Schizophrenia & Other Psychotic Disorders

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

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

CASE 1

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

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

CASE 2

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

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

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

Continue to: Approaching care with a relational ethics framework

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

Risks/benefits of breastfeeding by patients who have SMI

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

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

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

CP02212e16_t1.png

Limitations on breastfeeding on an inpatient unit

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

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

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

A framework to approaching the relational ethics decisions

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

CP02212e16_f1.png

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

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

Impact of involvement of Child Protective Services

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

CP02212e16_f2.png

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

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

Bottom Line

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

Related Resources

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

Drug Brand Names

Aripiprazole • Abilify
Olanzapine • Zyprexa
Risperidone • Risperdal

[embed:render:related:node:240620]

[embed:render:related:node:262580]

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

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

CASE 1

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

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

CASE 2

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

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

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

Continue to: Approaching care with a relational ethics framework

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

Risks/benefits of breastfeeding by patients who have SMI

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

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

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

CP02212e16_t1.png

Limitations on breastfeeding on an inpatient unit

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

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

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

A framework to approaching the relational ethics decisions

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

CP02212e16_f1.png

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

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

Impact of involvement of Child Protective Services

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

CP02212e16_f2.png

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

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

Bottom Line

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

Related Resources

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

Drug Brand Names

Aripiprazole • Abilify
Olanzapine • Zyprexa
Risperidone • Risperdal

[embed:render:related:node:240620]

[embed:render:related:node:262580]

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

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

CASE 1

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

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

CASE 2

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

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

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

Continue to: Approaching care with a relational ethics framework

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

Risks/benefits of breastfeeding by patients who have SMI

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

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

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

CP02212e16_t1.png

Limitations on breastfeeding on an inpatient unit

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

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

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

A framework to approaching the relational ethics decisions

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

CP02212e16_f1.png

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

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

Impact of involvement of Child Protective Services

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

CP02212e16_f2.png

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

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

Bottom Line

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

Related Resources

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

Drug Brand Names

Aripiprazole • Abilify
Olanzapine • Zyprexa
Risperidone • Risperdal

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Our psychiatric research, which found a high incidence of undiagnosed mental illness in mass shooters, was recently awarded the esteemed Psychodynamic Psychiatry Journal Prize for best paper published in the last 2 years (2022-2023). The editors noted our integrity in using quantitative data to argue against the common, careless assumption that mass shooters are not mentally ill.

Some of the mass shooters we studied were motivated by religious or political ideologies that were considered forms of terrorism. Given the current tragically violent landscape both at home and in Israel/Palestine, the “desire for destruction” is vital to understand.

Although there have been a limited number of psychiatric studies of perpetrators of mass shootings, our team took the first step to lay the groundwork by conducting a systematic, quantitative study. Our psychiatric research team’s research findings were published in the Journal of Clinical Psychopharmacology and then in greater detail in Psychodynamic Psychiatry,^1,2 which provided important context to the complicated backgrounds of these mass shooters who suffer from abuse, marginalization, and severe undiagnosed brain illness.³

Cerfolio_Nina_E_NY_web.jpg

The Mother Jones database of 115 mass shootings from 1982 to 2019 was used to study retrospectively 55 shooters in the United States. We developed a uniform, comprehensive, 62-item questionnaire to compile the data collection from multiple sources and record our psychiatric assessments of the assailants, using DSM-5 criteria. After developing this detailed psychiatric assessment questionnaire, psychiatric researchers evaluated the weight and quality of clinical evidence by (1) interviewing forensic psychiatrists who had assessed the assailant following the crime, and/or (2) reviewing court records of psychiatric evaluations conducted during the postcrime judicial proceedings to determine the prevalence of psychiatric illness. Rather than accepting diagnoses from forensic psychiatrists and/or court records, our team independently reviewed the clinical data gathered from multiple sources to apply the DSM-5 criteria to diagnose mental illness.

In most incidents in the database, the perpetrator died either during or shortly after the crime. We examined every case (n=35) in which the assailant survived, and criminal proceedings were instituted.

Of the 35 cases in which the assailant survived and criminal proceedings were instituted, there was insufficient information to make a diagnosis in 3 cases. Of the remaining 32 cases in which we had sufficient information, we determined that 87.5% had the following psychiatric diagnosis: 18 assailants (56%) had schizophrenia, while 10 assailants (31%) had other psychiatric diagnoses: 3 had bipolar I disorder, 2 had delusional disorders (persecutory), 2 had personality disorders (1 paranoid, 1 borderline), 2 had substance-related disorders without other psychiatric diagnosis, and 1 had post-traumatic stress disorder (PTSD).

Out of the 32 surviving assailants for whom we have sufficient evidence, 87.5% of perpetrators of mass shootings were diagnosed with major psychiatric illness, and none were treated appropriately with medication at the time of the crime. Four assailants (12.5%) had no psychiatric diagnosis that we could discern. Of the 18 surviving assailants with schizophrenia, no assailant was on antipsychotic medication for the treatment of schizophrenia prior to the crime. Of the 10 surviving assailants with other psychiatric illnesses, no assailant was on antipsychotic and/or appropriate medication.

In addition, we found that the clinical misdiagnosis of early-onset schizophrenia was associated with the worsening of many of these assailants’ psychotic symptoms. Many of our adolescent shooters prior to the massacre had been misdiagnosed with attention-deficit disorder (ADD), major depression disorder (MDD), or autism spectrum disorder.

Though the vast majority of those suffering from psychiatric illnesses who are appropriately treated are not violent, there is a growing body of scientific research that indicates a strong association of untreated brain illness with those who commit mass shootings.^4,5,6 This research demonstrates that such untreated illness combined with access to firearms poses a lethal threat to society.

Glick_Ira_D_CALIF_web.jpg

Most of the assailants also experienced profound estrangement, not only from families and friends, but most importantly from themselves. Being marginalized rendered them more vulnerable to their untreated psychiatric illness and to radicalization online, which fostered their violence. While there are complex reasons that a person is not diagnosed, there remains a vital need to decrease the stigma of mental illness to enable those with psychiatric illness to be more respected, less marginalized, and encouraged to receive effective psychiatric treatments.

Dr. Cerfolio is author of “Psychoanalytic and Spiritual Perspectives on Terrorism: Desire for Destruction.” She is clinical assistant professor at the Icahn School of Medicine at Mount Sinai, New York. Dr. Glick is Professor Emeritus, Department of Psychiatry and Behavioral Sciences at Stanford University School of Medicine, Stanford, Calif.

References

1. Glick ID, et al. Domestic Mass Shooters: The Association With Unmedicated and Untreated Psychiatric Illness. J Clin Psychopharmacol. 2021 Jul-Aug;41(4):366-369. doi: 10.1097/JCP.0000000000001417.

2. Cerfolio NE, et al. A Retrospective Observational Study of Psychosocial Determinants and Psychiatric Diagnoses of Mass Shooters in the United States. Psychodyn Psychiatry. 2022 Fall;50(3):1-16. doi: 10.1521/pdps.2022.50.5.001.

3. Cerfolio NE. The Parkland gunman, a horrific crime, and mental illness. The New York Times. 2022 Oct 14. www.nytimes.com/2022/10/14/opinion/letters/jan-6-panel-trump.html#link-5e2ccc1.

4. Corner E, et al. Mental Health Disorders and the Terrorist: A Research Note Probing Selection Effects and Disorder Prevalence. Stud Confl Terror. 2016 Jan;39(6):560–568. doi: 10.1080/1057610X.2015.1120099.

5. Gruenewald J, et al. Distinguishing “Loner” Attacks from Other Domestic Extremist Violence. Criminol Public Policy. 2013 Feb;12(1):65–91. doi: 10.1111/1745-9133.12008.

6. Lankford A. Detecting mental health problems and suicidal motives among terrorists and mass shooters. Crim Behav Ment Health. 2016 Dec;26(5):315-321. doi: 10.1002/cbm.2020.

Our psychiatric research, which found a high incidence of undiagnosed mental illness in mass shooters, was recently awarded the esteemed Psychodynamic Psychiatry Journal Prize for best paper published in the last 2 years (2022-2023). The editors noted our integrity in using quantitative data to argue against the common, careless assumption that mass shooters are not mentally ill.

Some of the mass shooters we studied were motivated by religious or political ideologies that were considered forms of terrorism. Given the current tragically violent landscape both at home and in Israel/Palestine, the “desire for destruction” is vital to understand.

Although there have been a limited number of psychiatric studies of perpetrators of mass shootings, our team took the first step to lay the groundwork by conducting a systematic, quantitative study. Our psychiatric research team’s research findings were published in the Journal of Clinical Psychopharmacology and then in greater detail in Psychodynamic Psychiatry,^1,2 which provided important context to the complicated backgrounds of these mass shooters who suffer from abuse, marginalization, and severe undiagnosed brain illness.³

Cerfolio_Nina_E_NY_web.jpg

The Mother Jones database of 115 mass shootings from 1982 to 2019 was used to study retrospectively 55 shooters in the United States. We developed a uniform, comprehensive, 62-item questionnaire to compile the data collection from multiple sources and record our psychiatric assessments of the assailants, using DSM-5 criteria. After developing this detailed psychiatric assessment questionnaire, psychiatric researchers evaluated the weight and quality of clinical evidence by (1) interviewing forensic psychiatrists who had assessed the assailant following the crime, and/or (2) reviewing court records of psychiatric evaluations conducted during the postcrime judicial proceedings to determine the prevalence of psychiatric illness. Rather than accepting diagnoses from forensic psychiatrists and/or court records, our team independently reviewed the clinical data gathered from multiple sources to apply the DSM-5 criteria to diagnose mental illness.

In most incidents in the database, the perpetrator died either during or shortly after the crime. We examined every case (n=35) in which the assailant survived, and criminal proceedings were instituted.

Of the 35 cases in which the assailant survived and criminal proceedings were instituted, there was insufficient information to make a diagnosis in 3 cases. Of the remaining 32 cases in which we had sufficient information, we determined that 87.5% had the following psychiatric diagnosis: 18 assailants (56%) had schizophrenia, while 10 assailants (31%) had other psychiatric diagnoses: 3 had bipolar I disorder, 2 had delusional disorders (persecutory), 2 had personality disorders (1 paranoid, 1 borderline), 2 had substance-related disorders without other psychiatric diagnosis, and 1 had post-traumatic stress disorder (PTSD).

Out of the 32 surviving assailants for whom we have sufficient evidence, 87.5% of perpetrators of mass shootings were diagnosed with major psychiatric illness, and none were treated appropriately with medication at the time of the crime. Four assailants (12.5%) had no psychiatric diagnosis that we could discern. Of the 18 surviving assailants with schizophrenia, no assailant was on antipsychotic medication for the treatment of schizophrenia prior to the crime. Of the 10 surviving assailants with other psychiatric illnesses, no assailant was on antipsychotic and/or appropriate medication.

In addition, we found that the clinical misdiagnosis of early-onset schizophrenia was associated with the worsening of many of these assailants’ psychotic symptoms. Many of our adolescent shooters prior to the massacre had been misdiagnosed with attention-deficit disorder (ADD), major depression disorder (MDD), or autism spectrum disorder.

Though the vast majority of those suffering from psychiatric illnesses who are appropriately treated are not violent, there is a growing body of scientific research that indicates a strong association of untreated brain illness with those who commit mass shootings.^4,5,6 This research demonstrates that such untreated illness combined with access to firearms poses a lethal threat to society.

Glick_Ira_D_CALIF_web.jpg

Most of the assailants also experienced profound estrangement, not only from families and friends, but most importantly from themselves. Being marginalized rendered them more vulnerable to their untreated psychiatric illness and to radicalization online, which fostered their violence. While there are complex reasons that a person is not diagnosed, there remains a vital need to decrease the stigma of mental illness to enable those with psychiatric illness to be more respected, less marginalized, and encouraged to receive effective psychiatric treatments.

Dr. Cerfolio is author of “Psychoanalytic and Spiritual Perspectives on Terrorism: Desire for Destruction.” She is clinical assistant professor at the Icahn School of Medicine at Mount Sinai, New York. Dr. Glick is Professor Emeritus, Department of Psychiatry and Behavioral Sciences at Stanford University School of Medicine, Stanford, Calif.

References

1. Glick ID, et al. Domestic Mass Shooters: The Association With Unmedicated and Untreated Psychiatric Illness. J Clin Psychopharmacol. 2021 Jul-Aug;41(4):366-369. doi: 10.1097/JCP.0000000000001417.

2. Cerfolio NE, et al. A Retrospective Observational Study of Psychosocial Determinants and Psychiatric Diagnoses of Mass Shooters in the United States. Psychodyn Psychiatry. 2022 Fall;50(3):1-16. doi: 10.1521/pdps.2022.50.5.001.

3. Cerfolio NE. The Parkland gunman, a horrific crime, and mental illness. The New York Times. 2022 Oct 14. www.nytimes.com/2022/10/14/opinion/letters/jan-6-panel-trump.html#link-5e2ccc1.

4. Corner E, et al. Mental Health Disorders and the Terrorist: A Research Note Probing Selection Effects and Disorder Prevalence. Stud Confl Terror. 2016 Jan;39(6):560–568. doi: 10.1080/1057610X.2015.1120099.

5. Gruenewald J, et al. Distinguishing “Loner” Attacks from Other Domestic Extremist Violence. Criminol Public Policy. 2013 Feb;12(1):65–91. doi: 10.1111/1745-9133.12008.

6. Lankford A. Detecting mental health problems and suicidal motives among terrorists and mass shooters. Crim Behav Ment Health. 2016 Dec;26(5):315-321. doi: 10.1002/cbm.2020.

Our psychiatric research, which found a high incidence of undiagnosed mental illness in mass shooters, was recently awarded the esteemed Psychodynamic Psychiatry Journal Prize for best paper published in the last 2 years (2022-2023). The editors noted our integrity in using quantitative data to argue against the common, careless assumption that mass shooters are not mentally ill.

Some of the mass shooters we studied were motivated by religious or political ideologies that were considered forms of terrorism. Given the current tragically violent landscape both at home and in Israel/Palestine, the “desire for destruction” is vital to understand.

Although there have been a limited number of psychiatric studies of perpetrators of mass shootings, our team took the first step to lay the groundwork by conducting a systematic, quantitative study. Our psychiatric research team’s research findings were published in the Journal of Clinical Psychopharmacology and then in greater detail in Psychodynamic Psychiatry,^1,2 which provided important context to the complicated backgrounds of these mass shooters who suffer from abuse, marginalization, and severe undiagnosed brain illness.³

Cerfolio_Nina_E_NY_web.jpg

The Mother Jones database of 115 mass shootings from 1982 to 2019 was used to study retrospectively 55 shooters in the United States. We developed a uniform, comprehensive, 62-item questionnaire to compile the data collection from multiple sources and record our psychiatric assessments of the assailants, using DSM-5 criteria. After developing this detailed psychiatric assessment questionnaire, psychiatric researchers evaluated the weight and quality of clinical evidence by (1) interviewing forensic psychiatrists who had assessed the assailant following the crime, and/or (2) reviewing court records of psychiatric evaluations conducted during the postcrime judicial proceedings to determine the prevalence of psychiatric illness. Rather than accepting diagnoses from forensic psychiatrists and/or court records, our team independently reviewed the clinical data gathered from multiple sources to apply the DSM-5 criteria to diagnose mental illness.

