation or to individual and relational dysfunction. Thus, individual problems are assessed and addressed in the context of the family, with attention to socioeconomic and other environmental stressors.
A family systems approach is distinguished less by who is in the room and more by the clinician’s attention to relationship systems in assessment and treatment planning. We need to consider how family members may contribute to – and be affected by – problem situations. Most importantly, regardless of the source of difficulties, we involve key family members who can contribute to needed changes. Interventions are aimed at modifying dysfunctional patterns, tapping family resources, and strengthening both individual and family functioning.
A family systemic lens is useful for working with all types of families, for example: refugee families, thinking through child adoption processes, working with families with specific social disadvantages, etc. Incorporating issues of race, gender, and sexual orientation is important in this work, as is working with larger systems such as schools, workplaces, and health care settings.
As opposed to previous viewpoints that family therapy is the only “family” skill to be taught during residency, the GAP committee proposes that psychiatric residents should be trained in skills of family inclusion, support, and psychoeducation, and that these skills should be taught throughout the residency. Our goal is to have residents be able to consider any case through a family systems lens, to understand how patients’ illnesses and their family systems have bidirectional effects on each other, to perform a basic assessment of family system functioning, and to use this information in diagnostic and treatment planning.
Training goals
Systems-based thinking will enable trainees to:
1. Ally with family members to work with the patient to comply with goals of care (for example, taking medications, complying with lifestyle changes, and maintaining sobriety).
- Teachers focus on engagement, joining with families.
2. Help patients understand the influences of their families in their own lives, such as intergenerational transmission of trauma and resilience.
- Teachers focus on the creation of a genogram, and the location of the individual within their family system.
3. Understand that mental health includes the creation and maintenance of healthy relationships.
- Teachers focus on assessing a willingness to listen to others’ points of view and the cocreation of a shared reality and belief system: a belief that relationships can change over time and how to create new family narratives.
4. Understand the impact of illness on the family unit and the impact of the family unit on illness.
- Teachers focus on the concept of a family system, clarifying the roles within the family, including caregiving responsibilities.
5. Assess the family for strengths and weaknesses.
- Teachers focus on how families maintain a healthy emotional climate, allocate roles, decide on rules, problem-solving abilities, and so on.
6. Gather information from multiple informants in the same room.
- Teachers focus on using communication techniques to elicit, guide, and redirect information from multiple individuals of a system with varying perspectives in the same room. Teachers help students understand that there are multiple realities in families and learn how to maintain multidirectional partiality.
Knowledge, skills, and attitudes across all treatment settings
Knowledge: Beginning level
- Healthy family functioning at the various phases of the family life cycle. Systems concepts are applicable to families, multidisciplinary teams in clinical settings, and medical/government organizations. However, family systems are distinguished by deep attachment bonds, specific generational hierarchy, goals of emotional safety and, for many families, child rearing.
- Systemic thinking, unlike a linear cause and effect model, examines the feedback loops by which multiple persons or groups arrive at a specific way of functioning.
- Understanding boundaries, subsystems, and feedback loops is critical to understanding interpersonal connections. Understand how the family affects and is affected by psychiatric and medical illnesses. Impact of interpersonal stress on biological systems. The role of expressed emotion (EE) in psychiatric illness. EE describes the level of criticism, hostility, and emotional overinvolvement in families. It has been studied extensively across the health care spectrum, and cultural variance is significant.
- The components of family psychoeducation, and its associated research in improving patient and family outcomes.
Knowledge: Advanced level
- Principles of adaptive and maladaptive relational functioning in family life and family organization, communication, problem solving, and emotional regulation. Role of family strengths, resilience in reducing vulnerability.
- Couple and family development over the life cycle.
- Understanding multigenerational patterns.
- How age, gender, class, culture, and spirituality affect family life.
- The variety of family forms (for example, single parent, stepfamilies, same-sex parents).
- Special issues in couples and families, including loss, divorce and remarriage, immigration, illness, secrets, affairs, violence, alcohol and substance abuse, sexuality, including LGBTQi. Relationship of families to larger systems, for example, schools, work, health care systems, government agencies.
Skills
- Family-interviewing skills, especially managing high levels of emotion and making room for multiple points of view.
- Promoting resilience, hope, and strength.
- Basic psychoeducation techniques, which includes providing a therapeutic space for emotional processing, providing information about the illness, skills such as better communication, problem-solving, and relapse drill and support.
- Collaborative treatment planning with family members and other helping professionals. Treatment planning should include all members of the system: patient, family members, and members of the treatment team. Good planning establishes a role for family members, helps define criteria for managing emergencies, looks for areas of strength and resilience and provides clear and realistic goals for treatment.
- Knowledge of, and referral to, local and national resources, both in the community and online.
Attitudes
- Appreciate the multiple points of view in a family.
- Interest in family members as people with their own needs and history.
- Including family members as a resource in recovery.
- Understand caregiver burden and rewards and that stress extends to all family members.
Training techniques
Most learning takes place at the level of patient, supervisor, and resident. It is critical that the resident sees faculty members dealing with patients in observed or shared family sessions, and /or sees videos made by faculty or professionally made videos. Attitudes are best learned by modeling.
Areas of focus can include time management, addressing the fear that family sessions may get out of control, and the influence of the residents’ own life experiences and background including potential generational or cultural differences on their assessment and interactions with patient family dynamics. In skill development, our goal is efficient interviewing, history taking, and support in controlling sessions.
It is difficult to specify which techniques are most useful in didactic sessions as each presenter will have a different skill set for engaging the class. The techniques that work best are the ones most comfortable to the presenter. Any technique that gets emotions involved, such as role play, sculpting, discussing movie clips, bringing in family members to discuss their experiences, or self-exploration, will generate the most powerful learning. If time permits, exploration of the resident’s own family, including a genogram, is an exceptionally helpful technique, especially if accompanied by asking the residents to interview their own families.
Adult didactic curriculum
The curriculum represents basic concepts. We have vignettes by the authors, if needed, but it is best if the class, including the supervisor, uses vignettes from their own experiences. Material for use in class is in references, but the class is urged to draw on their own experiences as this supports strength-based teaching. The following are key topics and concepts for each of the training years.
Basic concepts for PGY1 and PGY2
1. Where are you in the family and individual life cycles? What are your experiences with psychiatric illness in family/friends? Open discussion about how individual and family life cycles interact. Draw genograms of s/o in the class or with the supervisor.
2. Healthy family functioning and family resilience. Recommend asking residents to talk to their parents/elders about their lives and family life cycle when they were your age. Open discussion about what makes a healthy resilient family.
3. How do I connect with the family rather than just one person? How do you learn to hold multiple perspectives? How do I try not to take sides/multidirectional partiality? How do I see each person in a positive way? How do I focus on family strengths, rather than focusing on someone behaving badly (which is really hard because it is overlearned in individual therapy).
4. What are the common factors used across all therapies, both individual and family? When is it best to use an individual relational approach versus a family systemic approach?
5. How do I decide if a family needs support or education or family therapy?
6. Psychoeducation: Research, current use and cultural adaptations.
7. Attachment styles and couples therapy.
8. What is the evidence base behind our work?
System practice for PGY 3 and 4
These seminars follow the basic seminars. The focus is on clarification of what systems thinking means. Systems thinking or relational thinking is to be differentiated from systems-based practice. These lectures require knowledge of systemic practice. If there are no local experts, residency programs can reach out to national experts at the Association of Family Psychiatrists, for help with virtual/remote or in-person teaching.
Here is a list of other topics that should be covered:
- Relational formulation, nested subsystems, boundaries, history of these concepts, contributions to the development of family therapy.
- How to define and identify common systems concepts, such as circular patterns, feedback loops, and triangulation. Teach circular questioning. Framing. This concept is the family systems equivalent of insight. How to intervene to effect communication change and behavior change?
- Working at interfaces: community, legal, government, agencies, and so on, and other treaters, consultation. Include systemic and individual racism.
- Understanding the complexity of intimacy.
- Emergency situations. When to report regarding abuse. Dealing with family trauma.
- Varieties of family therapy; assumptions and major concepts.
*The new curriculum was written by The GAP Committee on the Family: Ellen Berman, MD; John Rolland, MD, MPH; John Sargent, MD; and me, and with guests Chayanin Foongsathaporn, MD; Sarah Nguyen, MD, MPH; Neha Sharma, DO; and Jodi Zik, MD. For the full curriculum, which includes residency milestones, site-specific training goals, references, and case studies, please access the Association of Family Psychiatry’s website: www.familypsychiatrists.org.Dr. Heru is professor of psychiatry at the University of Colorado Denver, Aurora. She is editor of “Working With Families in Medical Settings: A Multidisciplinary Guide for Psychiatrists and Other Health Professionals” (New York: Routledge, 2013). She has no conflicts of interest to disclose. Contact Dr. Heru at [email protected].
The Group for the Advancement of Psychiatry’s Committee on the Family published an updated curriculum in October 2021 on family-oriented care. The first curriculum, published in 2006, was nominated as the American Association of Directors of Psychiatric Residency Training model curriculum for family-oriented care. The updated curriculum, produced by the GAP family committee and guests, is shorter and more focused.
The following is a summary of the introduction and the highlights.
Introduction
Use of family systems–based techniques in the diagnosis and care of patients is a key evidence-based tool for psychiatric disorders. However, it is not a current Accreditation Council for Graduate Medical Education Training training requirement, and it is possible to complete psychiatry residency without exposure to this key framework.
Here, we highlight the importance of considering patients through a “family systems” lens and the incorporation of multiple individuals from an individual patient’s identified system in their care.
Current medicine curricula emphasize patient autonomy, one of the core pillars of ethics. Autonomy is the cornerstone of the everyday practice within medicine of communicating all risks, benefits, and alternatives of a proposed treatment to a patient making decisions about desired paths forward. This prevents paternalistic care in which the doctor “knows best” and makes decisions for the patient. Unfortunately, the emphasis of this pillar has morphed over time into the idea that the individual patient is the only person to whom this information should be provided or from whom information should be obtained.
Extensive research proves conclusively that family support, education, and psychoeducation improve both patient and family functioning in medical and psychiatric illness. as well as overlook the opportunity to use the structure and support system around a patient to strengthen their care and improve treatment outcomes.
The network and family dynamics around a patient can be critical to providing accurate information on medication adherence and symptoms, supporting recovery, and handling emergencies. Markedly improved patient outcomes occur when family members are seen as allies and offered support, assessment, and psychoeducation. In fact, the American Psychiatric Association’s Practice Guidelines on the treatment of schizophrenia (2020), major depressive disorder (2010), and bipolar disorder (2002) include the expectation that patients’ family members will be involved in the assessment and treatment of patients. Yet, training in how to incorporate these practices is often minimal or nonexistent during residency.
A family systems orientation is distinguished by its view of the family as a transactional system. Stressful events and problems of an individual member affect the whole family as a functional unit, with ripple effects for all members and their relationships. In turn, the family response – how the family handles problems – contributes significantly to positive adaptation or to individual and relational dysfunction. Thus, individual problems are assessed and addressed in the context of the family, with attention to socioeconomic and other environmental stressors.
A family systems approach is distinguished less by who is in the room and more by the clinician’s attention to relationship systems in assessment and treatment planning. We need to consider how family members may contribute to – and be affected by – problem situations. Most importantly, regardless of the source of difficulties, we involve key family members who can contribute to needed changes. Interventions are aimed at modifying dysfunctional patterns, tapping family resources, and strengthening both individual and family functioning.
A family systemic lens is useful for working with all types of families, for example: refugee families, thinking through child adoption processes, working with families with specific social disadvantages, etc. Incorporating issues of race, gender, and sexual orientation is important in this work, as is working with larger systems such as schools, workplaces, and health care settings.
As opposed to previous viewpoints that family therapy is the only “family” skill to be taught during residency, the GAP committee proposes that psychiatric residents should be trained in skills of family inclusion, support, and psychoeducation, and that these skills should be taught throughout the residency. Our goal is to have residents be able to consider any case through a family systems lens, to understand how patients’ illnesses and their family systems have bidirectional effects on each other, to perform a basic assessment of family system functioning, and to use this information in diagnostic and treatment planning.
Training goals
Systems-based thinking will enable trainees to:
1. Ally with family members to work with the patient to comply with goals of care (for example, taking medications, complying with lifestyle changes, and maintaining sobriety).
- Teachers focus on engagement, joining with families.
2. Help patients understand the influences of their families in their own lives, such as intergenerational transmission of trauma and resilience.
- Teachers focus on the creation of a genogram, and the location of the individual within their family system.
3. Understand that mental health includes the creation and maintenance of healthy relationships.
- Teachers focus on assessing a willingness to listen to others’ points of view and the cocreation of a shared reality and belief system: a belief that relationships can change over time and how to create new family narratives.
4. Understand the impact of illness on the family unit and the impact of the family unit on illness.
- Teachers focus on the concept of a family system, clarifying the roles within the family, including caregiving responsibilities.
5. Assess the family for strengths and weaknesses.
- Teachers focus on how families maintain a healthy emotional climate, allocate roles, decide on rules, problem-solving abilities, and so on.
6. Gather information from multiple informants in the same room.
- Teachers focus on using communication techniques to elicit, guide, and redirect information from multiple individuals of a system with varying perspectives in the same room. Teachers help students understand that there are multiple realities in families and learn how to maintain multidirectional partiality.
Knowledge, skills, and attitudes across all treatment settings
Knowledge: Beginning level
- Healthy family functioning at the various phases of the family life cycle. Systems concepts are applicable to families, multidisciplinary teams in clinical settings, and medical/government organizations. However, family systems are distinguished by deep attachment bonds, specific generational hierarchy, goals of emotional safety and, for many families, child rearing.
- Systemic thinking, unlike a linear cause and effect model, examines the feedback loops by which multiple persons or groups arrive at a specific way of functioning.
- Understanding boundaries, subsystems, and feedback loops is critical to understanding interpersonal connections. Understand how the family affects and is affected by psychiatric and medical illnesses. Impact of interpersonal stress on biological systems. The role of expressed emotion (EE) in psychiatric illness. EE describes the level of criticism, hostility, and emotional overinvolvement in families. It has been studied extensively across the health care spectrum, and cultural variance is significant.
- The components of family psychoeducation, and its associated research in improving patient and family outcomes.
Knowledge: Advanced level
- Principles of adaptive and maladaptive relational functioning in family life and family organization, communication, problem solving, and emotional regulation. Role of family strengths, resilience in reducing vulnerability.
- Couple and family development over the life cycle.
- Understanding multigenerational patterns.
- How age, gender, class, culture, and spirituality affect family life.
- The variety of family forms (for example, single parent, stepfamilies, same-sex parents).
- Special issues in couples and families, including loss, divorce and remarriage, immigration, illness, secrets, affairs, violence, alcohol and substance abuse, sexuality, including LGBTQi. Relationship of families to larger systems, for example, schools, work, health care systems, government agencies.
Skills
- Family-interviewing skills, especially managing high levels of emotion and making room for multiple points of view.
- Promoting resilience, hope, and strength.
- Basic psychoeducation techniques, which includes providing a therapeutic space for emotional processing, providing information about the illness, skills such as better communication, problem-solving, and relapse drill and support.
- Collaborative treatment planning with family members and other helping professionals. Treatment planning should include all members of the system: patient, family members, and members of the treatment team. Good planning establishes a role for family members, helps define criteria for managing emergencies, looks for areas of strength and resilience and provides clear and realistic goals for treatment.
- Knowledge of, and referral to, local and national resources, both in the community and online.
Attitudes
- Appreciate the multiple points of view in a family.
- Interest in family members as people with their own needs and history.
- Including family members as a resource in recovery.
- Understand caregiver burden and rewards and that stress extends to all family members.
Training techniques
Most learning takes place at the level of patient, supervisor, and resident. It is critical that the resident sees faculty members dealing with patients in observed or shared family sessions, and /or sees videos made by faculty or professionally made videos. Attitudes are best learned by modeling.
Areas of focus can include time management, addressing the fear that family sessions may get out of control, and the influence of the residents’ own life experiences and background including potential generational or cultural differences on their assessment and interactions with patient family dynamics. In skill development, our goal is efficient interviewing, history taking, and support in controlling sessions.
It is difficult to specify which techniques are most useful in didactic sessions as each presenter will have a different skill set for engaging the class. The techniques that work best are the ones most comfortable to the presenter. Any technique that gets emotions involved, such as role play, sculpting, discussing movie clips, bringing in family members to discuss their experiences, or self-exploration, will generate the most powerful learning. If time permits, exploration of the resident’s own family, including a genogram, is an exceptionally helpful technique, especially if accompanied by asking the residents to interview their own families.
Adult didactic curriculum
The curriculum represents basic concepts. We have vignettes by the authors, if needed, but it is best if the class, including the supervisor, uses vignettes from their own experiences. Material for use in class is in references, but the class is urged to draw on their own experiences as this supports strength-based teaching. The following are key topics and concepts for each of the training years.
Basic concepts for PGY1 and PGY2
1. Where are you in the family and individual life cycles? What are your experiences with psychiatric illness in family/friends? Open discussion about how individual and family life cycles interact. Draw genograms of s/o in the class or with the supervisor.
2. Healthy family functioning and family resilience. Recommend asking residents to talk to their parents/elders about their lives and family life cycle when they were your age. Open discussion about what makes a healthy resilient family.
3. How do I connect with the family rather than just one person? How do you learn to hold multiple perspectives? How do I try not to take sides/multidirectional partiality? How do I see each person in a positive way? How do I focus on family strengths, rather than focusing on someone behaving badly (which is really hard because it is overlearned in individual therapy).
4. What are the common factors used across all therapies, both individual and family? When is it best to use an individual relational approach versus a family systemic approach?
5. How do I decide if a family needs support or education or family therapy?
6. Psychoeducation: Research, current use and cultural adaptations.
7. Attachment styles and couples therapy.
8. What is the evidence base behind our work?
System practice for PGY 3 and 4
These seminars follow the basic seminars. The focus is on clarification of what systems thinking means. Systems thinking or relational thinking is to be differentiated from systems-based practice. These lectures require knowledge of systemic practice. If there are no local experts, residency programs can reach out to national experts at the Association of Family Psychiatrists, for help with virtual/remote or in-person teaching.
Here is a list of other topics that should be covered:
- Relational formulation, nested subsystems, boundaries, history of these concepts, contributions to the development of family therapy.
- How to define and identify common systems concepts, such as circular patterns, feedback loops, and triangulation. Teach circular questioning. Framing. This concept is the family systems equivalent of insight. How to intervene to effect communication change and behavior change?
- Working at interfaces: community, legal, government, agencies, and so on, and other treaters, consultation. Include systemic and individual racism.
- Understanding the complexity of intimacy.
- Emergency situations. When to report regarding abuse. Dealing with family trauma.
- Varieties of family therapy; assumptions and major concepts.
*The new curriculum was written by The GAP Committee on the Family: Ellen Berman, MD; John Rolland, MD, MPH; John Sargent, MD; and me, and with guests Chayanin Foongsathaporn, MD; Sarah Nguyen, MD, MPH; Neha Sharma, DO; and Jodi Zik, MD. For the full curriculum, which includes residency milestones, site-specific training goals, references, and case studies, please access the Association of Family Psychiatry’s website: www.familypsychiatrists.org.Dr. Heru is professor of psychiatry at the University of Colorado Denver, Aurora. She is editor of “Working With Families in Medical Settings: A Multidisciplinary Guide for Psychiatrists and Other Health Professionals” (New York: Routledge, 2013). She has no conflicts of interest to disclose. Contact Dr. Heru at [email protected].
The Group for the Advancement of Psychiatry’s Committee on the Family published an updated curriculum in October 2021 on family-oriented care. The first curriculum, published in 2006, was nominated as the American Association of Directors of Psychiatric Residency Training model curriculum for family-oriented care. The updated curriculum, produced by the GAP family committee and guests, is shorter and more focused.
The following is a summary of the introduction and the highlights.
Introduction
Use of family systems–based techniques in the diagnosis and care of patients is a key evidence-based tool for psychiatric disorders. However, it is not a current Accreditation Council for Graduate Medical Education Training training requirement, and it is possible to complete psychiatry residency without exposure to this key framework.
Here, we highlight the importance of considering patients through a “family systems” lens and the incorporation of multiple individuals from an individual patient’s identified system in their care.
Current medicine curricula emphasize patient autonomy, one of the core pillars of ethics. Autonomy is the cornerstone of the everyday practice within medicine of communicating all risks, benefits, and alternatives of a proposed treatment to a patient making decisions about desired paths forward. This prevents paternalistic care in which the doctor “knows best” and makes decisions for the patient. Unfortunately, the emphasis of this pillar has morphed over time into the idea that the individual patient is the only person to whom this information should be provided or from whom information should be obtained.
Extensive research proves conclusively that family support, education, and psychoeducation improve both patient and family functioning in medical and psychiatric illness. as well as overlook the opportunity to use the structure and support system around a patient to strengthen their care and improve treatment outcomes.
The network and family dynamics around a patient can be critical to providing accurate information on medication adherence and symptoms, supporting recovery, and handling emergencies. Markedly improved patient outcomes occur when family members are seen as allies and offered support, assessment, and psychoeducation. In fact, the American Psychiatric Association’s Practice Guidelines on the treatment of schizophrenia (2020), major depressive disorder (2010), and bipolar disorder (2002) include the expectation that patients’ family members will be involved in the assessment and treatment of patients. Yet, training in how to incorporate these practices is often minimal or nonexistent during residency.
A family systems orientation is distinguished by its view of the family as a transactional system. Stressful events and problems of an individual member affect the whole family as a functional unit, with ripple effects for all members and their relationships. In turn, the family response – how the family handles problems – contributes significantly to positive adaptation or to individual and relational dysfunction. Thus, individual problems are assessed and addressed in the context of the family, with attention to socioeconomic and other environmental stressors.
A family systems approach is distinguished less by who is in the room and more by the clinician’s attention to relationship systems in assessment and treatment planning. We need to consider how family members may contribute to – and be affected by – problem situations. Most importantly, regardless of the source of difficulties, we involve key family members who can contribute to needed changes. Interventions are aimed at modifying dysfunctional patterns, tapping family resources, and strengthening both individual and family functioning.
A family systemic lens is useful for working with all types of families, for example: refugee families, thinking through child adoption processes, working with families with specific social disadvantages, etc. Incorporating issues of race, gender, and sexual orientation is important in this work, as is working with larger systems such as schools, workplaces, and health care settings.
As opposed to previous viewpoints that family therapy is the only “family” skill to be taught during residency, the GAP committee proposes that psychiatric residents should be trained in skills of family inclusion, support, and psychoeducation, and that these skills should be taught throughout the residency. Our goal is to have residents be able to consider any case through a family systems lens, to understand how patients’ illnesses and their family systems have bidirectional effects on each other, to perform a basic assessment of family system functioning, and to use this information in diagnostic and treatment planning.
Training goals
Systems-based thinking will enable trainees to:
1. Ally with family members to work with the patient to comply with goals of care (for example, taking medications, complying with lifestyle changes, and maintaining sobriety).
- Teachers focus on engagement, joining with families.
2. Help patients understand the influences of their families in their own lives, such as intergenerational transmission of trauma and resilience.
- Teachers focus on the creation of a genogram, and the location of the individual within their family system.
3. Understand that mental health includes the creation and maintenance of healthy relationships.
- Teachers focus on assessing a willingness to listen to others’ points of view and the cocreation of a shared reality and belief system: a belief that relationships can change over time and how to create new family narratives.
4. Understand the impact of illness on the family unit and the impact of the family unit on illness.
- Teachers focus on the concept of a family system, clarifying the roles within the family, including caregiving responsibilities.
5. Assess the family for strengths and weaknesses.
- Teachers focus on how families maintain a healthy emotional climate, allocate roles, decide on rules, problem-solving abilities, and so on.
6. Gather information from multiple informants in the same room.
- Teachers focus on using communication techniques to elicit, guide, and redirect information from multiple individuals of a system with varying perspectives in the same room. Teachers help students understand that there are multiple realities in families and learn how to maintain multidirectional partiality.
Knowledge, skills, and attitudes across all treatment settings
Knowledge: Beginning level
- Healthy family functioning at the various phases of the family life cycle. Systems concepts are applicable to families, multidisciplinary teams in clinical settings, and medical/government organizations. However, family systems are distinguished by deep attachment bonds, specific generational hierarchy, goals of emotional safety and, for many families, child rearing.
- Systemic thinking, unlike a linear cause and effect model, examines the feedback loops by which multiple persons or groups arrive at a specific way of functioning.
- Understanding boundaries, subsystems, and feedback loops is critical to understanding interpersonal connections. Understand how the family affects and is affected by psychiatric and medical illnesses. Impact of interpersonal stress on biological systems. The role of expressed emotion (EE) in psychiatric illness. EE describes the level of criticism, hostility, and emotional overinvolvement in families. It has been studied extensively across the health care spectrum, and cultural variance is significant.
- The components of family psychoeducation, and its associated research in improving patient and family outcomes.
Knowledge: Advanced level
- Principles of adaptive and maladaptive relational functioning in family life and family organization, communication, problem solving, and emotional regulation. Role of family strengths, resilience in reducing vulnerability.
- Couple and family development over the life cycle.
- Understanding multigenerational patterns.
- How age, gender, class, culture, and spirituality affect family life.
- The variety of family forms (for example, single parent, stepfamilies, same-sex parents).
- Special issues in couples and families, including loss, divorce and remarriage, immigration, illness, secrets, affairs, violence, alcohol and substance abuse, sexuality, including LGBTQi. Relationship of families to larger systems, for example, schools, work, health care systems, government agencies.
Skills
- Family-interviewing skills, especially managing high levels of emotion and making room for multiple points of view.
- Promoting resilience, hope, and strength.
- Basic psychoeducation techniques, which includes providing a therapeutic space for emotional processing, providing information about the illness, skills such as better communication, problem-solving, and relapse drill and support.
- Collaborative treatment planning with family members and other helping professionals. Treatment planning should include all members of the system: patient, family members, and members of the treatment team. Good planning establishes a role for family members, helps define criteria for managing emergencies, looks for areas of strength and resilience and provides clear and realistic goals for treatment.
- Knowledge of, and referral to, local and national resources, both in the community and online.
Attitudes
- Appreciate the multiple points of view in a family.
- Interest in family members as people with their own needs and history.
- Including family members as a resource in recovery.
- Understand caregiver burden and rewards and that stress extends to all family members.
Training techniques
Most learning takes place at the level of patient, supervisor, and resident. It is critical that the resident sees faculty members dealing with patients in observed or shared family sessions, and /or sees videos made by faculty or professionally made videos. Attitudes are best learned by modeling.
Areas of focus can include time management, addressing the fear that family sessions may get out of control, and the influence of the residents’ own life experiences and background including potential generational or cultural differences on their assessment and interactions with patient family dynamics. In skill development, our goal is efficient interviewing, history taking, and support in controlling sessions.
It is difficult to specify which techniques are most useful in didactic sessions as each presenter will have a different skill set for engaging the class. The techniques that work best are the ones most comfortable to the presenter. Any technique that gets emotions involved, such as role play, sculpting, discussing movie clips, bringing in family members to discuss their experiences, or self-exploration, will generate the most powerful learning. If time permits, exploration of the resident’s own family, including a genogram, is an exceptionally helpful technique, especially if accompanied by asking the residents to interview their own families.
Adult didactic curriculum
The curriculum represents basic concepts. We have vignettes by the authors, if needed, but it is best if the class, including the supervisor, uses vignettes from their own experiences. Material for use in class is in references, but the class is urged to draw on their own experiences as this supports strength-based teaching. The following are key topics and concepts for each of the training years.
Basic concepts for PGY1 and PGY2
1. Where are you in the family and individual life cycles? What are your experiences with psychiatric illness in family/friends? Open discussion about how individual and family life cycles interact. Draw genograms of s/o in the class or with the supervisor.
2. Healthy family functioning and family resilience. Recommend asking residents to talk to their parents/elders about their lives and family life cycle when they were your age. Open discussion about what makes a healthy resilient family.
3. How do I connect with the family rather than just one person? How do you learn to hold multiple perspectives? How do I try not to take sides/multidirectional partiality? How do I see each person in a positive way? How do I focus on family strengths, rather than focusing on someone behaving badly (which is really hard because it is overlearned in individual therapy).
4. What are the common factors used across all therapies, both individual and family? When is it best to use an individual relational approach versus a family systemic approach?
5. How do I decide if a family needs support or education or family therapy?
6. Psychoeducation: Research, current use and cultural adaptations.
7. Attachment styles and couples therapy.
8. What is the evidence base behind our work?
System practice for PGY 3 and 4
These seminars follow the basic seminars. The focus is on clarification of what systems thinking means. Systems thinking or relational thinking is to be differentiated from systems-based practice. These lectures require knowledge of systemic practice. If there are no local experts, residency programs can reach out to national experts at the Association of Family Psychiatrists, for help with virtual/remote or in-person teaching.
Here is a list of other topics that should be covered:
- Relational formulation, nested subsystems, boundaries, history of these concepts, contributions to the development of family therapy.
- How to define and identify common systems concepts, such as circular patterns, feedback loops, and triangulation. Teach circular questioning. Framing. This concept is the family systems equivalent of insight. How to intervene to effect communication change and behavior change?
- Working at interfaces: community, legal, government, agencies, and so on, and other treaters, consultation. Include systemic and individual racism.
- Understanding the complexity of intimacy.
- Emergency situations. When to report regarding abuse. Dealing with family trauma.
- Varieties of family therapy; assumptions and major concepts.
*The new curriculum was written by The GAP Committee on the Family: Ellen Berman, MD; John Rolland, MD, MPH; John Sargent, MD; and me, and with guests Chayanin Foongsathaporn, MD; Sarah Nguyen, MD, MPH; Neha Sharma, DO; and Jodi Zik, MD. For the full curriculum, which includes residency milestones, site-specific training goals, references, and case studies, please access the Association of Family Psychiatry’s website: www.familypsychiatrists.org.Dr. Heru is professor of psychiatry at the University of Colorado Denver, Aurora. She is editor of “Working With Families in Medical Settings: A Multidisciplinary Guide for Psychiatrists and Other Health Professionals” (New York: Routledge, 2013). She has no conflicts of interest to disclose. Contact Dr. Heru at [email protected].
Stabilizing circadian rhythm tied to lower suicide risk in bipolar disorder
Social rhythm therapy (SRT), which uses behavioral strategies to support healthy sleep and other routines, is linked to improved mood and reduced suicide risk in young people with bipolar disorder (BD), early research suggests.