In most incidents in the database, the perpetrator died either during or shortly after the crime. We examined every case (n=35) in which the assailant survived, and criminal proceedings were instituted.

Of the 35 cases in which the assailant survived and criminal proceedings were instituted, there was insufficient information to make a diagnosis in 3 cases. Of the remaining 32 cases in which we had sufficient information, we determined that 87.5% had the following psychiatric diagnosis: 18 assailants (56%) had schizophrenia, while 10 assailants (31%) had other psychiatric diagnoses: 3 had bipolar I disorder, 2 had delusional disorders (persecutory), 2 had personality disorders (1 paranoid, 1 borderline), 2 had substance-related disorders without other psychiatric diagnosis, and 1 had post-traumatic stress disorder (PTSD).

Out of the 32 surviving assailants for whom we have sufficient evidence, 87.5% of perpetrators of mass shootings were diagnosed with major psychiatric illness, and none were treated appropriately with medication at the time of the crime. Four assailants (12.5%) had no psychiatric diagnosis that we could discern. Of the 18 surviving assailants with schizophrenia, no assailant was on antipsychotic medication for the treatment of schizophrenia prior to the crime. Of the 10 surviving assailants with other psychiatric illnesses, no assailant was on antipsychotic and/or appropriate medication.

In addition, we found that the clinical misdiagnosis of early-onset schizophrenia was associated with the worsening of many of these assailants’ psychotic symptoms. Many of our adolescent shooters prior to the massacre had been misdiagnosed with attention-deficit disorder (ADD), major depression disorder (MDD), or autism spectrum disorder.

Though the vast majority of those suffering from psychiatric illnesses who are appropriately treated are not violent, there is a growing body of scientific research that indicates a strong association of untreated brain illness with those who commit mass shootings.^4,5,6 This research demonstrates that such untreated illness combined with access to firearms poses a lethal threat to society.

Glick_Ira_D_CALIF_web.jpg

Most of the assailants also experienced profound estrangement, not only from families and friends, but most importantly from themselves. Being marginalized rendered them more vulnerable to their untreated psychiatric illness and to radicalization online, which fostered their violence. While there are complex reasons that a person is not diagnosed, there remains a vital need to decrease the stigma of mental illness to enable those with psychiatric illness to be more respected, less marginalized, and encouraged to receive effective psychiatric treatments.

Dr. Cerfolio is author of “Psychoanalytic and Spiritual Perspectives on Terrorism: Desire for Destruction.” She is clinical assistant professor at the Icahn School of Medicine at Mount Sinai, New York. Dr. Glick is Professor Emeritus, Department of Psychiatry and Behavioral Sciences at Stanford University School of Medicine, Stanford, Calif.

References

1. Glick ID, et al. Domestic Mass Shooters: The Association With Unmedicated and Untreated Psychiatric Illness. J Clin Psychopharmacol. 2021 Jul-Aug;41(4):366-369. doi: 10.1097/JCP.0000000000001417.

2. Cerfolio NE, et al. A Retrospective Observational Study of Psychosocial Determinants and Psychiatric Diagnoses of Mass Shooters in the United States. Psychodyn Psychiatry. 2022 Fall;50(3):1-16. doi: 10.1521/pdps.2022.50.5.001.

3. Cerfolio NE. The Parkland gunman, a horrific crime, and mental illness. The New York Times. 2022 Oct 14. www.nytimes.com/2022/10/14/opinion/letters/jan-6-panel-trump.html#link-5e2ccc1.

4. Corner E, et al. Mental Health Disorders and the Terrorist: A Research Note Probing Selection Effects and Disorder Prevalence. Stud Confl Terror. 2016 Jan;39(6):560–568. doi: 10.1080/1057610X.2015.1120099.

5. Gruenewald J, et al. Distinguishing “Loner” Attacks from Other Domestic Extremist Violence. Criminol Public Policy. 2013 Feb;12(1):65–91. doi: 10.1111/1745-9133.12008.

6. Lankford A. Detecting mental health problems and suicidal motives among terrorists and mass shooters. Crim Behav Ment Health. 2016 Dec;26(5):315-321. doi: 10.1002/cbm.2020.

Delirious mania is a syndrome characterized by the acute onset of severe hyperactivity, psychosis, catatonia, and intermittent confusion. While there have been growing reports of this phenomenon over the last 2 decades, it remains poorly recognized and understood.^1,2 There is no widely accepted nosology for delirious mania and the condition is absent from DSM-5, which magnifies the difficulties in making a timely diagnosis and initiating appropriate treatment. Delayed diagnosis and treatment may result in a detrimental outcome.^2,3 Delirious mania has also been labeled as lethal catatonia, specific febrile delirium, hyperactive or exhaustive mania, and Bell’s mania.^2,4,5 The characterization and diagnosis of this condition have a long and inconsistent history (Box^1,6-11).

Box

Delirious mania continues to be met with incertitude in clinical practice, and numerous inconsistencies have been reported in the literature. For example, some cases that have been reported as delirious mania had more evidence of primary delirium due to another medical condition or primary mania.^12,13 Other cases have demonstrated swift improvement of symptoms after monotherapy with antipsychotics without a trial of benzodiazepines or electroconvulsive therapy (ECT); the exclusion of a sudden onset questions the validity of the diagnosis and promotes the use of less efficacious treatments.^14,15 Other reports have confirmed that the diagnosis is missed when certain symptoms are more predominant, such as a thought disorder (acute schizophrenia), grandiosity and delusional ideation (bipolar disorder [BD]), and less commonly assessed catatonic signs (ambitendency, automatic obedience). These symptoms are mistakenly attributed to the respective disease.^1,16 This especially holds true when delirious mania is initially diagnosed as a primary psychosis, which leads to the administration of antipsychotics.¹⁷ Other cases have reported that delirious mania was resistant to treatment, but ECT was never pursued.¹⁸

In this review, we provide a more comprehensive perspective of the clinical presentation, pathogenesis, and management of delirious mania. We searched PubMed and Google Scholar using the keywords “delirious mania,” “delirious mania AND catatonia,” or “manic delirium.” Most articles we found were case reports, case series, or retrospective chart reviews. There were no systematic reviews, meta analyses, or randomized control trials (RCTs). The 12 articles included in this review consist of 7 individual case reports, 4 case series, and 1 retrospective chart review that describe a total of 36 cases (Table^{1,2,5,17,19-26}).

CP02212026_t1.png

Clinical presentation: What to look for

Patients with delirious mania typically develop symptoms extremely rapidly. In virtually all published literature, symptoms were reported to emerge within hours to days and consisted of severe forms of mania, psychosis, and delirium; 100% of the cases in our review had these symptoms. Commonly reported symptoms were:

• intense excitement
• emotional lability
• grandiose delusions
• profound insomnia
• pressured and rapid speech
• auditory and visual hallucinations
• hypersexuality
• thought disorganization.

Exquisite paranoia can also result in violent aggression (and may require the use of physical restraints). Patients may confine themselves to very small spaces (such as a closet) in response to the intense paranoia. Impairments in various neurocognitive domains—including inability to focus; disorientation; language and visuospatial disturbances; difficulty with shifting and sustaining attention; and short-term memory impairments—have been reported. Patients often cannot recall the events during the episode.^1,2,5,27,28

Catatonia has been closely associated with delirious mania.²⁹ Features of excited catatonia—such as excessive motor activity, negativism, grimacing, posturing, echolalia, echopraxia, stereotypy, automatic obedience, verbigeration, combativeness, impulsivity, and rigidity—typically accompany delirious mania.^1,5,10,19,27

In addition to these symptoms, patients may engage in specific behaviors. They may exhibit inappropriate toileting such as smearing feces on walls or in bags, fecal or urinary incontinence, disrobing or running naked in public places, or pouring liquid on the floor or on one’s head.^1,2

Continue to: Of the 36 cases...

Of the 36 cases reported in the literature we reviewed, 20 (55%) were female. Most patients had an underlining psychiatric condition, including BD (72%), major depressive disorder (8%), and schizophrenia (2%). Three patients had no psychiatric history.

Physical examination

On initial presentation, a patient with delirious mania may be dehydrated, with dry mucous membranes, pale conjunctiva, tongue dryness, and poor skin turgor.^28,30 Due to excessive motor activity, diaphoresis with tachycardia, fluctuating blood pressure, and fever may be present.³¹

Certain basic cognitive tasks should be assessed to determine the patient’s orientation to place, date, and time. Assess if the patient can recall recent events, names of objects, or perform serial 7s; clock drawing capabilities also should be ascertained.^1,2,5 A Mini-Mental State Examination is useful.³²

The Bush-Francis Catatonia Rating Scale should be used to elicit features of catatonia, such as waxy flexibility, negativism, gegenhalten, mitgehen, catalepsy, ambitendency, automatic obedience, and grasp reflex.¹⁰

Laboratory findings are nonspecific

Although no specific laboratory findings are associated with delirious mania, bloodwork and imaging are routinely investigated, especially if delirium characteristics are most striking. A complete blood count, chemistries, hepatic panel, thyroid functioning, blood and/or urine cultures, creatinine phosphokinase (CPK), and urinalysis can be ordered. Head imaging such as MRI and CT to rule out intracranial pathology are typically performed.¹⁹ However, the diagnosis of delirious mania is based on the presence of the phenotypic features, by verification of catatonia, and by the responsiveness to the treatment delivered.²⁹

Continue to: Pathogenisis: Several hypotheses

The pathogenesis of delirious mania is not well understood. There are several postulations but no salient theory. Most patients with delirious mania have an underlying systemic medical or psychiatric condition.

Mood disorders. Patients with BD or schizoaffective disorder are especially susceptible to delirious mania. The percentage of manic patients who present with delirious mania varies by study. One study suggested approximately 19% have features of the phenomenon,³³ while others estimated 15% to 25%.³⁴ Elias et al³⁵ calculated that 15% of patients with mania succumb to manic exhaustion; from this it can be reasonably concluded that these were cases of misdiagnosed delirious mania.

Delirium hypothesis. Patients with delirious mania typically have features of delirium, including fluctuation of consciousness, disorientation, and/or poor sleep-wake cycle.³⁶ During rapid eye movement (REM) and non-REM sleep, memory circuits are fortified. When there is a substantial loss of REM and non-REM sleep, these circuits become faulty, even after 1 night. Pathological brain waves on EEG reflect the inability to reinforce the memory circuits. Patients with these waves may develop hallucinations, bizarre delusions, and altered sensorium. ECT reduces the pathological slow wave morphologies, thus restoring the synaptic maintenance and correcting the incompetent circuitry. This can explain the robust and rapid response of ECT in a patient with delirious mania.^37,38

Neurotransmitter hypothesis. It has been shown that in patients with delirious mania there is dysregulation of dopamine transport, which leads to dopamine overflow in the synapse. In contrast to a drug effect (ie, cocaine or methamphetamine) that acts by inhibiting dopamine reuptake, dopamine overflow in delirious mania is caused by the loss of dopamine transporter regulation. This results in a dysfunctional dopaminergic state that precipitates an acute state of delirium and agitation.^39,40

Serotonin plays a role in mood disorders, including mania and depression.^41,42 More specifically, serotonin has been implicated in impulsivity and aggression as shown by reduced levels of CSF 5-hydroxyindoleacetic acid (5-HIAA) and depletion of 5-hydroxytryptophan (5-HTP).⁴³

Continue to: Alterations in gamma-aminobutyric acid (GABA) transmission...

Alterations in gamma-aminobutyric acid (GABA) transmission are known to occur in delirium and catatonia. In delirium, GABA signaling is increased, which disrupts the circadian rhythm and melatonin release, thus impairing the sleep-wake cycle.⁴⁴ Deficiencies in acetylcholine and melatonin are seen as well as excess of other neurotransmitters, including norepinephrine and glutamate.⁴⁵ Conversely, in catatonia, functional imaging studies found decreased GABA-A binding in orbito­frontal, prefrontal, parietal, and motor cortical regions.⁴⁶ A study analyzing 10 catatonic patients found decreased density of GABA-A receptors in the left sensorimotor cortex compared to psychiatric and healthy controls.⁴⁷

Other neurotransmitters, such as glutamate, at the N-methyl-D-aspartate receptors (NMDAR) have been hypothesized to be hyperactive, causing downstream dysregulation of GABA functioning.⁴⁸ However, the exact connection between delirious mania and all these receptors and neurotransmitters remains unknown.

Encephalitis hypothesis. The relationship between delirious mania and autoimmune encephalitis suggests delirious mania has etiologies other than a primary psychiatric illness. In a 2020 retrospective study⁴⁹ that analyzed 79 patients with anti-NMDAR encephalitis, 25.3% met criteria for delirious mania, and 95% of these patients had catatonic features. Dalmau et al⁵⁰ found that in many cases, patients tend to respond to ECT; in a cases series of 3 patients, 2 responded to benzodiazepines.

COVID-19 hypothesis. The SARS-CoV-2 virion has been associated with many neuropsychiatric complications, including mood, psychotic, and neurocognitive disorders.^51,52 There also have been cases of COVID-19–induced catatonia.^53-55 One case of delirious mania in a patient with COVID-19 has been reported.²¹ The general mechanism has been proposed to be related to the stimulation of the proinflammatory cytokines, such as tumor necrosis factor-alpha and interleukin-6, which the virus produces in large quantities.⁵⁶ These cytokines have been linked to psychosis and other psychiatric disorders.⁵⁷ The patient with COVID-19–induced delirious mania had elevated inflammatory markers, including erythrocyte sedimentation rate, C-reactive protein, ferritin, and D-dimer, which supports a proinflammatory state. This patient had a complete resolution of symptoms with ECT.²¹

Management: Benzodiazepines and ECT

A step-by-step algorithm for managing delirious mania is outlined in the Figure. Regardless of the underlining etiology, management of delirious mania consists of benzodiazepines (lorazepam and diazepam); prompt use of ECT, particularly for patients who do not improve with large doses of lorazepam; or (if applicable) continued treatment of the underlining medical condition, which does not preclude the use of benzodiazepines or ECT. Recent reports^27,58 have described details for using ECT for delirious mania, highlighting the use of high-energy dosing, bilateral electrode placement, and frequent sessions.

CP02212026_f1.png

Continue to: Knowing which medications...

Knowing which medications to avoid is as important as knowing which agents to administer. Be vigilant in avoiding high-potency antipsychotics, as these medications can worsen extrapyramidal symptoms and may precipitate seizures or neuroleptic malignant syndrome (NMS).²⁸ Anticholinergic agents should also be avoided because they worsen confusion. Although lithium is effective in BD, in delirious mania, high doses of lithium and haloperidol may cause severe encephalopathic syndromes, with symptoms that can include lethargy, tremors, cerebellar dysfunction, and worsened confusion; it may also cause widespread and irreversible brain damage.⁵⁹While positive outcomes have been documented when using a combination of antipsychotics and lithium,^8,60 this approach should be considered carefully and tailored to individual cases, taking into account the severity of manic and psychotic symptoms in addition to the level of catatonia.