The small study also showed SRT is both feasible and acceptable in this patient population.
Results showed SRT, which was primarily delivered via telehealth sessions, began to show efficacy approximately 6 weeks into the 12-week therapeutic program, the researchers noted.
“Improving the regularity of daily rhythms like sleep, physical activity, and social activities can be really robust in improving mental health and even reducing suicide risk,” study investigator Hilary P. Blumberg, MD, the John and Hope Furth Professor of Psychiatric Neuroscience and director of the mood disorders research program at Yale University, New Haven, Conn., said in an interview.
The findings are published in the American Journal of Psychotherapy.
Trigger for depression, mania
Previous research shows unstable circadian rhythms may trigger depressive and manic symptoms – and are risk factors for suicidal thoughts and behaviors. Although interpersonal and social rhythm therapy has shown promise in patients with mood disorders, there is little research focusing only on the social rhythm aspect of the therapy.
The researchers only examined SRT, modified to create a therapeutic program aimed at adolescents and young adults.
The study included 13 participants (mean age, 20.5 years) with BD and a score of 15 or more on the 29-item Hamilton Depression Rating Scale (HDRS-29) and/or a score of 12 or more on the Young Mania Rating Scale (YMRS).
Participants were enrolled in the National Institute of Mental Health Brain Emotion Circuitry Targeted Self-Monitoring and Regulation Therapy (BE-SMART) program, which requires MRI sessions at three in-person visits to assess brain changes with the therapy. All but one participant was taking mood-stabilizing medications.
“We didn’t ask them to come off medications because we didn’t want to exacerbate things,” said Dr. Blumberg. She added the therapeutic approach “could be adjunctive to further improve symptoms and reduce risk.”
The majority occurred on a secure video platform. Three were conducted in person.
Working with a therapist, participants were taught how to follow a daily routine. Dr. Blumberg noted this is not just a matter of going to sleep and getting up at the same time every day, but thoroughly reviewing details of all daily activities and routines, including who participants eat with and when, their exercise schedule, and social engagements.
Each week, participants completed the five-item version of the Social Rhythm Metric. At the end of the intervention, they also completed the Client Satisfaction Questionnaire (CSQ). Scores on the CSQ range from 8 to 32, with scores of 26-32 indicating “excellent” satisfaction.
In addition, participants and therapists completed the Working Alliance Inventory, which assesses the client-therapist relationship by asking about such things as degree of comfort and respect.
Before and after the intervention, participants reported the regularity of their social rhythms using the Brief Social Rhythm Scale (BSRS) and risk for suicidal behavior using a subscale of the Concise Health Risk Tracking (CHRT) scale.
High retention, ‘excellent satisfaction’
Results showed 10 of the 13 participants (9 females) completed all study procedures, for a retention rate of 77%. Treatment satisfaction was excellent (mean CSQ, 29.4).
Both therapists and participants had high scores on all aspects of the Working Alliance Inventory scale.
“High treatment retention, excellent client satisfaction, and strong working alliance scores support the feasibility and acceptability of this intervention for adolescents and young adults with bipolar disorder,” the investigators wrote.
Participants showed significant improvement in social rhythm regularity and reductions in depression and manic symptoms as well as suicide propensity (P = .016 for BSRS; .024 for HDRS-29; .028 for YMRS; and .028 for CHRT suicide propensity). Effect sizes were in the moderate to high range.
By the midpoint of the therapy, there were significant improvements in social rhythm regularity and suicide propensity and trend-level reductions in depression, suggesting the potential for early benefits.
Dr. Blumberg noted it is difficult to find a therapy that helps with both depressive and mania symptoms. “An antidepressant may reduce depression, but sometimes can worsen manic symptoms.”
Impact on emotional brain circuitry?
The association between improved regularity of social rhythms and reduced suicide propensity persisted even after controlling for mood symptom changes.
“Suicide risk was reduced not just because subjects were less depressed. There’s something about regularizing rhythms that can reduce suicide risk,” said Dr. Blumberg.
The reviewers noted that SRT administered remotely improves accessibility; and this intervention “is well suited to the future of psychotherapy delivery, which will undoubtedly include remote treatment delivery.”
The absence of a comparator condition was cited as a study limitation. The investigators noted the small sample size means the findings should be interpreted cautiously and verified in an adequately powered randomized controlled trial.
The researchers now have early results from the brain scanning component of the study. “Preliminary findings suggest the intervention seems to benefit emotional brain circuitry,” Dr. Blumberg said.
The researchers are about to embark on a new study funded by a grant from the American Foundation of Suicide Prevention. It will investigate SRT in preventing suicide in adolescents and adults to age 29 years with depression or BD.
In addition, the researchers have secured support from the Klingenstein Third Generation Foundation to research prevention in youth at risk for BD – and from Women’s Health Access Matters to examine the therapy in women 50 and older with depression, a population possibly at increased risk for dementia.
‘Promising’ results
Commenting on the findings, Michael Thase, MD, professor of psychiatry, University of Pennsylvania, and research psychiatrist at the Corporal Michael J. Crescenz Veterans Affairs Medical Center, both in Philadelphia, praised the study.
“It’s a very, very promising initial study because even though there’s no control group, it does show that participants liked the program, most finished it, and on average, people got quite a bit better,” said Dr. Thase, who was not involved with the research.
The treatment may be especially beneficial for young patients with bipolar disorder who, just by their very age, experience lifestyle disruptions, Dr. Thase noted. Results from a previous study of the therapeutic approach in adults showed “probably half of the adults didn’t take to it.”
However, not everyone in this new study benefited either, as some dropped out, which Dr. Thase noted is not atypical.
“No form of intervention is suitable for everyone,” he said.
The study was supported by grants from the National Institute of Mental Health, AIM Youth Mental Health Foundation, Klingenstein Third Generation Foundation, American Foundation for Suicide Prevention, International Bipolar Foundation, MQ Brighter Futures Program, For the Love of Travis Foundation, and the John and Hope Furth Endowment. Dr. Blumberg and Dr. Thase reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Social rhythm therapy (SRT), which uses behavioral strategies to support healthy sleep and other routines, is linked to improved mood and reduced suicide risk in young people with bipolar disorder (BD), early research suggests.
The small study also showed SRT is both feasible and acceptable in this patient population.
Results showed SRT, which was primarily delivered via telehealth sessions, began to show efficacy approximately 6 weeks into the 12-week therapeutic program, the researchers noted.
“Improving the regularity of daily rhythms like sleep, physical activity, and social activities can be really robust in improving mental health and even reducing suicide risk,” study investigator Hilary P. Blumberg, MD, the John and Hope Furth Professor of Psychiatric Neuroscience and director of the mood disorders research program at Yale University, New Haven, Conn., said in an interview.
The findings are published in the American Journal of Psychotherapy.
Trigger for depression, mania
Previous research shows unstable circadian rhythms may trigger depressive and manic symptoms – and are risk factors for suicidal thoughts and behaviors. Although interpersonal and social rhythm therapy has shown promise in patients with mood disorders, there is little research focusing only on the social rhythm aspect of the therapy.
The researchers only examined SRT, modified to create a therapeutic program aimed at adolescents and young adults.
The study included 13 participants (mean age, 20.5 years) with BD and a score of 15 or more on the 29-item Hamilton Depression Rating Scale (HDRS-29) and/or a score of 12 or more on the Young Mania Rating Scale (YMRS).
Participants were enrolled in the National Institute of Mental Health Brain Emotion Circuitry Targeted Self-Monitoring and Regulation Therapy (BE-SMART) program, which requires MRI sessions at three in-person visits to assess brain changes with the therapy. All but one participant was taking mood-stabilizing medications.
“We didn’t ask them to come off medications because we didn’t want to exacerbate things,” said Dr. Blumberg. She added the therapeutic approach “could be adjunctive to further improve symptoms and reduce risk.”
The majority occurred on a secure video platform. Three were conducted in person.
Working with a therapist, participants were taught how to follow a daily routine. Dr. Blumberg noted this is not just a matter of going to sleep and getting up at the same time every day, but thoroughly reviewing details of all daily activities and routines, including who participants eat with and when, their exercise schedule, and social engagements.
Each week, participants completed the five-item version of the Social Rhythm Metric. At the end of the intervention, they also completed the Client Satisfaction Questionnaire (CSQ). Scores on the CSQ range from 8 to 32, with scores of 26-32 indicating “excellent” satisfaction.
In addition, participants and therapists completed the Working Alliance Inventory, which assesses the client-therapist relationship by asking about such things as degree of comfort and respect.
Before and after the intervention, participants reported the regularity of their social rhythms using the Brief Social Rhythm Scale (BSRS) and risk for suicidal behavior using a subscale of the Concise Health Risk Tracking (CHRT) scale.
High retention, ‘excellent satisfaction’
Results showed 10 of the 13 participants (9 females) completed all study procedures, for a retention rate of 77%. Treatment satisfaction was excellent (mean CSQ, 29.4).
Both therapists and participants had high scores on all aspects of the Working Alliance Inventory scale.
“High treatment retention, excellent client satisfaction, and strong working alliance scores support the feasibility and acceptability of this intervention for adolescents and young adults with bipolar disorder,” the investigators wrote.
Participants showed significant improvement in social rhythm regularity and reductions in depression and manic symptoms as well as suicide propensity (P = .016 for BSRS; .024 for HDRS-29; .028 for YMRS; and .028 for CHRT suicide propensity). Effect sizes were in the moderate to high range.
By the midpoint of the therapy, there were significant improvements in social rhythm regularity and suicide propensity and trend-level reductions in depression, suggesting the potential for early benefits.
Dr. Blumberg noted it is difficult to find a therapy that helps with both depressive and mania symptoms. “An antidepressant may reduce depression, but sometimes can worsen manic symptoms.”
Impact on emotional brain circuitry?
The association between improved regularity of social rhythms and reduced suicide propensity persisted even after controlling for mood symptom changes.
“Suicide risk was reduced not just because subjects were less depressed. There’s something about regularizing rhythms that can reduce suicide risk,” said Dr. Blumberg.
The reviewers noted that SRT administered remotely improves accessibility; and this intervention “is well suited to the future of psychotherapy delivery, which will undoubtedly include remote treatment delivery.”
The absence of a comparator condition was cited as a study limitation. The investigators noted the small sample size means the findings should be interpreted cautiously and verified in an adequately powered randomized controlled trial.
The researchers now have early results from the brain scanning component of the study. “Preliminary findings suggest the intervention seems to benefit emotional brain circuitry,” Dr. Blumberg said.
The researchers are about to embark on a new study funded by a grant from the American Foundation of Suicide Prevention. It will investigate SRT in preventing suicide in adolescents and adults to age 29 years with depression or BD.
In addition, the researchers have secured support from the Klingenstein Third Generation Foundation to research prevention in youth at risk for BD – and from Women’s Health Access Matters to examine the therapy in women 50 and older with depression, a population possibly at increased risk for dementia.
‘Promising’ results
Commenting on the findings, Michael Thase, MD, professor of psychiatry, University of Pennsylvania, and research psychiatrist at the Corporal Michael J. Crescenz Veterans Affairs Medical Center, both in Philadelphia, praised the study.
“It’s a very, very promising initial study because even though there’s no control group, it does show that participants liked the program, most finished it, and on average, people got quite a bit better,” said Dr. Thase, who was not involved with the research.
The treatment may be especially beneficial for young patients with bipolar disorder who, just by their very age, experience lifestyle disruptions, Dr. Thase noted. Results from a previous study of the therapeutic approach in adults showed “probably half of the adults didn’t take to it.”
However, not everyone in this new study benefited either, as some dropped out, which Dr. Thase noted is not atypical.
“No form of intervention is suitable for everyone,” he said.
The study was supported by grants from the National Institute of Mental Health, AIM Youth Mental Health Foundation, Klingenstein Third Generation Foundation, American Foundation for Suicide Prevention, International Bipolar Foundation, MQ Brighter Futures Program, For the Love of Travis Foundation, and the John and Hope Furth Endowment. Dr. Blumberg and Dr. Thase reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Social rhythm therapy (SRT), which uses behavioral strategies to support healthy sleep and other routines, is linked to improved mood and reduced suicide risk in young people with bipolar disorder (BD), early research suggests.
The small study also showed SRT is both feasible and acceptable in this patient population.
Results showed SRT, which was primarily delivered via telehealth sessions, began to show efficacy approximately 6 weeks into the 12-week therapeutic program, the researchers noted.
“Improving the regularity of daily rhythms like sleep, physical activity, and social activities can be really robust in improving mental health and even reducing suicide risk,” study investigator Hilary P. Blumberg, MD, the John and Hope Furth Professor of Psychiatric Neuroscience and director of the mood disorders research program at Yale University, New Haven, Conn., said in an interview.
The findings are published in the American Journal of Psychotherapy.
Trigger for depression, mania
Previous research shows unstable circadian rhythms may trigger depressive and manic symptoms – and are risk factors for suicidal thoughts and behaviors. Although interpersonal and social rhythm therapy has shown promise in patients with mood disorders, there is little research focusing only on the social rhythm aspect of the therapy.
The researchers only examined SRT, modified to create a therapeutic program aimed at adolescents and young adults.
The study included 13 participants (mean age, 20.5 years) with BD and a score of 15 or more on the 29-item Hamilton Depression Rating Scale (HDRS-29) and/or a score of 12 or more on the Young Mania Rating Scale (YMRS).
Participants were enrolled in the National Institute of Mental Health Brain Emotion Circuitry Targeted Self-Monitoring and Regulation Therapy (BE-SMART) program, which requires MRI sessions at three in-person visits to assess brain changes with the therapy. All but one participant was taking mood-stabilizing medications.
“We didn’t ask them to come off medications because we didn’t want to exacerbate things,” said Dr. Blumberg. She added the therapeutic approach “could be adjunctive to further improve symptoms and reduce risk.”
The majority occurred on a secure video platform. Three were conducted in person.
Working with a therapist, participants were taught how to follow a daily routine. Dr. Blumberg noted this is not just a matter of going to sleep and getting up at the same time every day, but thoroughly reviewing details of all daily activities and routines, including who participants eat with and when, their exercise schedule, and social engagements.
Each week, participants completed the five-item version of the Social Rhythm Metric. At the end of the intervention, they also completed the Client Satisfaction Questionnaire (CSQ). Scores on the CSQ range from 8 to 32, with scores of 26-32 indicating “excellent” satisfaction.
In addition, participants and therapists completed the Working Alliance Inventory, which assesses the client-therapist relationship by asking about such things as degree of comfort and respect.
Before and after the intervention, participants reported the regularity of their social rhythms using the Brief Social Rhythm Scale (BSRS) and risk for suicidal behavior using a subscale of the Concise Health Risk Tracking (CHRT) scale.
High retention, ‘excellent satisfaction’
Results showed 10 of the 13 participants (9 females) completed all study procedures, for a retention rate of 77%. Treatment satisfaction was excellent (mean CSQ, 29.4).
Both therapists and participants had high scores on all aspects of the Working Alliance Inventory scale.
“High treatment retention, excellent client satisfaction, and strong working alliance scores support the feasibility and acceptability of this intervention for adolescents and young adults with bipolar disorder,” the investigators wrote.
Participants showed significant improvement in social rhythm regularity and reductions in depression and manic symptoms as well as suicide propensity (P = .016 for BSRS; .024 for HDRS-29; .028 for YMRS; and .028 for CHRT suicide propensity). Effect sizes were in the moderate to high range.
By the midpoint of the therapy, there were significant improvements in social rhythm regularity and suicide propensity and trend-level reductions in depression, suggesting the potential for early benefits.
Dr. Blumberg noted it is difficult to find a therapy that helps with both depressive and mania symptoms. “An antidepressant may reduce depression, but sometimes can worsen manic symptoms.”
Impact on emotional brain circuitry?
The association between improved regularity of social rhythms and reduced suicide propensity persisted even after controlling for mood symptom changes.
“Suicide risk was reduced not just because subjects were less depressed. There’s something about regularizing rhythms that can reduce suicide risk,” said Dr. Blumberg.
The reviewers noted that SRT administered remotely improves accessibility; and this intervention “is well suited to the future of psychotherapy delivery, which will undoubtedly include remote treatment delivery.”
The absence of a comparator condition was cited as a study limitation. The investigators noted the small sample size means the findings should be interpreted cautiously and verified in an adequately powered randomized controlled trial.
The researchers now have early results from the brain scanning component of the study. “Preliminary findings suggest the intervention seems to benefit emotional brain circuitry,” Dr. Blumberg said.
The researchers are about to embark on a new study funded by a grant from the American Foundation of Suicide Prevention. It will investigate SRT in preventing suicide in adolescents and adults to age 29 years with depression or BD.
In addition, the researchers have secured support from the Klingenstein Third Generation Foundation to research prevention in youth at risk for BD – and from Women’s Health Access Matters to examine the therapy in women 50 and older with depression, a population possibly at increased risk for dementia.
‘Promising’ results
Commenting on the findings, Michael Thase, MD, professor of psychiatry, University of Pennsylvania, and research psychiatrist at the Corporal Michael J. Crescenz Veterans Affairs Medical Center, both in Philadelphia, praised the study.
“It’s a very, very promising initial study because even though there’s no control group, it does show that participants liked the program, most finished it, and on average, people got quite a bit better,” said Dr. Thase, who was not involved with the research.
The treatment may be especially beneficial for young patients with bipolar disorder who, just by their very age, experience lifestyle disruptions, Dr. Thase noted. Results from a previous study of the therapeutic approach in adults showed “probably half of the adults didn’t take to it.”
However, not everyone in this new study benefited either, as some dropped out, which Dr. Thase noted is not atypical.
“No form of intervention is suitable for everyone,” he said.
The study was supported by grants from the National Institute of Mental Health, AIM Youth Mental Health Foundation, Klingenstein Third Generation Foundation, American Foundation for Suicide Prevention, International Bipolar Foundation, MQ Brighter Futures Program, For the Love of Travis Foundation, and the John and Hope Furth Endowment. Dr. Blumberg and Dr. Thase reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE AMERICAN JOURNAL OF PSYCHOTHERAPY
Despite the stigma, ECT remains a gold standard
For Clayton Lively, electroconvulsive therapy, or ECT, has been a lifesaver.
“ECT was like a last resort to treat mania and psychosis for bipolar disorder,” said the 31-year-old financial firm associate who lives in Silver Spring, Md. “I had tried lots of different medications.”
The first course of treatments – three times per week for several weeks – was in 2005. They helped tremendously. “I came down from my mania,” Mr. Lively said. “The hallucinations stopped. The psychosis disappeared.”
He reached a point where medications and psychotherapy worked again. And for a decade, his condition was under control.
But in 2017, another episode of hallucinations and mania jolted him off course. Intrusive thoughts returned. For instance, while driving, he would visualize veering off the road. The thoughts were jarring, and yet, he couldn’t stop them from recurring.
“I wasn’t sleeping, and it just kind of wreaked havoc on my life,” Mr. Lively recalled. “I ended up being hospitalized again.”
Once again, ECT came to the rescue – and yet again, in 2018. Now, he’s on an effective maintenance regimen, receiving ECT once every 4 weeks, after tapering down from more frequent sessions.
When a combination of antidepressants and psychotherapy fails to control severe mental illness, there’s hope on the horizon. ECT can be a reliably safe and effective option.
For some patients, using it as maintenance therapy makes sense, said Vaughn McCall, MD, editor-in-chief of The Journal of ECT and professor and chairman of psychiatry at the Medical College of Georgia in Augusta. “I would think of it the same way as you have to treat any chronic illness,” such as blood pressure medicine to keep hypertension in check and dialysis to prevent kidney failure.
Despite a cacophony of contrarian voices – mainly from the Church of Scientology – “the number of psychiatrists who see controversy in ECT is vanishingly small,” Dr. McCall said.
In weighing the pros and cons of ECT, he noted that “when you’re trying to decide if it’s worth doing a treatment, you’re looking at the effectiveness on one hand and the side effects on the other hand.”
The answer to that emerges from several scales measuring patients’ quality of life by posing questions such as: “After receiving ECT, are you more able or less able to take care of yourself, to work, and enjoy the company of other people?”
In the end, Dr. McCall said, “we’ve applied these scales in probably half a dozen studies or more, and they always show that the patients’ qualify of life as a group is improved.”
A recent study published in The Lancet Psychiatry provides a significant degree of reassurance that ECT – also called “electroshock” or colloquially just “shock” therapy – does not increase the risk of serious medical side effects. In fact, the study suggests a potential benefit in reducing suicide risk.
First performed in 1938, the treatment has been well documented in the medical literature. But negative portrayals in books and movies, such as the 1975 film “One Flew Over the Cuckoo’s Nest,” have contributed to casting it in an unfavorable light.
“Unfortunately, over the past decades and years, there’s a lot of stigma and fear around the treatment,” said the study’s lead author, Tyler Kaster, MD, a psychiatrist and clinical fellow in brain stimulation at the University of Toronto.
For the study, Canadian investigators reviewed the admission records of 10,000 patients hospitalized for at least 3 days because of a severe depressive episode. Nearly two-thirds of the patients were women, and the average age for the entire group approached 57 years.
While half of the patients underwent ECT, the others received medication and psychotherapy. Researchers found that the group undergoing ECT did not have a heightened risk of death over the next 30 days and were not any more likely to be hospitalized for a medical problem.
Previous ECT comparative studies were at high risk of bias because of their inability to sufficiently account for confounding variables and differences between those who received the treatment and those who did not. The current study employed “rigorous methods with careful attention to bias and confounding to overcome limitations of previous work,” the authors wrote.
They used propensity score matching, which included more than 75 variables, such as measures of cognitive impairment, depression severity, medication use, other illnesses, and use of psychiatric and various medical services, capacity to consent to treatment, and sociodemographic factors.
“This is really a landmark study in terms of showing the medical safety of ECT,” said Mark S. George, MD, professor of psychiatry and neurology at the Medical University of South Carolina, Charleston, who was not involved in the study.
He added that “ECT is a life-saving treatment” for individuals with severe depression. “It’s good that we have this option for our patients.”
The authors highlight that depression is a major cause of illness and disability worldwide, with many individuals failing to achieve remission from initial therapies. Treatment-resistant depression is often described as being nonresponsive “to two or more medication trials of adequate dose and duration from different classes,” they wrote. In these instances, the authors point out, there is little evidence that psychotherapy would be helpful.
“The reason we consider ECT is someone has very severe depression that hasn’t responded to medications and talk therapy,” Dr. Kaster said. “The advantage of ECT is that it’s very effective in those circumstances.”
Of all therapies for treatment-resistant depression, ECT has the highest success rate, with 60% of patients attaining remission, according to the study, which cites prior research.
Compared with neurosurgery, the procedure is not invasive but requires general anesthesia. While the patient is asleep, Dr. Kaster said, the treating clinician places an electrical stimulus on the patient’s scalp, causing a generalized seizure inside the brain that lasts from 15 seconds to 2 minutes.
A course of ECT usually takes a total of 8-12 treatments, delivered two to three times per week over a month to a month and a half, Dr. George said.
Some patients need a new course of ECT if they relapse after several months. Others are unable to control their depression between courses and require repeated doses for maintenance. The time between these ECT sessions varies for each individual, Dr. George said, but is typically one session every 3-4 weeks.
To improve the odds of staying well, patients typically need to continue taking antidepressants and engaging in psychotherapy.
“It helps improve the efficacy of ECT and also down the road helps prevent relapse,” Dr. Kaster said, noting that “depression is, unfortunately, a chronic illness. We don’t have a cure.”
Murat Altinay, MD, associate professor of psychiatry at the Cleveland Clinic and a mood disorders specialist, said his patients generally need to demonstrate a lack of response to at least three or four antidepressants before he considers recommending ECT.
Confusion, short-term memory impairment, and muscle aches and pains may occur after the procedure, but they are relatively mild. Patients are monitored in a recovery room before discharge from the hospital, Dr. Altinay said.
The first few treatments will affect everyday function. After that initial period, however, people can resume most of their daily activities, he said.
“Maybe they won’t be able to work full-time right away, but anecdotally, we have had patients who were able to go back to the workforce relatively quickly or while they’re getting ECT,” Dr. Altinay said.
More significant adverse events are very rare, he noted, although heart rate and blood pressure can become elevated because of the electrical stimulus.
Dr. Altinay said he is pleased that the large-scale journal article has been published to help dispel myths surrounding ECT. While psychiatrists feel that ECT is generally safe and effective, the public maintains a negative view.
“It is an underutilized treatment,” he said. “In the media, it is almost depicted as a barbaric and archaic treatment in psychiatry.”
Patients are afraid of major side effects such as personality changes. Some fear they will forget someone’s birthday or other important factual information, “but that kind of stuff obviously does not happen,” Dr. Altinay said.
Sometimes it’s not only the patients who are hesitant to try ECT; it’s the family members who express concerns, said Irving Reti, MBBS, professor of psychiatry and neuroscience and director of the brain stimulation program at the Johns Hopkins University, Baltimore.
“It varies from one patient to another how agreeable or reluctant or cautious they are about their treatment if the doctor thinks it’s indicated for them,” Dr. Reti said. “Family members’ concerns may be very legitimate but may also be influenced by stigma and misunderstanding about the treatment. They may also not fully appreciate the severity of their loved one’s depression that warrants the administration of ECT.”
Hospitalized patients who are at risk of suicide have benefited from ECT. “It’s very effective,” he said. “I think it’s still the gold standard for severe treatment-resistant depression and also particularly helpful in people who are acutely suicidal.”
Dr. George cautioned that psychiatrists and the public should beware of questionable online sources that attempt to discredit ECT. “A quick Google search will find plenty of nonmedical doctors, many funded through Scientology, who will speak poorly of ECT. But they do not use evidence-based arguments and commonly do not treat patients,” he said.
“All good practicing psychiatrists that I know are in favor of ECT, as it clearly saves lives,” Dr. George added. “We all hope that the future will provide refinements of ECT, or even disruptive technologies that are more effective and with less hassle and will make ECT as we do it now obsolete. But we are not there yet.”
A version of this article first appeared on Medscape.com.
For Clayton Lively, electroconvulsive therapy, or ECT, has been a lifesaver.
“ECT was like a last resort to treat mania and psychosis for bipolar disorder,” said the 31-year-old financial firm associate who lives in Silver Spring, Md. “I had tried lots of different medications.”
The first course of treatments – three times per week for several weeks – was in 2005. They helped tremendously. “I came down from my mania,” Mr. Lively said. “The hallucinations stopped. The psychosis disappeared.”
He reached a point where medications and psychotherapy worked again. And for a decade, his condition was under control.
But in 2017, another episode of hallucinations and mania jolted him off course. Intrusive thoughts returned. For instance, while driving, he would visualize veering off the road. The thoughts were jarring, and yet, he couldn’t stop them from recurring.
“I wasn’t sleeping, and it just kind of wreaked havoc on my life,” Mr. Lively recalled. “I ended up being hospitalized again.”
Once again, ECT came to the rescue – and yet again, in 2018. Now, he’s on an effective maintenance regimen, receiving ECT once every 4 weeks, after tapering down from more frequent sessions.
When a combination of antidepressants and psychotherapy fails to control severe mental illness, there’s hope on the horizon. ECT can be a reliably safe and effective option.
For some patients, using it as maintenance therapy makes sense, said Vaughn McCall, MD, editor-in-chief of The Journal of ECT and professor and chairman of psychiatry at the Medical College of Georgia in Augusta. “I would think of it the same way as you have to treat any chronic illness,” such as blood pressure medicine to keep hypertension in check and dialysis to prevent kidney failure.
Despite a cacophony of contrarian voices – mainly from the Church of Scientology – “the number of psychiatrists who see controversy in ECT is vanishingly small,” Dr. McCall said.
In weighing the pros and cons of ECT, he noted that “when you’re trying to decide if it’s worth doing a treatment, you’re looking at the effectiveness on one hand and the side effects on the other hand.”
The answer to that emerges from several scales measuring patients’ quality of life by posing questions such as: “After receiving ECT, are you more able or less able to take care of yourself, to work, and enjoy the company of other people?”
In the end, Dr. McCall said, “we’ve applied these scales in probably half a dozen studies or more, and they always show that the patients’ qualify of life as a group is improved.”
A recent study published in The Lancet Psychiatry provides a significant degree of reassurance that ECT – also called “electroshock” or colloquially just “shock” therapy – does not increase the risk of serious medical side effects. In fact, the study suggests a potential benefit in reducing suicide risk.
First performed in 1938, the treatment has been well documented in the medical literature. But negative portrayals in books and movies, such as the 1975 film “One Flew Over the Cuckoo’s Nest,” have contributed to casting it in an unfavorable light.
“Unfortunately, over the past decades and years, there’s a lot of stigma and fear around the treatment,” said the study’s lead author, Tyler Kaster, MD, a psychiatrist and clinical fellow in brain stimulation at the University of Toronto.
For the study, Canadian investigators reviewed the admission records of 10,000 patients hospitalized for at least 3 days because of a severe depressive episode. Nearly two-thirds of the patients were women, and the average age for the entire group approached 57 years.
While half of the patients underwent ECT, the others received medication and psychotherapy. Researchers found that the group undergoing ECT did not have a heightened risk of death over the next 30 days and were not any more likely to be hospitalized for a medical problem.
Previous ECT comparative studies were at high risk of bias because of their inability to sufficiently account for confounding variables and differences between those who received the treatment and those who did not. The current study employed “rigorous methods with careful attention to bias and confounding to overcome limitations of previous work,” the authors wrote.
They used propensity score matching, which included more than 75 variables, such as measures of cognitive impairment, depression severity, medication use, other illnesses, and use of psychiatric and various medical services, capacity to consent to treatment, and sociodemographic factors.
“This is really a landmark study in terms of showing the medical safety of ECT,” said Mark S. George, MD, professor of psychiatry and neurology at the Medical University of South Carolina, Charleston, who was not involved in the study.
He added that “ECT is a life-saving treatment” for individuals with severe depression. “It’s good that we have this option for our patients.”
The authors highlight that depression is a major cause of illness and disability worldwide, with many individuals failing to achieve remission from initial therapies. Treatment-resistant depression is often described as being nonresponsive “to two or more medication trials of adequate dose and duration from different classes,” they wrote. In these instances, the authors point out, there is little evidence that psychotherapy would be helpful.
“The reason we consider ECT is someone has very severe depression that hasn’t responded to medications and talk therapy,” Dr. Kaster said. “The advantage of ECT is that it’s very effective in those circumstances.”
Of all therapies for treatment-resistant depression, ECT has the highest success rate, with 60% of patients attaining remission, according to the study, which cites prior research.