Due to long periods of hyperactivity, withdrawal, and diaphoresis, patients with delirious mania may be severely dehydrated with metabolic derangements, including elevated CPK due to rhabdomyolysis from prolonged exertion, IM antipsychotics, or rigidity. To prevent acute renal failure, this must be immediately addressed with rapid fluid resuscitation and electrolyte repletion.⁶¹

Benzodiazepines. The rapid use of lorazepam should be initiated when delirious mania is suspected. Doses of 6 to 20 mg have been reported to be effective if tolerated.^5,20 Typically, high-dose lorazepam will not have the sedative effect that would normally occur in a patient who does not have delirious mania.² Lorazepam should be titrated until full resolution of symptoms. Doses up to 30 mg have been reported as effective and tolerable.⁶² In our literature review, 50% of patients (18/36) responded or partially responded to lorazepam. However, only 3 case reports documented a complete remission with lorazepam, and many patients needed ECT for remission of symptoms.

ECT is generally reserved for patients who are not helped by benzodiazepine therapy, which is estimated to be up to 20%.⁵ ECT is highly effective in delirious mania, with remission rates ranging from 80% to 100%.¹ ECT is also effective in acute non­delirious mania (comparable to depression); however, it is only used in a small minority of cases (0.2% to 12%).³⁵ In our review, 58% of cases (21/36) reported using ECT, and in all cases it resulted in complete remission.

A dramatic improvement can be seen even after a single ECT session, though most patients show improvement after 4 sessions or 3 to 7 days.^1,2,5 In our review, most patients received 4 to 12 sessions until achieving complete remission.

Continue to: No RCTs have evaluated...

No RCTs have evaluated ECT electrode placement in patients with delirious mania. However, several RCTs have investigated electrode placement in patients with acute nondelirious mania. Hiremani et al⁶³ found that bitemporal placement had a more rapid response rate than bifrontal placement, but there was no overall difference in response rate. Barekatain et al⁶⁴ found no difference between these 2 bilateral approaches. Many of the delirious mania cases report using a bilateral placement (including 42% of the ECT cases in our review) due to the emergent need for rapid relief of symptoms, which is especially necessary if the patient is experiencing hemodynamic instability, excessive violence, risk for self-harm, worsening delirium, or resistance to lorazepam.

Prognosis: Often fatal if left untreated

Patients with delirious mania are at high risk to progress to a more severe form of NMS or malignant catatonia. Therefore, high-potency antipsychotics should be avoided; mortality can be elevated from 60% without antipsychotics to 78% with antipsychotics.⁴ Some researchers estimate 75% to 78% of cases of delirious mania can be fatal if left untreated.^3,6

Bottom Line

Delirious mania is routinely mistaken for more conventional manic or psychotic disorders. Clinicians need to be able to rapidly recognize the symptoms of this syndrome, which include mania, psychosis, delirium, and possible catatonia, so they can avoid administering toxic agents and instead initiate effective treatments such as benzodiazepines and electroconvulsive therapy.

Related Resources

• Arsan C, Baker C, Wong J, et al. Delirious mania: an approach to diagnosis and treatment. Prim Care Companion CNS Disord. 2021;23(1):20f02744. doi:10.4088/PCC.20f02744
• Lamba G, Kennedy EA, Vu CP. Case report: ECT for delirious mania. Clinical Psychiatry News. December 14, 2021. https://www.mdedge.com/psychiatry/article/249909/bipolar-disorder/case-report-ect-delirious-mania

Drug Brand Names

Diazepam • Valium
Haloperidol • Haldol
Lithium • Eskalith, Lithobid
Lorazepam • Ativan

[embed:render:related:node:249909]

Delirious mania is a syndrome characterized by the acute onset of severe hyperactivity, psychosis, catatonia, and intermittent confusion. While there have been growing reports of this phenomenon over the last 2 decades, it remains poorly recognized and understood.^1,2 There is no widely accepted nosology for delirious mania and the condition is absent from DSM-5, which magnifies the difficulties in making a timely diagnosis and initiating appropriate treatment. Delayed diagnosis and treatment may result in a detrimental outcome.^2,3 Delirious mania has also been labeled as lethal catatonia, specific febrile delirium, hyperactive or exhaustive mania, and Bell’s mania.^2,4,5 The characterization and diagnosis of this condition have a long and inconsistent history (Box^1,6-11).

Box

Delirious mania continues to be met with incertitude in clinical practice, and numerous inconsistencies have been reported in the literature. For example, some cases that have been reported as delirious mania had more evidence of primary delirium due to another medical condition or primary mania.^12,13 Other cases have demonstrated swift improvement of symptoms after monotherapy with antipsychotics without a trial of benzodiazepines or electroconvulsive therapy (ECT); the exclusion of a sudden onset questions the validity of the diagnosis and promotes the use of less efficacious treatments.^14,15 Other reports have confirmed that the diagnosis is missed when certain symptoms are more predominant, such as a thought disorder (acute schizophrenia), grandiosity and delusional ideation (bipolar disorder [BD]), and less commonly assessed catatonic signs (ambitendency, automatic obedience). These symptoms are mistakenly attributed to the respective disease.^1,16 This especially holds true when delirious mania is initially diagnosed as a primary psychosis, which leads to the administration of antipsychotics.¹⁷ Other cases have reported that delirious mania was resistant to treatment, but ECT was never pursued.¹⁸

In this review, we provide a more comprehensive perspective of the clinical presentation, pathogenesis, and management of delirious mania. We searched PubMed and Google Scholar using the keywords “delirious mania,” “delirious mania AND catatonia,” or “manic delirium.” Most articles we found were case reports, case series, or retrospective chart reviews. There were no systematic reviews, meta analyses, or randomized control trials (RCTs). The 12 articles included in this review consist of 7 individual case reports, 4 case series, and 1 retrospective chart review that describe a total of 36 cases (Table^{1,2,5,17,19-26}).

CP02212026_t1.png

Clinical presentation: What to look for

Patients with delirious mania typically develop symptoms extremely rapidly. In virtually all published literature, symptoms were reported to emerge within hours to days and consisted of severe forms of mania, psychosis, and delirium; 100% of the cases in our review had these symptoms. Commonly reported symptoms were:

• intense excitement
• emotional lability
• grandiose delusions
• profound insomnia
• pressured and rapid speech
• auditory and visual hallucinations
• hypersexuality
• thought disorganization.

Exquisite paranoia can also result in violent aggression (and may require the use of physical restraints). Patients may confine themselves to very small spaces (such as a closet) in response to the intense paranoia. Impairments in various neurocognitive domains—including inability to focus; disorientation; language and visuospatial disturbances; difficulty with shifting and sustaining attention; and short-term memory impairments—have been reported. Patients often cannot recall the events during the episode.^1,2,5,27,28

Catatonia has been closely associated with delirious mania.²⁹ Features of excited catatonia—such as excessive motor activity, negativism, grimacing, posturing, echolalia, echopraxia, stereotypy, automatic obedience, verbigeration, combativeness, impulsivity, and rigidity—typically accompany delirious mania.^1,5,10,19,27

In addition to these symptoms, patients may engage in specific behaviors. They may exhibit inappropriate toileting such as smearing feces on walls or in bags, fecal or urinary incontinence, disrobing or running naked in public places, or pouring liquid on the floor or on one’s head.^1,2

Continue to: Of the 36 cases...

Of the 36 cases reported in the literature we reviewed, 20 (55%) were female. Most patients had an underlining psychiatric condition, including BD (72%), major depressive disorder (8%), and schizophrenia (2%). Three patients had no psychiatric history.

Physical examination

On initial presentation, a patient with delirious mania may be dehydrated, with dry mucous membranes, pale conjunctiva, tongue dryness, and poor skin turgor.^28,30 Due to excessive motor activity, diaphoresis with tachycardia, fluctuating blood pressure, and fever may be present.³¹

Certain basic cognitive tasks should be assessed to determine the patient’s orientation to place, date, and time. Assess if the patient can recall recent events, names of objects, or perform serial 7s; clock drawing capabilities also should be ascertained.^1,2,5 A Mini-Mental State Examination is useful.³²

The Bush-Francis Catatonia Rating Scale should be used to elicit features of catatonia, such as waxy flexibility, negativism, gegenhalten, mitgehen, catalepsy, ambitendency, automatic obedience, and grasp reflex.¹⁰

Laboratory findings are nonspecific

Although no specific laboratory findings are associated with delirious mania, bloodwork and imaging are routinely investigated, especially if delirium characteristics are most striking. A complete blood count, chemistries, hepatic panel, thyroid functioning, blood and/or urine cultures, creatinine phosphokinase (CPK), and urinalysis can be ordered. Head imaging such as MRI and CT to rule out intracranial pathology are typically performed.¹⁹ However, the diagnosis of delirious mania is based on the presence of the phenotypic features, by verification of catatonia, and by the responsiveness to the treatment delivered.²⁹

Continue to: Pathogenisis: Several hypotheses

The pathogenesis of delirious mania is not well understood. There are several postulations but no salient theory. Most patients with delirious mania have an underlying systemic medical or psychiatric condition.

Mood disorders. Patients with BD or schizoaffective disorder are especially susceptible to delirious mania. The percentage of manic patients who present with delirious mania varies by study. One study suggested approximately 19% have features of the phenomenon,³³ while others estimated 15% to 25%.³⁴ Elias et al³⁵ calculated that 15% of patients with mania succumb to manic exhaustion; from this it can be reasonably concluded that these were cases of misdiagnosed delirious mania.

Delirium hypothesis. Patients with delirious mania typically have features of delirium, including fluctuation of consciousness, disorientation, and/or poor sleep-wake cycle.³⁶ During rapid eye movement (REM) and non-REM sleep, memory circuits are fortified. When there is a substantial loss of REM and non-REM sleep, these circuits become faulty, even after 1 night. Pathological brain waves on EEG reflect the inability to reinforce the memory circuits. Patients with these waves may develop hallucinations, bizarre delusions, and altered sensorium. ECT reduces the pathological slow wave morphologies, thus restoring the synaptic maintenance and correcting the incompetent circuitry. This can explain the robust and rapid response of ECT in a patient with delirious mania.^37,38

Neurotransmitter hypothesis. It has been shown that in patients with delirious mania there is dysregulation of dopamine transport, which leads to dopamine overflow in the synapse. In contrast to a drug effect (ie, cocaine or methamphetamine) that acts by inhibiting dopamine reuptake, dopamine overflow in delirious mania is caused by the loss of dopamine transporter regulation. This results in a dysfunctional dopaminergic state that precipitates an acute state of delirium and agitation.^39,40

Serotonin plays a role in mood disorders, including mania and depression.^41,42 More specifically, serotonin has been implicated in impulsivity and aggression as shown by reduced levels of CSF 5-hydroxyindoleacetic acid (5-HIAA) and depletion of 5-hydroxytryptophan (5-HTP).⁴³

Continue to: Alterations in gamma-aminobutyric acid (GABA) transmission...

Alterations in gamma-aminobutyric acid (GABA) transmission are known to occur in delirium and catatonia. In delirium, GABA signaling is increased, which disrupts the circadian rhythm and melatonin release, thus impairing the sleep-wake cycle.⁴⁴ Deficiencies in acetylcholine and melatonin are seen as well as excess of other neurotransmitters, including norepinephrine and glutamate.⁴⁵ Conversely, in catatonia, functional imaging studies found decreased GABA-A binding in orbito­frontal, prefrontal, parietal, and motor cortical regions.⁴⁶ A study analyzing 10 catatonic patients found decreased density of GABA-A receptors in the left sensorimotor cortex compared to psychiatric and healthy controls.⁴⁷

Other neurotransmitters, such as glutamate, at the N-methyl-D-aspartate receptors (NMDAR) have been hypothesized to be hyperactive, causing downstream dysregulation of GABA functioning.⁴⁸ However, the exact connection between delirious mania and all these receptors and neurotransmitters remains unknown.

Encephalitis hypothesis. The relationship between delirious mania and autoimmune encephalitis suggests delirious mania has etiologies other than a primary psychiatric illness. In a 2020 retrospective study⁴⁹ that analyzed 79 patients with anti-NMDAR encephalitis, 25.3% met criteria for delirious mania, and 95% of these patients had catatonic features. Dalmau et al⁵⁰ found that in many cases, patients tend to respond to ECT; in a cases series of 3 patients, 2 responded to benzodiazepines.

COVID-19 hypothesis. The SARS-CoV-2 virion has been associated with many neuropsychiatric complications, including mood, psychotic, and neurocognitive disorders.^51,52 There also have been cases of COVID-19–induced catatonia.^53-55 One case of delirious mania in a patient with COVID-19 has been reported.²¹ The general mechanism has been proposed to be related to the stimulation of the proinflammatory cytokines, such as tumor necrosis factor-alpha and interleukin-6, which the virus produces in large quantities.⁵⁶ These cytokines have been linked to psychosis and other psychiatric disorders.⁵⁷ The patient with COVID-19–induced delirious mania had elevated inflammatory markers, including erythrocyte sedimentation rate, C-reactive protein, ferritin, and D-dimer, which supports a proinflammatory state. This patient had a complete resolution of symptoms with ECT.²¹

Management: Benzodiazepines and ECT

A step-by-step algorithm for managing delirious mania is outlined in the Figure. Regardless of the underlining etiology, management of delirious mania consists of benzodiazepines (lorazepam and diazepam); prompt use of ECT, particularly for patients who do not improve with large doses of lorazepam; or (if applicable) continued treatment of the underlining medical condition, which does not preclude the use of benzodiazepines or ECT. Recent reports^27,58 have described details for using ECT for delirious mania, highlighting the use of high-energy dosing, bilateral electrode placement, and frequent sessions.

CP02212026_f1.png

Continue to: Knowing which medications...

Knowing which medications to avoid is as important as knowing which agents to administer. Be vigilant in avoiding high-potency antipsychotics, as these medications can worsen extrapyramidal symptoms and may precipitate seizures or neuroleptic malignant syndrome (NMS).²⁸ Anticholinergic agents should also be avoided because they worsen confusion. Although lithium is effective in BD, in delirious mania, high doses of lithium and haloperidol may cause severe encephalopathic syndromes, with symptoms that can include lethargy, tremors, cerebellar dysfunction, and worsened confusion; it may also cause widespread and irreversible brain damage.⁵⁹While positive outcomes have been documented when using a combination of antipsychotics and lithium,^8,60 this approach should be considered carefully and tailored to individual cases, taking into account the severity of manic and psychotic symptoms in addition to the level of catatonia.

Due to long periods of hyperactivity, withdrawal, and diaphoresis, patients with delirious mania may be severely dehydrated with metabolic derangements, including elevated CPK due to rhabdomyolysis from prolonged exertion, IM antipsychotics, or rigidity. To prevent acute renal failure, this must be immediately addressed with rapid fluid resuscitation and electrolyte repletion.⁶¹

Benzodiazepines. The rapid use of lorazepam should be initiated when delirious mania is suspected. Doses of 6 to 20 mg have been reported to be effective if tolerated.^5,20 Typically, high-dose lorazepam will not have the sedative effect that would normally occur in a patient who does not have delirious mania.² Lorazepam should be titrated until full resolution of symptoms. Doses up to 30 mg have been reported as effective and tolerable.⁶² In our literature review, 50% of patients (18/36) responded or partially responded to lorazepam. However, only 3 case reports documented a complete remission with lorazepam, and many patients needed ECT for remission of symptoms.