Compared with neurosurgery, the procedure is not invasive but requires general anesthesia. While the patient is asleep, Dr. Kaster said, the treating clinician places an electrical stimulus on the patient’s scalp, causing a generalized seizure inside the brain that lasts from 15 seconds to 2 minutes.
A course of ECT usually takes a total of 8-12 treatments, delivered two to three times per week over a month to a month and a half, Dr. George said.
Some patients need a new course of ECT if they relapse after several months. Others are unable to control their depression between courses and require repeated doses for maintenance. The time between these ECT sessions varies for each individual, Dr. George said, but is typically one session every 3-4 weeks.
To improve the odds of staying well, patients typically need to continue taking antidepressants and engaging in psychotherapy.
“It helps improve the efficacy of ECT and also down the road helps prevent relapse,” Dr. Kaster said, noting that “depression is, unfortunately, a chronic illness. We don’t have a cure.”
Murat Altinay, MD, associate professor of psychiatry at the Cleveland Clinic and a mood disorders specialist, said his patients generally need to demonstrate a lack of response to at least three or four antidepressants before he considers recommending ECT.
Confusion, short-term memory impairment, and muscle aches and pains may occur after the procedure, but they are relatively mild. Patients are monitored in a recovery room before discharge from the hospital, Dr. Altinay said.
The first few treatments will affect everyday function. After that initial period, however, people can resume most of their daily activities, he said.
“Maybe they won’t be able to work full-time right away, but anecdotally, we have had patients who were able to go back to the workforce relatively quickly or while they’re getting ECT,” Dr. Altinay said.
More significant adverse events are very rare, he noted, although heart rate and blood pressure can become elevated because of the electrical stimulus.
Dr. Altinay said he is pleased that the large-scale journal article has been published to help dispel myths surrounding ECT. While psychiatrists feel that ECT is generally safe and effective, the public maintains a negative view.
“It is an underutilized treatment,” he said. “In the media, it is almost depicted as a barbaric and archaic treatment in psychiatry.”
Patients are afraid of major side effects such as personality changes. Some fear they will forget someone’s birthday or other important factual information, “but that kind of stuff obviously does not happen,” Dr. Altinay said.
Sometimes it’s not only the patients who are hesitant to try ECT; it’s the family members who express concerns, said Irving Reti, MBBS, professor of psychiatry and neuroscience and director of the brain stimulation program at the Johns Hopkins University, Baltimore.
“It varies from one patient to another how agreeable or reluctant or cautious they are about their treatment if the doctor thinks it’s indicated for them,” Dr. Reti said. “Family members’ concerns may be very legitimate but may also be influenced by stigma and misunderstanding about the treatment. They may also not fully appreciate the severity of their loved one’s depression that warrants the administration of ECT.”
Hospitalized patients who are at risk of suicide have benefited from ECT. “It’s very effective,” he said. “I think it’s still the gold standard for severe treatment-resistant depression and also particularly helpful in people who are acutely suicidal.”
Dr. George cautioned that psychiatrists and the public should beware of questionable online sources that attempt to discredit ECT. “A quick Google search will find plenty of nonmedical doctors, many funded through Scientology, who will speak poorly of ECT. But they do not use evidence-based arguments and commonly do not treat patients,” he said.
“All good practicing psychiatrists that I know are in favor of ECT, as it clearly saves lives,” Dr. George added. “We all hope that the future will provide refinements of ECT, or even disruptive technologies that are more effective and with less hassle and will make ECT as we do it now obsolete. But we are not there yet.”
A version of this article first appeared on Medscape.com.
For Clayton Lively, electroconvulsive therapy, or ECT, has been a lifesaver.
“ECT was like a last resort to treat mania and psychosis for bipolar disorder,” said the 31-year-old financial firm associate who lives in Silver Spring, Md. “I had tried lots of different medications.”
The first course of treatments – three times per week for several weeks – was in 2005. They helped tremendously. “I came down from my mania,” Mr. Lively said. “The hallucinations stopped. The psychosis disappeared.”
He reached a point where medications and psychotherapy worked again. And for a decade, his condition was under control.
But in 2017, another episode of hallucinations and mania jolted him off course. Intrusive thoughts returned. For instance, while driving, he would visualize veering off the road. The thoughts were jarring, and yet, he couldn’t stop them from recurring.
“I wasn’t sleeping, and it just kind of wreaked havoc on my life,” Mr. Lively recalled. “I ended up being hospitalized again.”
Once again, ECT came to the rescue – and yet again, in 2018. Now, he’s on an effective maintenance regimen, receiving ECT once every 4 weeks, after tapering down from more frequent sessions.
When a combination of antidepressants and psychotherapy fails to control severe mental illness, there’s hope on the horizon. ECT can be a reliably safe and effective option.
For some patients, using it as maintenance therapy makes sense, said Vaughn McCall, MD, editor-in-chief of The Journal of ECT and professor and chairman of psychiatry at the Medical College of Georgia in Augusta. “I would think of it the same way as you have to treat any chronic illness,” such as blood pressure medicine to keep hypertension in check and dialysis to prevent kidney failure.
Despite a cacophony of contrarian voices – mainly from the Church of Scientology – “the number of psychiatrists who see controversy in ECT is vanishingly small,” Dr. McCall said.
In weighing the pros and cons of ECT, he noted that “when you’re trying to decide if it’s worth doing a treatment, you’re looking at the effectiveness on one hand and the side effects on the other hand.”
The answer to that emerges from several scales measuring patients’ quality of life by posing questions such as: “After receiving ECT, are you more able or less able to take care of yourself, to work, and enjoy the company of other people?”
In the end, Dr. McCall said, “we’ve applied these scales in probably half a dozen studies or more, and they always show that the patients’ qualify of life as a group is improved.”
A recent study published in The Lancet Psychiatry provides a significant degree of reassurance that ECT – also called “electroshock” or colloquially just “shock” therapy – does not increase the risk of serious medical side effects. In fact, the study suggests a potential benefit in reducing suicide risk.
First performed in 1938, the treatment has been well documented in the medical literature. But negative portrayals in books and movies, such as the 1975 film “One Flew Over the Cuckoo’s Nest,” have contributed to casting it in an unfavorable light.
“Unfortunately, over the past decades and years, there’s a lot of stigma and fear around the treatment,” said the study’s lead author, Tyler Kaster, MD, a psychiatrist and clinical fellow in brain stimulation at the University of Toronto.
For the study, Canadian investigators reviewed the admission records of 10,000 patients hospitalized for at least 3 days because of a severe depressive episode. Nearly two-thirds of the patients were women, and the average age for the entire group approached 57 years.
While half of the patients underwent ECT, the others received medication and psychotherapy. Researchers found that the group undergoing ECT did not have a heightened risk of death over the next 30 days and were not any more likely to be hospitalized for a medical problem.
Previous ECT comparative studies were at high risk of bias because of their inability to sufficiently account for confounding variables and differences between those who received the treatment and those who did not. The current study employed “rigorous methods with careful attention to bias and confounding to overcome limitations of previous work,” the authors wrote.
They used propensity score matching, which included more than 75 variables, such as measures of cognitive impairment, depression severity, medication use, other illnesses, and use of psychiatric and various medical services, capacity to consent to treatment, and sociodemographic factors.
“This is really a landmark study in terms of showing the medical safety of ECT,” said Mark S. George, MD, professor of psychiatry and neurology at the Medical University of South Carolina, Charleston, who was not involved in the study.
He added that “ECT is a life-saving treatment” for individuals with severe depression. “It’s good that we have this option for our patients.”
The authors highlight that depression is a major cause of illness and disability worldwide, with many individuals failing to achieve remission from initial therapies. Treatment-resistant depression is often described as being nonresponsive “to two or more medication trials of adequate dose and duration from different classes,” they wrote. In these instances, the authors point out, there is little evidence that psychotherapy would be helpful.
“The reason we consider ECT is someone has very severe depression that hasn’t responded to medications and talk therapy,” Dr. Kaster said. “The advantage of ECT is that it’s very effective in those circumstances.”
Of all therapies for treatment-resistant depression, ECT has the highest success rate, with 60% of patients attaining remission, according to the study, which cites prior research.
Compared with neurosurgery, the procedure is not invasive but requires general anesthesia. While the patient is asleep, Dr. Kaster said, the treating clinician places an electrical stimulus on the patient’s scalp, causing a generalized seizure inside the brain that lasts from 15 seconds to 2 minutes.
A course of ECT usually takes a total of 8-12 treatments, delivered two to three times per week over a month to a month and a half, Dr. George said.
Some patients need a new course of ECT if they relapse after several months. Others are unable to control their depression between courses and require repeated doses for maintenance. The time between these ECT sessions varies for each individual, Dr. George said, but is typically one session every 3-4 weeks.
To improve the odds of staying well, patients typically need to continue taking antidepressants and engaging in psychotherapy.
“It helps improve the efficacy of ECT and also down the road helps prevent relapse,” Dr. Kaster said, noting that “depression is, unfortunately, a chronic illness. We don’t have a cure.”
Murat Altinay, MD, associate professor of psychiatry at the Cleveland Clinic and a mood disorders specialist, said his patients generally need to demonstrate a lack of response to at least three or four antidepressants before he considers recommending ECT.
Confusion, short-term memory impairment, and muscle aches and pains may occur after the procedure, but they are relatively mild. Patients are monitored in a recovery room before discharge from the hospital, Dr. Altinay said.
The first few treatments will affect everyday function. After that initial period, however, people can resume most of their daily activities, he said.
“Maybe they won’t be able to work full-time right away, but anecdotally, we have had patients who were able to go back to the workforce relatively quickly or while they’re getting ECT,” Dr. Altinay said.
More significant adverse events are very rare, he noted, although heart rate and blood pressure can become elevated because of the electrical stimulus.
Dr. Altinay said he is pleased that the large-scale journal article has been published to help dispel myths surrounding ECT. While psychiatrists feel that ECT is generally safe and effective, the public maintains a negative view.
“It is an underutilized treatment,” he said. “In the media, it is almost depicted as a barbaric and archaic treatment in psychiatry.”
Patients are afraid of major side effects such as personality changes. Some fear they will forget someone’s birthday or other important factual information, “but that kind of stuff obviously does not happen,” Dr. Altinay said.
Sometimes it’s not only the patients who are hesitant to try ECT; it’s the family members who express concerns, said Irving Reti, MBBS, professor of psychiatry and neuroscience and director of the brain stimulation program at the Johns Hopkins University, Baltimore.
“It varies from one patient to another how agreeable or reluctant or cautious they are about their treatment if the doctor thinks it’s indicated for them,” Dr. Reti said. “Family members’ concerns may be very legitimate but may also be influenced by stigma and misunderstanding about the treatment. They may also not fully appreciate the severity of their loved one’s depression that warrants the administration of ECT.”
Hospitalized patients who are at risk of suicide have benefited from ECT. “It’s very effective,” he said. “I think it’s still the gold standard for severe treatment-resistant depression and also particularly helpful in people who are acutely suicidal.”
Dr. George cautioned that psychiatrists and the public should beware of questionable online sources that attempt to discredit ECT. “A quick Google search will find plenty of nonmedical doctors, many funded through Scientology, who will speak poorly of ECT. But they do not use evidence-based arguments and commonly do not treat patients,” he said.
“All good practicing psychiatrists that I know are in favor of ECT, as it clearly saves lives,” Dr. George added. “We all hope that the future will provide refinements of ECT, or even disruptive technologies that are more effective and with less hassle and will make ECT as we do it now obsolete. But we are not there yet.”
A version of this article first appeared on Medscape.com.
Olanzapine-samidorphan combination for schizophrenia or bipolar I disorder
Approved by the FDA on May 28, 2021, olanzapine-samidorphan combination (OSC) (Lybalvi, manufactured and distributed by Alkermes, Inc. Waltham, MA USA) is intended to help mitigate some of the weight gain that can be anticipated with the use of olanzapine alone (Table).1-3 Olanzapine (Zyprexa, originally manufactured and distributed by Eli Lilly and Company/Lilly USA, LLC, Indianapolis, IN USA) is a second-generation antipsychotic that has been available for a quarter century.4 Although highly efficacious,5,6 olanzapine has been associated with weight gain, at times substantial, as well as disturbances in glucose and lipid metabolism.7 The addition of samidorphan, an opioid antagonist, to olanzapine in a single tablet may act to decrease the amount of long-term weight gain that can be expected for some patients taking olanzapine alone, consequently minimizing the anticipated increase in waist circumference (a proxy for the measurement of burden imposed by metabolically active adipose tissue). Approval of OSC for the treatment of schizophrenia was based on 2 pivotal randomized controlled trials and their extension studies.8-11 Approval of OSC for bipolar I disorder (acute treatment of manic/mixed episodes as a monotherapy or adjunctive to lithium or valproate, and as a monotherapy maintenance treatment) was based on legacy studies conducted with olanzapine, after establishing that samidorphan does not alter the pharmacokinetics of olanzapine, including in combination with lithium or valproate.3,12,13 OSC should be distinguished from a different combination product, olanzapine-fluoxetine combination (Symbyax, originally manufactured and distributed by Eli Lilly and Company/Lilly USA, LLC, Indianapolis, IN USA), approved for acute depressive episodes associated with bipolar I disorder and for treatment-resistant depression.14
OSC offers the potential to consider olanzapine earlier in the treatment of schizophrenia or bipolar I disorder, especially among practitioners who might otherwise be hesitant to prescribe this agent because of concerns over the risk of excessive weight gain.
OSC is available in 4 dosage strengths containing 5 mg, 10 mg, 15 mg, or 20 mg of olanzapine; all tablets contain 10 mg of samidorphan.2 The recommended starting dose for OSC mirrors the language contained in the legacy olanzapine product label.4 For schizophrenia, the recommended initial dose (olanzapine/samidorphan) is 5 mg/10 mg or 10 mg/10 mg once daily. For bipolar I manic or mixed episodes, the recommended starting dose for monotherapy is 10 mg/10 mg or 15 mg/10 mg, and for use with lithium or valproate, 10 mg/10 mg. For all indications, the recommended target dose can be 10 mg/10 mg, 15 mg/10 mg, or 20 mg/10 mg, with 5 mg/10 mg as an additional potential dose for maintenance monotherapy of bipolar I disorder. The maximum dose is 20 mg/10 mg once daily. Because the amount of samidorphan in each tablet is fixed at 10 mg, combining tablets of OSC, or cutting OSC tablets in half, is not advisable.
Continue to: How it works...
How it works
Product labeling notes that olanzapine is an atypical antipsychotic, that its efficacy in schizophrenia or bipolar I disorder could be mediated through a combination of dopamine and serotonin type 2 (5HT2) antagonism, and that the mechanism of action of samidorphan could be mediated through opioid receptor antagonism.2
The pharmacodynamic profile of olanzapine is complex.2 It binds with high affinity to the following receptors: serotonin 5HT2A/2C, 5HT6 (Ki = 4, 11, and 5 nM, respectively), dopamine D1-4 (Ki = 11-31 nM), histamine H1 (Ki = 7 nM), and adrenergic alpha-1 receptors (Ki = 19 nM). Olanzapine is an antagonist with moderate affinity binding for serotonin 5HT3 (Ki = 57 nM) and muscarinic M1-5 (Ki = 73, 96, 132, 32, and 48 nM, respectively). Olanzapine binds with low affinity to gamma aminobutyric acid type A (GABA-A), benzodiazepine, and beta-adrenergic receptors (Ki >10 µM). Olanzapine’s muscarinic receptor affinity can explain why olanzapine can be associated with constipation, dry mouth, and tachycardia, all adverse reactions possibly related to cholinergic antagonism. Thus, OSC should be used with caution in patients with a current diagnosis or prior history of urinary retention, clinically significant prostatic hypertrophy, constipation, or a history of paralytic ileus or related conditions; a potential drug-drug interaction can be anticipated with concomitant use of anticholinergic medications.2 Other pharmacodynamic drug-drug interactions that can occur with the olanzapine component of OSC include the possibility that diazepam, alcohol, or other CNS-acting drugs may potentiate orthostatic hypotension, and there may be a need to reduce the dosage of concomitantly prescribed antihypertensive drugs in patients being treated for hypertension. Moreover, OSC is not recommended in patients receiving levodopa and dopamine agonists.
Samidorphan binds to the mu-, kappa-, and delta-opioid receptors (Ki = .052, .23, and 2.7 nM, respectively).2 Samidorphan is an antagonist at the mu-opioid receptors with partial agonist activity at kappa- and delta-opioid receptors. A major human metabolite of samidorphan (N-dealkylated) binds to the mu-, kappa-, and delta-opioid receptors (Ki = .26, 23, and 56 nM, respectively), and functions as a mu-opioid receptor agonist. The N-oxide major human metabolite binds to mu-, kappa-, and delta-opioid receptors (Ki = 8, 110, and 280 nM, respectively) and functions as a mu-opioid receptor antagonist. This profile differs from that of other opioid antagonists such as naltrexone.15,16
OSC is not a scheduled drug subject to the Controlled Substances Act. Because samidorphan functions as an opioid antagonist, OSC is contraindicated in patients using opioids or undergoing acute opioid withdrawal.2
Regarding cardiac electrophysiology, OSC was not observed to prolong the electrocardiogram QTc interval to any clinically relevant extent when tested at doses up to 30 mg/30 mg (1.5 times and 3 times the maximum recommended daily dosage of olanzapine and samidorphan, respectively).17
Clinical pharmacokinetics
The pharmacokinetics of both olanzapine and samidorphan are linear over the clinical dose range and there is no pharmacokinetic interaction between olanzapine and samidorphan after oral administration of OSC.2 Coadministration of OSC with lithium or valproate does not have a clinically significant effect on systemic exposure of lithium or valproate.13 OSC steady-state concentrations of olanzapine and samidorphan are reached within 7 days, with accumulation at steady state being 2-fold for olanzapine and 1.3-fold for samidorphan (at 5 days). Elimination half-life for olanzapine is 35 to 52 hours, and for samidorphan, 7 to 11 hours. Olanzapine is metabolized primarily via UGT1A4 and CYP1A2, whereas samidorphan is primarily metabolized by CYP3A4. Consequently, concomitant use of OSC with strong CYP3A4 inducers is not recommended. The recommendation regarding CYP1A2 modulators and OSC are similar to those for olanzapine2,4: consider reducing the dosage of the olanzapine component in OSC when used concomitantly with strong CYP1A2 inhibitors, and consider increasing the dosage of the olanzapine component in OSC when used concomitantly with CYP1A2 inducers. Because cigarette smoke contains polycyclic aromatic hydrocarbons that act as CYP1A2 inducers,18 olanzapine clearance is much higher in smokers than in nonsmokers.2 This translates to potentially clinically relevant differences when optimizing the dose. In a study of patients with schizophrenia, olanzapine concentrations were lower in self-reported smokers (16.5, 34.2, and 60.9 ng/mL) than in self-reported nonsmokers (25.6, 43.4, and 113.2 ng/mL) for dosages of 10, 20, and 40 mg/d, respectively.19 In contrast, samidorphan pharmacokinetics are not affected by smoking status.2
No dose adjustment of OSC is needed in patients with hepatic or renal impairment; however, OSC is not recommended for patients with end-stage renal disease because this has not been specifically studied.2
Continue to: Efficacy...
Efficacy
The efficacy of OSC in the treatment of schizophrenia in adults is supported, in part, by the extensive legacy of studies of orally administered olanzapine.2 For OSC specifically, acute efficacy was primarily demonstrated in a randomized, double-blind, phase 3, 4-week study establishing superiority vs placebo in acutely exacerbated patients with schizophrenia.8 Mitigation of weight gain was assessed separately in a randomized, double-blind, phase 3, 24-week study comparing OSC with olanzapine in non-acute outpatients with schizophrenia.10 Both of these 2 trials were accompanied by 52-week open-label extension studies.9,11
The 4-week study evaluated the antipsychotic efficacy of OSC in 401 patients experiencing an acute exacerbation or relapse of schizophrenia who required inpatient treatment.8 Patients were required to have a Positive and Negative Syndrome Scale (PANSS) total score ≥80, with a score ≥4 on at least 3 of selected positive symptoms, and a Clinical Global Impression-Severity (CGI-S) score ≥4 at baseline and screening. Patients were required to be inpatients for the first 2 weeks of the study, and were encouraged to remain as inpatients for all 4 weeks. Patients were randomized to receive OSC, olanzapine, or placebo. Dosing was once-daily and flexible based on clinical response and tolerability for the first 2 weeks of the study, and fixed thereafter. Patients assigned to OSC could receive 10 mg/10 mg or 20 mg/10 mg, and patients randomized to olanzapine could receive 10 mg or 20 mg. The study compared OSC with placebo, with olanzapine serving as an active control. Treatment with OSC resulted in significant improvements in symptoms compared with placebo at Week 4, as measured by changes in PANSS total scores from baseline. Improvement in PANSS scores with OSC relative to placebo was similar to that observed with olanzapine. The antipsychotic efficacy of OSC relative to placebo was also supported by improvements in CGI-S scores. Thus, the inclusion of samidorphan in OSC did not negatively impact the antipsychotic efficacy of olanzapine.
In the 24-week study, 561 patients were randomized to OSC or olanzapine.10 There was no placebo control. Patients were treated with doses of OSC 10 mg/10 mg or 20 mg/10 mg, or with doses of olanzapine 10 mg or 20 mg. Dosing was flexible for the first 4 weeks of the study and fixed thereafter. Eligible patients were age 18 to 55 years (younger than the 4-week study, where the maximum age was 70 years), with a body mass index of 18 to 30 kg/m2 (lower than the upper limit of 40 kg/m2 used in the 4-week study). In contrast to the acutely exacerbated patients in the 4-week study, patients were required to have a PANSS total score of 50 to 90, CGI-S score ≤4, and symptoms suitable for outpatient treatment. The co-primary endpoints were percent change from baseline in body weight and proportion of patients who gained ≥10% body weight at Week 24. Treatment with OSC or olanzapine resulted in similar improvements in PANSS total and CGI-S scores, but treatment with OSC was associated with statistically significantly less weight gain than treatment with olanzapine, and with a smaller proportion of patients who gained ≥10% body weight. The least squares mean percent weight change from baseline to the end of treatment was 4.2% with OSC vs 6.6% with olanzapine. Although patients treated with OSC or olanzapine had similar weight gain for the first 4 weeks of treatment, OSC weight gain stabilized after approximately the 6th week, whereas patients who received olanzapine continued to gain weight throughout the remainder of the treatment period. The risk of gaining ≥10% body weight from baseline was reduced by 50% with OSC compared with olanzapine. Moreover, the odds of gaining ≥7% body weight from baseline at Week 24 were also reduced by 50% for OSC compared with olanzapine. OSC was also associated with smaller increases in waist circumference compared with olanzapine, which was observable as early as Week 1. The risk of experiencing a 5-cm increase in waist circumference was 50% lower for patients treated with OSC vs olanzapine, a relevant threshold in assessing risk of all-cause mortality and cardiovascular disease.20 However, changes in metabolic laboratory parameters in patients treated with OSC or olanzapine were generally small and were similar between groups. In addition, there were little differences between the 2 treatment groups in metabolic parameter changes considered to be of potential clinical significance, based on commonly used thresholds.
Patients on stable, chronic olanzapine therapy were not specifically studied, so the weight effect of switching from olanzapine to OSC is unknown.For bipolar I manic or mixed episodes, the use of OSC as monotherapy or in combination with lithium or valproate, as well as for maintenance monotherapy, was approved based on legacy clinical trials with olanzapine, as described in product labeling,2,4 as well as pharmacokinetic data evidencing that OSC did not have a clinically significant effect on the pharmacokinetics of lithium or valproate.13 A study is in progress to evaluate the effect of OSC compared with olanzapine on body weight in young adults with schizophrenia, schizophreniform, or bipolar I disorder who are early in their illness (ClinicalTrials.gov identifier: NCT03187769).
Overall tolerability and safety
The systemic safety and tolerability profile for OSC would be expected to be similar to that for olanzapine, unless there are adverse events that are specifically related to the samidorphan component. In the 4-week acute study described above,8 adverse events that occurred at least twice the rate of placebo with OSC included increased weight (18.7%, 14.3%, 3.0%, for OSC, olanzapine, and placebo, respectively), somnolence (9.0%, 9.8%, 2.2%), dry mouth (7.5%, 5.3%, 0.7%), and headache (6.0%, 5.3%, 3.0%). In the 24-week study,10 which did not have a placebo control, the most commonly reported adverse events (≥10% of patients) were increased weight (24.8% vs 36.2% for OSC vs olanzapine), somnolence (21.2% vs 18.1%), dry mouth (12.8% vs 8.0%), and increased appetite (10.9% vs 12.3%). In both studies, rates of discontinuation due to adverse events were low and similar between groups (in the 4-week study, 1.5% for OSC, 2.3% for olanzapine, and 5.2% for placebo; in the 24-week study, 12.0% for OSC and 9.8% for olanzapine).
In the 2 open-label, phase 3, 52-week extension studies,9,11 long-term tolerability was evidenced by low rates discontinuation due to adverse events (≤6%). Neither extension study reported any clinically meaningful changes over time in hematology, biochemistry, vital signs, or electrocardiogram parameters.3 In addition to durability of antipsychotic response as evidenced by sustained improvements in PANSS and CGI-S scores over time, waist circumference and weight remained stable, and the observed long-term changes in weight were consistent with weight changes observed with other second-generation antipsychotics.3 Long-term changes in metabolic laboratory parameter values were small and remained stable, and there was little change in glycosylated hemoglobin (hemoglobin A1c) values, which suggests that glycemic control was maintained with long-term OSC treatment.3 Caveats to consider are that the extension studies were open label without comparators, and they may have selected for patients who responded favorably to OSC treatment in the preceding studies.3Warnings and precautions in OSC product labeling are generally similar to those for other second-generation antipsychotics,21 other than warnings and precautions specifically related to samidorphan being an opioid antagonist, and special mention of “Drug Reaction with Eosinophilia and Systemic Symptoms” and “Anticholinergic (Antimuscarinic) Effects” warnings, which also are contained in the olanzapine legacy label.2,4
Summary
Olanzapine has a plethora of evidence supporting its robust efficacy profile5,6; however, its use is stymied by an unfavorable weight and metabolic profile.7 OSC may help mitigate at least some of the weight gain that would be expected with the use of olanzapine alone in the long-term treatment of patients with schizophrenia or bipolar I disorder. The addition of samidorphan does not deleteriously affect the efficacy of olanzapine, but decreases the risk of gaining ≥10% or ≥7% of baseline body weight by approximately 50% compared with olanzapine alone. Increase in waist circumference, a proxy for how much metabolically active fat one has, is lower with OSC than it is with olanzapine. Because samidorphan is an opioid receptor antagonist, OSC is contraindicated in patients using opioids and in those undergoing acute opioid withdrawal. Dosage strengths available for OSC parallel those for olanzapine, and all strengths including the same fixed dose of samidorphan—10 mg—so advise patients not to double up on the tablets, and to not split them.
Related Resource
• Olanzapine and samidorphan (Lybalvi) prescribing information. https://www.lybalvi.com/lybalvi-prescribing-information.pdf
Drug Brand Names
Diazepam • Valium
Lithium • Eskalith, Lithobid
Olanzapine • Zyprexa
Olanzapine-fluoxetine combination • Symbyax
Olanzapine-samidorphan combination • Lybalvi
Valproate • Depakote, Depakene
Bottom Line
Olanzapine-samidorphan combination (OSC) is intended to mitigate some of the weight gain anticipated when using olanzapine alone. For clinicians who have prescribed olanzapine and have seen its therapeutic benefits, OSC will be a welcome addition to the therapeutic armamentarium. For practitioners who may have avoided olanzapine entirely, OSC can provide another means of offering this therapeutic option and counter “olanzapine hesitancy.”
1. US Food and Drug Administration. NDA 213378 approval letter. May 28, 2021. Accessed November 24, 2021. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213378Orig1Orig2s000Approv.pdf
2. Alkermes, Inc. LYBALVI™ (olanzapine and samidorphan) tablets, for oral use. Prescribing information. May 2021. Accessed November 24, 2021. https://www.lybalvi.com/lybalvi-prescribing-information.pdf
3. Citrome L, Graham C, Simmons A, et al. An evidence-based review of OLZ/SAM for treatment of adults with schizophrenia or bipolar I disorder. Neuropsychiatr Dis Treat. 2021;17:2885-2904.
4. Eli Lilly and Company. ZYPREXA (olanzapine) tablet for oral use; ZYPREXA ZYDIS (olanzapine) tablet, orally disintegrating for oral use; ZYPREXA intramuscular (olanzapine) injection, powder, for solution for intramuscular use. Prescribing information. February 2021. Accessed November 24, 2021. https://pi.lilly.com/us/zyprexa-pi.pdf
5. Citrome L, McEvoy JP, Todtenkopf MS, et al. A commentary on the efficacy of olanzapine for the treatment of schizophrenia: the past, present, and future. Neuropsychiatr Dis Treat. 2019;15:2559-2569.
6. Meftah AM, Deckler E, Citrome L, et al. New discoveries for an old drug: a review of recent olanzapine research. Postgrad Med. 2020;132(1):80-90.
7. Citrome L, Holt RI, Walker DJ, et al. Weight gain and changes in metabolic variables following olanzapine treatment in schizophrenia and bipolar disorder. Clin Drug Investig. 2011;31(7):455-482.
8. Potkin SG, Kunovac J, Silverman BL, et al. Efficacy and safety of a combination of olanzapine and samidorphan in adult patients with an acute exacerbation of schizophrenia: outcomes from the randomized, phase 3 ENLIGHTEN-1 study. J Clin Psychiatry. 2020;81(2):19m12769.
9. Yagoda S, Graham C, Simmons A, et al. Long-term safety and durability of effect with a combination of olanzapine and samidorphan in patients with schizophrenia: results from a 1-year open-label extension study. CNS Spectr. 2021;26(4):383-392.
10. Correll CU, Newcomer JW, Silverman B, et al. Effects of olanzapine combined with samidorphan on weight gain in schizophrenia: a 24-week phase 3 study. Am J Psychiatry. 2020;177(12):1168-1178.
11. Kahn RS, Silverman BL, DiPetrillo L, et al. A phase 3, multicenter study to assess the 1-year safety and tolerability of a combination of olanzapine and samidorphan in patients with schizophrenia: results from the ENLIGHTEN-2 long-term extension. Schizophr Res. 2021;232:45-53.
12. US Food and Drug Administration. Drug approval package: Lybalvi. June 26, 2021. Accessed November 24, 2021. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213378Orig1Orig2s000TOC.cfm
13. Sun L, Yagoda S, Yao B, et al. Combination of olanzapine and samidorphan has no clinically significant effect on the pharmacokinetics of lithium or valproate. Clin Drug Investig. 2020;40(1):55-64.
14. Eli Lilly and Company. SYMBYAX (olanzapine and fluoxetine) capsules for oral use. Prescribing information. September 2021. Accessed November 24, 2021. https://pi.lilly.com/us/symbyax-pi.pdf
15. Wentland MP, Lu Q, Lou R, et al. Synthesis and opioid receptor binding properties of a highly potent 4-hydroxy analogue of naltrexone. Bioorg Med Chem Lett. 2005;15(8):2107-2110.
16. Lee MW, Fujioka K. Naltrexone for the treatment of obesity: review and update. Expert Opin Pharmacother. 2009;10(11):1841-1845.
17. Sun L, Yagoda S, Xue H, et al. Combination of olanzapine and samidorphan has no clinically relevant effects on ECG parameters, including the QTc interval: results from a phase 1 QT/QTc study. Prog Neuropsychopharmacol Biol Psychiatry. 2020;100:109881.
18. Zhou SF, Yang LP, Zhou ZW, et al. Insights into the substrate specificity, inhibitors, regulation, and polymorphisms and the clinical impact of human cytochrome P450 1A2. AAPS J. 2009;11(3):481-494.
19. Citrome L, Stauffer VL, Chen L, et al. Olanzapine plasma concentrations after treatment with 10, 20, and 40 mg/d in patients with schizophrenia: an analysis of correlations with efficacy, weight gain, and prolactin concentration. J Clin Psychopharmacol. 2009;29(3):278-283.
20. Cerhan JR, Moore SC, Jacobs EJ, et al. A pooled analysis of waist circumference and mortality in 650,000 adults. Mayo Clin Proc. 2014;89(3):335-345.
21. Citrome L, Nasrallah HA. On-label on the table: what the package insert informs us about the tolerability profile of oral atypical antipsychotics, and what it does not. Expert Opin Pharmacother. 2012;13(11):1599-1613.
Approved by the FDA on May 28, 2021, olanzapine-samidorphan combination (OSC) (Lybalvi, manufactured and distributed by Alkermes, Inc. Waltham, MA USA) is intended to help mitigate some of the weight gain that can be anticipated with the use of olanzapine alone (Table).1-3 Olanzapine (Zyprexa, originally manufactured and distributed by Eli Lilly and Company/Lilly USA, LLC, Indianapolis, IN USA) is a second-generation antipsychotic that has been available for a quarter century.4 Although highly efficacious,5,6 olanzapine has been associated with weight gain, at times substantial, as well as disturbances in glucose and lipid metabolism.7 The addition of samidorphan, an opioid antagonist, to olanzapine in a single tablet may act to decrease the amount of long-term weight gain that can be expected for some patients taking olanzapine alone, consequently minimizing the anticipated increase in waist circumference (a proxy for the measurement of burden imposed by metabolically active adipose tissue). Approval of OSC for the treatment of schizophrenia was based on 2 pivotal randomized controlled trials and their extension studies.8-11 Approval of OSC for bipolar I disorder (acute treatment of manic/mixed episodes as a monotherapy or adjunctive to lithium or valproate, and as a monotherapy maintenance treatment) was based on legacy studies conducted with olanzapine, after establishing that samidorphan does not alter the pharmacokinetics of olanzapine, including in combination with lithium or valproate.3,12,13 OSC should be distinguished from a different combination product, olanzapine-fluoxetine combination (Symbyax, originally manufactured and distributed by Eli Lilly and Company/Lilly USA, LLC, Indianapolis, IN USA), approved for acute depressive episodes associated with bipolar I disorder and for treatment-resistant depression.14
OSC offers the potential to consider olanzapine earlier in the treatment of schizophrenia or bipolar I disorder, especially among practitioners who might otherwise be hesitant to prescribe this agent because of concerns over the risk of excessive weight gain.
OSC is available in 4 dosage strengths containing 5 mg, 10 mg, 15 mg, or 20 mg of olanzapine; all tablets contain 10 mg of samidorphan.2 The recommended starting dose for OSC mirrors the language contained in the legacy olanzapine product label.4 For schizophrenia, the recommended initial dose (olanzapine/samidorphan) is 5 mg/10 mg or 10 mg/10 mg once daily. For bipolar I manic or mixed episodes, the recommended starting dose for monotherapy is 10 mg/10 mg or 15 mg/10 mg, and for use with lithium or valproate, 10 mg/10 mg. For all indications, the recommended target dose can be 10 mg/10 mg, 15 mg/10 mg, or 20 mg/10 mg, with 5 mg/10 mg as an additional potential dose for maintenance monotherapy of bipolar I disorder. The maximum dose is 20 mg/10 mg once daily. Because the amount of samidorphan in each tablet is fixed at 10 mg, combining tablets of OSC, or cutting OSC tablets in half, is not advisable.
Continue to: How it works...
How it works
Product labeling notes that olanzapine is an atypical antipsychotic, that its efficacy in schizophrenia or bipolar I disorder could be mediated through a combination of dopamine and serotonin type 2 (5HT2) antagonism, and that the mechanism of action of samidorphan could be mediated through opioid receptor antagonism.2
The pharmacodynamic profile of olanzapine is complex.2 It binds with high affinity to the following receptors: serotonin 5HT2A/2C, 5HT6 (Ki = 4, 11, and 5 nM, respectively), dopamine D1-4 (Ki = 11-31 nM), histamine H1 (Ki = 7 nM), and adrenergic alpha-1 receptors (Ki = 19 nM). Olanzapine is an antagonist with moderate affinity binding for serotonin 5HT3 (Ki = 57 nM) and muscarinic M1-5 (Ki = 73, 96, 132, 32, and 48 nM, respectively). Olanzapine binds with low affinity to gamma aminobutyric acid type A (GABA-A), benzodiazepine, and beta-adrenergic receptors (Ki >10 µM). Olanzapine’s muscarinic receptor affinity can explain why olanzapine can be associated with constipation, dry mouth, and tachycardia, all adverse reactions possibly related to cholinergic antagonism. Thus, OSC should be used with caution in patients with a current diagnosis or prior history of urinary retention, clinically significant prostatic hypertrophy, constipation, or a history of paralytic ileus or related conditions; a potential drug-drug interaction can be anticipated with concomitant use of anticholinergic medications.2 Other pharmacodynamic drug-drug interactions that can occur with the olanzapine component of OSC include the possibility that diazepam, alcohol, or other CNS-acting drugs may potentiate orthostatic hypotension, and there may be a need to reduce the dosage of concomitantly prescribed antihypertensive drugs in patients being treated for hypertension. Moreover, OSC is not recommended in patients receiving levodopa and dopamine agonists.
Samidorphan binds to the mu-, kappa-, and delta-opioid receptors (Ki = .052, .23, and 2.7 nM, respectively).2 Samidorphan is an antagonist at the mu-opioid receptors with partial agonist activity at kappa- and delta-opioid receptors. A major human metabolite of samidorphan (N-dealkylated) binds to the mu-, kappa-, and delta-opioid receptors (Ki = .26, 23, and 56 nM, respectively), and functions as a mu-opioid receptor agonist. The N-oxide major human metabolite binds to mu-, kappa-, and delta-opioid receptors (Ki = 8, 110, and 280 nM, respectively) and functions as a mu-opioid receptor antagonist. This profile differs from that of other opioid antagonists such as naltrexone.15,16
OSC is not a scheduled drug subject to the Controlled Substances Act. Because samidorphan functions as an opioid antagonist, OSC is contraindicated in patients using opioids or undergoing acute opioid withdrawal.2
Regarding cardiac electrophysiology, OSC was not observed to prolong the electrocardiogram QTc interval to any clinically relevant extent when tested at doses up to 30 mg/30 mg (1.5 times and 3 times the maximum recommended daily dosage of olanzapine and samidorphan, respectively).17
Clinical pharmacokinetics
The pharmacokinetics of both olanzapine and samidorphan are linear over the clinical dose range and there is no pharmacokinetic interaction between olanzapine and samidorphan after oral administration of OSC.2 Coadministration of OSC with lithium or valproate does not have a clinically significant effect on systemic exposure of lithium or valproate.13 OSC steady-state concentrations of olanzapine and samidorphan are reached within 7 days, with accumulation at steady state being 2-fold for olanzapine and 1.3-fold for samidorphan (at 5 days). Elimination half-life for olanzapine is 35 to 52 hours, and for samidorphan, 7 to 11 hours. Olanzapine is metabolized primarily via UGT1A4 and CYP1A2, whereas samidorphan is primarily metabolized by CYP3A4. Consequently, concomitant use of OSC with strong CYP3A4 inducers is not recommended. The recommendation regarding CYP1A2 modulators and OSC are similar to those for olanzapine2,4: consider reducing the dosage of the olanzapine component in OSC when used concomitantly with strong CYP1A2 inhibitors, and consider increasing the dosage of the olanzapine component in OSC when used concomitantly with CYP1A2 inducers. Because cigarette smoke contains polycyclic aromatic hydrocarbons that act as CYP1A2 inducers,18 olanzapine clearance is much higher in smokers than in nonsmokers.2 This translates to potentially clinically relevant differences when optimizing the dose. In a study of patients with schizophrenia, olanzapine concentrations were lower in self-reported smokers (16.5, 34.2, and 60.9 ng/mL) than in self-reported nonsmokers (25.6, 43.4, and 113.2 ng/mL) for dosages of 10, 20, and 40 mg/d, respectively.19 In contrast, samidorphan pharmacokinetics are not affected by smoking status.2
No dose adjustment of OSC is needed in patients with hepatic or renal impairment; however, OSC is not recommended for patients with end-stage renal disease because this has not been specifically studied.2
Continue to: Efficacy...
Efficacy
The efficacy of OSC in the treatment of schizophrenia in adults is supported, in part, by the extensive legacy of studies of orally administered olanzapine.2 For OSC specifically, acute efficacy was primarily demonstrated in a randomized, double-blind, phase 3, 4-week study establishing superiority vs placebo in acutely exacerbated patients with schizophrenia.8 Mitigation of weight gain was assessed separately in a randomized, double-blind, phase 3, 24-week study comparing OSC with olanzapine in non-acute outpatients with schizophrenia.10 Both of these 2 trials were accompanied by 52-week open-label extension studies.9,11
The 4-week study evaluated the antipsychotic efficacy of OSC in 401 patients experiencing an acute exacerbation or relapse of schizophrenia who required inpatient treatment.8 Patients were required to have a Positive and Negative Syndrome Scale (PANSS) total score ≥80, with a score ≥4 on at least 3 of selected positive symptoms, and a Clinical Global Impression-Severity (CGI-S) score ≥4 at baseline and screening. Patients were required to be inpatients for the first 2 weeks of the study, and were encouraged to remain as inpatients for all 4 weeks. Patients were randomized to receive OSC, olanzapine, or placebo. Dosing was once-daily and flexible based on clinical response and tolerability for the first 2 weeks of the study, and fixed thereafter. Patients assigned to OSC could receive 10 mg/10 mg or 20 mg/10 mg, and patients randomized to olanzapine could receive 10 mg or 20 mg. The study compared OSC with placebo, with olanzapine serving as an active control. Treatment with OSC resulted in significant improvements in symptoms compared with placebo at Week 4, as measured by changes in PANSS total scores from baseline. Improvement in PANSS scores with OSC relative to placebo was similar to that observed with olanzapine. The antipsychotic efficacy of OSC relative to placebo was also supported by improvements in CGI-S scores. Thus, the inclusion of samidorphan in OSC did not negatively impact the antipsychotic efficacy of olanzapine.
In the 24-week study, 561 patients were randomized to OSC or olanzapine.10 There was no placebo control. Patients were treated with doses of OSC 10 mg/10 mg or 20 mg/10 mg, or with doses of olanzapine 10 mg or 20 mg. Dosing was flexible for the first 4 weeks of the study and fixed thereafter. Eligible patients were age 18 to 55 years (younger than the 4-week study, where the maximum age was 70 years), with a body mass index of 18 to 30 kg/m2 (lower than the upper limit of 40 kg/m2 used in the 4-week study). In contrast to the acutely exacerbated patients in the 4-week study, patients were required to have a PANSS total score of 50 to 90, CGI-S score ≤4, and symptoms suitable for outpatient treatment. The co-primary endpoints were percent change from baseline in body weight and proportion of patients who gained ≥10% body weight at Week 24. Treatment with OSC or olanzapine resulted in similar improvements in PANSS total and CGI-S scores, but treatment with OSC was associated with statistically significantly less weight gain than treatment with olanzapine, and with a smaller proportion of patients who gained ≥10% body weight. The least squares mean percent weight change from baseline to the end of treatment was 4.2% with OSC vs 6.6% with olanzapine. Although patients treated with OSC or olanzapine had similar weight gain for the first 4 weeks of treatment, OSC weight gain stabilized after approximately the 6th week, whereas patients who received olanzapine continued to gain weight throughout the remainder of the treatment period. The risk of gaining ≥10% body weight from baseline was reduced by 50% with OSC compared with olanzapine. Moreover, the odds of gaining ≥7% body weight from baseline at Week 24 were also reduced by 50% for OSC compared with olanzapine. OSC was also associated with smaller increases in waist circumference compared with olanzapine, which was observable as early as Week 1. The risk of experiencing a 5-cm increase in waist circumference was 50% lower for patients treated with OSC vs olanzapine, a relevant threshold in assessing risk of all-cause mortality and cardiovascular disease.20 However, changes in metabolic laboratory parameters in patients treated with OSC or olanzapine were generally small and were similar between groups. In addition, there were little differences between the 2 treatment groups in metabolic parameter changes considered to be of potential clinical significance, based on commonly used thresholds.
Patients on stable, chronic olanzapine therapy were not specifically studied, so the weight effect of switching from olanzapine to OSC is unknown.For bipolar I manic or mixed episodes, the use of OSC as monotherapy or in combination with lithium or valproate, as well as for maintenance monotherapy, was approved based on legacy clinical trials with olanzapine, as described in product labeling,2,4 as well as pharmacokinetic data evidencing that OSC did not have a clinically significant effect on the pharmacokinetics of lithium or valproate.13 A study is in progress to evaluate the effect of OSC compared with olanzapine on body weight in young adults with schizophrenia, schizophreniform, or bipolar I disorder who are early in their illness (ClinicalTrials.gov identifier: NCT03187769).
Overall tolerability and safety
The systemic safety and tolerability profile for OSC would be expected to be similar to that for olanzapine, unless there are adverse events that are specifically related to the samidorphan component. In the 4-week acute study described above,8 adverse events that occurred at least twice the rate of placebo with OSC included increased weight (18.7%, 14.3%, 3.0%, for OSC, olanzapine, and placebo, respectively), somnolence (9.0%, 9.8%, 2.2%), dry mouth (7.5%, 5.3%, 0.7%), and headache (6.0%, 5.3%, 3.0%). In the 24-week study,10 which did not have a placebo control, the most commonly reported adverse events (≥10% of patients) were increased weight (24.8% vs 36.2% for OSC vs olanzapine), somnolence (21.2% vs 18.1%), dry mouth (12.8% vs 8.0%), and increased appetite (10.9% vs 12.3%). In both studies, rates of discontinuation due to adverse events were low and similar between groups (in the 4-week study, 1.5% for OSC, 2.3% for olanzapine, and 5.2% for placebo; in the 24-week study, 12.0% for OSC and 9.8% for olanzapine).
In the 2 open-label, phase 3, 52-week extension studies,9,11 long-term tolerability was evidenced by low rates discontinuation due to adverse events (≤6%). Neither extension study reported any clinically meaningful changes over time in hematology, biochemistry, vital signs, or electrocardiogram parameters.3 In addition to durability of antipsychotic response as evidenced by sustained improvements in PANSS and CGI-S scores over time, waist circumference and weight remained stable, and the observed long-term changes in weight were consistent with weight changes observed with other second-generation antipsychotics.3 Long-term changes in metabolic laboratory parameter values were small and remained stable, and there was little change in glycosylated hemoglobin (hemoglobin A1c) values, which suggests that glycemic control was maintained with long-term OSC treatment.3 Caveats to consider are that the extension studies were open label without comparators, and they may have selected for patients who responded favorably to OSC treatment in the preceding studies.3Warnings and precautions in OSC product labeling are generally similar to those for other second-generation antipsychotics,21 other than warnings and precautions specifically related to samidorphan being an opioid antagonist, and special mention of “Drug Reaction with Eosinophilia and Systemic Symptoms” and “Anticholinergic (Antimuscarinic) Effects” warnings, which also are contained in the olanzapine legacy label.2,4
Summary
Olanzapine has a plethora of evidence supporting its robust efficacy profile5,6; however, its use is stymied by an unfavorable weight and metabolic profile.7 OSC may help mitigate at least some of the weight gain that would be expected with the use of olanzapine alone in the long-term treatment of patients with schizophrenia or bipolar I disorder. The addition of samidorphan does not deleteriously affect the efficacy of olanzapine, but decreases the risk of gaining ≥10% or ≥7% of baseline body weight by approximately 50% compared with olanzapine alone. Increase in waist circumference, a proxy for how much metabolically active fat one has, is lower with OSC than it is with olanzapine. Because samidorphan is an opioid receptor antagonist, OSC is contraindicated in patients using opioids and in those undergoing acute opioid withdrawal. Dosage strengths available for OSC parallel those for olanzapine, and all strengths including the same fixed dose of samidorphan—10 mg—so advise patients not to double up on the tablets, and to not split them.
Related Resource
• Olanzapine and samidorphan (Lybalvi) prescribing information. https://www.lybalvi.com/lybalvi-prescribing-information.pdf
Drug Brand Names
Diazepam • Valium
Lithium • Eskalith, Lithobid
Olanzapine • Zyprexa
Olanzapine-fluoxetine combination • Symbyax
Olanzapine-samidorphan combination • Lybalvi
Valproate • Depakote, Depakene
Bottom Line
Olanzapine-samidorphan combination (OSC) is intended to mitigate some of the weight gain anticipated when using olanzapine alone. For clinicians who have prescribed olanzapine and have seen its therapeutic benefits, OSC will be a welcome addition to the therapeutic armamentarium. For practitioners who may have avoided olanzapine entirely, OSC can provide another means of offering this therapeutic option and counter “olanzapine hesitancy.”
Approved by the FDA on May 28, 2021, olanzapine-samidorphan combination (OSC) (Lybalvi, manufactured and distributed by Alkermes, Inc. Waltham, MA USA) is intended to help mitigate some of the weight gain that can be anticipated with the use of olanzapine alone (Table).1-3 Olanzapine (Zyprexa, originally manufactured and distributed by Eli Lilly and Company/Lilly USA, LLC, Indianapolis, IN USA) is a second-generation antipsychotic that has been available for a quarter century.4 Although highly efficacious,5,6 olanzapine has been associated with weight gain, at times substantial, as well as disturbances in glucose and lipid metabolism.7 The addition of samidorphan, an opioid antagonist, to olanzapine in a single tablet may act to decrease the amount of long-term weight gain that can be expected for some patients taking olanzapine alone, consequently minimizing the anticipated increase in waist circumference (a proxy for the measurement of burden imposed by metabolically active adipose tissue). Approval of OSC for the treatment of schizophrenia was based on 2 pivotal randomized controlled trials and their extension studies.8-11 Approval of OSC for bipolar I disorder (acute treatment of manic/mixed episodes as a monotherapy or adjunctive to lithium or valproate, and as a monotherapy maintenance treatment) was based on legacy studies conducted with olanzapine, after establishing that samidorphan does not alter the pharmacokinetics of olanzapine, including in combination with lithium or valproate.3,12,13 OSC should be distinguished from a different combination product, olanzapine-fluoxetine combination (Symbyax, originally manufactured and distributed by Eli Lilly and Company/Lilly USA, LLC, Indianapolis, IN USA), approved for acute depressive episodes associated with bipolar I disorder and for treatment-resistant depression.14
OSC offers the potential to consider olanzapine earlier in the treatment of schizophrenia or bipolar I disorder, especially among practitioners who might otherwise be hesitant to prescribe this agent because of concerns over the risk of excessive weight gain.
OSC is available in 4 dosage strengths containing 5 mg, 10 mg, 15 mg, or 20 mg of olanzapine; all tablets contain 10 mg of samidorphan.2 The recommended starting dose for OSC mirrors the language contained in the legacy olanzapine product label.4 For schizophrenia, the recommended initial dose (olanzapine/samidorphan) is 5 mg/10 mg or 10 mg/10 mg once daily. For bipolar I manic or mixed episodes, the recommended starting dose for monotherapy is 10 mg/10 mg or 15 mg/10 mg, and for use with lithium or valproate, 10 mg/10 mg. For all indications, the recommended target dose can be 10 mg/10 mg, 15 mg/10 mg, or 20 mg/10 mg, with 5 mg/10 mg as an additional potential dose for maintenance monotherapy of bipolar I disorder. The maximum dose is 20 mg/10 mg once daily. Because the amount of samidorphan in each tablet is fixed at 10 mg, combining tablets of OSC, or cutting OSC tablets in half, is not advisable.
Continue to: How it works...
How it works
Product labeling notes that olanzapine is an atypical antipsychotic, that its efficacy in schizophrenia or bipolar I disorder could be mediated through a combination of dopamine and serotonin type 2 (5HT2) antagonism, and that the mechanism of action of samidorphan could be mediated through opioid receptor antagonism.2
The pharmacodynamic profile of olanzapine is complex.2 It binds with high affinity to the following receptors: serotonin 5HT2A/2C, 5HT6 (Ki = 4, 11, and 5 nM, respectively), dopamine D1-4 (Ki = 11-31 nM), histamine H1 (Ki = 7 nM), and adrenergic alpha-1 receptors (Ki = 19 nM). Olanzapine is an antagonist with moderate affinity binding for serotonin 5HT3 (Ki = 57 nM) and muscarinic M1-5 (Ki = 73, 96, 132, 32, and 48 nM, respectively). Olanzapine binds with low affinity to gamma aminobutyric acid type A (GABA-A), benzodiazepine, and beta-adrenergic receptors (Ki >10 µM). Olanzapine’s muscarinic receptor affinity can explain why olanzapine can be associated with constipation, dry mouth, and tachycardia, all adverse reactions possibly related to cholinergic antagonism. Thus, OSC should be used with caution in patients with a current diagnosis or prior history of urinary retention, clinically significant prostatic hypertrophy, constipation, or a history of paralytic ileus or related conditions; a potential drug-drug interaction can be anticipated with concomitant use of anticholinergic medications.2 Other pharmacodynamic drug-drug interactions that can occur with the olanzapine component of OSC include the possibility that diazepam, alcohol, or other CNS-acting drugs may potentiate orthostatic hypotension, and there may be a need to reduce the dosage of concomitantly prescribed antihypertensive drugs in patients being treated for hypertension. Moreover, OSC is not recommended in patients receiving levodopa and dopamine agonists.
Samidorphan binds to the mu-, kappa-, and delta-opioid receptors (Ki = .052, .23, and 2.7 nM, respectively).2 Samidorphan is an antagonist at the mu-opioid receptors with partial agonist activity at kappa- and delta-opioid receptors. A major human metabolite of samidorphan (N-dealkylated) binds to the mu-, kappa-, and delta-opioid receptors (Ki = .26, 23, and 56 nM, respectively), and functions as a mu-opioid receptor agonist. The N-oxide major human metabolite binds to mu-, kappa-, and delta-opioid receptors (Ki = 8, 110, and 280 nM, respectively) and functions as a mu-opioid receptor antagonist. This profile differs from that of other opioid antagonists such as naltrexone.15,16
OSC is not a scheduled drug subject to the Controlled Substances Act. Because samidorphan functions as an opioid antagonist, OSC is contraindicated in patients using opioids or undergoing acute opioid withdrawal.2
Regarding cardiac electrophysiology, OSC was not observed to prolong the electrocardiogram QTc interval to any clinically relevant extent when tested at doses up to 30 mg/30 mg (1.5 times and 3 times the maximum recommended daily dosage of olanzapine and samidorphan, respectively).17
Clinical pharmacokinetics
The pharmacokinetics of both olanzapine and samidorphan are linear over the clinical dose range and there is no pharmacokinetic interaction between olanzapine and samidorphan after oral administration of OSC.2 Coadministration of OSC with lithium or valproate does not have a clinically significant effect on systemic exposure of lithium or valproate.13 OSC steady-state concentrations of olanzapine and samidorphan are reached within 7 days, with accumulation at steady state being 2-fold for olanzapine and 1.3-fold for samidorphan (at 5 days). Elimination half-life for olanzapine is 35 to 52 hours, and for samidorphan, 7 to 11 hours. Olanzapine is metabolized primarily via UGT1A4 and CYP1A2, whereas samidorphan is primarily metabolized by CYP3A4. Consequently, concomitant use of OSC with strong CYP3A4 inducers is not recommended. The recommendation regarding CYP1A2 modulators and OSC are similar to those for olanzapine2,4: consider reducing the dosage of the olanzapine component in OSC when used concomitantly with strong CYP1A2 inhibitors, and consider increasing the dosage of the olanzapine component in OSC when used concomitantly with CYP1A2 inducers. Because cigarette smoke contains polycyclic aromatic hydrocarbons that act as CYP1A2 inducers,18 olanzapine clearance is much higher in smokers than in nonsmokers.2 This translates to potentially clinically relevant differences when optimizing the dose. In a study of patients with schizophrenia, olanzapine concentrations were lower in self-reported smokers (16.5, 34.2, and 60.9 ng/mL) than in self-reported nonsmokers (25.6, 43.4, and 113.2 ng/mL) for dosages of 10, 20, and 40 mg/d, respectively.19 In contrast, samidorphan pharmacokinetics are not affected by smoking status.2
No dose adjustment of OSC is needed in patients with hepatic or renal impairment; however, OSC is not recommended for patients with end-stage renal disease because this has not been specifically studied.2
Continue to: Efficacy...
Efficacy
The efficacy of OSC in the treatment of schizophrenia in adults is supported, in part, by the extensive legacy of studies of orally administered olanzapine.2 For OSC specifically, acute efficacy was primarily demonstrated in a randomized, double-blind, phase 3, 4-week study establishing superiority vs placebo in acutely exacerbated patients with schizophrenia.8 Mitigation of weight gain was assessed separately in a randomized, double-blind, phase 3, 24-week study comparing OSC with olanzapine in non-acute outpatients with schizophrenia.10 Both of these 2 trials were accompanied by 52-week open-label extension studies.9,11
The 4-week study evaluated the antipsychotic efficacy of OSC in 401 patients experiencing an acute exacerbation or relapse of schizophrenia who required inpatient treatment.8 Patients were required to have a Positive and Negative Syndrome Scale (PANSS) total score ≥80, with a score ≥4 on at least 3 of selected positive symptoms, and a Clinical Global Impression-Severity (CGI-S) score ≥4 at baseline and screening. Patients were required to be inpatients for the first 2 weeks of the study, and were encouraged to remain as inpatients for all 4 weeks. Patients were randomized to receive OSC, olanzapine, or placebo. Dosing was once-daily and flexible based on clinical response and tolerability for the first 2 weeks of the study, and fixed thereafter. Patients assigned to OSC could receive 10 mg/10 mg or 20 mg/10 mg, and patients randomized to olanzapine could receive 10 mg or 20 mg. The study compared OSC with placebo, with olanzapine serving as an active control. Treatment with OSC resulted in significant improvements in symptoms compared with placebo at Week 4, as measured by changes in PANSS total scores from baseline. Improvement in PANSS scores with OSC relative to placebo was similar to that observed with olanzapine. The antipsychotic efficacy of OSC relative to placebo was also supported by improvements in CGI-S scores. Thus, the inclusion of samidorphan in OSC did not negatively impact the antipsychotic efficacy of olanzapine.
In the 24-week study, 561 patients were randomized to OSC or olanzapine.10 There was no placebo control. Patients were treated with doses of OSC 10 mg/10 mg or 20 mg/10 mg, or with doses of olanzapine 10 mg or 20 mg. Dosing was flexible for the first 4 weeks of the study and fixed thereafter. Eligible patients were age 18 to 55 years (younger than the 4-week study, where the maximum age was 70 years), with a body mass index of 18 to 30 kg/m2 (lower than the upper limit of 40 kg/m2 used in the 4-week study). In contrast to the acutely exacerbated patients in the 4-week study, patients were required to have a PANSS total score of 50 to 90, CGI-S score ≤4, and symptoms suitable for outpatient treatment. The co-primary endpoints were percent change from baseline in body weight and proportion of patients who gained ≥10% body weight at Week 24. Treatment with OSC or olanzapine resulted in similar improvements in PANSS total and CGI-S scores, but treatment with OSC was associated with statistically significantly less weight gain than treatment with olanzapine, and with a smaller proportion of patients who gained ≥10% body weight. The least squares mean percent weight change from baseline to the end of treatment was 4.2% with OSC vs 6.6% with olanzapine. Although patients treated with OSC or olanzapine had similar weight gain for the first 4 weeks of treatment, OSC weight gain stabilized after approximately the 6th week, whereas patients who received olanzapine continued to gain weight throughout the remainder of the treatment period. The risk of gaining ≥10% body weight from baseline was reduced by 50% with OSC compared with olanzapine. Moreover, the odds of gaining ≥7% body weight from baseline at Week 24 were also reduced by 50% for OSC compared with olanzapine. OSC was also associated with smaller increases in waist circumference compared with olanzapine, which was observable as early as Week 1. The risk of experiencing a 5-cm increase in waist circumference was 50% lower for patients treated with OSC vs olanzapine, a relevant threshold in assessing risk of all-cause mortality and cardiovascular disease.20 However, changes in metabolic laboratory parameters in patients treated with OSC or olanzapine were generally small and were similar between groups. In addition, there were little differences between the 2 treatment groups in metabolic parameter changes considered to be of potential clinical significance, based on commonly used thresholds.
Patients on stable, chronic olanzapine therapy were not specifically studied, so the weight effect of switching from olanzapine to OSC is unknown.For bipolar I manic or mixed episodes, the use of OSC as monotherapy or in combination with lithium or valproate, as well as for maintenance monotherapy, was approved based on legacy clinical trials with olanzapine, as described in product labeling,2,4 as well as pharmacokinetic data evidencing that OSC did not have a clinically significant effect on the pharmacokinetics of lithium or valproate.13 A study is in progress to evaluate the effect of OSC compared with olanzapine on body weight in young adults with schizophrenia, schizophreniform, or bipolar I disorder who are early in their illness (ClinicalTrials.gov identifier: NCT03187769).