ECT is generally reserved for patients who are not helped by benzodiazepine therapy, which is estimated to be up to 20%.⁵ ECT is highly effective in delirious mania, with remission rates ranging from 80% to 100%.¹ ECT is also effective in acute non­delirious mania (comparable to depression); however, it is only used in a small minority of cases (0.2% to 12%).³⁵ In our review, 58% of cases (21/36) reported using ECT, and in all cases it resulted in complete remission.

A dramatic improvement can be seen even after a single ECT session, though most patients show improvement after 4 sessions or 3 to 7 days.^1,2,5 In our review, most patients received 4 to 12 sessions until achieving complete remission.

Continue to: No RCTs have evaluated...

No RCTs have evaluated ECT electrode placement in patients with delirious mania. However, several RCTs have investigated electrode placement in patients with acute nondelirious mania. Hiremani et al⁶³ found that bitemporal placement had a more rapid response rate than bifrontal placement, but there was no overall difference in response rate. Barekatain et al⁶⁴ found no difference between these 2 bilateral approaches. Many of the delirious mania cases report using a bilateral placement (including 42% of the ECT cases in our review) due to the emergent need for rapid relief of symptoms, which is especially necessary if the patient is experiencing hemodynamic instability, excessive violence, risk for self-harm, worsening delirium, or resistance to lorazepam.

Prognosis: Often fatal if left untreated

Patients with delirious mania are at high risk to progress to a more severe form of NMS or malignant catatonia. Therefore, high-potency antipsychotics should be avoided; mortality can be elevated from 60% without antipsychotics to 78% with antipsychotics.⁴ Some researchers estimate 75% to 78% of cases of delirious mania can be fatal if left untreated.^3,6

Bottom Line

Delirious mania is routinely mistaken for more conventional manic or psychotic disorders. Clinicians need to be able to rapidly recognize the symptoms of this syndrome, which include mania, psychosis, delirium, and possible catatonia, so they can avoid administering toxic agents and instead initiate effective treatments such as benzodiazepines and electroconvulsive therapy.

Related Resources

• Arsan C, Baker C, Wong J, et al. Delirious mania: an approach to diagnosis and treatment. Prim Care Companion CNS Disord. 2021;23(1):20f02744. doi:10.4088/PCC.20f02744
• Lamba G, Kennedy EA, Vu CP. Case report: ECT for delirious mania. Clinical Psychiatry News. December 14, 2021. https://www.mdedge.com/psychiatry/article/249909/bipolar-disorder/case-report-ect-delirious-mania

Drug Brand Names

Diazepam • Valium
Haloperidol • Haldol
Lithium • Eskalith, Lithobid
Lorazepam • Ativan

[embed:render:related:node:249909]

Delirious mania is a syndrome characterized by the acute onset of severe hyperactivity, psychosis, catatonia, and intermittent confusion. While there have been growing reports of this phenomenon over the last 2 decades, it remains poorly recognized and understood.^1,2 There is no widely accepted nosology for delirious mania and the condition is absent from DSM-5, which magnifies the difficulties in making a timely diagnosis and initiating appropriate treatment. Delayed diagnosis and treatment may result in a detrimental outcome.^2,3 Delirious mania has also been labeled as lethal catatonia, specific febrile delirium, hyperactive or exhaustive mania, and Bell’s mania.^2,4,5 The characterization and diagnosis of this condition have a long and inconsistent history (Box^1,6-11).

Box

Delirious mania continues to be met with incertitude in clinical practice, and numerous inconsistencies have been reported in the literature. For example, some cases that have been reported as delirious mania had more evidence of primary delirium due to another medical condition or primary mania.^12,13 Other cases have demonstrated swift improvement of symptoms after monotherapy with antipsychotics without a trial of benzodiazepines or electroconvulsive therapy (ECT); the exclusion of a sudden onset questions the validity of the diagnosis and promotes the use of less efficacious treatments.^14,15 Other reports have confirmed that the diagnosis is missed when certain symptoms are more predominant, such as a thought disorder (acute schizophrenia), grandiosity and delusional ideation (bipolar disorder [BD]), and less commonly assessed catatonic signs (ambitendency, automatic obedience). These symptoms are mistakenly attributed to the respective disease.^1,16 This especially holds true when delirious mania is initially diagnosed as a primary psychosis, which leads to the administration of antipsychotics.¹⁷ Other cases have reported that delirious mania was resistant to treatment, but ECT was never pursued.¹⁸

In this review, we provide a more comprehensive perspective of the clinical presentation, pathogenesis, and management of delirious mania. We searched PubMed and Google Scholar using the keywords “delirious mania,” “delirious mania AND catatonia,” or “manic delirium.” Most articles we found were case reports, case series, or retrospective chart reviews. There were no systematic reviews, meta analyses, or randomized control trials (RCTs). The 12 articles included in this review consist of 7 individual case reports, 4 case series, and 1 retrospective chart review that describe a total of 36 cases (Table^{1,2,5,17,19-26}).

CP02212026_t1.png

Clinical presentation: What to look for

Patients with delirious mania typically develop symptoms extremely rapidly. In virtually all published literature, symptoms were reported to emerge within hours to days and consisted of severe forms of mania, psychosis, and delirium; 100% of the cases in our review had these symptoms. Commonly reported symptoms were:

• intense excitement
• emotional lability
• grandiose delusions
• profound insomnia
• pressured and rapid speech
• auditory and visual hallucinations
• hypersexuality
• thought disorganization.

Exquisite paranoia can also result in violent aggression (and may require the use of physical restraints). Patients may confine themselves to very small spaces (such as a closet) in response to the intense paranoia. Impairments in various neurocognitive domains—including inability to focus; disorientation; language and visuospatial disturbances; difficulty with shifting and sustaining attention; and short-term memory impairments—have been reported. Patients often cannot recall the events during the episode.^1,2,5,27,28

Catatonia has been closely associated with delirious mania.²⁹ Features of excited catatonia—such as excessive motor activity, negativism, grimacing, posturing, echolalia, echopraxia, stereotypy, automatic obedience, verbigeration, combativeness, impulsivity, and rigidity—typically accompany delirious mania.^1,5,10,19,27

In addition to these symptoms, patients may engage in specific behaviors. They may exhibit inappropriate toileting such as smearing feces on walls or in bags, fecal or urinary incontinence, disrobing or running naked in public places, or pouring liquid on the floor or on one’s head.^1,2

Continue to: Of the 36 cases...

Of the 36 cases reported in the literature we reviewed, 20 (55%) were female. Most patients had an underlining psychiatric condition, including BD (72%), major depressive disorder (8%), and schizophrenia (2%). Three patients had no psychiatric history.

Physical examination

On initial presentation, a patient with delirious mania may be dehydrated, with dry mucous membranes, pale conjunctiva, tongue dryness, and poor skin turgor.^28,30 Due to excessive motor activity, diaphoresis with tachycardia, fluctuating blood pressure, and fever may be present.³¹

Certain basic cognitive tasks should be assessed to determine the patient’s orientation to place, date, and time. Assess if the patient can recall recent events, names of objects, or perform serial 7s; clock drawing capabilities also should be ascertained.^1,2,5 A Mini-Mental State Examination is useful.³²

The Bush-Francis Catatonia Rating Scale should be used to elicit features of catatonia, such as waxy flexibility, negativism, gegenhalten, mitgehen, catalepsy, ambitendency, automatic obedience, and grasp reflex.¹⁰

Laboratory findings are nonspecific

Although no specific laboratory findings are associated with delirious mania, bloodwork and imaging are routinely investigated, especially if delirium characteristics are most striking. A complete blood count, chemistries, hepatic panel, thyroid functioning, blood and/or urine cultures, creatinine phosphokinase (CPK), and urinalysis can be ordered. Head imaging such as MRI and CT to rule out intracranial pathology are typically performed.¹⁹ However, the diagnosis of delirious mania is based on the presence of the phenotypic features, by verification of catatonia, and by the responsiveness to the treatment delivered.²⁹

Continue to: Pathogenisis: Several hypotheses

The pathogenesis of delirious mania is not well understood. There are several postulations but no salient theory. Most patients with delirious mania have an underlying systemic medical or psychiatric condition.

Mood disorders. Patients with BD or schizoaffective disorder are especially susceptible to delirious mania. The percentage of manic patients who present with delirious mania varies by study. One study suggested approximately 19% have features of the phenomenon,³³ while others estimated 15% to 25%.³⁴ Elias et al³⁵ calculated that 15% of patients with mania succumb to manic exhaustion; from this it can be reasonably concluded that these were cases of misdiagnosed delirious mania.

Delirium hypothesis. Patients with delirious mania typically have features of delirium, including fluctuation of consciousness, disorientation, and/or poor sleep-wake cycle.³⁶ During rapid eye movement (REM) and non-REM sleep, memory circuits are fortified. When there is a substantial loss of REM and non-REM sleep, these circuits become faulty, even after 1 night. Pathological brain waves on EEG reflect the inability to reinforce the memory circuits. Patients with these waves may develop hallucinations, bizarre delusions, and altered sensorium. ECT reduces the pathological slow wave morphologies, thus restoring the synaptic maintenance and correcting the incompetent circuitry. This can explain the robust and rapid response of ECT in a patient with delirious mania.^37,38

Neurotransmitter hypothesis. It has been shown that in patients with delirious mania there is dysregulation of dopamine transport, which leads to dopamine overflow in the synapse. In contrast to a drug effect (ie, cocaine or methamphetamine) that acts by inhibiting dopamine reuptake, dopamine overflow in delirious mania is caused by the loss of dopamine transporter regulation. This results in a dysfunctional dopaminergic state that precipitates an acute state of delirium and agitation.^39,40

Serotonin plays a role in mood disorders, including mania and depression.^41,42 More specifically, serotonin has been implicated in impulsivity and aggression as shown by reduced levels of CSF 5-hydroxyindoleacetic acid (5-HIAA) and depletion of 5-hydroxytryptophan (5-HTP).⁴³

Continue to: Alterations in gamma-aminobutyric acid (GABA) transmission...

Alterations in gamma-aminobutyric acid (GABA) transmission are known to occur in delirium and catatonia. In delirium, GABA signaling is increased, which disrupts the circadian rhythm and melatonin release, thus impairing the sleep-wake cycle.⁴⁴ Deficiencies in acetylcholine and melatonin are seen as well as excess of other neurotransmitters, including norepinephrine and glutamate.⁴⁵ Conversely, in catatonia, functional imaging studies found decreased GABA-A binding in orbito­frontal, prefrontal, parietal, and motor cortical regions.⁴⁶ A study analyzing 10 catatonic patients found decreased density of GABA-A receptors in the left sensorimotor cortex compared to psychiatric and healthy controls.⁴⁷

Other neurotransmitters, such as glutamate, at the N-methyl-D-aspartate receptors (NMDAR) have been hypothesized to be hyperactive, causing downstream dysregulation of GABA functioning.⁴⁸ However, the exact connection between delirious mania and all these receptors and neurotransmitters remains unknown.

Encephalitis hypothesis. The relationship between delirious mania and autoimmune encephalitis suggests delirious mania has etiologies other than a primary psychiatric illness. In a 2020 retrospective study⁴⁹ that analyzed 79 patients with anti-NMDAR encephalitis, 25.3% met criteria for delirious mania, and 95% of these patients had catatonic features. Dalmau et al⁵⁰ found that in many cases, patients tend to respond to ECT; in a cases series of 3 patients, 2 responded to benzodiazepines.

COVID-19 hypothesis. The SARS-CoV-2 virion has been associated with many neuropsychiatric complications, including mood, psychotic, and neurocognitive disorders.^51,52 There also have been cases of COVID-19–induced catatonia.^53-55 One case of delirious mania in a patient with COVID-19 has been reported.²¹ The general mechanism has been proposed to be related to the stimulation of the proinflammatory cytokines, such as tumor necrosis factor-alpha and interleukin-6, which the virus produces in large quantities.⁵⁶ These cytokines have been linked to psychosis and other psychiatric disorders.⁵⁷ The patient with COVID-19–induced delirious mania had elevated inflammatory markers, including erythrocyte sedimentation rate, C-reactive protein, ferritin, and D-dimer, which supports a proinflammatory state. This patient had a complete resolution of symptoms with ECT.²¹

Management: Benzodiazepines and ECT

A step-by-step algorithm for managing delirious mania is outlined in the Figure. Regardless of the underlining etiology, management of delirious mania consists of benzodiazepines (lorazepam and diazepam); prompt use of ECT, particularly for patients who do not improve with large doses of lorazepam; or (if applicable) continued treatment of the underlining medical condition, which does not preclude the use of benzodiazepines or ECT. Recent reports^27,58 have described details for using ECT for delirious mania, highlighting the use of high-energy dosing, bilateral electrode placement, and frequent sessions.

CP02212026_f1.png

Continue to: Knowing which medications...

Knowing which medications to avoid is as important as knowing which agents to administer. Be vigilant in avoiding high-potency antipsychotics, as these medications can worsen extrapyramidal symptoms and may precipitate seizures or neuroleptic malignant syndrome (NMS).²⁸ Anticholinergic agents should also be avoided because they worsen confusion. Although lithium is effective in BD, in delirious mania, high doses of lithium and haloperidol may cause severe encephalopathic syndromes, with symptoms that can include lethargy, tremors, cerebellar dysfunction, and worsened confusion; it may also cause widespread and irreversible brain damage.⁵⁹While positive outcomes have been documented when using a combination of antipsychotics and lithium,^8,60 this approach should be considered carefully and tailored to individual cases, taking into account the severity of manic and psychotic symptoms in addition to the level of catatonia.

Due to long periods of hyperactivity, withdrawal, and diaphoresis, patients with delirious mania may be severely dehydrated with metabolic derangements, including elevated CPK due to rhabdomyolysis from prolonged exertion, IM antipsychotics, or rigidity. To prevent acute renal failure, this must be immediately addressed with rapid fluid resuscitation and electrolyte repletion.⁶¹

Benzodiazepines. The rapid use of lorazepam should be initiated when delirious mania is suspected. Doses of 6 to 20 mg have been reported to be effective if tolerated.^5,20 Typically, high-dose lorazepam will not have the sedative effect that would normally occur in a patient who does not have delirious mania.² Lorazepam should be titrated until full resolution of symptoms. Doses up to 30 mg have been reported as effective and tolerable.⁶² In our literature review, 50% of patients (18/36) responded or partially responded to lorazepam. However, only 3 case reports documented a complete remission with lorazepam, and many patients needed ECT for remission of symptoms.

ECT is generally reserved for patients who are not helped by benzodiazepine therapy, which is estimated to be up to 20%.⁵ ECT is highly effective in delirious mania, with remission rates ranging from 80% to 100%.¹ ECT is also effective in acute non­delirious mania (comparable to depression); however, it is only used in a small minority of cases (0.2% to 12%).³⁵ In our review, 58% of cases (21/36) reported using ECT, and in all cases it resulted in complete remission.

A dramatic improvement can be seen even after a single ECT session, though most patients show improvement after 4 sessions or 3 to 7 days.^1,2,5 In our review, most patients received 4 to 12 sessions until achieving complete remission.

Continue to: No RCTs have evaluated...