Overall tolerability and safety
The systemic safety and tolerability profile for OSC would be expected to be similar to that for olanzapine, unless there are adverse events that are specifically related to the samidorphan component. In the 4-week acute study described above,8 adverse events that occurred at least twice the rate of placebo with OSC included increased weight (18.7%, 14.3%, 3.0%, for OSC, olanzapine, and placebo, respectively), somnolence (9.0%, 9.8%, 2.2%), dry mouth (7.5%, 5.3%, 0.7%), and headache (6.0%, 5.3%, 3.0%). In the 24-week study,10 which did not have a placebo control, the most commonly reported adverse events (≥10% of patients) were increased weight (24.8% vs 36.2% for OSC vs olanzapine), somnolence (21.2% vs 18.1%), dry mouth (12.8% vs 8.0%), and increased appetite (10.9% vs 12.3%). In both studies, rates of discontinuation due to adverse events were low and similar between groups (in the 4-week study, 1.5% for OSC, 2.3% for olanzapine, and 5.2% for placebo; in the 24-week study, 12.0% for OSC and 9.8% for olanzapine).
In the 2 open-label, phase 3, 52-week extension studies,9,11 long-term tolerability was evidenced by low rates discontinuation due to adverse events (≤6%). Neither extension study reported any clinically meaningful changes over time in hematology, biochemistry, vital signs, or electrocardiogram parameters.3 In addition to durability of antipsychotic response as evidenced by sustained improvements in PANSS and CGI-S scores over time, waist circumference and weight remained stable, and the observed long-term changes in weight were consistent with weight changes observed with other second-generation antipsychotics.3 Long-term changes in metabolic laboratory parameter values were small and remained stable, and there was little change in glycosylated hemoglobin (hemoglobin A1c) values, which suggests that glycemic control was maintained with long-term OSC treatment.3 Caveats to consider are that the extension studies were open label without comparators, and they may have selected for patients who responded favorably to OSC treatment in the preceding studies.3Warnings and precautions in OSC product labeling are generally similar to those for other second-generation antipsychotics,21 other than warnings and precautions specifically related to samidorphan being an opioid antagonist, and special mention of “Drug Reaction with Eosinophilia and Systemic Symptoms” and “Anticholinergic (Antimuscarinic) Effects” warnings, which also are contained in the olanzapine legacy label.2,4
Summary
Olanzapine has a plethora of evidence supporting its robust efficacy profile5,6; however, its use is stymied by an unfavorable weight and metabolic profile.7 OSC may help mitigate at least some of the weight gain that would be expected with the use of olanzapine alone in the long-term treatment of patients with schizophrenia or bipolar I disorder. The addition of samidorphan does not deleteriously affect the efficacy of olanzapine, but decreases the risk of gaining ≥10% or ≥7% of baseline body weight by approximately 50% compared with olanzapine alone. Increase in waist circumference, a proxy for how much metabolically active fat one has, is lower with OSC than it is with olanzapine. Because samidorphan is an opioid receptor antagonist, OSC is contraindicated in patients using opioids and in those undergoing acute opioid withdrawal. Dosage strengths available for OSC parallel those for olanzapine, and all strengths including the same fixed dose of samidorphan—10 mg—so advise patients not to double up on the tablets, and to not split them.
Related Resource
• Olanzapine and samidorphan (Lybalvi) prescribing information. https://www.lybalvi.com/lybalvi-prescribing-information.pdf
Drug Brand Names
Diazepam • Valium
Lithium • Eskalith, Lithobid
Olanzapine • Zyprexa
Olanzapine-fluoxetine combination • Symbyax
Olanzapine-samidorphan combination • Lybalvi
Valproate • Depakote, Depakene
Bottom Line
Olanzapine-samidorphan combination (OSC) is intended to mitigate some of the weight gain anticipated when using olanzapine alone. For clinicians who have prescribed olanzapine and have seen its therapeutic benefits, OSC will be a welcome addition to the therapeutic armamentarium. For practitioners who may have avoided olanzapine entirely, OSC can provide another means of offering this therapeutic option and counter “olanzapine hesitancy.”
1. US Food and Drug Administration. NDA 213378 approval letter. May 28, 2021. Accessed November 24, 2021. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213378Orig1Orig2s000Approv.pdf
2. Alkermes, Inc. LYBALVI™ (olanzapine and samidorphan) tablets, for oral use. Prescribing information. May 2021. Accessed November 24, 2021. https://www.lybalvi.com/lybalvi-prescribing-information.pdf
3. Citrome L, Graham C, Simmons A, et al. An evidence-based review of OLZ/SAM for treatment of adults with schizophrenia or bipolar I disorder. Neuropsychiatr Dis Treat. 2021;17:2885-2904.
4. Eli Lilly and Company. ZYPREXA (olanzapine) tablet for oral use; ZYPREXA ZYDIS (olanzapine) tablet, orally disintegrating for oral use; ZYPREXA intramuscular (olanzapine) injection, powder, for solution for intramuscular use. Prescribing information. February 2021. Accessed November 24, 2021. https://pi.lilly.com/us/zyprexa-pi.pdf
5. Citrome L, McEvoy JP, Todtenkopf MS, et al. A commentary on the efficacy of olanzapine for the treatment of schizophrenia: the past, present, and future. Neuropsychiatr Dis Treat. 2019;15:2559-2569.
6. Meftah AM, Deckler E, Citrome L, et al. New discoveries for an old drug: a review of recent olanzapine research. Postgrad Med. 2020;132(1):80-90.
7. Citrome L, Holt RI, Walker DJ, et al. Weight gain and changes in metabolic variables following olanzapine treatment in schizophrenia and bipolar disorder. Clin Drug Investig. 2011;31(7):455-482.
8. Potkin SG, Kunovac J, Silverman BL, et al. Efficacy and safety of a combination of olanzapine and samidorphan in adult patients with an acute exacerbation of schizophrenia: outcomes from the randomized, phase 3 ENLIGHTEN-1 study. J Clin Psychiatry. 2020;81(2):19m12769.
9. Yagoda S, Graham C, Simmons A, et al. Long-term safety and durability of effect with a combination of olanzapine and samidorphan in patients with schizophrenia: results from a 1-year open-label extension study. CNS Spectr. 2021;26(4):383-392.
10. Correll CU, Newcomer JW, Silverman B, et al. Effects of olanzapine combined with samidorphan on weight gain in schizophrenia: a 24-week phase 3 study. Am J Psychiatry. 2020;177(12):1168-1178.
11. Kahn RS, Silverman BL, DiPetrillo L, et al. A phase 3, multicenter study to assess the 1-year safety and tolerability of a combination of olanzapine and samidorphan in patients with schizophrenia: results from the ENLIGHTEN-2 long-term extension. Schizophr Res. 2021;232:45-53.
12. US Food and Drug Administration. Drug approval package: Lybalvi. June 26, 2021. Accessed November 24, 2021. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213378Orig1Orig2s000TOC.cfm
13. Sun L, Yagoda S, Yao B, et al. Combination of olanzapine and samidorphan has no clinically significant effect on the pharmacokinetics of lithium or valproate. Clin Drug Investig. 2020;40(1):55-64.
14. Eli Lilly and Company. SYMBYAX (olanzapine and fluoxetine) capsules for oral use. Prescribing information. September 2021. Accessed November 24, 2021. https://pi.lilly.com/us/symbyax-pi.pdf
15. Wentland MP, Lu Q, Lou R, et al. Synthesis and opioid receptor binding properties of a highly potent 4-hydroxy analogue of naltrexone. Bioorg Med Chem Lett. 2005;15(8):2107-2110.
16. Lee MW, Fujioka K. Naltrexone for the treatment of obesity: review and update. Expert Opin Pharmacother. 2009;10(11):1841-1845.
17. Sun L, Yagoda S, Xue H, et al. Combination of olanzapine and samidorphan has no clinically relevant effects on ECG parameters, including the QTc interval: results from a phase 1 QT/QTc study. Prog Neuropsychopharmacol Biol Psychiatry. 2020;100:109881.
18. Zhou SF, Yang LP, Zhou ZW, et al. Insights into the substrate specificity, inhibitors, regulation, and polymorphisms and the clinical impact of human cytochrome P450 1A2. AAPS J. 2009;11(3):481-494.
19. Citrome L, Stauffer VL, Chen L, et al. Olanzapine plasma concentrations after treatment with 10, 20, and 40 mg/d in patients with schizophrenia: an analysis of correlations with efficacy, weight gain, and prolactin concentration. J Clin Psychopharmacol. 2009;29(3):278-283.
20. Cerhan JR, Moore SC, Jacobs EJ, et al. A pooled analysis of waist circumference and mortality in 650,000 adults. Mayo Clin Proc. 2014;89(3):335-345.
21. Citrome L, Nasrallah HA. On-label on the table: what the package insert informs us about the tolerability profile of oral atypical antipsychotics, and what it does not. Expert Opin Pharmacother. 2012;13(11):1599-1613.
1. US Food and Drug Administration. NDA 213378 approval letter. May 28, 2021. Accessed November 24, 2021. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213378Orig1Orig2s000Approv.pdf
2. Alkermes, Inc. LYBALVI™ (olanzapine and samidorphan) tablets, for oral use. Prescribing information. May 2021. Accessed November 24, 2021. https://www.lybalvi.com/lybalvi-prescribing-information.pdf
3. Citrome L, Graham C, Simmons A, et al. An evidence-based review of OLZ/SAM for treatment of adults with schizophrenia or bipolar I disorder. Neuropsychiatr Dis Treat. 2021;17:2885-2904.
4. Eli Lilly and Company. ZYPREXA (olanzapine) tablet for oral use; ZYPREXA ZYDIS (olanzapine) tablet, orally disintegrating for oral use; ZYPREXA intramuscular (olanzapine) injection, powder, for solution for intramuscular use. Prescribing information. February 2021. Accessed November 24, 2021. https://pi.lilly.com/us/zyprexa-pi.pdf
5. Citrome L, McEvoy JP, Todtenkopf MS, et al. A commentary on the efficacy of olanzapine for the treatment of schizophrenia: the past, present, and future. Neuropsychiatr Dis Treat. 2019;15:2559-2569.
6. Meftah AM, Deckler E, Citrome L, et al. New discoveries for an old drug: a review of recent olanzapine research. Postgrad Med. 2020;132(1):80-90.
7. Citrome L, Holt RI, Walker DJ, et al. Weight gain and changes in metabolic variables following olanzapine treatment in schizophrenia and bipolar disorder. Clin Drug Investig. 2011;31(7):455-482.
8. Potkin SG, Kunovac J, Silverman BL, et al. Efficacy and safety of a combination of olanzapine and samidorphan in adult patients with an acute exacerbation of schizophrenia: outcomes from the randomized, phase 3 ENLIGHTEN-1 study. J Clin Psychiatry. 2020;81(2):19m12769.
9. Yagoda S, Graham C, Simmons A, et al. Long-term safety and durability of effect with a combination of olanzapine and samidorphan in patients with schizophrenia: results from a 1-year open-label extension study. CNS Spectr. 2021;26(4):383-392.
10. Correll CU, Newcomer JW, Silverman B, et al. Effects of olanzapine combined with samidorphan on weight gain in schizophrenia: a 24-week phase 3 study. Am J Psychiatry. 2020;177(12):1168-1178.
11. Kahn RS, Silverman BL, DiPetrillo L, et al. A phase 3, multicenter study to assess the 1-year safety and tolerability of a combination of olanzapine and samidorphan in patients with schizophrenia: results from the ENLIGHTEN-2 long-term extension. Schizophr Res. 2021;232:45-53.
12. US Food and Drug Administration. Drug approval package: Lybalvi. June 26, 2021. Accessed November 24, 2021. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213378Orig1Orig2s000TOC.cfm
13. Sun L, Yagoda S, Yao B, et al. Combination of olanzapine and samidorphan has no clinically significant effect on the pharmacokinetics of lithium or valproate. Clin Drug Investig. 2020;40(1):55-64.
14. Eli Lilly and Company. SYMBYAX (olanzapine and fluoxetine) capsules for oral use. Prescribing information. September 2021. Accessed November 24, 2021. https://pi.lilly.com/us/symbyax-pi.pdf
15. Wentland MP, Lu Q, Lou R, et al. Synthesis and opioid receptor binding properties of a highly potent 4-hydroxy analogue of naltrexone. Bioorg Med Chem Lett. 2005;15(8):2107-2110.
16. Lee MW, Fujioka K. Naltrexone for the treatment of obesity: review and update. Expert Opin Pharmacother. 2009;10(11):1841-1845.
17. Sun L, Yagoda S, Xue H, et al. Combination of olanzapine and samidorphan has no clinically relevant effects on ECG parameters, including the QTc interval: results from a phase 1 QT/QTc study. Prog Neuropsychopharmacol Biol Psychiatry. 2020;100:109881.
18. Zhou SF, Yang LP, Zhou ZW, et al. Insights into the substrate specificity, inhibitors, regulation, and polymorphisms and the clinical impact of human cytochrome P450 1A2. AAPS J. 2009;11(3):481-494.
19. Citrome L, Stauffer VL, Chen L, et al. Olanzapine plasma concentrations after treatment with 10, 20, and 40 mg/d in patients with schizophrenia: an analysis of correlations with efficacy, weight gain, and prolactin concentration. J Clin Psychopharmacol. 2009;29(3):278-283.
20. Cerhan JR, Moore SC, Jacobs EJ, et al. A pooled analysis of waist circumference and mortality in 650,000 adults. Mayo Clin Proc. 2014;89(3):335-345.
21. Citrome L, Nasrallah HA. On-label on the table: what the package insert informs us about the tolerability profile of oral atypical antipsychotics, and what it does not. Expert Opin Pharmacother. 2012;13(11):1599-1613.
Treating homeless patients: Book offers key insights
As a psychiatrist dedicated to working with people who are experiencing homelessness, I was very impressed with the new book edited by Col. (Ret.) Elspeth Cameron Ritchie, MD, MPH, and Maria D. Llorente, MD, about treating and providing services to this vulnerable population.
The book, “Clinical Management of the Homeless Patient: Social, Psychiatric, and Medical Issues” (Cham, Switzerland: Springer Nature Switzerland, 2021), offers an in-depth review and analysis of the biopsychosocial complexities that affect how medical and behavioral health conditions present in those who are unhoused. Notably, the book recommends with great sensitivity best practices to address these conditions with care, understanding, and love.
This text, invaluable in particular for those of us clinicians who work with people experiencing homelessness (PEH), provides a historical context of homelessness in the United States, an evaluation of the current state, and indispensable guidance for medical and behavioral health practitioners, case managers, housing navigators, and policy makers alike. It also serves as an inspiring source for those who are considering work in the public sector while reminding those of us in the field why we continue to do this challenging and rewarding work.
Tips can provide hope to clinicians
The volume is divided into four clear sections that are easy to navigate depending on your area of expertise and interest. Each chapter consolidates an extensive literature review into an intriguing and thought-provoking analysis. Part I, “The Big Picture – Social and Medical Issues,” focuses on conditions that disproportionately affect those who are unhoused. The authors offer a glimpse into the unique challenges of managing routine health conditions. They also detail the practical knowledge that’s needed to best care for our most vulnerable neighbors; for example, promoting a shared decision-making model; simplifying treatment plans; prescribing, when possible, medications that are dosed daily – instead of multiple times per day; allowing for walk-in appointments; and addressing cultural, linguistic, and educational barriers.
Most chapters highlight informative case examples that bring the text to life. It can be heartbreaking to recognize and witness the inhumane conditions in which PEH live, and these practical tips and suggestions for future policies based on best practices can help prevent burnout and provide hope for those who care for this community.
Part II, “Psychiatric Issues and Treatments,” presents a brief yet comprehensive history on homelessness, beginning with the deep shame that PEH experienced in Colonial times as the result of cultural and religious influences. Sadly, that negative judgment continues to this day.
The authors also explain how deinstitutionalization and transinstitutionalization have shaped the current state of homelessness, including why many PEH receive their care in emergency departments while incarcerated. This section highlights the barriers of care that are created not just by the patient, but also by the clinicians and systems of care – and what’s needed practically to overcome those challenges.
I appreciate the chapter on substance use disorders. It reminds us that the most commonly used substance among PEH is tobacco, which has serious health effects and for which we have treatment; nevertheless, . This section also provides examples of the trauma-informed language to use when addressing difficult and sometimes stigmatizing topics, such as survival sex and trauma history.
The evidence-based discussion continues in Part III with a focus on topics that everyone working with PEH should understand, including food insecurity, the criminal justice system, and sex trafficking. Part IV highlights best practices that should be replicated in every community, including Housing First approaches, medical respite care, and multiple Veterans Administration programs.
Throughout the text, major themes reverberate across the chapters, beginning with empathy. All who work with PEH must understand the conditions and challenges PEH face every day that affect their physical and mental health. The authors offer a stark and pointed reminder that being unhoused amounts to a full-time job just to meet basic needs. In addition, the devastating role of trauma and structural racism in creating and promoting the conditions that lead someone to be unhoused cannot be underestimated.
Fortunately, the primary aim of the book is to highlight solutions, and it’s here that the book shines. While some interventions are well-known, such as the importance of working in multidisciplinary teams, building trust and rapport with our patients, and urging clinicians and institutions to examine their own judgments and biases that might interfere with humane treatment, other suggestions will lead some readers into new territory. The authors, for example, maintain that we need more data and evidence-based research that include PEH. They also make a case for more preventive care and enhanced professional education for all health care workers that centers on trauma-informed care, social determinants of health, and the unique needs of especially vulnerable communities, such as the unhoused LBGTQ+ community and policies that promote best practices, such as Housing First. The book is a stirring read. It offers both inspiration and practical guidance for all who are currently working with or interested in caring for people experiencing homelessness.
Dr. Bird is a psychiatrist with Alameda County Health Care for the Homeless and the TRUST Clinic in Oakland, Calif. She also is a cofounder of StreetHealth, a backpack street medicine team that provides psychiatric and substance use disorder treatment to people experiencing homelessness in downtown Oakland.
Dr. Bird has no disclosures.
As a psychiatrist dedicated to working with people who are experiencing homelessness, I was very impressed with the new book edited by Col. (Ret.) Elspeth Cameron Ritchie, MD, MPH, and Maria D. Llorente, MD, about treating and providing services to this vulnerable population.
The book, “Clinical Management of the Homeless Patient: Social, Psychiatric, and Medical Issues” (Cham, Switzerland: Springer Nature Switzerland, 2021), offers an in-depth review and analysis of the biopsychosocial complexities that affect how medical and behavioral health conditions present in those who are unhoused. Notably, the book recommends with great sensitivity best practices to address these conditions with care, understanding, and love.
This text, invaluable in particular for those of us clinicians who work with people experiencing homelessness (PEH), provides a historical context of homelessness in the United States, an evaluation of the current state, and indispensable guidance for medical and behavioral health practitioners, case managers, housing navigators, and policy makers alike. It also serves as an inspiring source for those who are considering work in the public sector while reminding those of us in the field why we continue to do this challenging and rewarding work.
Tips can provide hope to clinicians
The volume is divided into four clear sections that are easy to navigate depending on your area of expertise and interest. Each chapter consolidates an extensive literature review into an intriguing and thought-provoking analysis. Part I, “The Big Picture – Social and Medical Issues,” focuses on conditions that disproportionately affect those who are unhoused. The authors offer a glimpse into the unique challenges of managing routine health conditions. They also detail the practical knowledge that’s needed to best care for our most vulnerable neighbors; for example, promoting a shared decision-making model; simplifying treatment plans; prescribing, when possible, medications that are dosed daily – instead of multiple times per day; allowing for walk-in appointments; and addressing cultural, linguistic, and educational barriers.
Most chapters highlight informative case examples that bring the text to life. It can be heartbreaking to recognize and witness the inhumane conditions in which PEH live, and these practical tips and suggestions for future policies based on best practices can help prevent burnout and provide hope for those who care for this community.
Part II, “Psychiatric Issues and Treatments,” presents a brief yet comprehensive history on homelessness, beginning with the deep shame that PEH experienced in Colonial times as the result of cultural and religious influences. Sadly, that negative judgment continues to this day.
The authors also explain how deinstitutionalization and transinstitutionalization have shaped the current state of homelessness, including why many PEH receive their care in emergency departments while incarcerated. This section highlights the barriers of care that are created not just by the patient, but also by the clinicians and systems of care – and what’s needed practically to overcome those challenges.
I appreciate the chapter on substance use disorders. It reminds us that the most commonly used substance among PEH is tobacco, which has serious health effects and for which we have treatment; nevertheless, . This section also provides examples of the trauma-informed language to use when addressing difficult and sometimes stigmatizing topics, such as survival sex and trauma history.
The evidence-based discussion continues in Part III with a focus on topics that everyone working with PEH should understand, including food insecurity, the criminal justice system, and sex trafficking. Part IV highlights best practices that should be replicated in every community, including Housing First approaches, medical respite care, and multiple Veterans Administration programs.
Throughout the text, major themes reverberate across the chapters, beginning with empathy. All who work with PEH must understand the conditions and challenges PEH face every day that affect their physical and mental health. The authors offer a stark and pointed reminder that being unhoused amounts to a full-time job just to meet basic needs. In addition, the devastating role of trauma and structural racism in creating and promoting the conditions that lead someone to be unhoused cannot be underestimated.
Fortunately, the primary aim of the book is to highlight solutions, and it’s here that the book shines. While some interventions are well-known, such as the importance of working in multidisciplinary teams, building trust and rapport with our patients, and urging clinicians and institutions to examine their own judgments and biases that might interfere with humane treatment, other suggestions will lead some readers into new territory. The authors, for example, maintain that we need more data and evidence-based research that include PEH. They also make a case for more preventive care and enhanced professional education for all health care workers that centers on trauma-informed care, social determinants of health, and the unique needs of especially vulnerable communities, such as the unhoused LBGTQ+ community and policies that promote best practices, such as Housing First. The book is a stirring read. It offers both inspiration and practical guidance for all who are currently working with or interested in caring for people experiencing homelessness.
Dr. Bird is a psychiatrist with Alameda County Health Care for the Homeless and the TRUST Clinic in Oakland, Calif. She also is a cofounder of StreetHealth, a backpack street medicine team that provides psychiatric and substance use disorder treatment to people experiencing homelessness in downtown Oakland.
Dr. Bird has no disclosures.
As a psychiatrist dedicated to working with people who are experiencing homelessness, I was very impressed with the new book edited by Col. (Ret.) Elspeth Cameron Ritchie, MD, MPH, and Maria D. Llorente, MD, about treating and providing services to this vulnerable population.
The book, “Clinical Management of the Homeless Patient: Social, Psychiatric, and Medical Issues” (Cham, Switzerland: Springer Nature Switzerland, 2021), offers an in-depth review and analysis of the biopsychosocial complexities that affect how medical and behavioral health conditions present in those who are unhoused. Notably, the book recommends with great sensitivity best practices to address these conditions with care, understanding, and love.
This text, invaluable in particular for those of us clinicians who work with people experiencing homelessness (PEH), provides a historical context of homelessness in the United States, an evaluation of the current state, and indispensable guidance for medical and behavioral health practitioners, case managers, housing navigators, and policy makers alike. It also serves as an inspiring source for those who are considering work in the public sector while reminding those of us in the field why we continue to do this challenging and rewarding work.
Tips can provide hope to clinicians
The volume is divided into four clear sections that are easy to navigate depending on your area of expertise and interest. Each chapter consolidates an extensive literature review into an intriguing and thought-provoking analysis. Part I, “The Big Picture – Social and Medical Issues,” focuses on conditions that disproportionately affect those who are unhoused. The authors offer a glimpse into the unique challenges of managing routine health conditions. They also detail the practical knowledge that’s needed to best care for our most vulnerable neighbors; for example, promoting a shared decision-making model; simplifying treatment plans; prescribing, when possible, medications that are dosed daily – instead of multiple times per day; allowing for walk-in appointments; and addressing cultural, linguistic, and educational barriers.
Most chapters highlight informative case examples that bring the text to life. It can be heartbreaking to recognize and witness the inhumane conditions in which PEH live, and these practical tips and suggestions for future policies based on best practices can help prevent burnout and provide hope for those who care for this community.
Part II, “Psychiatric Issues and Treatments,” presents a brief yet comprehensive history on homelessness, beginning with the deep shame that PEH experienced in Colonial times as the result of cultural and religious influences. Sadly, that negative judgment continues to this day.
The authors also explain how deinstitutionalization and transinstitutionalization have shaped the current state of homelessness, including why many PEH receive their care in emergency departments while incarcerated. This section highlights the barriers of care that are created not just by the patient, but also by the clinicians and systems of care – and what’s needed practically to overcome those challenges.
I appreciate the chapter on substance use disorders. It reminds us that the most commonly used substance among PEH is tobacco, which has serious health effects and for which we have treatment; nevertheless, . This section also provides examples of the trauma-informed language to use when addressing difficult and sometimes stigmatizing topics, such as survival sex and trauma history.
The evidence-based discussion continues in Part III with a focus on topics that everyone working with PEH should understand, including food insecurity, the criminal justice system, and sex trafficking. Part IV highlights best practices that should be replicated in every community, including Housing First approaches, medical respite care, and multiple Veterans Administration programs.
Throughout the text, major themes reverberate across the chapters, beginning with empathy. All who work with PEH must understand the conditions and challenges PEH face every day that affect their physical and mental health. The authors offer a stark and pointed reminder that being unhoused amounts to a full-time job just to meet basic needs. In addition, the devastating role of trauma and structural racism in creating and promoting the conditions that lead someone to be unhoused cannot be underestimated.
Fortunately, the primary aim of the book is to highlight solutions, and it’s here that the book shines. While some interventions are well-known, such as the importance of working in multidisciplinary teams, building trust and rapport with our patients, and urging clinicians and institutions to examine their own judgments and biases that might interfere with humane treatment, other suggestions will lead some readers into new territory. The authors, for example, maintain that we need more data and evidence-based research that include PEH. They also make a case for more preventive care and enhanced professional education for all health care workers that centers on trauma-informed care, social determinants of health, and the unique needs of especially vulnerable communities, such as the unhoused LBGTQ+ community and policies that promote best practices, such as Housing First. The book is a stirring read. It offers both inspiration and practical guidance for all who are currently working with or interested in caring for people experiencing homelessness.
Dr. Bird is a psychiatrist with Alameda County Health Care for the Homeless and the TRUST Clinic in Oakland, Calif. She also is a cofounder of StreetHealth, a backpack street medicine team that provides psychiatric and substance use disorder treatment to people experiencing homelessness in downtown Oakland.
Dr. Bird has no disclosures.
FDA grants new indication to lumateperone (Caplyta) for bipolar depression
The Food and Drug Administration has expanded approval of lumateperone (Caplyta) to include treatment of adults with depressive episodes associated with bipolar I and II disorder, as monotherapy or adjunctive therapy with lithium or valproate.
This makes lumateperone the only FDA-approved drug for this indication.
“The efficacy, and favorable safety and tolerability profile, make Caplyta an important treatment option for the millions of patients living with bipolar I or II depression and represents a major development for these patients,” Roger McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, and head of the mood disorders psychopharmacology unit, said in a company news release.
Lumateperone was first approved by the FDA in 2019 for the treatment of adults with schizophrenia.
‘Positioned to launch immediately’
that showed treatment with lumateperone, alone or with lithium or valproate, significantly improved depressive symptoms for patients with major depressive episodes associated with bipolar I and bipolar II disorders.
In these studies, treatment with a 42-mg once-daily dose was associated with significantly greater improvement from baseline in Montgomery-Åsberg Depression Rating Scale score versus placebo.
Lumateperone also showed a statistically significant improvement in the key secondary endpoint relating to clinical global impression of bipolar disorder.
Somnolence/sedation, dizziness, nausea, and dry mouth were the most commonly reported adverse events associated with the medication. Minimal changes were observed in weight and vital signs and in results of metabolic or endocrine assessments. Incidence of extrapyramidal symptom–related events was low and was similar to those with placebo.
Sharon Mates, PhD, chairman and CEO of Intra-Cellular Therapies, noted in the same press release that the company is “positioned to launch immediately and are excited to offer Caplyta to the millions of patients living with bipolar depression.”
Full prescribing information is available online.
A version of this article first appeared on Medscape.com.
The Food and Drug Administration has expanded approval of lumateperone (Caplyta) to include treatment of adults with depressive episodes associated with bipolar I and II disorder, as monotherapy or adjunctive therapy with lithium or valproate.
This makes lumateperone the only FDA-approved drug for this indication.
“The efficacy, and favorable safety and tolerability profile, make Caplyta an important treatment option for the millions of patients living with bipolar I or II depression and represents a major development for these patients,” Roger McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, and head of the mood disorders psychopharmacology unit, said in a company news release.
Lumateperone was first approved by the FDA in 2019 for the treatment of adults with schizophrenia.
‘Positioned to launch immediately’
that showed treatment with lumateperone, alone or with lithium or valproate, significantly improved depressive symptoms for patients with major depressive episodes associated with bipolar I and bipolar II disorders.
In these studies, treatment with a 42-mg once-daily dose was associated with significantly greater improvement from baseline in Montgomery-Åsberg Depression Rating Scale score versus placebo.
Lumateperone also showed a statistically significant improvement in the key secondary endpoint relating to clinical global impression of bipolar disorder.
Somnolence/sedation, dizziness, nausea, and dry mouth were the most commonly reported adverse events associated with the medication. Minimal changes were observed in weight and vital signs and in results of metabolic or endocrine assessments. Incidence of extrapyramidal symptom–related events was low and was similar to those with placebo.
Sharon Mates, PhD, chairman and CEO of Intra-Cellular Therapies, noted in the same press release that the company is “positioned to launch immediately and are excited to offer Caplyta to the millions of patients living with bipolar depression.”
Full prescribing information is available online.
A version of this article first appeared on Medscape.com.
The Food and Drug Administration has expanded approval of lumateperone (Caplyta) to include treatment of adults with depressive episodes associated with bipolar I and II disorder, as monotherapy or adjunctive therapy with lithium or valproate.
This makes lumateperone the only FDA-approved drug for this indication.
“The efficacy, and favorable safety and tolerability profile, make Caplyta an important treatment option for the millions of patients living with bipolar I or II depression and represents a major development for these patients,” Roger McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, and head of the mood disorders psychopharmacology unit, said in a company news release.
Lumateperone was first approved by the FDA in 2019 for the treatment of adults with schizophrenia.
‘Positioned to launch immediately’
that showed treatment with lumateperone, alone or with lithium or valproate, significantly improved depressive symptoms for patients with major depressive episodes associated with bipolar I and bipolar II disorders.
In these studies, treatment with a 42-mg once-daily dose was associated with significantly greater improvement from baseline in Montgomery-Åsberg Depression Rating Scale score versus placebo.
Lumateperone also showed a statistically significant improvement in the key secondary endpoint relating to clinical global impression of bipolar disorder.
Somnolence/sedation, dizziness, nausea, and dry mouth were the most commonly reported adverse events associated with the medication. Minimal changes were observed in weight and vital signs and in results of metabolic or endocrine assessments. Incidence of extrapyramidal symptom–related events was low and was similar to those with placebo.
Sharon Mates, PhD, chairman and CEO of Intra-Cellular Therapies, noted in the same press release that the company is “positioned to launch immediately and are excited to offer Caplyta to the millions of patients living with bipolar depression.”
Full prescribing information is available online.
A version of this article first appeared on Medscape.com.
More evidence ties some antipsychotics to increased breast cancer risk
New research provides more evidence that antipsychotics that raise prolactin levels are tied to a significantly increased risk for breast cancer.
The relative risk for breast cancer was 62% higher in women who took category 1 antipsychotic medications associated with high prolactin levels. These include haloperidol (Haldol), paliperidone (Invega), and risperidone (Risperdal). Additionally, the risk was 54% higher in those taking category 2 antipsychotics that have mid-range effects on prolactin. These include iloperidone (Fanapt), lurasidone (Latuda), and olanzapine (Zyprexa).
In contrast, category 3 antipsychotics which have a lesser effect on prolactin levels were not associated with any increase in breast cancer risk. These drugs include aripiprazole (Abilify), asenapine (Saphris), brexpiprazole (Rexulti), cariprazine (Vraylar), clozapine (multiple brands), quetiapine (Seroquel), and ziprasidone (Geodon).
While the “absolute” breast cancer risk for these drugs is unclear, “we can make the case that high circulating prolactin levels are associated with breast cancer risk. This follows what is already known about prolactin from prior studies, notably the nurses’ health studies,” Tahir Rahman, MD, associate professor of psychiatry, Washington University School of Medicine, St. Louis, told this news organization.
“We don’t want to alarm patients taking antipsychotic drugs for life-threatening mental health problems, but we also think it is time for doctors to track prolactin levels and vigilantly monitor their patients who are being treated with antipsychotics,” Dr. Rahman added in a news release.
The study was published online Dec. 3 in the Journal of Clinical Psychopharmacology.
Test prolactin levels
Using administrative claims data, the researchers evaluated breast cancer risk in women aged 18-64 exposed to antipsychotic medications compared with anticonvulsants and/or lithium.
They identified 914 cases of invasive breast cancer among 540,737 women.
Roughly 52% of the study population filled at least one prescription for a category 3 antipsychotic agent, whereas 15% filled at least one prescription for a category 1 agent; 49% of women filled at least one prescription for an anticonvulsant medication during the study period.
Exposure to all antipsychotics was independently associated with a 35% increased risk for breast cancer (adjusted hazard ratio, 1.35; 95% CI, 1.14-1.61), the study team found.
Compared with anticonvulsants or lithium, the risk for breast cancer was significantly increased for high prolactin (category 1) antipsychotics (adjusted hazard ratio, 1.62; 95% CI, 1.30-2.03) and for mid-prolactin (category 2) drugs (aHR 1.54; 95% CI, 1.19-1.99), with no increased risk for category 3 antipsychotics.
“Our research is obviously of interest for preventing breast cancer in antipsychotic-treated patients. Checking a blood prolactin level is cheap and easy [and a high level is] fairly simple to mitigate,” said Dr. Rahman.
A matter of debate
Reached for comment, Christoph Correll, MD, professor of psychiatry and molecular medicine, Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, said, “The potential elevation of breast cancer risk depending on the dose and time of treatment with antipsychotic medications with varying degrees of prolactin-raising properties has been a topic of research and matter of debate.”
This new study “adds another data point indicating that antipsychotics that are associated on average with a higher prolactin-raising effect than other antipsychotics may increase the risk of breast cancer in women to some degree,” said Dr. Correll, who was not involved with the study.
However, he cautioned that “naturalistic data are always vulnerable to residual confounding, for example, unmeasured effects that could also at least partially explain the results, and the follow-up time of only 4 years (maximum 6 years) in this study was relatively short.
“Nevertheless, given availability of many different antipsychotics with varying degrees of prolactin-raising potential, in women requiring antipsychotic treatment, less prolactin-raising antipsychotics may be preferable,” Dr. Correll said.
“In women receiving prolactin-raising antipsychotics for medium- and longer-term maintenance therapy, prolactin levels should be monitored,” he added.
When an elevated prolactin level is detected, this should be addressed “either via dose reduction, a switch to an alternative antipsychotic that does not raise prolactin levels significantly, or the addition of a partial or full D2 agonist when the prolactin-raising antipsychotic should be continued based on individualized risk assessment,” Dr. Correll advised.
This work was supported by an award from the Alvin J. Siteman Cancer Center; the National Cancer Institute and the National Center for Advancing Translational Sciences of the National Institutes of Health; the Taylor Family Institute for Innovative Psychiatric Research; and the Center for Brain Research in Mood Disorders. The authors have disclosed no relevant financial relationships. Dr. Correll has received royalties from UpToDate and is a stock option holder of LB Pharma.
A version of this article first appeared on Medscape.com.
New research provides more evidence that antipsychotics that raise prolactin levels are tied to a significantly increased risk for breast cancer.
The relative risk for breast cancer was 62% higher in women who took category 1 antipsychotic medications associated with high prolactin levels. These include haloperidol (Haldol), paliperidone (Invega), and risperidone (Risperdal). Additionally, the risk was 54% higher in those taking category 2 antipsychotics that have mid-range effects on prolactin. These include iloperidone (Fanapt), lurasidone (Latuda), and olanzapine (Zyprexa).
In contrast, category 3 antipsychotics which have a lesser effect on prolactin levels were not associated with any increase in breast cancer risk. These drugs include aripiprazole (Abilify), asenapine (Saphris), brexpiprazole (Rexulti), cariprazine (Vraylar), clozapine (multiple brands), quetiapine (Seroquel), and ziprasidone (Geodon).
While the “absolute” breast cancer risk for these drugs is unclear, “we can make the case that high circulating prolactin levels are associated with breast cancer risk. This follows what is already known about prolactin from prior studies, notably the nurses’ health studies,” Tahir Rahman, MD, associate professor of psychiatry, Washington University School of Medicine, St. Louis, told this news organization.
“We don’t want to alarm patients taking antipsychotic drugs for life-threatening mental health problems, but we also think it is time for doctors to track prolactin levels and vigilantly monitor their patients who are being treated with antipsychotics,” Dr. Rahman added in a news release.
The study was published online Dec. 3 in the Journal of Clinical Psychopharmacology.
Test prolactin levels
Using administrative claims data, the researchers evaluated breast cancer risk in women aged 18-64 exposed to antipsychotic medications compared with anticonvulsants and/or lithium.
They identified 914 cases of invasive breast cancer among 540,737 women.
Roughly 52% of the study population filled at least one prescription for a category 3 antipsychotic agent, whereas 15% filled at least one prescription for a category 1 agent; 49% of women filled at least one prescription for an anticonvulsant medication during the study period.
Exposure to all antipsychotics was independently associated with a 35% increased risk for breast cancer (adjusted hazard ratio, 1.35; 95% CI, 1.14-1.61), the study team found.
Compared with anticonvulsants or lithium, the risk for breast cancer was significantly increased for high prolactin (category 1) antipsychotics (adjusted hazard ratio, 1.62; 95% CI, 1.30-2.03) and for mid-prolactin (category 2) drugs (aHR 1.54; 95% CI, 1.19-1.99), with no increased risk for category 3 antipsychotics.
“Our research is obviously of interest for preventing breast cancer in antipsychotic-treated patients. Checking a blood prolactin level is cheap and easy [and a high level is] fairly simple to mitigate,” said Dr. Rahman.
A matter of debate
Reached for comment, Christoph Correll, MD, professor of psychiatry and molecular medicine, Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, said, “The potential elevation of breast cancer risk depending on the dose and time of treatment with antipsychotic medications with varying degrees of prolactin-raising properties has been a topic of research and matter of debate.”
This new study “adds another data point indicating that antipsychotics that are associated on average with a higher prolactin-raising effect than other antipsychotics may increase the risk of breast cancer in women to some degree,” said Dr. Correll, who was not involved with the study.
However, he cautioned that “naturalistic data are always vulnerable to residual confounding, for example, unmeasured effects that could also at least partially explain the results, and the follow-up time of only 4 years (maximum 6 years) in this study was relatively short.
“Nevertheless, given availability of many different antipsychotics with varying degrees of prolactin-raising potential, in women requiring antipsychotic treatment, less prolactin-raising antipsychotics may be preferable,” Dr. Correll said.
“In women receiving prolactin-raising antipsychotics for medium- and longer-term maintenance therapy, prolactin levels should be monitored,” he added.
When an elevated prolactin level is detected, this should be addressed “either via dose reduction, a switch to an alternative antipsychotic that does not raise prolactin levels significantly, or the addition of a partial or full D2 agonist when the prolactin-raising antipsychotic should be continued based on individualized risk assessment,” Dr. Correll advised.
This work was supported by an award from the Alvin J. Siteman Cancer Center; the National Cancer Institute and the National Center for Advancing Translational Sciences of the National Institutes of Health; the Taylor Family Institute for Innovative Psychiatric Research; and the Center for Brain Research in Mood Disorders. The authors have disclosed no relevant financial relationships. Dr. Correll has received royalties from UpToDate and is a stock option holder of LB Pharma.
A version of this article first appeared on Medscape.com.
New research provides more evidence that antipsychotics that raise prolactin levels are tied to a significantly increased risk for breast cancer.
The relative risk for breast cancer was 62% higher in women who took category 1 antipsychotic medications associated with high prolactin levels. These include haloperidol (Haldol), paliperidone (Invega), and risperidone (Risperdal). Additionally, the risk was 54% higher in those taking category 2 antipsychotics that have mid-range effects on prolactin. These include iloperidone (Fanapt), lurasidone (Latuda), and olanzapine (Zyprexa).
In contrast, category 3 antipsychotics which have a lesser effect on prolactin levels were not associated with any increase in breast cancer risk. These drugs include aripiprazole (Abilify), asenapine (Saphris), brexpiprazole (Rexulti), cariprazine (Vraylar), clozapine (multiple brands), quetiapine (Seroquel), and ziprasidone (Geodon).
While the “absolute” breast cancer risk for these drugs is unclear, “we can make the case that high circulating prolactin levels are associated with breast cancer risk. This follows what is already known about prolactin from prior studies, notably the nurses’ health studies,” Tahir Rahman, MD, associate professor of psychiatry, Washington University School of Medicine, St. Louis, told this news organization.
“We don’t want to alarm patients taking antipsychotic drugs for life-threatening mental health problems, but we also think it is time for doctors to track prolactin levels and vigilantly monitor their patients who are being treated with antipsychotics,” Dr. Rahman added in a news release.
The study was published online Dec. 3 in the Journal of Clinical Psychopharmacology.
Test prolactin levels
Using administrative claims data, the researchers evaluated breast cancer risk in women aged 18-64 exposed to antipsychotic medications compared with anticonvulsants and/or lithium.
They identified 914 cases of invasive breast cancer among 540,737 women.
Roughly 52% of the study population filled at least one prescription for a category 3 antipsychotic agent, whereas 15% filled at least one prescription for a category 1 agent; 49% of women filled at least one prescription for an anticonvulsant medication during the study period.
Exposure to all antipsychotics was independently associated with a 35% increased risk for breast cancer (adjusted hazard ratio, 1.35; 95% CI, 1.14-1.61), the study team found.
Compared with anticonvulsants or lithium, the risk for breast cancer was significantly increased for high prolactin (category 1) antipsychotics (adjusted hazard ratio, 1.62; 95% CI, 1.30-2.03) and for mid-prolactin (category 2) drugs (aHR 1.54; 95% CI, 1.19-1.99), with no increased risk for category 3 antipsychotics.
“Our research is obviously of interest for preventing breast cancer in antipsychotic-treated patients. Checking a blood prolactin level is cheap and easy [and a high level is] fairly simple to mitigate,” said Dr. Rahman.
A matter of debate
Reached for comment, Christoph Correll, MD, professor of psychiatry and molecular medicine, Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, said, “The potential elevation of breast cancer risk depending on the dose and time of treatment with antipsychotic medications with varying degrees of prolactin-raising properties has been a topic of research and matter of debate.”
This new study “adds another data point indicating that antipsychotics that are associated on average with a higher prolactin-raising effect than other antipsychotics may increase the risk of breast cancer in women to some degree,” said Dr. Correll, who was not involved with the study.
However, he cautioned that “naturalistic data are always vulnerable to residual confounding, for example, unmeasured effects that could also at least partially explain the results, and the follow-up time of only 4 years (maximum 6 years) in this study was relatively short.
“Nevertheless, given availability of many different antipsychotics with varying degrees of prolactin-raising potential, in women requiring antipsychotic treatment, less prolactin-raising antipsychotics may be preferable,” Dr. Correll said.
“In women receiving prolactin-raising antipsychotics for medium- and longer-term maintenance therapy, prolactin levels should be monitored,” he added.
When an elevated prolactin level is detected, this should be addressed “either via dose reduction, a switch to an alternative antipsychotic that does not raise prolactin levels significantly, or the addition of a partial or full D2 agonist when the prolactin-raising antipsychotic should be continued based on individualized risk assessment,” Dr. Correll advised.
This work was supported by an award from the Alvin J. Siteman Cancer Center; the National Cancer Institute and the National Center for Advancing Translational Sciences of the National Institutes of Health; the Taylor Family Institute for Innovative Psychiatric Research; and the Center for Brain Research in Mood Disorders. The authors have disclosed no relevant financial relationships. Dr. Correll has received royalties from UpToDate and is a stock option holder of LB Pharma.
A version of this article first appeared on Medscape.com.
FROM THE JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY
Case report: ECT for delirious mania
Delirious mania is a diagnostic term used in variety of settings, including the emergency department and inpatient psychiatry, but it does not have formal criteria established in the DSM-5. Delirious mania was first described in the 1800s and was referred to as “Bell’s Mania.”
As the late Max Fink, MD, wrote in the journal Bipolar Disorders (2002 Feb 23. doi: 10.1034/j.1399-561.1999.10112.x), delirious mania is considered to be a syndrome of the acute onset of the excitement, grandiosity, emotional lability, delusions, and insomnia characteristic of mania, and the disorientation and altered consciousness characteristic of delirium.
Such patients can be considered as having a component of bipolar I disorder, comprising mania with psychotic features. Delirious mania is associated with higher rates of morbidity and mortality, and demonstrates limited response to conventional treatment guidelines. Therefore, early detection and decisive treatment are imperative. The concurrence of delirium and mania is not unusual, yet currently there are no universal accepted treatment guidelines for delirious mania (BMC Psychiatry. 2012 Jun 21. doi: 10.1186/1471-244X-12-65). The purpose of this case report is to inspire and support community psychiatric clinicians in managing such complex cases and to improve behavioral health care outcomes. To protect our patient’s identity, we changed several key identifiers.
The treatment plan emerges
This case is of a middle-aged man with an established diagnosis of bipolar disorder. He was referred to the ED because of worsening manic symptoms marked by mood lability, pressured speech, grandiose delusions, tangential thought processes, poor insight, and impaired sleep.
Laboratory studies in the ED revealed hyponatremia and serum sodium of 126meq/l (ref. range: 135-146). The patient’s toxicology screen was positive for benzodiazepines. He was stabilized on the medical floor and then transitioned to inpatient psychiatry.
Before his admission to psychiatry, the patient’s medications were alprazolam 1 mg at bed time, bupropion 100 mg twice daily, loxapine 25 mg morning and 50 mg at bed time, olanzapine 20 mg at bedtime and 5 mg twice daily, risperidone 2 mg twice daily and oxcarbazepine 900 mg twice daily.
The bupropion was discontinued because of manic behavior, and the patient’s dose of oxcarbazepine was lowered from 900 mg twice daily to 450 mg twice daily because of hyponatremia. Our team continued to administer risperidone, olanzapine, loxapine, and alprazolam to the patient. However, he was agitated and disorganized on the psychiatry floor. In addition, we noticed that the patient exhibited confusion, disorientation, an inability to connect with reality, and periods of profound agitation.
The patient was frequently restrained physically, and medications were administered to him for safety and containment. The use of benzodiazepines and anticholinergics was minimized. However, we noticed that the patient acted paranoid, disinhibited, and combative, and he became difficult to restrain. He seemed to have a high pain tolerance, responded to internal stimuli, and began hallucinating and displaying aggressive behavior toward staff persons.
It became apparent that the patient’s circadian rhythm had been altered. He slept for only a couple of hours during the day. During the course of treatment, in one incidence, the patient became agitated and charged at a nurse. Subsequently, the patient hit his head on a wall and fell – suffering a head strike and lacerations.
The team conducted investigations, including labs and neuroimaging, to make sure that the patient was OK. His CT head scan proved unremarkable. Liver function tests revealed mild transaminitis. His TSH, folate, B12, and B1 levels were normal.
We then placed the patient in a single room with continuous behavior monitoring. His recovery seemed to take a long time with trials of different antipsychotic medications, including olanzapine, loxapine, risperidone, and paliperidone. Because of his poor response to medications, the team considered using electroconvulsive therapy (ECT).
However, the patient was unable to give informed consent for ECT because of his impaired mental status. At this point, our team submitted a substitute treatment plan that included ECT to the court for approval, and the court approved our plan.
After receiving approximately four bilateral ECT procedures three times a week, the patient’s condition started to improve gradually. He received total of 11 procedures.
Our patient became alert to time, place, and person, and his circadian rhythm normalized. Soon, his delirium cleared, and he demonstrated marked improvement in both insight into his illness and behavioral control. His grandiose delusions were still present, but he was easily redirectable. In addition, our patient demonstrated improved reality testing. He was able to be discharged home following medication adjustments and with community supports within a few short weeks of receiving ECT.
As Bo-Shyan Lee, MD, and associates reported (BMC Psychiatry. 2012 Jun 21;12:65. doi: 10.1186/1471-244X-12-65), delirious mania is closely related to catatonia. Although there are different definitions for delirium and catatonia, even the most lethal form of catatonia meets the criteria for delirium. ECT is a well established first-line treatment for catatonia. This tool has been shown to be highly effective in the treatment of delirious mania. Delirious mania can be life-threatening and should be managed aggressively. The most common causes of death are heart failure from arrhythmias, cardiac arrest, and respiratory failure. ECT is a safe treatment, and, as Dr. Fink argued, the mortality rate is even less than that associated with normal pregnancies (World J Biol Psychiatry. 2001 Jan;2[1]:1-8). In light of the safety and effectiveness of ECT, we think the tool should be considered not only in university hospital settings but as an early intervention in community settings. This case warrants further research in exploring hyperactive delirium and delirious mania.
Dr. Lamba is BR-2 unit medical director at BayRidge Hospital in Lynn, Mass. Ms. Kennedy is an attending clinician at BayRidge. Dr. Vu is medical director at BayRidge. He also serves as associate chief of psychiatry at Beverly (Mass.) Hospital and at Addison Gilbert Hospital in Gloucester, Mass. Dr. Lamba, Ms. Kennedy, and Dr. Vu have no disclosures.
Delirious mania is a diagnostic term used in variety of settings, including the emergency department and inpatient psychiatry, but it does not have formal criteria established in the DSM-5. Delirious mania was first described in the 1800s and was referred to as “Bell’s Mania.”
As the late Max Fink, MD, wrote in the journal Bipolar Disorders (2002 Feb 23. doi: 10.1034/j.1399-561.1999.10112.x), delirious mania is considered to be a syndrome of the acute onset of the excitement, grandiosity, emotional lability, delusions, and insomnia characteristic of mania, and the disorientation and altered consciousness characteristic of delirium.
Such patients can be considered as having a component of bipolar I disorder, comprising mania with psychotic features. Delirious mania is associated with higher rates of morbidity and mortality, and demonstrates limited response to conventional treatment guidelines. Therefore, early detection and decisive treatment are imperative. The concurrence of delirium and mania is not unusual, yet currently there are no universal accepted treatment guidelines for delirious mania (BMC Psychiatry. 2012 Jun 21. doi: 10.1186/1471-244X-12-65). The purpose of this case report is to inspire and support community psychiatric clinicians in managing such complex cases and to improve behavioral health care outcomes. To protect our patient’s identity, we changed several key identifiers.
The treatment plan emerges
This case is of a middle-aged man with an established diagnosis of bipolar disorder. He was referred to the ED because of worsening manic symptoms marked by mood lability, pressured speech, grandiose delusions, tangential thought processes, poor insight, and impaired sleep.
Laboratory studies in the ED revealed hyponatremia and serum sodium of 126meq/l (ref. range: 135-146). The patient’s toxicology screen was positive for benzodiazepines. He was stabilized on the medical floor and then transitioned to inpatient psychiatry.
Before his admission to psychiatry, the patient’s medications were alprazolam 1 mg at bed time, bupropion 100 mg twice daily, loxapine 25 mg morning and 50 mg at bed time, olanzapine 20 mg at bedtime and 5 mg twice daily, risperidone 2 mg twice daily and oxcarbazepine 900 mg twice daily.
The bupropion was discontinued because of manic behavior, and the patient’s dose of oxcarbazepine was lowered from 900 mg twice daily to 450 mg twice daily because of hyponatremia. Our team continued to administer risperidone, olanzapine, loxapine, and alprazolam to the patient. However, he was agitated and disorganized on the psychiatry floor. In addition, we noticed that the patient exhibited confusion, disorientation, an inability to connect with reality, and periods of profound agitation.
The patient was frequently restrained physically, and medications were administered to him for safety and containment. The use of benzodiazepines and anticholinergics was minimized. However, we noticed that the patient acted paranoid, disinhibited, and combative, and he became difficult to restrain. He seemed to have a high pain tolerance, responded to internal stimuli, and began hallucinating and displaying aggressive behavior toward staff persons.
It became apparent that the patient’s circadian rhythm had been altered. He slept for only a couple of hours during the day. During the course of treatment, in one incidence, the patient became agitated and charged at a nurse. Subsequently, the patient hit his head on a wall and fell – suffering a head strike and lacerations.
The team conducted investigations, including labs and neuroimaging, to make sure that the patient was OK. His CT head scan proved unremarkable. Liver function tests revealed mild transaminitis. His TSH, folate, B12, and B1 levels were normal.
We then placed the patient in a single room with continuous behavior monitoring. His recovery seemed to take a long time with trials of different antipsychotic medications, including olanzapine, loxapine, risperidone, and paliperidone. Because of his poor response to medications, the team considered using electroconvulsive therapy (ECT).
However, the patient was unable to give informed consent for ECT because of his impaired mental status. At this point, our team submitted a substitute treatment plan that included ECT to the court for approval, and the court approved our plan.
After receiving approximately four bilateral ECT procedures three times a week, the patient’s condition started to improve gradually. He received total of 11 procedures.
Our patient became alert to time, place, and person, and his circadian rhythm normalized. Soon, his delirium cleared, and he demonstrated marked improvement in both insight into his illness and behavioral control. His grandiose delusions were still present, but he was easily redirectable. In addition, our patient demonstrated improved reality testing. He was able to be discharged home following medication adjustments and with community supports within a few short weeks of receiving ECT.
As Bo-Shyan Lee, MD, and associates reported (BMC Psychiatry. 2012 Jun 21;12:65. doi: 10.1186/1471-244X-12-65), delirious mania is closely related to catatonia. Although there are different definitions for delirium and catatonia, even the most lethal form of catatonia meets the criteria for delirium. ECT is a well established first-line treatment for catatonia. This tool has been shown to be highly effective in the treatment of delirious mania. Delirious mania can be life-threatening and should be managed aggressively. The most common causes of death are heart failure from arrhythmias, cardiac arrest, and respiratory failure. ECT is a safe treatment, and, as Dr. Fink argued, the mortality rate is even less than that associated with normal pregnancies (World J Biol Psychiatry. 2001 Jan;2[1]:1-8). In light of the safety and effectiveness of ECT, we think the tool should be considered not only in university hospital settings but as an early intervention in community settings. This case warrants further research in exploring hyperactive delirium and delirious mania.
Dr. Lamba is BR-2 unit medical director at BayRidge Hospital in Lynn, Mass. Ms. Kennedy is an attending clinician at BayRidge. Dr. Vu is medical director at BayRidge. He also serves as associate chief of psychiatry at Beverly (Mass.) Hospital and at Addison Gilbert Hospital in Gloucester, Mass. Dr. Lamba, Ms. Kennedy, and Dr. Vu have no disclosures.
Delirious mania is a diagnostic term used in variety of settings, including the emergency department and inpatient psychiatry, but it does not have formal criteria established in the DSM-5. Delirious mania was first described in the 1800s and was referred to as “Bell’s Mania.”
As the late Max Fink, MD, wrote in the journal Bipolar Disorders (2002 Feb 23. doi: 10.1034/j.1399-561.1999.10112.x), delirious mania is considered to be a syndrome of the acute onset of the excitement, grandiosity, emotional lability, delusions, and insomnia characteristic of mania, and the disorientation and altered consciousness characteristic of delirium.
Such patients can be considered as having a component of bipolar I disorder, comprising mania with psychotic features. Delirious mania is associated with higher rates of morbidity and mortality, and demonstrates limited response to conventional treatment guidelines. Therefore, early detection and decisive treatment are imperative. The concurrence of delirium and mania is not unusual, yet currently there are no universal accepted treatment guidelines for delirious mania (BMC Psychiatry. 2012 Jun 21. doi: 10.1186/1471-244X-12-65). The purpose of this case report is to inspire and support community psychiatric clinicians in managing such complex cases and to improve behavioral health care outcomes. To protect our patient’s identity, we changed several key identifiers.
The treatment plan emerges
This case is of a middle-aged man with an established diagnosis of bipolar disorder. He was referred to the ED because of worsening manic symptoms marked by mood lability, pressured speech, grandiose delusions, tangential thought processes, poor insight, and impaired sleep.
Laboratory studies in the ED revealed hyponatremia and serum sodium of 126meq/l (ref. range: 135-146). The patient’s toxicology screen was positive for benzodiazepines. He was stabilized on the medical floor and then transitioned to inpatient psychiatry.
Before his admission to psychiatry, the patient’s medications were alprazolam 1 mg at bed time, bupropion 100 mg twice daily, loxapine 25 mg morning and 50 mg at bed time, olanzapine 20 mg at bedtime and 5 mg twice daily, risperidone 2 mg twice daily and oxcarbazepine 900 mg twice daily.
The bupropion was discontinued because of manic behavior, and the patient’s dose of oxcarbazepine was lowered from 900 mg twice daily to 450 mg twice daily because of hyponatremia. Our team continued to administer risperidone, olanzapine, loxapine, and alprazolam to the patient. However, he was agitated and disorganized on the psychiatry floor. In addition, we noticed that the patient exhibited confusion, disorientation, an inability to connect with reality, and periods of profound agitation.
The patient was frequently restrained physically, and medications were administered to him for safety and containment. The use of benzodiazepines and anticholinergics was minimized. However, we noticed that the patient acted paranoid, disinhibited, and combative, and he became difficult to restrain. He seemed to have a high pain tolerance, responded to internal stimuli, and began hallucinating and displaying aggressive behavior toward staff persons.
It became apparent that the patient’s circadian rhythm had been altered. He slept for only a couple of hours during the day. During the course of treatment, in one incidence, the patient became agitated and charged at a nurse. Subsequently, the patient hit his head on a wall and fell – suffering a head strike and lacerations.
The team conducted investigations, including labs and neuroimaging, to make sure that the patient was OK. His CT head scan proved unremarkable. Liver function tests revealed mild transaminitis. His TSH, folate, B12, and B1 levels were normal.
We then placed the patient in a single room with continuous behavior monitoring. His recovery seemed to take a long time with trials of different antipsychotic medications, including olanzapine, loxapine, risperidone, and paliperidone. Because of his poor response to medications, the team considered using electroconvulsive therapy (ECT).
However, the patient was unable to give informed consent for ECT because of his impaired mental status. At this point, our team submitted a substitute treatment plan that included ECT to the court for approval, and the court approved our plan.
After receiving approximately four bilateral ECT procedures three times a week, the patient’s condition started to improve gradually. He received total of 11 procedures.
Our patient became alert to time, place, and person, and his circadian rhythm normalized. Soon, his delirium cleared, and he demonstrated marked improvement in both insight into his illness and behavioral control. His grandiose delusions were still present, but he was easily redirectable. In addition, our patient demonstrated improved reality testing. He was able to be discharged home following medication adjustments and with community supports within a few short weeks of receiving ECT.
As Bo-Shyan Lee, MD, and associates reported (BMC Psychiatry. 2012 Jun 21;12:65. doi: 10.1186/1471-244X-12-65), delirious mania is closely related to catatonia. Although there are different definitions for delirium and catatonia, even the most lethal form of catatonia meets the criteria for delirium. ECT is a well established first-line treatment for catatonia. This tool has been shown to be highly effective in the treatment of delirious mania. Delirious mania can be life-threatening and should be managed aggressively. The most common causes of death are heart failure from arrhythmias, cardiac arrest, and respiratory failure. ECT is a safe treatment, and, as Dr. Fink argued, the mortality rate is even less than that associated with normal pregnancies (World J Biol Psychiatry. 2001 Jan;2[1]:1-8). In light of the safety and effectiveness of ECT, we think the tool should be considered not only in university hospital settings but as an early intervention in community settings. This case warrants further research in exploring hyperactive delirium and delirious mania.
Dr. Lamba is BR-2 unit medical director at BayRidge Hospital in Lynn, Mass. Ms. Kennedy is an attending clinician at BayRidge. Dr. Vu is medical director at BayRidge. He also serves as associate chief of psychiatry at Beverly (Mass.) Hospital and at Addison Gilbert Hospital in Gloucester, Mass. Dr. Lamba, Ms. Kennedy, and Dr. Vu have no disclosures.
Is it bipolar disorder, or a complex form of PTSD?
CASE A long history of suicidality
Mr. X, age 26, who has a history of bipolar II disorder and multiple inpatient admissions, presents to a state hospital after a suicide attempt by gunshot. He reports that throughout his lifetime, he has had >20 suicide attempts, often by overdose.