No RCTs have evaluated ECT electrode placement in patients with delirious mania. However, several RCTs have investigated electrode placement in patients with acute nondelirious mania. Hiremani et al⁶³ found that bitemporal placement had a more rapid response rate than bifrontal placement, but there was no overall difference in response rate. Barekatain et al⁶⁴ found no difference between these 2 bilateral approaches. Many of the delirious mania cases report using a bilateral placement (including 42% of the ECT cases in our review) due to the emergent need for rapid relief of symptoms, which is especially necessary if the patient is experiencing hemodynamic instability, excessive violence, risk for self-harm, worsening delirium, or resistance to lorazepam.

Prognosis: Often fatal if left untreated

Patients with delirious mania are at high risk to progress to a more severe form of NMS or malignant catatonia. Therefore, high-potency antipsychotics should be avoided; mortality can be elevated from 60% without antipsychotics to 78% with antipsychotics.⁴ Some researchers estimate 75% to 78% of cases of delirious mania can be fatal if left untreated.^3,6

Bottom Line

Delirious mania is routinely mistaken for more conventional manic or psychotic disorders. Clinicians need to be able to rapidly recognize the symptoms of this syndrome, which include mania, psychosis, delirium, and possible catatonia, so they can avoid administering toxic agents and instead initiate effective treatments such as benzodiazepines and electroconvulsive therapy.

Related Resources

• Arsan C, Baker C, Wong J, et al. Delirious mania: an approach to diagnosis and treatment. Prim Care Companion CNS Disord. 2021;23(1):20f02744. doi:10.4088/PCC.20f02744
• Lamba G, Kennedy EA, Vu CP. Case report: ECT for delirious mania. Clinical Psychiatry News. December 14, 2021. https://www.mdedge.com/psychiatry/article/249909/bipolar-disorder/case-report-ect-delirious-mania

Drug Brand Names

Diazepam • Valium
Haloperidol • Haldol
Lithium • Eskalith, Lithobid
Lorazepam • Ativan

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Approximately 1 in 200 individuals will be diagnosed with schizophrenia in their lifetime.¹ DSM-5 criteria for the diagnosis of schizophrenia require the presence of ≥2 of 5 symptoms: delusions, hallucinations, disordered speech, grossly disorganized (or catatonic) behavior, and negative symptoms such as flat affect or avolition.² Multiple studies have found increased rates of cannabis use among patients with schizophrenia. Because cognitive deficits are the chief predictor of clinical outcomes and quality of life in individuals with schizophrenia, the cognitive effects of cannabis use among these patients are of clinical significance.³ As legislation increasingly allows for the sale, possession, and consumption of cannabis, it is crucial to provide clinicians with evidence-based recommendations for treating patients who regularly use cannabis (approximately 8% of the adult population³). In this article, we analyze several peer-reviewed studies to investigate the impact of cannabis use on the onset and development of schizophrenia.

A look at substance-induced psychosis

Schizophrenia is associated with several structural brain changes, and some of these changes may be influenced by cannabis use (Box⁴). The biochemical etiology of schizophrenia is poorly understood but thought to involve dopamine, glutamate, serotonin, and gamma-aminobutyric acid. Certain positive symptoms, such as hallucinations, are uniquely human and difficult to study in animal models.⁵ Psychoactive substance use, especially cannabis, is frequently comorbid with schizophrenia. Additionally, certain individuals may be more predisposed to substance-induced psychosis than others based on genetic variation and underlying brain structure changes.⁴ Substance-induced psychosis is a psychotic state following the ingestion of a psychoactive substance or drug withdrawal lasting ≥48 hours.⁶ The psychoactive effects of cannabis have been associated with an exacerbation of existing schizophrenia symptoms.⁷ In 1998, Hall⁷ proposed 2 hypotheses to explain the relationship between cannabis and psychosis. The first was that heavy consumption of cannabis triggers a specific type of cannabis psychosis.⁷ The second was that cannabis use exacerbates existing schizophrenia, making the symptoms worse.⁷ Hall⁷ concluded that there was a complicated interaction among an individual’s vulnerability to their stressors, environment, and genetics.

Box

Cannabis, COMT, and homocysteine

Great advances have been made in our ability to examine the association between genetics and metabolism. One example of this is the interaction between the catechol-O-methyltransferase (COMT) gene and the active component of cannabis, delta-9-tetra­hydrocannabinol (THC). COMT codes for an enzyme that degrades cortical dopamine. The Val158Met polymorphism of this gene increases COMT activity, leading to increased dopamine catabolism, and thus decreased levels of extracellular dopamine, which induces an increase in mesolimbic dopaminergic activity, thereby increasing susceptibility to psychosis.³

In a study that genotyped 135 patients with schizophrenia, the Val158Met polymorphism was present in 29.63% of participants.³ Because THC can induce episodes of psychosis, individuals with this polymorphism may be at a higher risk of developing schizophrenia. Compared to Met carrier control participants with similar histories of cannabis consumption, those with the Val158Met polymorphism demonstrated markedly worse performance on tests of verbal fluency and processing speed.³ This is clinically significant because cognitive impairments are a major prognostic factor in schizophrenia, and identifying patients with this polymorphism could help personalize interventions for those who consume cannabis and are at risk of developing schizophrenia.

A study that evaluated 56 patients with first-episode schizophrenia found that having a history of cannabis abuse was associated with significantly higher levels of homocysteine as well as lower levels of high-density lipoprotein and vitamin B12.⁸ Homocysteine is an agonist at the glutamate binding site and a partial antagonist at the glycine co-agonist site in the N-methyl-D-aspartate receptor, which suggests that homocysteine may contribute to hypofunctioning of glutamate transmission; this is implicated in the development of schizophrenia. These increases in homocysteine are also found in siblings of patients with schizophrenia, which indicates a possible association between the methylenetetrahydrofolate (MTHFR) gene and schizophrenia.⁸

The C677T polymorphism in MTHFR may predict the risk of developing metabolic syndrome in patients taking second-generation antipsychotics.⁸ Elevations in homocysteine by as little as 5 μmol/L may increase schizophrenia risk by 70% compared to controls, possibly due to homocysteine initiating neuronal apoptosis, catalyzing dysfunction of the mitochondria, or increasing oxidative stress.⁸ There is a positive correlation between homocysteine levels and severity of negative symptoms (P = .006) and general psychopathology (P = .008) of schizophrenia when analyzed using the Positive and Negative Syndrome Scale.⁸ Negative symptoms such as blunted affect, apathy, anhedonia, and loss of motivation significantly impact the social and economic outcomes of patients diagnosed with schizophrenia.

Research paints a mixed picture

A Danish study analyzed the rates of conversion to schizophrenia or bipolar disorder (BD) among 6,788 individuals who received a diagnosis of substance-induced psychosis from 1994 to 2014.⁶ Ten comparison participants were selected for each case participant, matched on sex and year/month of birth. Participants were followed until the first occurrence of schizophrenia or BD, death, or emigration from Denmark. Substances implicated in the initial psychotic episode included cannabis, alcohol, opioids, sedatives, cocaine, amphetamines, hallucinogens, and combinations of substances.

Continue to: The overall conversion rate...

The overall conversion rate over 20 years was 32.2% (95% CI, 29.7 to 34.9), with 26.0% developing schizophrenia vs 8.4% developing BD.⁶ Of the substances involved, cannabis was the most common, implicated in 41.2% (95% CI, 36.6 to 46.2) of cases.⁶ One-half of male patients converted within 2.0 years and one-half of female patients converted within 4.4 years after a cannabis-induced psychosis.⁶

This study had several limitations. It could not account for any short-term psychotic symptoms experienced by the general population, especially after cannabis use. Such patients might not seek treatment. Thus, the results might not be generalizable to the general population. The study did not evaluate if conversion rates differed based on continued substance use following the psychosis episode, or the amount of each substance taken prior to the episode. Dose-dependence was not well elucidated, and this study only looked at patients from Denmark and did not account for socioeconomic status.⁶

Another Danish study looked at the influences of gender and cannabis use in the early course of the disease in 133 patients with schizophrenia.⁹ These researchers found that male gender was a significant predictor of earlier onset of dysfunction socially and in the workplace, as well as a higher risk of developing negative symptoms. However, compared to gender, cannabis use was a stronger predictor of age at first psychotic episode. For cannabis users, the median age of onset of negative symptoms was 23.7, compared to 38.4 for nonusers (P < .001).⁹

Cannabis use is significantly elevated among individuals with psychosis, with a 12-month prevalence of 29.2% compared to 4.0% among the general population of the United States.¹⁰ In a study that assessed 229 patients with a schizophrenia spectrum disorder during their first hospitalization and 6 months, 2 years, 4 years, and 10 years later, Foti et al¹⁰ found that the lifetime rate of cannabis use was 66.2%. Survival analysis found cannabis use doubled the risk of the onset of psychosis compared to nonusers of the same age (hazard ratio [HR] = 1.97; 95% CI, 1.48 to 2.62, P < .001), even after adjusting for socioeconomic status, age, and gender (HR = 1.34; 95% CI, 1.01 to 1.77, P < .05).¹⁰ Additionally, Foti et al¹⁰ found significant positive correlations between psychotic symptoms and cannabis use in patients with schizophrenia over the course of 10 years. An increase in symptoms was associated with a higher likelihood of cannabis use, and a decrease in symptoms was correlated with a lower likelihood of use (adjusted odds ratio = 1.64; 95% CI, 1.12 to 2.43, P < .0125).¹⁰

Ortiz-Medina et al¹¹ conducted a meta-analysis of 22 studies of 15 cohorts from healthy populations and 12 other cohort follow-up studies that evaluated the onset of psychotic symptoms in individuals who used cannabis. Most studies found associations between cannabis use and the onset of symptoms of schizophrenia, and most determined cannabis was also a major risk factor for other psychotic disorders. Analyses of dose-dependence indicated that repeated cannabis use increased the risk of developing psychotic symptoms. This risk is increased when an individual starts using cannabis before age 15.¹¹ Age seemed to be a stronger predictor of onset and outcome than sex, with no significant differences between men and women. One study in this review found that approximately 8% to 13% cases of schizophrenia may have been solely due to cannabis.¹¹ The most significant limitation to the studies analyzed in this review is that retrospective studies utilize self-reported questionnaires.

Continue to: Other researchers have found...

Other researchers have found it would take a relatively high number of individuals to stop using cannabis to prevent 1 case of schizophrenia. In a study of data from England and Wales, Hickman et al¹² evaluated the best available estimates of the incidence of schizophrenia, rates of heavy and light cannabis use, and risk that cannabis causes schizophrenia to determine the number needed to prevent (NNP) 1 case of schizophrenia. They estimated that it would require approximately 2,800 men age 20 to 24 (90% CI, 2,018 to 4,530) and 4,700 men age 35 to 39 (90% CI, 3,114 to 8,416) who heavily used cannabis to stop their consumption to prevent 1 case of schizophrenia.¹² For women with heavy cannabis use, the mean NNP was 5,470 for women age 25 to 29 (90% CI, 3,640 to 9,839) and 10,870 for women age 35 to 39 (90% CI, 6,786 to 22,732).¹² For light cannabis users, the NNP was 4 to 5 times higher than the NNP for heavy cannabis users. This suggests that clinical interventions aimed at preventing dependence on cannabis would be more effective than interventions aimed at eliminating cannabis use.

Medical cannabis and increased potency

In recent years, the use of medical cannabis, which is used to address adverse effects of chemotherapy as well as neuropathic pain, Parkinson’s disease, and epilepsy, has been increasing.¹³ However, there is a lack of well-conducted randomized clinical trials evaluating medical cannabis’ efficacy and safety. As medical cannabis continues to gain public acceptance and more states permit its legal use, patients and physicians should be fully informed of the known adverse effects, including impaired attention, learning, and motivation.¹³

Several studies have drawn attention to the dose-dependence of many of cannabis’ effects. Since at least the 1960s, the concentration of THC in cannabis has increased substantially, thus increasing its potency. Based on 66,747 samples across 8 studies, 1 meta-analysis estimated that THC concentrations in herbal cannabis increased by 0.29% (P < .001) each year between 1970 and 2017.¹⁴ Similarly, THC concentrations in cannabis resins were found to have increased by 0.57% (P = .017) each year between 1975 and 2017.¹⁴ Cannabis products with high concentrations of THC carry an increased risk of addiction and mental health disorders.¹⁴

Identifying those at highest risk

Despite ongoing research, scientific consensus on the relationship of cannabis to schizophrenia and psychosis has yet to be reached. The disparity between the relatively high prevalence of regular adult use of cannabis (8%⁷)and the low incidence of cannabis-induced psychosis suggests that cannabis use alone is unlikely to lead to episodes of psychosis in individuals who are not predisposed to such episodes. Sarrazin et al¹⁵ evaluated 170 patients with schizophrenia, 31 of whom had cannabis use disorder. They found no significant difference in lifetime symptom dimensions between groups, and proposed that cannabis-associated schizophrenia should not be categorized as a distinct clinical entity of schizophrenia with specific features.¹⁵

Policies that encourage follow-up of patients after episodes of drug-induced psychosis may mitigate the adverse social and economic effects of schizophrenia. Currently, these policies are not widely implemented in health care institutions, possibly because psychotic symptoms may fade after the drug’s effects have dissipated. Despite this, these patients are at high risk of developing schizophrenia and self-harm. New-onset schizophrenia should be promptly identified because delayed diagnosis is associated with worse prognosis.⁶ Additionally, identifying genetic susceptibilities to schizophrenia—such as the Val158Met polymorphisms—in individuals who use cannabis could help clinicians manage or slow the onset or progression of schizophrenia.³ Motivational interviewing strategies should be used to minimize or eliminate cannabis use in individuals with active schizophrenia or psychosis, thus preventing worse outcomes.

Bottom Line

Identifying susceptibilities to schizophrenia may guide interventions in patients who use cannabis. Several large studies have suggested that cannabis use may exacerbate symptoms and worsen the prognosis of schizophrenia. Motivational interviewing strategies aimed at minimizing cannabis use may improve outcomes in patients with schizophrenia.

Related Resources

• Khokhar JY, Dwiel LL, Henricks AM, et al. The link between schizophrenia and substance use disorder: a unifying hypothesis. Schizophr Res. 2018;194:78-85. doi:10.1016/j. schres.2017.04.016
• Otite ES, Solanky A, Doumas S. Adolescents, THC, and the risk of psychosis. Current Psychiatry. 2021;20(12):e1-e2. doi:10.12788/cp.0197

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Approximately 1 in 200 individuals will be diagnosed with schizophrenia in their lifetime.¹ DSM-5 criteria for the diagnosis of schizophrenia require the presence of ≥2 of 5 symptoms: delusions, hallucinations, disordered speech, grossly disorganized (or catatonic) behavior, and negative symptoms such as flat affect or avolition.² Multiple studies have found increased rates of cannabis use among patients with schizophrenia. Because cognitive deficits are the chief predictor of clinical outcomes and quality of life in individuals with schizophrenia, the cognitive effects of cannabis use among these patients are of clinical significance.³ As legislation increasingly allows for the sale, possession, and consumption of cannabis, it is crucial to provide clinicians with evidence-based recommendations for treating patients who regularly use cannabis (approximately 8% of the adult population³). In this article, we analyze several peer-reviewed studies to investigate the impact of cannabis use on the onset and development of schizophrenia.