Mr. X is admitted to the hospital under a temporary detention order. He is initially adherent and cooperative with his psychiatric evaluations.
HISTORY Chronic physical and emotional pain
Mr. X is single, unemployed, and lives with his mother and nephew. He was diagnosed with bipolar II disorder during adolescence and receives sertraline, 50 mg twice a day, and lamotrigine, 100 mg twice a day, to which he reports adherence. He also was taking clonazepam and zolpidem, dosages unknown.
His medical history is significant for severe childhood liver disease and inflammatory bowel disease. He dropped out of school during high school due to his multiple medical conditions, which resulted in a significantly diminished overall childhood experience, interrupted developmental trajectory, and chronic physical and emotional pain. He has never been employed and receives financial support through disability benefits. He spends his days on the internet or watching television. He reports daily cigarette and marijuana use and occasional alcohol use, but no other substance use. His mother helps manage his medical conditions and is his main support. His biological father was abusive towards his mother and absent for most of Mr. X’s life. Beyond his mother and therapist, Mr. X has minimal other interpersonal interactions, and reports feeling isolated, lonely, and frustrated.
EVALUATION Agitated and aggressive while hospitalized
Upon learning that he is being involuntarily committed, Mr. X becomes physically aggressive, makes verbal threats, and throws objects across his room. He is given diphenhydramine, 50 mg, haloperidol, 5 mg, and lorazepam, 2 mg, all of which are ordered on an as-needed basis. Mr. X is placed in an emergency restraint chair and put in seclusion. The episode resolves within an hour with reassurance and attention from the treatment team; the rapid escalation from and return to a calmer state is indicative of situational, stress-induced mood lability and impulsivity. Mr. X is counseled on maintaining safety and appropriate behavior, and is advised to ask for medication if he feels agitated or unable to control his behaviors. To maintain safe and appropriate behavior, he requires daily counseling and expectation management regarding his treatment timeline. No further aggressive incidents are noted throughout his hospitalization, and he requires only minimal use of the as-needed medications.
[polldaddy:10983392]
The authors’ observations
The least appropriate therapy for Mr. X would be exposure and response prevention, which allows patients to face their fears without the need to soothe or relieve related feelings with a compulsive act. It is designed to improve specific behavioral deficits most often associated with obsessive-compulsive disorder, a diagnosis inconsistent with Mr. X’s history and presentation. Trauma-focused CBT could facilitate healing from Mr. X’s childhood trauma/adverse childhood experiences, and DBT might help with his anger, maladaptive coping strategies, and chronic suicidality. Motivational interviewing might help with his substance use and his apparent lack of motivation for other forms of social engagement, including seeking employment.
Based on Mr. X’s history of trauma and chronic physical and emotional pain, the treatment team reevaluated him and reconsidered his original diagnosis.
Continue to: EVALUATION A closer look at the diagnosis...
EVALUATION A closer look at the diagnosis
After meeting with Mr. X, the treatment team begins to piece together a more robust picture of him. They review his childhood trauma involving his biological father, his chronic and limiting medical illnesses, and his restricted and somewhat regressive level of functioning. Further, they consider his >20 suicide attempts, numerous psychiatric hospitalizations, and mood and behavioral lability and reactivity. Based on its review, the treatment team concludes that a diagnosis of bipolar disorder II or major depressive disorder is not fully adequate to describe Mr. X’s clinical picture.
At no point during his hospitalization does Mr. X meet full criteria for a major depressive episode or display mania or hypomania. The treatment team considers posttraumatic stress disorder (PTSD) in the setting of chronic, repetitive trauma given Mr. X’s nightmares, dissociative behavior, anger, negative cognitions, and intrusive symptoms. However, not all his symptoms fall within the diagnostic criteria of PTSD. There are also elements of borderline personality disorder in Mr. X’s history, most notably his multiple suicide attempts, emotional lability, and disrupted interpersonal attachments. In this context, a diagnosis of complex PTSD (CPTSD) seems most appropriate in capturing the array of trauma-related symptoms with which he presents.
Complex PTSD
Since at least the early to mid-1990s, there has been recognition of a qualitatively distinct clinical picture that can emerge when an individual’s exposure to trauma or adversity is chronic or repetitive, causing not only familiar PTSD symptomatology but also alterations in self-perception, interpersonal functioning, and affective instability. Complex PTSD was first described by Judith Herman, MD, in 1992 as a distinct entity from PTSD.1 She theorized that PTSD derives primarily from singular traumatic events, while a distinct clinical syndrome might arise after prolonged, repeated trauma.1 A diagnosis of CPTSD might arise in situations with more chronicity than a classic single circumscribed traumatic event, such as being held in captivity, under the control of perpetrators for extended periods of time, imprisoned, or subject to prolonged sexual abuse. Herman’s description of CPTSD identifies 3 areas of psychopathology that extend beyond PTSD1:
- symptomatic refers to the complex, diffuse, and tenacious symptom presentation
- characterological focuses on the personality changes in terms of dissociation, ego-fragmentation, and identity complications
- vulnerability describes characteristic repeated harm with respect to self-mutilation or other self-injurious behaviors, and suicidality.
Taxometrics, official recognition, and controversy
Complex PTSD was proposed for inclusion in DSM-IV as “Disorders of Extreme Stress Not Otherwise Specified,” or DESNOS. Reportedly, it was interpreted as a severe presentation of PTSD, and therefore not included in the manual as a separate diagnosis.2 In contrast, ICD-10 included a CPTSD-like entity of “Enduring Personality Change After Catastrophic Event” (EPCACE). Although the existence of CPTSD as a categorically distinct diagnosis in the psychiatric mainstream has been debated and discussed for years, with many arguably unaware of its existence, clinicians and researchers specializing in trauma are well-versed in its clinical utility. As such, CPTSD was again discussed during the development of DSM-5. In an apparent attempt to balance this clinical utility with ongoing concerns about its validity as a diagnostically distinct syndrome, DSM-5 did not officially recognize CPTSD, but added several criteria to PTSD referencing changes in self-perception, affective instability, and dysphoria, as well as a dissociative subtype, effectively expanding the scope of a PTSD diagnosis to also include CPTSD symptoms when applicable. ICD-11 has taken a different direction, and officially recognizes CPTSD as a distinct diagnosis.
ICD-11 presents CPTSD as a “sibling” disorder, which it distinguishes from PTSD with high levels of dissociation, depression, and borderline personality disorder traits.3 Within this framework, the diagnosis of CPTSD requires that the PTSD criteria be met in addition to symptoms that fall into a “disturbances of self-organization” category. When parsing the symptoms of the “disturbances of self-organization” category, the overlap with borderline personality disorder symptoms is apparent.4 This overlap has given rise to yet another controversy regarding CPTSD’s categorical validity; in addition to its distinctness from PTSD, its distinctness from borderline personality disorder has also been debated. In a study examining the similarity between CPTSD and borderline personality disorder, Jowett et al5 concluded that CPTSD was associated with greater exposure to multiple traumas earlier in life and resulted in higher functional impairment than borderline personality disorder, ultimately supporting CPTSD as a separate entity with features that overlap borderline personality disorder.5 According to Ford and Courtois6 “the evidence ... suggests that a sub-group of BPD patients—who often but not always have comorbid PTSD—may be best understood and treated if CPTSD is explicitly addressed as well—and in some cases, in lieu of—BPD.”
PTSD and CPTSD may therefore both be understood to fall within a spectrum of trauma diagnoses; this paradigm postulates that there exists a wide variety of posttraumatic patient presentations, perhaps on a continuum. On the less severe side of the trauma spectrum, the symptoms traditionally seen and characterized as PTSD (such as hypervigilance, nightmares, and flashbacks) may be found, while, with increasingly severe or prolonged trauma, there may be a tendency to see more complex elements (such as dissociation, personality changes mimicking borderline personality disorder, depression, anxiety, self-injurious behavior, and suicidality).7 Nevertheless, controversy about discriminant validity still exists. A review article by Resnick et al8 argued that the existing evidence is not strong enough to support CPTSD as a standalone entity. However, Resnick et al8 agreed that a singular PTSD diagnosis has limitations, and that there is a need for more research in the field of trauma psychiatry.
Continue to: Utility of the diagnostic conceptualization...
Utility of the diagnostic conceptualization
Although the controversy surrounding the distinction of CPTSD demands categorical clarity with respect to PTSD and borderline personality disorder as a means of resolution, the diagnosis has practical applications that should not limit its use in clinical formulation or treatment planning. Comorbid diagnoses do not prevent clinicians from diagnosing and treating patients who present with complicated manifestations of trauma.9 In fact, having overlapping diagnoses would highlight the array of patient presentations that can be seen in the posttraumatic condition. Furthermore, in the pursuit of individualized care approaches, the addition of CPTSD as a diagnostic conception would allow for more integrated treatment options using a multi-modular approach.10
The addition of CPTSD as a diagnosis is helpful in determining the etiology of a patient’s presentation and therefore formulating the most appropriate treatment plan. While the 2-pronged approach of psychopharmacology and therapy is the central dogma of psychiatric care, there are many specific options to consider for each. By viewing such patients through the lens of trauma as opposed to depression and anxiety, there is a clear shift in treatment that has the potential to make more lasting impacts and progress.11
CPTSD may coexist with PTSD, but it extends beyond it to include a pleomorphic symptom picture encompassing personality changes and a high risk for repeated harm. Failure to correctly classify a patient’s presentation as a response to repetitive, prolonged trauma may result in discrimination and inappropriate or ineffective treatment recommendations.
For a comparison of the diagnostic criteria of PTSD, CPTSD, and borderline personality disorder, see Table 112, Table 2,13,14, and Table 312.
Patients with CPTSD
One of the authors (NR) has cared for several similar individuals presenting for treatment with vague diagnoses of “chronic depression and anxiety” for years, sometimes with a speculative bipolar disorder diagnosis due to situational mood swings or reactivity, and a generally poor response to both medications and psychotherapy. These patients were frustrated because none of the diagnoses seemed to fully “fit” with their pattern of symptoms or subjective experience, and treatment seemed minimally helpful. Very often, their social history revealed a variety of adversities or traumatic events, such as childhood sexual or physical abuse, a home environment plagued by domestic violence, or being raised by one or both parents with their own history of trauma, or perhaps a personality or substance use disorder. Although many of these patients’ symptom profiles aligned only partially with “typical” PTSD, they were often better captured by CPTSD, with a focus on negative self-perception and impact on close relationships. Helping the patient “connect the dots” to create a more continuous narrative, and consequently reconceptualizing the diagnosis as a complex trauma disorder, has proven effective in a number of these cases, allowing the patient to make sense of their symptoms in the context of their personal history, reducing stigma, and allowing for different avenues with medication, therapy, and self-understanding. It can also help to validate the impact of a patient’s adverse experiences and encourage a patient to view their symptoms as an understandable or even once-adaptive response to traumatic stress, rather than a sign of personal weakness or defectiveness.
TREATMENT A trauma-focused approach
Once the treatment team considersMr. X’s significant childhood trauma and reconceptualizes his behaviors through this lens, treatment is adjusted accordingly. His significant reactivity, dissociative symptoms, social impairment, and repeated suicide attempts are better understood and have more significance through a trauma lens, which provides a better explanation than a primary mood disorder.
Therapeutic interventions in the hospital are tailored according to the treatment team’s new insight. Specific DBT skills are practiced, insight-oriented therapy and motivational interviewing are used, and Mr. X and his therapist begin to explore his trauma, both from his biological father and from his intense stressors experienced because of his medical issues.
Mr. X’s mother, who is very involved in his care, is provided with education on this conceptualization and given instruction on trauma-focused therapies in the outpatient setting. While Mr. X’s medication regimen is not changed significantly, for some patients, the reformulation from a primary mood or anxiety disorder to a trauma disorder might require a change in the pharmacotherapy regimen to address behavioral symptoms such as mood reactivity or issues with sleep.
OUTCOME Decreased intensity of suicidal thoughts
By the time of discharge, Mr. X has maintained safety, with no further outbursts, and subjectively reports feeling more understood and validated. Although chronic suicidal ideation can take months or years of treatment to resolve, at the time of discharge Mr. X reports a decreased intensity of these thoughts, and no acute suicidal ideation, plan, or intent. His discharge planning emphasizes ongoing work specifically related to coping with symptoms of traumatic stress, and the involvement of his main social support in facilitating this work.
The authors’ observations
As a caveat, it may be in some cases that chronic negative affect, dysphoria, and self-perception are better understood as a comorbid depressive disorder rather than subsumed into a PTSD/ CPTSD diagnosis. Also, because situational mood instability and impulsivity are often interpreted as bipolar disorder, a history of hypomania and mania should be ruled out. In Mr. X’s case, the diagnostic reformulation did not significantly impact pharmacotherapy because the target symptoms of mood instability, irritability, anxiety, and depression remained, despite the change in diagnosis.
Although the DSM-5 PTSD criteria effectively incorporate many CPTSD elements, we argue that this inclusivity comes at the expense of appreciating CPTSD as a qualitatively distinct condition, and we prefer ICD-11’s recognition of CPTSD as a separate diagnosis that incorporates PTSD criteria but extends the definition to include negative self-concept, affect dysregulation, and interpersonal difficulties.
Related Resources
- US Department of Veterans Affairs. PTSD: National Center for PTSD. Published January 1, 2007. https://www.ptsd.va.gov/ professional/treat/essentials/complex_ptsd.asp
- Jowett S, Karatzias T, Shevlin M, et al. Differentiating symptom profiles of ICD-11 PTSD, complex PTSD, and borderline personality disorder: a latent class analysis in a multiply traumatized sample. Personality disorders: theory, research, and treatment. 2020;11(1):36.
Drug Brand Names
Clonazepam • Klonopin
Haloperidol • Haldol
Lamotrigine • Lamictal
Lorazepam • Ativan
Sertraline • Zoloft
Zolpidem • Ambien
Bottom Line
Consider a diagnosis of complex posttraumatic stress disorder (CPTSD) when providing care for patients with chronic depression and suicidality with a history of trauma or childhood adversity. This reformulation can allow clinicians to understand the contributing factors more holistically; align with the patient more effectively; appreciate past and present interpersonal, psychological, and psychosocial factors that may precipitate and perpetuate symptoms; and allow for treatment recommendations beyond those of mood and anxiety disorders.
1. Herman JL. Complex PTSD: a syndrome in survivors of prolonged and repeated trauma. J Trauma Stress. 1992;5(3):377-391.
2. Friedman MJ. Finalizing PTSD in DSM-5: getting here from there and where to go next. J Trauma Stress. 2013;26(5):548-556. doi: 10.1002/jts.21840 3. Hyland P, Shevlin M, Fyvie C, et al. Posttraumatic stress disorder and complex posttraumatic stress disorder in DSM-5 and ICD-11: clinical and behavioral correlates. J Trauma Stress. 2018; 31(12):174-180.
4. Brand B, Loewenstein R. Dissociative disorders: an overview of assessment, phenomenology and treatment. Psychiatric Times. Published 2010. Accessed October 4, 2021. https://www.researchgate.net/profile/Bethany-Brand/publication/231337464_Dissociative_Disorders_An_Overview_of_Assessment_Phenomonology_and_Treatment/links/09e415068c721ef9b5000000/Dissociative-Disorders-An-Overview-of-Assessment-Phenomonology-and-Treatment.pdf
5. Jowett S, Karatzias T, Shevlin M, et al. Differentiating symptom profiles of ICD-11 PTSD, complex PTSD, and borderline personality disorder: a latent class analysis in a multiply traumatized sample. Personality Disorders: theory, research, and treatment. 2020;11(1):36.
6. Ford JD, Courtois CA. Complex PTSD, affect dysregulation, and borderline personality disorder. Bord Personal Disord Emot Dysregul. 2014;1:9. doi.org/10.1186/2051-6673-1-9
7. van der Kolk BA. The trauma spectrum: the interaction of biological and social events in the genesis of the trauma response. J Trauma Stress. 1998;1(3):273-290.
8. Resnick PA, Bovin MJ, Calloway AL, et al. A critical evaluation of the complex PTSD literature: implications for DSM-5. J Trauma Stress. 2012;25(3);241-251.
9. Herman J. CPTSD is a distinct entity: comment on Resick et al. J Trauma Stress. 2012;25(3): 256-257.
10. Karatzias T, Cloitre M. Treating adults with complex posttraumatic stress disorder using a modular approach to treatment: rationale, evidence, and directions for future research. J Trauma Stress. 2019;32(6):870-876.
11. Perry S, Cooper AM, Michels R. The psychodynamic formulation: its purpose, structure, and clinical application. Am J Psych. 1987;144(5):543-550.
12. Diagnostic and statistical manual of mental disorders, 5th ed. American Psychiatric Association; 2013.
13. International Classification of Diseases, 11th revision. 2019; World Health Organization.
14. US Department of Veterans Affairs. PTSD: National Center for PTSD. Complex PTSD. Published January 1, 2007. Accessed October 4, 2021. https://www.ptsd.va.gov/professional/treat/essentials/complex_ptsd.asp
CASE A long history of suicidality
Mr. X, age 26, who has a history of bipolar II disorder and multiple inpatient admissions, presents to a state hospital after a suicide attempt by gunshot. He reports that throughout his lifetime, he has had >20 suicide attempts, often by overdose.
Mr. X is admitted to the hospital under a temporary detention order. He is initially adherent and cooperative with his psychiatric evaluations.
HISTORY Chronic physical and emotional pain
Mr. X is single, unemployed, and lives with his mother and nephew. He was diagnosed with bipolar II disorder during adolescence and receives sertraline, 50 mg twice a day, and lamotrigine, 100 mg twice a day, to which he reports adherence. He also was taking clonazepam and zolpidem, dosages unknown.
His medical history is significant for severe childhood liver disease and inflammatory bowel disease. He dropped out of school during high school due to his multiple medical conditions, which resulted in a significantly diminished overall childhood experience, interrupted developmental trajectory, and chronic physical and emotional pain. He has never been employed and receives financial support through disability benefits. He spends his days on the internet or watching television. He reports daily cigarette and marijuana use and occasional alcohol use, but no other substance use. His mother helps manage his medical conditions and is his main support. His biological father was abusive towards his mother and absent for most of Mr. X’s life. Beyond his mother and therapist, Mr. X has minimal other interpersonal interactions, and reports feeling isolated, lonely, and frustrated.
EVALUATION Agitated and aggressive while hospitalized
Upon learning that he is being involuntarily committed, Mr. X becomes physically aggressive, makes verbal threats, and throws objects across his room. He is given diphenhydramine, 50 mg, haloperidol, 5 mg, and lorazepam, 2 mg, all of which are ordered on an as-needed basis. Mr. X is placed in an emergency restraint chair and put in seclusion. The episode resolves within an hour with reassurance and attention from the treatment team; the rapid escalation from and return to a calmer state is indicative of situational, stress-induced mood lability and impulsivity. Mr. X is counseled on maintaining safety and appropriate behavior, and is advised to ask for medication if he feels agitated or unable to control his behaviors. To maintain safe and appropriate behavior, he requires daily counseling and expectation management regarding his treatment timeline. No further aggressive incidents are noted throughout his hospitalization, and he requires only minimal use of the as-needed medications.
[polldaddy:10983392]
The authors’ observations
The least appropriate therapy for Mr. X would be exposure and response prevention, which allows patients to face their fears without the need to soothe or relieve related feelings with a compulsive act. It is designed to improve specific behavioral deficits most often associated with obsessive-compulsive disorder, a diagnosis inconsistent with Mr. X’s history and presentation. Trauma-focused CBT could facilitate healing from Mr. X’s childhood trauma/adverse childhood experiences, and DBT might help with his anger, maladaptive coping strategies, and chronic suicidality. Motivational interviewing might help with his substance use and his apparent lack of motivation for other forms of social engagement, including seeking employment.
Based on Mr. X’s history of trauma and chronic physical and emotional pain, the treatment team reevaluated him and reconsidered his original diagnosis.
Continue to: EVALUATION A closer look at the diagnosis...
EVALUATION A closer look at the diagnosis
After meeting with Mr. X, the treatment team begins to piece together a more robust picture of him. They review his childhood trauma involving his biological father, his chronic and limiting medical illnesses, and his restricted and somewhat regressive level of functioning. Further, they consider his >20 suicide attempts, numerous psychiatric hospitalizations, and mood and behavioral lability and reactivity. Based on its review, the treatment team concludes that a diagnosis of bipolar disorder II or major depressive disorder is not fully adequate to describe Mr. X’s clinical picture.
At no point during his hospitalization does Mr. X meet full criteria for a major depressive episode or display mania or hypomania. The treatment team considers posttraumatic stress disorder (PTSD) in the setting of chronic, repetitive trauma given Mr. X’s nightmares, dissociative behavior, anger, negative cognitions, and intrusive symptoms. However, not all his symptoms fall within the diagnostic criteria of PTSD. There are also elements of borderline personality disorder in Mr. X’s history, most notably his multiple suicide attempts, emotional lability, and disrupted interpersonal attachments. In this context, a diagnosis of complex PTSD (CPTSD) seems most appropriate in capturing the array of trauma-related symptoms with which he presents.
Complex PTSD
Since at least the early to mid-1990s, there has been recognition of a qualitatively distinct clinical picture that can emerge when an individual’s exposure to trauma or adversity is chronic or repetitive, causing not only familiar PTSD symptomatology but also alterations in self-perception, interpersonal functioning, and affective instability. Complex PTSD was first described by Judith Herman, MD, in 1992 as a distinct entity from PTSD.1 She theorized that PTSD derives primarily from singular traumatic events, while a distinct clinical syndrome might arise after prolonged, repeated trauma.1 A diagnosis of CPTSD might arise in situations with more chronicity than a classic single circumscribed traumatic event, such as being held in captivity, under the control of perpetrators for extended periods of time, imprisoned, or subject to prolonged sexual abuse. Herman’s description of CPTSD identifies 3 areas of psychopathology that extend beyond PTSD1:
- symptomatic refers to the complex, diffuse, and tenacious symptom presentation
- characterological focuses on the personality changes in terms of dissociation, ego-fragmentation, and identity complications
- vulnerability describes characteristic repeated harm with respect to self-mutilation or other self-injurious behaviors, and suicidality.
Taxometrics, official recognition, and controversy
Complex PTSD was proposed for inclusion in DSM-IV as “Disorders of Extreme Stress Not Otherwise Specified,” or DESNOS. Reportedly, it was interpreted as a severe presentation of PTSD, and therefore not included in the manual as a separate diagnosis.2 In contrast, ICD-10 included a CPTSD-like entity of “Enduring Personality Change After Catastrophic Event” (EPCACE). Although the existence of CPTSD as a categorically distinct diagnosis in the psychiatric mainstream has been debated and discussed for years, with many arguably unaware of its existence, clinicians and researchers specializing in trauma are well-versed in its clinical utility. As such, CPTSD was again discussed during the development of DSM-5. In an apparent attempt to balance this clinical utility with ongoing concerns about its validity as a diagnostically distinct syndrome, DSM-5 did not officially recognize CPTSD, but added several criteria to PTSD referencing changes in self-perception, affective instability, and dysphoria, as well as a dissociative subtype, effectively expanding the scope of a PTSD diagnosis to also include CPTSD symptoms when applicable. ICD-11 has taken a different direction, and officially recognizes CPTSD as a distinct diagnosis.
ICD-11 presents CPTSD as a “sibling” disorder, which it distinguishes from PTSD with high levels of dissociation, depression, and borderline personality disorder traits.3 Within this framework, the diagnosis of CPTSD requires that the PTSD criteria be met in addition to symptoms that fall into a “disturbances of self-organization” category. When parsing the symptoms of the “disturbances of self-organization” category, the overlap with borderline personality disorder symptoms is apparent.4 This overlap has given rise to yet another controversy regarding CPTSD’s categorical validity; in addition to its distinctness from PTSD, its distinctness from borderline personality disorder has also been debated. In a study examining the similarity between CPTSD and borderline personality disorder, Jowett et al5 concluded that CPTSD was associated with greater exposure to multiple traumas earlier in life and resulted in higher functional impairment than borderline personality disorder, ultimately supporting CPTSD as a separate entity with features that overlap borderline personality disorder.5 According to Ford and Courtois6 “the evidence ... suggests that a sub-group of BPD patients—who often but not always have comorbid PTSD—may be best understood and treated if CPTSD is explicitly addressed as well—and in some cases, in lieu of—BPD.”
PTSD and CPTSD may therefore both be understood to fall within a spectrum of trauma diagnoses; this paradigm postulates that there exists a wide variety of posttraumatic patient presentations, perhaps on a continuum. On the less severe side of the trauma spectrum, the symptoms traditionally seen and characterized as PTSD (such as hypervigilance, nightmares, and flashbacks) may be found, while, with increasingly severe or prolonged trauma, there may be a tendency to see more complex elements (such as dissociation, personality changes mimicking borderline personality disorder, depression, anxiety, self-injurious behavior, and suicidality).7 Nevertheless, controversy about discriminant validity still exists. A review article by Resnick et al8 argued that the existing evidence is not strong enough to support CPTSD as a standalone entity. However, Resnick et al8 agreed that a singular PTSD diagnosis has limitations, and that there is a need for more research in the field of trauma psychiatry.
Continue to: Utility of the diagnostic conceptualization...
Utility of the diagnostic conceptualization
Although the controversy surrounding the distinction of CPTSD demands categorical clarity with respect to PTSD and borderline personality disorder as a means of resolution, the diagnosis has practical applications that should not limit its use in clinical formulation or treatment planning. Comorbid diagnoses do not prevent clinicians from diagnosing and treating patients who present with complicated manifestations of trauma.9 In fact, having overlapping diagnoses would highlight the array of patient presentations that can be seen in the posttraumatic condition. Furthermore, in the pursuit of individualized care approaches, the addition of CPTSD as a diagnostic conception would allow for more integrated treatment options using a multi-modular approach.10
The addition of CPTSD as a diagnosis is helpful in determining the etiology of a patient’s presentation and therefore formulating the most appropriate treatment plan. While the 2-pronged approach of psychopharmacology and therapy is the central dogma of psychiatric care, there are many specific options to consider for each. By viewing such patients through the lens of trauma as opposed to depression and anxiety, there is a clear shift in treatment that has the potential to make more lasting impacts and progress.11
CPTSD may coexist with PTSD, but it extends beyond it to include a pleomorphic symptom picture encompassing personality changes and a high risk for repeated harm. Failure to correctly classify a patient’s presentation as a response to repetitive, prolonged trauma may result in discrimination and inappropriate or ineffective treatment recommendations.
For a comparison of the diagnostic criteria of PTSD, CPTSD, and borderline personality disorder, see Table 112, Table 2,13,14, and Table 312.
Patients with CPTSD
One of the authors (NR) has cared for several similar individuals presenting for treatment with vague diagnoses of “chronic depression and anxiety” for years, sometimes with a speculative bipolar disorder diagnosis due to situational mood swings or reactivity, and a generally poor response to both medications and psychotherapy. These patients were frustrated because none of the diagnoses seemed to fully “fit” with their pattern of symptoms or subjective experience, and treatment seemed minimally helpful. Very often, their social history revealed a variety of adversities or traumatic events, such as childhood sexual or physical abuse, a home environment plagued by domestic violence, or being raised by one or both parents with their own history of trauma, or perhaps a personality or substance use disorder. Although many of these patients’ symptom profiles aligned only partially with “typical” PTSD, they were often better captured by CPTSD, with a focus on negative self-perception and impact on close relationships. Helping the patient “connect the dots” to create a more continuous narrative, and consequently reconceptualizing the diagnosis as a complex trauma disorder, has proven effective in a number of these cases, allowing the patient to make sense of their symptoms in the context of their personal history, reducing stigma, and allowing for different avenues with medication, therapy, and self-understanding. It can also help to validate the impact of a patient’s adverse experiences and encourage a patient to view their symptoms as an understandable or even once-adaptive response to traumatic stress, rather than a sign of personal weakness or defectiveness.
TREATMENT A trauma-focused approach
Once the treatment team considersMr. X’s significant childhood trauma and reconceptualizes his behaviors through this lens, treatment is adjusted accordingly. His significant reactivity, dissociative symptoms, social impairment, and repeated suicide attempts are better understood and have more significance through a trauma lens, which provides a better explanation than a primary mood disorder.
Therapeutic interventions in the hospital are tailored according to the treatment team’s new insight. Specific DBT skills are practiced, insight-oriented therapy and motivational interviewing are used, and Mr. X and his therapist begin to explore his trauma, both from his biological father and from his intense stressors experienced because of his medical issues.
Mr. X’s mother, who is very involved in his care, is provided with education on this conceptualization and given instruction on trauma-focused therapies in the outpatient setting. While Mr. X’s medication regimen is not changed significantly, for some patients, the reformulation from a primary mood or anxiety disorder to a trauma disorder might require a change in the pharmacotherapy regimen to address behavioral symptoms such as mood reactivity or issues with sleep.
OUTCOME Decreased intensity of suicidal thoughts
By the time of discharge, Mr. X has maintained safety, with no further outbursts, and subjectively reports feeling more understood and validated. Although chronic suicidal ideation can take months or years of treatment to resolve, at the time of discharge Mr. X reports a decreased intensity of these thoughts, and no acute suicidal ideation, plan, or intent. His discharge planning emphasizes ongoing work specifically related to coping with symptoms of traumatic stress, and the involvement of his main social support in facilitating this work.
The authors’ observations
As a caveat, it may be in some cases that chronic negative affect, dysphoria, and self-perception are better understood as a comorbid depressive disorder rather than subsumed into a PTSD/ CPTSD diagnosis. Also, because situational mood instability and impulsivity are often interpreted as bipolar disorder, a history of hypomania and mania should be ruled out. In Mr. X’s case, the diagnostic reformulation did not significantly impact pharmacotherapy because the target symptoms of mood instability, irritability, anxiety, and depression remained, despite the change in diagnosis.
Although the DSM-5 PTSD criteria effectively incorporate many CPTSD elements, we argue that this inclusivity comes at the expense of appreciating CPTSD as a qualitatively distinct condition, and we prefer ICD-11’s recognition of CPTSD as a separate diagnosis that incorporates PTSD criteria but extends the definition to include negative self-concept, affect dysregulation, and interpersonal difficulties.
Related Resources
- US Department of Veterans Affairs. PTSD: National Center for PTSD. Published January 1, 2007. https://www.ptsd.va.gov/ professional/treat/essentials/complex_ptsd.asp
- Jowett S, Karatzias T, Shevlin M, et al. Differentiating symptom profiles of ICD-11 PTSD, complex PTSD, and borderline personality disorder: a latent class analysis in a multiply traumatized sample. Personality disorders: theory, research, and treatment. 2020;11(1):36.