A look at substance-induced psychosis

Schizophrenia is associated with several structural brain changes, and some of these changes may be influenced by cannabis use (Box⁴). The biochemical etiology of schizophrenia is poorly understood but thought to involve dopamine, glutamate, serotonin, and gamma-aminobutyric acid. Certain positive symptoms, such as hallucinations, are uniquely human and difficult to study in animal models.⁵ Psychoactive substance use, especially cannabis, is frequently comorbid with schizophrenia. Additionally, certain individuals may be more predisposed to substance-induced psychosis than others based on genetic variation and underlying brain structure changes.⁴ Substance-induced psychosis is a psychotic state following the ingestion of a psychoactive substance or drug withdrawal lasting ≥48 hours.⁶ The psychoactive effects of cannabis have been associated with an exacerbation of existing schizophrenia symptoms.⁷ In 1998, Hall⁷ proposed 2 hypotheses to explain the relationship between cannabis and psychosis. The first was that heavy consumption of cannabis triggers a specific type of cannabis psychosis.⁷ The second was that cannabis use exacerbates existing schizophrenia, making the symptoms worse.⁷ Hall⁷ concluded that there was a complicated interaction among an individual’s vulnerability to their stressors, environment, and genetics.

Box

Cannabis, COMT, and homocysteine

Great advances have been made in our ability to examine the association between genetics and metabolism. One example of this is the interaction between the catechol-O-methyltransferase (COMT) gene and the active component of cannabis, delta-9-tetra­hydrocannabinol (THC). COMT codes for an enzyme that degrades cortical dopamine. The Val158Met polymorphism of this gene increases COMT activity, leading to increased dopamine catabolism, and thus decreased levels of extracellular dopamine, which induces an increase in mesolimbic dopaminergic activity, thereby increasing susceptibility to psychosis.³

In a study that genotyped 135 patients with schizophrenia, the Val158Met polymorphism was present in 29.63% of participants.³ Because THC can induce episodes of psychosis, individuals with this polymorphism may be at a higher risk of developing schizophrenia. Compared to Met carrier control participants with similar histories of cannabis consumption, those with the Val158Met polymorphism demonstrated markedly worse performance on tests of verbal fluency and processing speed.³ This is clinically significant because cognitive impairments are a major prognostic factor in schizophrenia, and identifying patients with this polymorphism could help personalize interventions for those who consume cannabis and are at risk of developing schizophrenia.

A study that evaluated 56 patients with first-episode schizophrenia found that having a history of cannabis abuse was associated with significantly higher levels of homocysteine as well as lower levels of high-density lipoprotein and vitamin B12.⁸ Homocysteine is an agonist at the glutamate binding site and a partial antagonist at the glycine co-agonist site in the N-methyl-D-aspartate receptor, which suggests that homocysteine may contribute to hypofunctioning of glutamate transmission; this is implicated in the development of schizophrenia. These increases in homocysteine are also found in siblings of patients with schizophrenia, which indicates a possible association between the methylenetetrahydrofolate (MTHFR) gene and schizophrenia.⁸

The C677T polymorphism in MTHFR may predict the risk of developing metabolic syndrome in patients taking second-generation antipsychotics.⁸ Elevations in homocysteine by as little as 5 μmol/L may increase schizophrenia risk by 70% compared to controls, possibly due to homocysteine initiating neuronal apoptosis, catalyzing dysfunction of the mitochondria, or increasing oxidative stress.⁸ There is a positive correlation between homocysteine levels and severity of negative symptoms (P = .006) and general psychopathology (P = .008) of schizophrenia when analyzed using the Positive and Negative Syndrome Scale.⁸ Negative symptoms such as blunted affect, apathy, anhedonia, and loss of motivation significantly impact the social and economic outcomes of patients diagnosed with schizophrenia.

Research paints a mixed picture

A Danish study analyzed the rates of conversion to schizophrenia or bipolar disorder (BD) among 6,788 individuals who received a diagnosis of substance-induced psychosis from 1994 to 2014.⁶ Ten comparison participants were selected for each case participant, matched on sex and year/month of birth. Participants were followed until the first occurrence of schizophrenia or BD, death, or emigration from Denmark. Substances implicated in the initial psychotic episode included cannabis, alcohol, opioids, sedatives, cocaine, amphetamines, hallucinogens, and combinations of substances.

Continue to: The overall conversion rate...

The overall conversion rate over 20 years was 32.2% (95% CI, 29.7 to 34.9), with 26.0% developing schizophrenia vs 8.4% developing BD.⁶ Of the substances involved, cannabis was the most common, implicated in 41.2% (95% CI, 36.6 to 46.2) of cases.⁶ One-half of male patients converted within 2.0 years and one-half of female patients converted within 4.4 years after a cannabis-induced psychosis.⁶

This study had several limitations. It could not account for any short-term psychotic symptoms experienced by the general population, especially after cannabis use. Such patients might not seek treatment. Thus, the results might not be generalizable to the general population. The study did not evaluate if conversion rates differed based on continued substance use following the psychosis episode, or the amount of each substance taken prior to the episode. Dose-dependence was not well elucidated, and this study only looked at patients from Denmark and did not account for socioeconomic status.⁶

Another Danish study looked at the influences of gender and cannabis use in the early course of the disease in 133 patients with schizophrenia.⁹ These researchers found that male gender was a significant predictor of earlier onset of dysfunction socially and in the workplace, as well as a higher risk of developing negative symptoms. However, compared to gender, cannabis use was a stronger predictor of age at first psychotic episode. For cannabis users, the median age of onset of negative symptoms was 23.7, compared to 38.4 for nonusers (P < .001).⁹

Cannabis use is significantly elevated among individuals with psychosis, with a 12-month prevalence of 29.2% compared to 4.0% among the general population of the United States.¹⁰ In a study that assessed 229 patients with a schizophrenia spectrum disorder during their first hospitalization and 6 months, 2 years, 4 years, and 10 years later, Foti et al¹⁰ found that the lifetime rate of cannabis use was 66.2%. Survival analysis found cannabis use doubled the risk of the onset of psychosis compared to nonusers of the same age (hazard ratio [HR] = 1.97; 95% CI, 1.48 to 2.62, P < .001), even after adjusting for socioeconomic status, age, and gender (HR = 1.34; 95% CI, 1.01 to 1.77, P < .05).¹⁰ Additionally, Foti et al¹⁰ found significant positive correlations between psychotic symptoms and cannabis use in patients with schizophrenia over the course of 10 years. An increase in symptoms was associated with a higher likelihood of cannabis use, and a decrease in symptoms was correlated with a lower likelihood of use (adjusted odds ratio = 1.64; 95% CI, 1.12 to 2.43, P < .0125).¹⁰

Ortiz-Medina et al¹¹ conducted a meta-analysis of 22 studies of 15 cohorts from healthy populations and 12 other cohort follow-up studies that evaluated the onset of psychotic symptoms in individuals who used cannabis. Most studies found associations between cannabis use and the onset of symptoms of schizophrenia, and most determined cannabis was also a major risk factor for other psychotic disorders. Analyses of dose-dependence indicated that repeated cannabis use increased the risk of developing psychotic symptoms. This risk is increased when an individual starts using cannabis before age 15.¹¹ Age seemed to be a stronger predictor of onset and outcome than sex, with no significant differences between men and women. One study in this review found that approximately 8% to 13% cases of schizophrenia may have been solely due to cannabis.¹¹ The most significant limitation to the studies analyzed in this review is that retrospective studies utilize self-reported questionnaires.

Continue to: Other researchers have found...

Other researchers have found it would take a relatively high number of individuals to stop using cannabis to prevent 1 case of schizophrenia. In a study of data from England and Wales, Hickman et al¹² evaluated the best available estimates of the incidence of schizophrenia, rates of heavy and light cannabis use, and risk that cannabis causes schizophrenia to determine the number needed to prevent (NNP) 1 case of schizophrenia. They estimated that it would require approximately 2,800 men age 20 to 24 (90% CI, 2,018 to 4,530) and 4,700 men age 35 to 39 (90% CI, 3,114 to 8,416) who heavily used cannabis to stop their consumption to prevent 1 case of schizophrenia.¹² For women with heavy cannabis use, the mean NNP was 5,470 for women age 25 to 29 (90% CI, 3,640 to 9,839) and 10,870 for women age 35 to 39 (90% CI, 6,786 to 22,732).¹² For light cannabis users, the NNP was 4 to 5 times higher than the NNP for heavy cannabis users. This suggests that clinical interventions aimed at preventing dependence on cannabis would be more effective than interventions aimed at eliminating cannabis use.

Medical cannabis and increased potency

In recent years, the use of medical cannabis, which is used to address adverse effects of chemotherapy as well as neuropathic pain, Parkinson’s disease, and epilepsy, has been increasing.¹³ However, there is a lack of well-conducted randomized clinical trials evaluating medical cannabis’ efficacy and safety. As medical cannabis continues to gain public acceptance and more states permit its legal use, patients and physicians should be fully informed of the known adverse effects, including impaired attention, learning, and motivation.¹³

Several studies have drawn attention to the dose-dependence of many of cannabis’ effects. Since at least the 1960s, the concentration of THC in cannabis has increased substantially, thus increasing its potency. Based on 66,747 samples across 8 studies, 1 meta-analysis estimated that THC concentrations in herbal cannabis increased by 0.29% (P < .001) each year between 1970 and 2017.¹⁴ Similarly, THC concentrations in cannabis resins were found to have increased by 0.57% (P = .017) each year between 1975 and 2017.¹⁴ Cannabis products with high concentrations of THC carry an increased risk of addiction and mental health disorders.¹⁴

Identifying those at highest risk

Despite ongoing research, scientific consensus on the relationship of cannabis to schizophrenia and psychosis has yet to be reached. The disparity between the relatively high prevalence of regular adult use of cannabis (8%⁷)and the low incidence of cannabis-induced psychosis suggests that cannabis use alone is unlikely to lead to episodes of psychosis in individuals who are not predisposed to such episodes. Sarrazin et al¹⁵ evaluated 170 patients with schizophrenia, 31 of whom had cannabis use disorder. They found no significant difference in lifetime symptom dimensions between groups, and proposed that cannabis-associated schizophrenia should not be categorized as a distinct clinical entity of schizophrenia with specific features.¹⁵

Policies that encourage follow-up of patients after episodes of drug-induced psychosis may mitigate the adverse social and economic effects of schizophrenia. Currently, these policies are not widely implemented in health care institutions, possibly because psychotic symptoms may fade after the drug’s effects have dissipated. Despite this, these patients are at high risk of developing schizophrenia and self-harm. New-onset schizophrenia should be promptly identified because delayed diagnosis is associated with worse prognosis.⁶ Additionally, identifying genetic susceptibilities to schizophrenia—such as the Val158Met polymorphisms—in individuals who use cannabis could help clinicians manage or slow the onset or progression of schizophrenia.³ Motivational interviewing strategies should be used to minimize or eliminate cannabis use in individuals with active schizophrenia or psychosis, thus preventing worse outcomes.

Bottom Line

Identifying susceptibilities to schizophrenia may guide interventions in patients who use cannabis. Several large studies have suggested that cannabis use may exacerbate symptoms and worsen the prognosis of schizophrenia. Motivational interviewing strategies aimed at minimizing cannabis use may improve outcomes in patients with schizophrenia.

Related Resources

• Khokhar JY, Dwiel LL, Henricks AM, et al. The link between schizophrenia and substance use disorder: a unifying hypothesis. Schizophr Res. 2018;194:78-85. doi:10.1016/j. schres.2017.04.016
• Otite ES, Solanky A, Doumas S. Adolescents, THC, and the risk of psychosis. Current Psychiatry. 2021;20(12):e1-e2. doi:10.12788/cp.0197

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Approximately 1 in 200 individuals will be diagnosed with schizophrenia in their lifetime.¹ DSM-5 criteria for the diagnosis of schizophrenia require the presence of ≥2 of 5 symptoms: delusions, hallucinations, disordered speech, grossly disorganized (or catatonic) behavior, and negative symptoms such as flat affect or avolition.² Multiple studies have found increased rates of cannabis use among patients with schizophrenia. Because cognitive deficits are the chief predictor of clinical outcomes and quality of life in individuals with schizophrenia, the cognitive effects of cannabis use among these patients are of clinical significance.³ As legislation increasingly allows for the sale, possession, and consumption of cannabis, it is crucial to provide clinicians with evidence-based recommendations for treating patients who regularly use cannabis (approximately 8% of the adult population³). In this article, we analyze several peer-reviewed studies to investigate the impact of cannabis use on the onset and development of schizophrenia.

A look at substance-induced psychosis

Schizophrenia is associated with several structural brain changes, and some of these changes may be influenced by cannabis use (Box⁴). The biochemical etiology of schizophrenia is poorly understood but thought to involve dopamine, glutamate, serotonin, and gamma-aminobutyric acid. Certain positive symptoms, such as hallucinations, are uniquely human and difficult to study in animal models.⁵ Psychoactive substance use, especially cannabis, is frequently comorbid with schizophrenia. Additionally, certain individuals may be more predisposed to substance-induced psychosis than others based on genetic variation and underlying brain structure changes.⁴ Substance-induced psychosis is a psychotic state following the ingestion of a psychoactive substance or drug withdrawal lasting ≥48 hours.⁶ The psychoactive effects of cannabis have been associated with an exacerbation of existing schizophrenia symptoms.⁷ In 1998, Hall⁷ proposed 2 hypotheses to explain the relationship between cannabis and psychosis. The first was that heavy consumption of cannabis triggers a specific type of cannabis psychosis.⁷ The second was that cannabis use exacerbates existing schizophrenia, making the symptoms worse.⁷ Hall⁷ concluded that there was a complicated interaction among an individual’s vulnerability to their stressors, environment, and genetics.

Box

Cannabis, COMT, and homocysteine

Great advances have been made in our ability to examine the association between genetics and metabolism. One example of this is the interaction between the catechol-O-methyltransferase (COMT) gene and the active component of cannabis, delta-9-tetra­hydrocannabinol (THC). COMT codes for an enzyme that degrades cortical dopamine. The Val158Met polymorphism of this gene increases COMT activity, leading to increased dopamine catabolism, and thus decreased levels of extracellular dopamine, which induces an increase in mesolimbic dopaminergic activity, thereby increasing susceptibility to psychosis.³

In a study that genotyped 135 patients with schizophrenia, the Val158Met polymorphism was present in 29.63% of participants.³ Because THC can induce episodes of psychosis, individuals with this polymorphism may be at a higher risk of developing schizophrenia. Compared to Met carrier control participants with similar histories of cannabis consumption, those with the Val158Met polymorphism demonstrated markedly worse performance on tests of verbal fluency and processing speed.³ This is clinically significant because cognitive impairments are a major prognostic factor in schizophrenia, and identifying patients with this polymorphism could help personalize interventions for those who consume cannabis and are at risk of developing schizophrenia.

A study that evaluated 56 patients with first-episode schizophrenia found that having a history of cannabis abuse was associated with significantly higher levels of homocysteine as well as lower levels of high-density lipoprotein and vitamin B12.⁸ Homocysteine is an agonist at the glutamate binding site and a partial antagonist at the glycine co-agonist site in the N-methyl-D-aspartate receptor, which suggests that homocysteine may contribute to hypofunctioning of glutamate transmission; this is implicated in the development of schizophrenia. These increases in homocysteine are also found in siblings of patients with schizophrenia, which indicates a possible association between the methylenetetrahydrofolate (MTHFR) gene and schizophrenia.⁸

The C677T polymorphism in MTHFR may predict the risk of developing metabolic syndrome in patients taking second-generation antipsychotics.⁸ Elevations in homocysteine by as little as 5 μmol/L may increase schizophrenia risk by 70% compared to controls, possibly due to homocysteine initiating neuronal apoptosis, catalyzing dysfunction of the mitochondria, or increasing oxidative stress.⁸ There is a positive correlation between homocysteine levels and severity of negative symptoms (P = .006) and general psychopathology (P = .008) of schizophrenia when analyzed using the Positive and Negative Syndrome Scale.⁸ Negative symptoms such as blunted affect, apathy, anhedonia, and loss of motivation significantly impact the social and economic outcomes of patients diagnosed with schizophrenia.

Research paints a mixed picture

A Danish study analyzed the rates of conversion to schizophrenia or bipolar disorder (BD) among 6,788 individuals who received a diagnosis of substance-induced psychosis from 1994 to 2014.⁶ Ten comparison participants were selected for each case participant, matched on sex and year/month of birth. Participants were followed until the first occurrence of schizophrenia or BD, death, or emigration from Denmark. Substances implicated in the initial psychotic episode included cannabis, alcohol, opioids, sedatives, cocaine, amphetamines, hallucinogens, and combinations of substances.

Continue to: The overall conversion rate...

The overall conversion rate over 20 years was 32.2% (95% CI, 29.7 to 34.9), with 26.0% developing schizophrenia vs 8.4% developing BD.⁶ Of the substances involved, cannabis was the most common, implicated in 41.2% (95% CI, 36.6 to 46.2) of cases.⁶ One-half of male patients converted within 2.0 years and one-half of female patients converted within 4.4 years after a cannabis-induced psychosis.⁶

This study had several limitations. It could not account for any short-term psychotic symptoms experienced by the general population, especially after cannabis use. Such patients might not seek treatment. Thus, the results might not be generalizable to the general population. The study did not evaluate if conversion rates differed based on continued substance use following the psychosis episode, or the amount of each substance taken prior to the episode. Dose-dependence was not well elucidated, and this study only looked at patients from Denmark and did not account for socioeconomic status.⁶

Another Danish study looked at the influences of gender and cannabis use in the early course of the disease in 133 patients with schizophrenia.⁹ These researchers found that male gender was a significant predictor of earlier onset of dysfunction socially and in the workplace, as well as a higher risk of developing negative symptoms. However, compared to gender, cannabis use was a stronger predictor of age at first psychotic episode. For cannabis users, the median age of onset of negative symptoms was 23.7, compared to 38.4 for nonusers (P < .001).⁹

Cannabis use is significantly elevated among individuals with psychosis, with a 12-month prevalence of 29.2% compared to 4.0% among the general population of the United States.¹⁰ In a study that assessed 229 patients with a schizophrenia spectrum disorder during their first hospitalization and 6 months, 2 years, 4 years, and 10 years later, Foti et al¹⁰ found that the lifetime rate of cannabis use was 66.2%. Survival analysis found cannabis use doubled the risk of the onset of psychosis compared to nonusers of the same age (hazard ratio [HR] = 1.97; 95% CI, 1.48 to 2.62, P < .001), even after adjusting for socioeconomic status, age, and gender (HR = 1.34; 95% CI, 1.01 to 1.77, P < .05).¹⁰ Additionally, Foti et al¹⁰ found significant positive correlations between psychotic symptoms and cannabis use in patients with schizophrenia over the course of 10 years. An increase in symptoms was associated with a higher likelihood of cannabis use, and a decrease in symptoms was correlated with a lower likelihood of use (adjusted odds ratio = 1.64; 95% CI, 1.12 to 2.43, P < .0125).¹⁰

Ortiz-Medina et al¹¹ conducted a meta-analysis of 22 studies of 15 cohorts from healthy populations and 12 other cohort follow-up studies that evaluated the onset of psychotic symptoms in individuals who used cannabis. Most studies found associations between cannabis use and the onset of symptoms of schizophrenia, and most determined cannabis was also a major risk factor for other psychotic disorders. Analyses of dose-dependence indicated that repeated cannabis use increased the risk of developing psychotic symptoms. This risk is increased when an individual starts using cannabis before age 15.¹¹ Age seemed to be a stronger predictor of onset and outcome than sex, with no significant differences between men and women. One study in this review found that approximately 8% to 13% cases of schizophrenia may have been solely due to cannabis.¹¹ The most significant limitation to the studies analyzed in this review is that retrospective studies utilize self-reported questionnaires.

Continue to: Other researchers have found...

Other researchers have found it would take a relatively high number of individuals to stop using cannabis to prevent 1 case of schizophrenia. In a study of data from England and Wales, Hickman et al¹² evaluated the best available estimates of the incidence of schizophrenia, rates of heavy and light cannabis use, and risk that cannabis causes schizophrenia to determine the number needed to prevent (NNP) 1 case of schizophrenia. They estimated that it would require approximately 2,800 men age 20 to 24 (90% CI, 2,018 to 4,530) and 4,700 men age 35 to 39 (90% CI, 3,114 to 8,416) who heavily used cannabis to stop their consumption to prevent 1 case of schizophrenia.¹² For women with heavy cannabis use, the mean NNP was 5,470 for women age 25 to 29 (90% CI, 3,640 to 9,839) and 10,870 for women age 35 to 39 (90% CI, 6,786 to 22,732).¹² For light cannabis users, the NNP was 4 to 5 times higher than the NNP for heavy cannabis users. This suggests that clinical interventions aimed at preventing dependence on cannabis would be more effective than interventions aimed at eliminating cannabis use.

Medical cannabis and increased potency

In recent years, the use of medical cannabis, which is used to address adverse effects of chemotherapy as well as neuropathic pain, Parkinson’s disease, and epilepsy, has been increasing.¹³ However, there is a lack of well-conducted randomized clinical trials evaluating medical cannabis’ efficacy and safety. As medical cannabis continues to gain public acceptance and more states permit its legal use, patients and physicians should be fully informed of the known adverse effects, including impaired attention, learning, and motivation.¹³

Several studies have drawn attention to the dose-dependence of many of cannabis’ effects. Since at least the 1960s, the concentration of THC in cannabis has increased substantially, thus increasing its potency. Based on 66,747 samples across 8 studies, 1 meta-analysis estimated that THC concentrations in herbal cannabis increased by 0.29% (P < .001) each year between 1970 and 2017.¹⁴ Similarly, THC concentrations in cannabis resins were found to have increased by 0.57% (P = .017) each year between 1975 and 2017.¹⁴ Cannabis products with high concentrations of THC carry an increased risk of addiction and mental health disorders.¹⁴

Identifying those at highest risk

Despite ongoing research, scientific consensus on the relationship of cannabis to schizophrenia and psychosis has yet to be reached. The disparity between the relatively high prevalence of regular adult use of cannabis (8%⁷)and the low incidence of cannabis-induced psychosis suggests that cannabis use alone is unlikely to lead to episodes of psychosis in individuals who are not predisposed to such episodes. Sarrazin et al¹⁵ evaluated 170 patients with schizophrenia, 31 of whom had cannabis use disorder. They found no significant difference in lifetime symptom dimensions between groups, and proposed that cannabis-associated schizophrenia should not be categorized as a distinct clinical entity of schizophrenia with specific features.¹⁵

Policies that encourage follow-up of patients after episodes of drug-induced psychosis may mitigate the adverse social and economic effects of schizophrenia. Currently, these policies are not widely implemented in health care institutions, possibly because psychotic symptoms may fade after the drug’s effects have dissipated. Despite this, these patients are at high risk of developing schizophrenia and self-harm. New-onset schizophrenia should be promptly identified because delayed diagnosis is associated with worse prognosis.⁶ Additionally, identifying genetic susceptibilities to schizophrenia—such as the Val158Met polymorphisms—in individuals who use cannabis could help clinicians manage or slow the onset or progression of schizophrenia.³ Motivational interviewing strategies should be used to minimize or eliminate cannabis use in individuals with active schizophrenia or psychosis, thus preventing worse outcomes.

Bottom Line

Identifying susceptibilities to schizophrenia may guide interventions in patients who use cannabis. Several large studies have suggested that cannabis use may exacerbate symptoms and worsen the prognosis of schizophrenia. Motivational interviewing strategies aimed at minimizing cannabis use may improve outcomes in patients with schizophrenia.

Related Resources

• Khokhar JY, Dwiel LL, Henricks AM, et al. The link between schizophrenia and substance use disorder: a unifying hypothesis. Schizophr Res. 2018;194:78-85. doi:10.1016/j. schres.2017.04.016
• Otite ES, Solanky A, Doumas S. Adolescents, THC, and the risk of psychosis. Current Psychiatry. 2021;20(12):e1-e2. doi:10.12788/cp.0197

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CASE Thoughts of harming baby

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

HISTORY Depression and possible auditory hallucinations

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

EVALUATION Distressing thoughts and discontinued medications

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

[polldaddy:13041928]

The authors’ observations

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

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

CP02212048_t1.png

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

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

Continue to: The prevalence of OCD...

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

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

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

TREATMENT Involuntary hospitalization

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

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

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Continue to: The authors' observations

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

CP02212048_f1.png

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

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

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

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

Continue to: Patients who have experienced...

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

OUTCOME Improved mood

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

The authors’ observations

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

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

Bottom Line

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

Related Resources

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

Drug Brand Names

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

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CASE Thoughts of harming baby

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

HISTORY Depression and possible auditory hallucinations

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

EVALUATION Distressing thoughts and discontinued medications

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

[polldaddy:13041928]

The authors’ observations

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

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

CP02212048_t1.png

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

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

Continue to: The prevalence of OCD...

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

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

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

TREATMENT Involuntary hospitalization

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

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

[polldaddy:13041932]

Continue to: The authors' observations

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

CP02212048_f1.png

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

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

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

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

Continue to: Patients who have experienced...

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

OUTCOME Improved mood

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

The authors’ observations

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

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

Bottom Line

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

Related Resources

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

Drug Brand Names

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

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[embed:render:related:node:197703]

CASE Thoughts of harming baby

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

HISTORY Depression and possible auditory hallucinations

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

EVALUATION Distressing thoughts and discontinued medications

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

[polldaddy:13041928]

The authors’ observations

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

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

CP02212048_t1.png

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

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

Continue to: The prevalence of OCD...

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

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

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

TREATMENT Involuntary hospitalization

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

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

[polldaddy:13041932]

Continue to: The authors' observations

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

CP02212048_f1.png

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

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

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

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

Continue to: Patients who have experienced...

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

OUTCOME Improved mood

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

The authors’ observations

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

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

Bottom Line

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

Related Resources

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

Drug Brand Names

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

[embed:render:related:node:199890]

[embed:render:related:node:197703]

TOPLINE:

Black psychiatric inpatients are 85% more likely to be restrained with a physical or mechanical hold or with medication than White patients, and often for longer periods, new research suggests.

METHODOLOGY:

• The study, part of a larger retrospective chart review of inpatient psychiatric electronic medical records (EMRs), included 29,739 adolescents (aged 12-17 years) and adults admitted because of severe and disruptive psychiatric illness or concerns about self-harm.
• A restraint event was defined as a physician-ordered physical or mechanical hold in which patients are unable to move their limbs, body, or head or are given medication to restrict their movement.
• Researchers used scores on the Dynamic Appraisal of Situational Aggression (DASA) at admission to assess risk for aggression among high-risk psychiatric inpatients (scores ranged from a low of 0 to a high of 7).
• From restraint event data extracted from the EMR, researchers investigated whether restraint frequency or duration was affected by “adultification,” a form of racial bias in which adolescents are perceived as being older than their actual age and are treated accordingly.

TAKEAWAY:

• Of the entire cohort, 1867 (6.3%) experienced a restraint event, and 27,872 (93.7%) did not.
• Compared with White patients, restraint was 85% more likely among Black patients (adjusted odds ratio, 1.85; P < .001) and 36% more likely among multiracial patients (aOR, 1.36; P = .006), which researchers suggest may reflect systemic racism within psychiatry and medicine, as well as an implicit or learned perception that people of color are more aggressive and dangerous.
• Lower DASA score at admission (P = .001), shorter length of stay (P < .001), adult age (P = .001), female sex (P = .042), and Black race, compared with White race (P = .001), were significantly associated with longer restraint duration, which may serve as a proxy for psychiatric symptom severity.
• Neither age group alone (adolescent or adult) nor the interaction of race and age group was significantly associated with experiencing a restraint event, suggesting no evidence of “adultification.”

IN PRACTICE:

It’s important to raise awareness about racial differences in restraint events in inpatient psychiatric settings, the authors write, adding that addressing overcrowding and investing in bias assessment and restraint education may reduce bias in the care of agitated patients and the use of restraints.

SOURCE:

The study was carried out by Sonali Singal, BS, Institute of Behavioral Science, Feinstein Institutes for Medical Research, Manhasset, N.Y., and colleagues. It was published online  in Psychiatric Services.

LIMITATIONS:

The variables analyzed in the study were limited by the retrospective chart review and by the available EMR data, which may have contained entry errors. Although the investigators used DASA scores to control for differences in aggression, they could not control for symptom severity. The study could not examine the impact of race on seclusion (involuntary confinement), a variable often examined in tandem with restraint, because there were too few such events. The analysis also did not control for substance use disorder, which can influence a patient’s behavior and be related to restraint use.

DISCLOSURES:

Ms. Singal reported no relevant financial relationships. The original article has disclosures of other authors.

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

TOPLINE:

Black psychiatric inpatients are 85% more likely to be restrained with a physical or mechanical hold or with medication than White patients, and often for longer periods, new research suggests.

METHODOLOGY:

• The study, part of a larger retrospective chart review of inpatient psychiatric electronic medical records (EMRs), included 29,739 adolescents (aged 12-17 years) and adults admitted because of severe and disruptive psychiatric illness or concerns about self-harm.
• A restraint event was defined as a physician-ordered physical or mechanical hold in which patients are unable to move their limbs, body, or head or are given medication to restrict their movement.
• Researchers used scores on the Dynamic Appraisal of Situational Aggression (DASA) at admission to assess risk for aggression among high-risk psychiatric inpatients (scores ranged from a low of 0 to a high of 7).
• From restraint event data extracted from the EMR, researchers investigated whether restraint frequency or duration was affected by “adultification,” a form of racial bias in which adolescents are perceived as being older than their actual age and are treated accordingly.

TAKEAWAY:

• Of the entire cohort, 1867 (6.3%) experienced a restraint event, and 27,872 (93.7%) did not.
• Compared with White patients, restraint was 85% more likely among Black patients (adjusted odds ratio, 1.85; P < .001) and 36% more likely among multiracial patients (aOR, 1.36; P = .006), which researchers suggest may reflect systemic racism within psychiatry and medicine, as well as an implicit or learned perception that people of color are more aggressive and dangerous.
• Lower DASA score at admission (P = .001), shorter length of stay (P < .001), adult age (P = .001), female sex (P = .042), and Black race, compared with White race (P = .001), were significantly associated with longer restraint duration, which may serve as a proxy for psychiatric symptom severity.
• Neither age group alone (adolescent or adult) nor the interaction of race and age group was significantly associated with experiencing a restraint event, suggesting no evidence of “adultification.”