Drug Brand Names
Clonazepam • Klonopin
Haloperidol • Haldol
Lamotrigine • Lamictal
Lorazepam • Ativan
Sertraline • Zoloft
Zolpidem • Ambien
Bottom Line
Consider a diagnosis of complex posttraumatic stress disorder (CPTSD) when providing care for patients with chronic depression and suicidality with a history of trauma or childhood adversity. This reformulation can allow clinicians to understand the contributing factors more holistically; align with the patient more effectively; appreciate past and present interpersonal, psychological, and psychosocial factors that may precipitate and perpetuate symptoms; and allow for treatment recommendations beyond those of mood and anxiety disorders.
CASE A long history of suicidality
Mr. X, age 26, who has a history of bipolar II disorder and multiple inpatient admissions, presents to a state hospital after a suicide attempt by gunshot. He reports that throughout his lifetime, he has had >20 suicide attempts, often by overdose.
Mr. X is admitted to the hospital under a temporary detention order. He is initially adherent and cooperative with his psychiatric evaluations.
HISTORY Chronic physical and emotional pain
Mr. X is single, unemployed, and lives with his mother and nephew. He was diagnosed with bipolar II disorder during adolescence and receives sertraline, 50 mg twice a day, and lamotrigine, 100 mg twice a day, to which he reports adherence. He also was taking clonazepam and zolpidem, dosages unknown.
His medical history is significant for severe childhood liver disease and inflammatory bowel disease. He dropped out of school during high school due to his multiple medical conditions, which resulted in a significantly diminished overall childhood experience, interrupted developmental trajectory, and chronic physical and emotional pain. He has never been employed and receives financial support through disability benefits. He spends his days on the internet or watching television. He reports daily cigarette and marijuana use and occasional alcohol use, but no other substance use. His mother helps manage his medical conditions and is his main support. His biological father was abusive towards his mother and absent for most of Mr. X’s life. Beyond his mother and therapist, Mr. X has minimal other interpersonal interactions, and reports feeling isolated, lonely, and frustrated.
EVALUATION Agitated and aggressive while hospitalized
Upon learning that he is being involuntarily committed, Mr. X becomes physically aggressive, makes verbal threats, and throws objects across his room. He is given diphenhydramine, 50 mg, haloperidol, 5 mg, and lorazepam, 2 mg, all of which are ordered on an as-needed basis. Mr. X is placed in an emergency restraint chair and put in seclusion. The episode resolves within an hour with reassurance and attention from the treatment team; the rapid escalation from and return to a calmer state is indicative of situational, stress-induced mood lability and impulsivity. Mr. X is counseled on maintaining safety and appropriate behavior, and is advised to ask for medication if he feels agitated or unable to control his behaviors. To maintain safe and appropriate behavior, he requires daily counseling and expectation management regarding his treatment timeline. No further aggressive incidents are noted throughout his hospitalization, and he requires only minimal use of the as-needed medications.
[polldaddy:10983392]
The authors’ observations
The least appropriate therapy for Mr. X would be exposure and response prevention, which allows patients to face their fears without the need to soothe or relieve related feelings with a compulsive act. It is designed to improve specific behavioral deficits most often associated with obsessive-compulsive disorder, a diagnosis inconsistent with Mr. X’s history and presentation. Trauma-focused CBT could facilitate healing from Mr. X’s childhood trauma/adverse childhood experiences, and DBT might help with his anger, maladaptive coping strategies, and chronic suicidality. Motivational interviewing might help with his substance use and his apparent lack of motivation for other forms of social engagement, including seeking employment.
Based on Mr. X’s history of trauma and chronic physical and emotional pain, the treatment team reevaluated him and reconsidered his original diagnosis.
Continue to: EVALUATION A closer look at the diagnosis...
EVALUATION A closer look at the diagnosis
After meeting with Mr. X, the treatment team begins to piece together a more robust picture of him. They review his childhood trauma involving his biological father, his chronic and limiting medical illnesses, and his restricted and somewhat regressive level of functioning. Further, they consider his >20 suicide attempts, numerous psychiatric hospitalizations, and mood and behavioral lability and reactivity. Based on its review, the treatment team concludes that a diagnosis of bipolar disorder II or major depressive disorder is not fully adequate to describe Mr. X’s clinical picture.
At no point during his hospitalization does Mr. X meet full criteria for a major depressive episode or display mania or hypomania. The treatment team considers posttraumatic stress disorder (PTSD) in the setting of chronic, repetitive trauma given Mr. X’s nightmares, dissociative behavior, anger, negative cognitions, and intrusive symptoms. However, not all his symptoms fall within the diagnostic criteria of PTSD. There are also elements of borderline personality disorder in Mr. X’s history, most notably his multiple suicide attempts, emotional lability, and disrupted interpersonal attachments. In this context, a diagnosis of complex PTSD (CPTSD) seems most appropriate in capturing the array of trauma-related symptoms with which he presents.
Complex PTSD
Since at least the early to mid-1990s, there has been recognition of a qualitatively distinct clinical picture that can emerge when an individual’s exposure to trauma or adversity is chronic or repetitive, causing not only familiar PTSD symptomatology but also alterations in self-perception, interpersonal functioning, and affective instability. Complex PTSD was first described by Judith Herman, MD, in 1992 as a distinct entity from PTSD.1 She theorized that PTSD derives primarily from singular traumatic events, while a distinct clinical syndrome might arise after prolonged, repeated trauma.1 A diagnosis of CPTSD might arise in situations with more chronicity than a classic single circumscribed traumatic event, such as being held in captivity, under the control of perpetrators for extended periods of time, imprisoned, or subject to prolonged sexual abuse. Herman’s description of CPTSD identifies 3 areas of psychopathology that extend beyond PTSD1:
- symptomatic refers to the complex, diffuse, and tenacious symptom presentation
- characterological focuses on the personality changes in terms of dissociation, ego-fragmentation, and identity complications
- vulnerability describes characteristic repeated harm with respect to self-mutilation or other self-injurious behaviors, and suicidality.
Taxometrics, official recognition, and controversy
Complex PTSD was proposed for inclusion in DSM-IV as “Disorders of Extreme Stress Not Otherwise Specified,” or DESNOS. Reportedly, it was interpreted as a severe presentation of PTSD, and therefore not included in the manual as a separate diagnosis.2 In contrast, ICD-10 included a CPTSD-like entity of “Enduring Personality Change After Catastrophic Event” (EPCACE). Although the existence of CPTSD as a categorically distinct diagnosis in the psychiatric mainstream has been debated and discussed for years, with many arguably unaware of its existence, clinicians and researchers specializing in trauma are well-versed in its clinical utility. As such, CPTSD was again discussed during the development of DSM-5. In an apparent attempt to balance this clinical utility with ongoing concerns about its validity as a diagnostically distinct syndrome, DSM-5 did not officially recognize CPTSD, but added several criteria to PTSD referencing changes in self-perception, affective instability, and dysphoria, as well as a dissociative subtype, effectively expanding the scope of a PTSD diagnosis to also include CPTSD symptoms when applicable. ICD-11 has taken a different direction, and officially recognizes CPTSD as a distinct diagnosis.
ICD-11 presents CPTSD as a “sibling” disorder, which it distinguishes from PTSD with high levels of dissociation, depression, and borderline personality disorder traits.3 Within this framework, the diagnosis of CPTSD requires that the PTSD criteria be met in addition to symptoms that fall into a “disturbances of self-organization” category. When parsing the symptoms of the “disturbances of self-organization” category, the overlap with borderline personality disorder symptoms is apparent.4 This overlap has given rise to yet another controversy regarding CPTSD’s categorical validity; in addition to its distinctness from PTSD, its distinctness from borderline personality disorder has also been debated. In a study examining the similarity between CPTSD and borderline personality disorder, Jowett et al5 concluded that CPTSD was associated with greater exposure to multiple traumas earlier in life and resulted in higher functional impairment than borderline personality disorder, ultimately supporting CPTSD as a separate entity with features that overlap borderline personality disorder.5 According to Ford and Courtois6 “the evidence ... suggests that a sub-group of BPD patients—who often but not always have comorbid PTSD—may be best understood and treated if CPTSD is explicitly addressed as well—and in some cases, in lieu of—BPD.”
PTSD and CPTSD may therefore both be understood to fall within a spectrum of trauma diagnoses; this paradigm postulates that there exists a wide variety of posttraumatic patient presentations, perhaps on a continuum. On the less severe side of the trauma spectrum, the symptoms traditionally seen and characterized as PTSD (such as hypervigilance, nightmares, and flashbacks) may be found, while, with increasingly severe or prolonged trauma, there may be a tendency to see more complex elements (such as dissociation, personality changes mimicking borderline personality disorder, depression, anxiety, self-injurious behavior, and suicidality).7 Nevertheless, controversy about discriminant validity still exists. A review article by Resnick et al8 argued that the existing evidence is not strong enough to support CPTSD as a standalone entity. However, Resnick et al8 agreed that a singular PTSD diagnosis has limitations, and that there is a need for more research in the field of trauma psychiatry.
Continue to: Utility of the diagnostic conceptualization...
Utility of the diagnostic conceptualization
Although the controversy surrounding the distinction of CPTSD demands categorical clarity with respect to PTSD and borderline personality disorder as a means of resolution, the diagnosis has practical applications that should not limit its use in clinical formulation or treatment planning. Comorbid diagnoses do not prevent clinicians from diagnosing and treating patients who present with complicated manifestations of trauma.9 In fact, having overlapping diagnoses would highlight the array of patient presentations that can be seen in the posttraumatic condition. Furthermore, in the pursuit of individualized care approaches, the addition of CPTSD as a diagnostic conception would allow for more integrated treatment options using a multi-modular approach.10
The addition of CPTSD as a diagnosis is helpful in determining the etiology of a patient’s presentation and therefore formulating the most appropriate treatment plan. While the 2-pronged approach of psychopharmacology and therapy is the central dogma of psychiatric care, there are many specific options to consider for each. By viewing such patients through the lens of trauma as opposed to depression and anxiety, there is a clear shift in treatment that has the potential to make more lasting impacts and progress.11
CPTSD may coexist with PTSD, but it extends beyond it to include a pleomorphic symptom picture encompassing personality changes and a high risk for repeated harm. Failure to correctly classify a patient’s presentation as a response to repetitive, prolonged trauma may result in discrimination and inappropriate or ineffective treatment recommendations.
For a comparison of the diagnostic criteria of PTSD, CPTSD, and borderline personality disorder, see Table 112, Table 2,13,14, and Table 312.
Patients with CPTSD
One of the authors (NR) has cared for several similar individuals presenting for treatment with vague diagnoses of “chronic depression and anxiety” for years, sometimes with a speculative bipolar disorder diagnosis due to situational mood swings or reactivity, and a generally poor response to both medications and psychotherapy. These patients were frustrated because none of the diagnoses seemed to fully “fit” with their pattern of symptoms or subjective experience, and treatment seemed minimally helpful. Very often, their social history revealed a variety of adversities or traumatic events, such as childhood sexual or physical abuse, a home environment plagued by domestic violence, or being raised by one or both parents with their own history of trauma, or perhaps a personality or substance use disorder. Although many of these patients’ symptom profiles aligned only partially with “typical” PTSD, they were often better captured by CPTSD, with a focus on negative self-perception and impact on close relationships. Helping the patient “connect the dots” to create a more continuous narrative, and consequently reconceptualizing the diagnosis as a complex trauma disorder, has proven effective in a number of these cases, allowing the patient to make sense of their symptoms in the context of their personal history, reducing stigma, and allowing for different avenues with medication, therapy, and self-understanding. It can also help to validate the impact of a patient’s adverse experiences and encourage a patient to view their symptoms as an understandable or even once-adaptive response to traumatic stress, rather than a sign of personal weakness or defectiveness.
TREATMENT A trauma-focused approach
Once the treatment team considersMr. X’s significant childhood trauma and reconceptualizes his behaviors through this lens, treatment is adjusted accordingly. His significant reactivity, dissociative symptoms, social impairment, and repeated suicide attempts are better understood and have more significance through a trauma lens, which provides a better explanation than a primary mood disorder.
Therapeutic interventions in the hospital are tailored according to the treatment team’s new insight. Specific DBT skills are practiced, insight-oriented therapy and motivational interviewing are used, and Mr. X and his therapist begin to explore his trauma, both from his biological father and from his intense stressors experienced because of his medical issues.
Mr. X’s mother, who is very involved in his care, is provided with education on this conceptualization and given instruction on trauma-focused therapies in the outpatient setting. While Mr. X’s medication regimen is not changed significantly, for some patients, the reformulation from a primary mood or anxiety disorder to a trauma disorder might require a change in the pharmacotherapy regimen to address behavioral symptoms such as mood reactivity or issues with sleep.
OUTCOME Decreased intensity of suicidal thoughts
By the time of discharge, Mr. X has maintained safety, with no further outbursts, and subjectively reports feeling more understood and validated. Although chronic suicidal ideation can take months or years of treatment to resolve, at the time of discharge Mr. X reports a decreased intensity of these thoughts, and no acute suicidal ideation, plan, or intent. His discharge planning emphasizes ongoing work specifically related to coping with symptoms of traumatic stress, and the involvement of his main social support in facilitating this work.
The authors’ observations
As a caveat, it may be in some cases that chronic negative affect, dysphoria, and self-perception are better understood as a comorbid depressive disorder rather than subsumed into a PTSD/ CPTSD diagnosis. Also, because situational mood instability and impulsivity are often interpreted as bipolar disorder, a history of hypomania and mania should be ruled out. In Mr. X’s case, the diagnostic reformulation did not significantly impact pharmacotherapy because the target symptoms of mood instability, irritability, anxiety, and depression remained, despite the change in diagnosis.
Although the DSM-5 PTSD criteria effectively incorporate many CPTSD elements, we argue that this inclusivity comes at the expense of appreciating CPTSD as a qualitatively distinct condition, and we prefer ICD-11’s recognition of CPTSD as a separate diagnosis that incorporates PTSD criteria but extends the definition to include negative self-concept, affect dysregulation, and interpersonal difficulties.
Related Resources
- US Department of Veterans Affairs. PTSD: National Center for PTSD. Published January 1, 2007. https://www.ptsd.va.gov/ professional/treat/essentials/complex_ptsd.asp
- Jowett S, Karatzias T, Shevlin M, et al. Differentiating symptom profiles of ICD-11 PTSD, complex PTSD, and borderline personality disorder: a latent class analysis in a multiply traumatized sample. Personality disorders: theory, research, and treatment. 2020;11(1):36.
Drug Brand Names
Clonazepam • Klonopin
Haloperidol • Haldol
Lamotrigine • Lamictal
Lorazepam • Ativan
Sertraline • Zoloft
Zolpidem • Ambien
Bottom Line
Consider a diagnosis of complex posttraumatic stress disorder (CPTSD) when providing care for patients with chronic depression and suicidality with a history of trauma or childhood adversity. This reformulation can allow clinicians to understand the contributing factors more holistically; align with the patient more effectively; appreciate past and present interpersonal, psychological, and psychosocial factors that may precipitate and perpetuate symptoms; and allow for treatment recommendations beyond those of mood and anxiety disorders.
1. Herman JL. Complex PTSD: a syndrome in survivors of prolonged and repeated trauma. J Trauma Stress. 1992;5(3):377-391.
2. Friedman MJ. Finalizing PTSD in DSM-5: getting here from there and where to go next. J Trauma Stress. 2013;26(5):548-556. doi: 10.1002/jts.21840 3. Hyland P, Shevlin M, Fyvie C, et al. Posttraumatic stress disorder and complex posttraumatic stress disorder in DSM-5 and ICD-11: clinical and behavioral correlates. J Trauma Stress. 2018; 31(12):174-180.
4. Brand B, Loewenstein R. Dissociative disorders: an overview of assessment, phenomenology and treatment. Psychiatric Times. Published 2010. Accessed October 4, 2021. https://www.researchgate.net/profile/Bethany-Brand/publication/231337464_Dissociative_Disorders_An_Overview_of_Assessment_Phenomonology_and_Treatment/links/09e415068c721ef9b5000000/Dissociative-Disorders-An-Overview-of-Assessment-Phenomonology-and-Treatment.pdf
5. Jowett S, Karatzias T, Shevlin M, et al. Differentiating symptom profiles of ICD-11 PTSD, complex PTSD, and borderline personality disorder: a latent class analysis in a multiply traumatized sample. Personality Disorders: theory, research, and treatment. 2020;11(1):36.
6. Ford JD, Courtois CA. Complex PTSD, affect dysregulation, and borderline personality disorder. Bord Personal Disord Emot Dysregul. 2014;1:9. doi.org/10.1186/2051-6673-1-9
7. van der Kolk BA. The trauma spectrum: the interaction of biological and social events in the genesis of the trauma response. J Trauma Stress. 1998;1(3):273-290.
8. Resnick PA, Bovin MJ, Calloway AL, et al. A critical evaluation of the complex PTSD literature: implications for DSM-5. J Trauma Stress. 2012;25(3);241-251.
9. Herman J. CPTSD is a distinct entity: comment on Resick et al. J Trauma Stress. 2012;25(3): 256-257.
10. Karatzias T, Cloitre M. Treating adults with complex posttraumatic stress disorder using a modular approach to treatment: rationale, evidence, and directions for future research. J Trauma Stress. 2019;32(6):870-876.
11. Perry S, Cooper AM, Michels R. The psychodynamic formulation: its purpose, structure, and clinical application. Am J Psych. 1987;144(5):543-550.
12. Diagnostic and statistical manual of mental disorders, 5th ed. American Psychiatric Association; 2013.
13. International Classification of Diseases, 11th revision. 2019; World Health Organization.
14. US Department of Veterans Affairs. PTSD: National Center for PTSD. Complex PTSD. Published January 1, 2007. Accessed October 4, 2021. https://www.ptsd.va.gov/professional/treat/essentials/complex_ptsd.asp
1. Herman JL. Complex PTSD: a syndrome in survivors of prolonged and repeated trauma. J Trauma Stress. 1992;5(3):377-391.
2. Friedman MJ. Finalizing PTSD in DSM-5: getting here from there and where to go next. J Trauma Stress. 2013;26(5):548-556. doi: 10.1002/jts.21840 3. Hyland P, Shevlin M, Fyvie C, et al. Posttraumatic stress disorder and complex posttraumatic stress disorder in DSM-5 and ICD-11: clinical and behavioral correlates. J Trauma Stress. 2018; 31(12):174-180.
4. Brand B, Loewenstein R. Dissociative disorders: an overview of assessment, phenomenology and treatment. Psychiatric Times. Published 2010. Accessed October 4, 2021. https://www.researchgate.net/profile/Bethany-Brand/publication/231337464_Dissociative_Disorders_An_Overview_of_Assessment_Phenomonology_and_Treatment/links/09e415068c721ef9b5000000/Dissociative-Disorders-An-Overview-of-Assessment-Phenomonology-and-Treatment.pdf
5. Jowett S, Karatzias T, Shevlin M, et al. Differentiating symptom profiles of ICD-11 PTSD, complex PTSD, and borderline personality disorder: a latent class analysis in a multiply traumatized sample. Personality Disorders: theory, research, and treatment. 2020;11(1):36.
6. Ford JD, Courtois CA. Complex PTSD, affect dysregulation, and borderline personality disorder. Bord Personal Disord Emot Dysregul. 2014;1:9. doi.org/10.1186/2051-6673-1-9
7. van der Kolk BA. The trauma spectrum: the interaction of biological and social events in the genesis of the trauma response. J Trauma Stress. 1998;1(3):273-290.
8. Resnick PA, Bovin MJ, Calloway AL, et al. A critical evaluation of the complex PTSD literature: implications for DSM-5. J Trauma Stress. 2012;25(3);241-251.
9. Herman J. CPTSD is a distinct entity: comment on Resick et al. J Trauma Stress. 2012;25(3): 256-257.
10. Karatzias T, Cloitre M. Treating adults with complex posttraumatic stress disorder using a modular approach to treatment: rationale, evidence, and directions for future research. J Trauma Stress. 2019;32(6):870-876.
11. Perry S, Cooper AM, Michels R. The psychodynamic formulation: its purpose, structure, and clinical application. Am J Psych. 1987;144(5):543-550.
12. Diagnostic and statistical manual of mental disorders, 5th ed. American Psychiatric Association; 2013.
13. International Classification of Diseases, 11th revision. 2019; World Health Organization.
14. US Department of Veterans Affairs. PTSD: National Center for PTSD. Complex PTSD. Published January 1, 2007. Accessed October 4, 2021. https://www.ptsd.va.gov/professional/treat/essentials/complex_ptsd.asp
COVID-19 mortality risk factors: An unexpected finding
Schizophrenia and severe mood and anxiety disorders are associated with a significantly lower risk of COVID-19 but are tied to a two- to fourfold increased risk of death from the virus, new research shows.
The study results held after the researchers controlled for other risk factors, and they contradict an earlier study that showed no increased mortality risk associated with mood or anxiety disorders. The findings come as the overall number of deaths in the United States approaches 800,000.
“These patients were less likely to be infected because they were probably less exposed, but once they have the infection, they are more prone to worse outcomes,” lead author Antonio L. Teixeira, MD, PhD, professor of psychiatry with McGovern Medical School at the University of Texas Health Science Center at Houston, said in an interview.
The study was published online Nov. 23 in JAMA Network Open.
Unexpected finding
Researchers analyzed electronic health records for 2.5 million adults with private health insurance who were tested for COVID-19 in 2020.
The overall positivity rate for the entire cohort was 11.91%, and patients with severe psychiatric illness fell below that rate. Positivity rates were 9.86% for people with schizophrenia or mood disorders and 11.17% among those with anxiety disorder.
Despite their lower positivity rate, patients with schizophrenia had the highest odds of death from COVID-19 after adjustment for age, race, body mass index, and comorbidities (aOR, 3.74; 95% confidence interval, 2.66-5.24).
Those results were not very surprising, Dr. Teixeira said, as earlier studies have reported similar findings. However,
Patients with mood disorders were nearly three times as likely to die (aOR, 2.76; 95% CI, 2.00-3.81), and those with anxiety disorders had more than double the mortality risk (aOR, 2.34; 95% CI, 1.68-3.27).
“We were expecting some increase, but there was strong evidence in those populations as well,” he said. “We were especially surprised at the data on patients with anxiety disorders.”
An outstanding question
These findings contradict a study published Jan. 27, 2021, in JAMA Psychiatry, that showed no significant increase in mortality risk among those with mood or anxiety disorders.
Study methodology and timing might explain some of the differences, Katlyn Nemani, MD, a research assistant professor of psychiatry at New York University, who led that earlier study, said in an interview.
Dr. Nemani’s study had a smaller study sample, examined mortality over a 30-day period after a positive COVID-19 test, and was limited to the peak of the pandemic in New York, between March and May 2020. Dr. Teixeira’s team examined a full year of data and assessed mortality for 7 days following a positive test.
“It is possible patients with some psychiatric disorders were less likely to receive or successfully respond to treatment for severe COVD-19 which evolved during the course of the pandemic,” Dr. Nemani said, adding that it’s also possible that differences in mortality in the days following infection became attenuated over time.
While a meta-analysis published in July and reported by this news organization at that time did show higher COVID-19 mortality among patients with mood disorders, the risk was far lower than that reported in this new study. That report, which included 33 studies in 22 countries, also found no increase in risk among those with anxiety disorder.
In October, the Centers for Disease Control and Prevention added mood disorders to the list of medical conditions that increase the risk for more severe COVID-19. Schizophrenia was already on that list.
“The outstanding question is what underlies this increased risk,” Dr. Nemani said. “Future studies focused on immune-mediated mechanisms and other potential explanations will help guide targeted interventions to reduce morbidity and mortality in this vulnerable population.”
Funding for the study was not disclosed. Dr. Teixeira and Dr. Nemani report no conflicts of interest.
A version of this article first appeared on Medscape.com.
Schizophrenia and severe mood and anxiety disorders are associated with a significantly lower risk of COVID-19 but are tied to a two- to fourfold increased risk of death from the virus, new research shows.
The study results held after the researchers controlled for other risk factors, and they contradict an earlier study that showed no increased mortality risk associated with mood or anxiety disorders. The findings come as the overall number of deaths in the United States approaches 800,000.
“These patients were less likely to be infected because they were probably less exposed, but once they have the infection, they are more prone to worse outcomes,” lead author Antonio L. Teixeira, MD, PhD, professor of psychiatry with McGovern Medical School at the University of Texas Health Science Center at Houston, said in an interview.
The study was published online Nov. 23 in JAMA Network Open.
Unexpected finding
Researchers analyzed electronic health records for 2.5 million adults with private health insurance who were tested for COVID-19 in 2020.
The overall positivity rate for the entire cohort was 11.91%, and patients with severe psychiatric illness fell below that rate. Positivity rates were 9.86% for people with schizophrenia or mood disorders and 11.17% among those with anxiety disorder.
Despite their lower positivity rate, patients with schizophrenia had the highest odds of death from COVID-19 after adjustment for age, race, body mass index, and comorbidities (aOR, 3.74; 95% confidence interval, 2.66-5.24).
Those results were not very surprising, Dr. Teixeira said, as earlier studies have reported similar findings. However,
Patients with mood disorders were nearly three times as likely to die (aOR, 2.76; 95% CI, 2.00-3.81), and those with anxiety disorders had more than double the mortality risk (aOR, 2.34; 95% CI, 1.68-3.27).
“We were expecting some increase, but there was strong evidence in those populations as well,” he said. “We were especially surprised at the data on patients with anxiety disorders.”
An outstanding question
These findings contradict a study published Jan. 27, 2021, in JAMA Psychiatry, that showed no significant increase in mortality risk among those with mood or anxiety disorders.
Study methodology and timing might explain some of the differences, Katlyn Nemani, MD, a research assistant professor of psychiatry at New York University, who led that earlier study, said in an interview.
Dr. Nemani’s study had a smaller study sample, examined mortality over a 30-day period after a positive COVID-19 test, and was limited to the peak of the pandemic in New York, between March and May 2020. Dr. Teixeira’s team examined a full year of data and assessed mortality for 7 days following a positive test.
“It is possible patients with some psychiatric disorders were less likely to receive or successfully respond to treatment for severe COVD-19 which evolved during the course of the pandemic,” Dr. Nemani said, adding that it’s also possible that differences in mortality in the days following infection became attenuated over time.
While a meta-analysis published in July and reported by this news organization at that time did show higher COVID-19 mortality among patients with mood disorders, the risk was far lower than that reported in this new study. That report, which included 33 studies in 22 countries, also found no increase in risk among those with anxiety disorder.
In October, the Centers for Disease Control and Prevention added mood disorders to the list of medical conditions that increase the risk for more severe COVID-19. Schizophrenia was already on that list.
“The outstanding question is what underlies this increased risk,” Dr. Nemani said. “Future studies focused on immune-mediated mechanisms and other potential explanations will help guide targeted interventions to reduce morbidity and mortality in this vulnerable population.”
Funding for the study was not disclosed. Dr. Teixeira and Dr. Nemani report no conflicts of interest.
A version of this article first appeared on Medscape.com.
Schizophrenia and severe mood and anxiety disorders are associated with a significantly lower risk of COVID-19 but are tied to a two- to fourfold increased risk of death from the virus, new research shows.
The study results held after the researchers controlled for other risk factors, and they contradict an earlier study that showed no increased mortality risk associated with mood or anxiety disorders. The findings come as the overall number of deaths in the United States approaches 800,000.
“These patients were less likely to be infected because they were probably less exposed, but once they have the infection, they are more prone to worse outcomes,” lead author Antonio L. Teixeira, MD, PhD, professor of psychiatry with McGovern Medical School at the University of Texas Health Science Center at Houston, said in an interview.
The study was published online Nov. 23 in JAMA Network Open.
Unexpected finding
Researchers analyzed electronic health records for 2.5 million adults with private health insurance who were tested for COVID-19 in 2020.
The overall positivity rate for the entire cohort was 11.91%, and patients with severe psychiatric illness fell below that rate. Positivity rates were 9.86% for people with schizophrenia or mood disorders and 11.17% among those with anxiety disorder.
Despite their lower positivity rate, patients with schizophrenia had the highest odds of death from COVID-19 after adjustment for age, race, body mass index, and comorbidities (aOR, 3.74; 95% confidence interval, 2.66-5.24).
Those results were not very surprising, Dr. Teixeira said, as earlier studies have reported similar findings. However,
Patients with mood disorders were nearly three times as likely to die (aOR, 2.76; 95% CI, 2.00-3.81), and those with anxiety disorders had more than double the mortality risk (aOR, 2.34; 95% CI, 1.68-3.27).
“We were expecting some increase, but there was strong evidence in those populations as well,” he said. “We were especially surprised at the data on patients with anxiety disorders.”
An outstanding question
These findings contradict a study published Jan. 27, 2021, in JAMA Psychiatry, that showed no significant increase in mortality risk among those with mood or anxiety disorders.
Study methodology and timing might explain some of the differences, Katlyn Nemani, MD, a research assistant professor of psychiatry at New York University, who led that earlier study, said in an interview.
Dr. Nemani’s study had a smaller study sample, examined mortality over a 30-day period after a positive COVID-19 test, and was limited to the peak of the pandemic in New York, between March and May 2020. Dr. Teixeira’s team examined a full year of data and assessed mortality for 7 days following a positive test.
“It is possible patients with some psychiatric disorders were less likely to receive or successfully respond to treatment for severe COVD-19 which evolved during the course of the pandemic,” Dr. Nemani said, adding that it’s also possible that differences in mortality in the days following infection became attenuated over time.
While a meta-analysis published in July and reported by this news organization at that time did show higher COVID-19 mortality among patients with mood disorders, the risk was far lower than that reported in this new study. That report, which included 33 studies in 22 countries, also found no increase in risk among those with anxiety disorder.
In October, the Centers for Disease Control and Prevention added mood disorders to the list of medical conditions that increase the risk for more severe COVID-19. Schizophrenia was already on that list.
“The outstanding question is what underlies this increased risk,” Dr. Nemani said. “Future studies focused on immune-mediated mechanisms and other potential explanations will help guide targeted interventions to reduce morbidity and mortality in this vulnerable population.”
Funding for the study was not disclosed. Dr. Teixeira and Dr. Nemani report no conflicts of interest.
A version of this article first appeared on Medscape.com.
FROM JAMA NETWORK OPEN