IN PRACTICE:

It’s important to raise awareness about racial differences in restraint events in inpatient psychiatric settings, the authors write, adding that addressing overcrowding and investing in bias assessment and restraint education may reduce bias in the care of agitated patients and the use of restraints.

SOURCE:

The study was carried out by Sonali Singal, BS, Institute of Behavioral Science, Feinstein Institutes for Medical Research, Manhasset, N.Y., and colleagues. It was published online  in Psychiatric Services.

LIMITATIONS:

The variables analyzed in the study were limited by the retrospective chart review and by the available EMR data, which may have contained entry errors. Although the investigators used DASA scores to control for differences in aggression, they could not control for symptom severity. The study could not examine the impact of race on seclusion (involuntary confinement), a variable often examined in tandem with restraint, because there were too few such events. The analysis also did not control for substance use disorder, which can influence a patient’s behavior and be related to restraint use.

DISCLOSURES:

Ms. Singal reported no relevant financial relationships. The original article has disclosures of other authors.

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

TOPLINE:

Black psychiatric inpatients are 85% more likely to be restrained with a physical or mechanical hold or with medication than White patients, and often for longer periods, new research suggests.

METHODOLOGY:

• The study, part of a larger retrospective chart review of inpatient psychiatric electronic medical records (EMRs), included 29,739 adolescents (aged 12-17 years) and adults admitted because of severe and disruptive psychiatric illness or concerns about self-harm.
• A restraint event was defined as a physician-ordered physical or mechanical hold in which patients are unable to move their limbs, body, or head or are given medication to restrict their movement.
• Researchers used scores on the Dynamic Appraisal of Situational Aggression (DASA) at admission to assess risk for aggression among high-risk psychiatric inpatients (scores ranged from a low of 0 to a high of 7).
• From restraint event data extracted from the EMR, researchers investigated whether restraint frequency or duration was affected by “adultification,” a form of racial bias in which adolescents are perceived as being older than their actual age and are treated accordingly.

TAKEAWAY:

• Of the entire cohort, 1867 (6.3%) experienced a restraint event, and 27,872 (93.7%) did not.
• Compared with White patients, restraint was 85% more likely among Black patients (adjusted odds ratio, 1.85; P < .001) and 36% more likely among multiracial patients (aOR, 1.36; P = .006), which researchers suggest may reflect systemic racism within psychiatry and medicine, as well as an implicit or learned perception that people of color are more aggressive and dangerous.
• Lower DASA score at admission (P = .001), shorter length of stay (P < .001), adult age (P = .001), female sex (P = .042), and Black race, compared with White race (P = .001), were significantly associated with longer restraint duration, which may serve as a proxy for psychiatric symptom severity.
• Neither age group alone (adolescent or adult) nor the interaction of race and age group was significantly associated with experiencing a restraint event, suggesting no evidence of “adultification.”

IN PRACTICE:

It’s important to raise awareness about racial differences in restraint events in inpatient psychiatric settings, the authors write, adding that addressing overcrowding and investing in bias assessment and restraint education may reduce bias in the care of agitated patients and the use of restraints.

SOURCE:

The study was carried out by Sonali Singal, BS, Institute of Behavioral Science, Feinstein Institutes for Medical Research, Manhasset, N.Y., and colleagues. It was published online  in Psychiatric Services.

LIMITATIONS:

The variables analyzed in the study were limited by the retrospective chart review and by the available EMR data, which may have contained entry errors. Although the investigators used DASA scores to control for differences in aggression, they could not control for symptom severity. The study could not examine the impact of race on seclusion (involuntary confinement), a variable often examined in tandem with restraint, because there were too few such events. The analysis also did not control for substance use disorder, which can influence a patient’s behavior and be related to restraint use.

DISCLOSURES:

Ms. Singal reported no relevant financial relationships. The original article has disclosures of other authors.

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

CP02211033_pp.png

Ms. K, age 32, presents to the psychiatric clinic for a routine follow-up. Her history includes agoraphobia, attention-deficit/hyperactivity disorder, and schizoaffective disorder. Ms. K’s current medications are oral hydroxyzine 50 mg 4 times daily as needed for anxiety and paliperidone palmitate 234 mg IM monthly. Since her last follow-up, she has been switched from oral sertraline 150 mg/d to oral paroxetine 20 mg/d. Ms. K reports having constipation (which improves by taking oral docusate 100 mg twice daily) and generalized hyperhidrosis. She wants to alleviate the hyperhidrosis without changing her paroxetine because that medication improved her symptoms.

Hyperhidrosis—excessive sweating not need­ed to maintain a normal body temperature—is an uncommon and uncomfortable adverse effect of many medications, including psychotropics.¹ This long-term adverse effect typically is not dose-related and does not remit with continued therapy.²Table 1^1-3 lists psychotropic medications associated with hyperhidrosis as well as postulated mechanisms.

CP02211033_t1.png

The incidence of medication-induced hyperhidrosis is unknown,but for psychotropic medications it is estimated to be 5% to 20%.³ Patients may not report hyperhidrosis due to embarrassment; in clinical trials, reporting measures may be inconsistent and, in some cases, misleading. For example, it is possible hyperhidrosis that appears to be associated with buprenorphine is actually a symptom of the withdrawal syndrome rather than a direct effect of the medication. Also, some medications, including certain psychotropics (eg, paroxetine⁴ and topiramate³) may cause either hyperhidrosis or hypohidrosis (decreased sweating). Few medications carry labeled warnings for hypohidrosis; the condition generally is not of clinical concern unless patients experience heat intolerance or hyperthermia.³

Psychotropic-induced hyperhidrosis is likely an idiopathic effect. There are few known predisposing factors, but some medications carry a greater risk than others. In a meta-analysis, Beyer et al² found certain selective serotonin reuptake inhibitors (SSRIs), such as sertraline and paroxetine, had a higher risk of causing hyperhidrosis. Fluvoxamine, bupropion, and vortioxetine had the lowest risk. The class risk for SSRIs was comparable to that of serotonin-norepinephrine reuptake inhibitors (SNRIs), which all carried a comparable risk. In this analysis, neither indication nor dose were reliable indicators of risk of causing hyperhidrosis. However, the study found that for both SSRIs and SNRIs, increased affinity for the dopamine transporter was correlated with an increased risk of hyperhidrosis.²

Treatment

Treatment of hyperhidrosis depends on its cause and presentation.⁵ Hyperhidrosis may be categorized as primary (idiopathic) or secondary (also termed diaphoresis), and either focal or generalized.⁶ Many treatment recommendations focus on primary or focal hyperhidrosis and prioritize topical therapies.⁵ Because medication-induced hyperhidrosis most commonly presents as generalized³ and thus affects a large body surface area, the use of topical therapies is precluded. Topical therapy for psychotropic-induced hyperhidrosis should be pursued only if the patient’s sweating is localized.

Treating medication-induced hyperhidrosis becomes more complicated if it is not possible to alter the inciting medication (ie, because the medication is effective or the patient is resistant to change). In such scenarios, discontinuing the medication and initiating an alternative therapy may not be effective or feasible.² For generalized presentations of medication-induced hyperhidrosis, if the inciting medication cannot be altered, initiating an oral systemic therapy is the preferred treatment.^3,5

Oral anticholinergic medications (eg, benztropine, glycopyrrolate, and oxybutynin),^4-6 act directly on muscarinic receptors within the eccrine sweat glands to decrease or stop sweating. They are considered first-line for generalized hyperhidrosis but may be inappropriate for psychotropic-induced hyperhidrosis because many psychotropics (eg, tricyclic antidepressants, paroxetine, olanzapine, quetiapine, and clozapine) have anticholinergic properties. Adding an anticholinergic medication to these patients’ regimens may increase the adverse effect burden and worsen cognitive deficits. Additionally, approximately one-third of patients discontinue anticholinergic medications due to tolerability issues (eg, dry mouth).

Continue to: However, anticholinergic medications...

However, anticholinergic medications may still have a role in treating psychotropic-induced hyperhidrosis. Benztropine^3,7,8 and cyproheptadine^2,3,9 may be effective options, though their role in treating psychotropic-induced hyperhidrosis should be limited and reserved for patients who have another compelling indication for these medications (eg, extrapyramidal symptoms) or when other treatment options are ineffective or intolerable.

Avoiding anticholinergic medications can also be justified based on the proposed mechanism of psychotropic-induced hyperhidrosis as an extension of the medication’s toxic effects. Conceptualizing psychotropic-induced hyperhidrosis as similar to the diaphoresis and hyperthermia observed in neuroleptic malignant syndrome and serotonin syndrome offers a clearer target for treatment. Though the specifics of the mechanisms remain unknown,² many medications that cause hyperhidrosis do so by increasing sweat gland secretions, either directly by increasing cholinergic activity or indirectly via increased sympathetic transmission.

Considering this pathophysiology, another target for psychotropic-induced hyperhidrosis may be altered and/or excessive catecholamine activity. The use of medications such as clonidine,^3-6 propranolol,^4-6 or terazosin^2,3,10 should be considered given their beneficial effects on the activation of the sympathetic nervous system, although clonidine also possesses anticholinergic activity. The calcium channel blocker diltiazem can improve hyperhidrosis symptoms by interfering with the calcium signaling necessary for normal sweat gland function.^4,5 Comorbid cardiovascular diseases and tachycardia, an adverse effect of many psychotropic medications, may also be managed with these treatment options. Some research suggests using benzodiazepines to treat psychotropic-induced hyperhidrosis.^4-6 As is the case for anticholinergic medications, the use of benzodiazepines would require another compelling indication for long-term use.

Table 2^3,4,6-8,10 provides recommended dosing and caveats for the use of these medications and other potentially appropriate medications.

CP02211033_t2.png

Research of investigational treatments for generalized hyperhidrosis is ongoing. It is possible some of these medications may have a future role in the treatment of psychotropic-induced hyperhidrosis, with improved efficacy and better tolerability.

Continue to: CASE CONTINUED

CASE CONTINUED

Because Ms. K’s medication-induced hyperhidrosis is generalized and therefore ineligible for topical therapies, and because the inciting medication (paroxetine) cannot be switched to an alternative, the treatment team considers adding an oral medication. Treatment with an anticholinergic medication, such as benztropine, is not preferred due to the anticholinergic activity associated with paroxetine and Ms. K’s history of constipation. After discussing other oral treatment options with Ms. K, the team ultimately decides to initiate propranolol at a low dose (5 mg twice daily) to minimize the chances of an interaction with paroxetine, and titrate based on efficacy and tolerability.

Related Resources

• International Hyperhidrosis Society. Hyperhidrosis treatment overview. www.sweathelp.org/hyperhidrosis-treatments/treatment-overview.html

Drug Brand Names

Acamprosate • Campral
Aripiprazole • Abilify
Buprenorphine • Sublocade
Buprenorphine/naloxone • Zubsolv
Bupropion • Wellbutrin
Carbamazepine • Tegretol
Citalopram • Celexa
Clomipramine • Anafranil
Clonidine • Catapres
Clozapine • Clozaril
Desipramine • Norpramin
Desvenlafaxine • Pristiq
Dextroamphetamine/amphetamine • Adderall
Diltiazem • Cardizem
Divalproex • Depakote
Donepezil • Aricept
Doxepin • Silenor
Duloxetine • Cymbalta
Escitalopram • Lexapro
Eszopiclone • Lunesta
Fluoxetine • Prozac
Fluvoxamine • Luvox
Guanfacine • Intuniv
Glycopyrrolate • Cuvposa
Hydroxyzine • Vistaril
Imipramine • Tofranil
Levomilnacipran • Fetzima
Lisdexamfetamine • Vyvanse
Methadone • Dolophine, Methadose
Modafinil • Provigil
Nortriptyline • Pamelor
Olanzapine • Zyprexa
Paliperidone palmitate • Invega Sustenna
Paroxetine • Paxil
Phenelzine • Nardil
Pimozide • Orap
Protriptyline • Vivactil
Quetiapine • Seroquel
Rivastigmine • Exelon
Selegiline transdermal • Emsam
Sertraline • Zoloft
Temazepam • Restoril
Thiothixene • Navane
Tiagabine • Gabitril
Topiramate • Topamax
Tranylcypromine • Parnate
Vilazodone • Viibryd
Vortioxetine • Trintellix
Zaleplon • Sonata
Ziprasidone • Geodon
Zolpidem • Ambien
Zonisamide • Zonegran

CP02211033_pp.png

Ms. K, age 32, presents to the psychiatric clinic for a routine follow-up. Her history includes agoraphobia, attention-deficit/hyperactivity disorder, and schizoaffective disorder. Ms. K’s current medications are oral hydroxyzine 50 mg 4 times daily as needed for anxiety and paliperidone palmitate 234 mg IM monthly. Since her last follow-up, she has been switched from oral sertraline 150 mg/d to oral paroxetine 20 mg/d. Ms. K reports having constipation (which improves by taking oral docusate 100 mg twice daily) and generalized hyperhidrosis. She wants to alleviate the hyperhidrosis without changing her paroxetine because that medication improved her symptoms.

Hyperhidrosis—excessive sweating not need­ed to maintain a normal body temperature—is an uncommon and uncomfortable adverse effect of many medications, including psychotropics.¹ This long-term adverse effect typically is not dose-related and does not remit with continued therapy.²Table 1^1-3 lists psychotropic medications associated with hyperhidrosis as well as postulated mechanisms.

CP02211033_t1.png

The incidence of medication-induced hyperhidrosis is unknown,but for psychotropic medications it is estimated to be 5% to 20%.³ Patients may not report hyperhidrosis due to embarrassment; in clinical trials, reporting measures may be inconsistent and, in some cases, misleading. For example, it is possible hyperhidrosis that appears to be associated with buprenorphine is actually a symptom of the withdrawal syndrome rather than a direct effect of the medication. Also, some medications, including certain psychotropics (eg, paroxetine⁴ and topiramate³) may cause either hyperhidrosis or hypohidrosis (decreased sweating). Few medications carry labeled warnings for hypohidrosis; the condition generally is not of clinical concern unless patients experience heat intolerance or hyperthermia.³

Psychotropic-induced hyperhidrosis is likely an idiopathic effect. There are few known predisposing factors, but some medications carry a greater risk than others. In a meta-analysis, Beyer et al² found certain selective serotonin reuptake inhibitors (SSRIs), such as sertraline and paroxetine, had a higher risk of causing hyperhidrosis. Fluvoxamine, bupropion, and vortioxetine had the lowest risk. The class risk for SSRIs was comparable to that of serotonin-norepinephrine reuptake inhibitors (SNRIs), which all carried a comparable risk. In this analysis, neither indication nor dose were reliable indicators of risk of causing hyperhidrosis. However, the study found that for both SSRIs and SNRIs, increased affinity for the dopamine transporter was correlated with an increased risk of hyperhidrosis.²

Treatment

Treatment of hyperhidrosis depends on its cause and presentation.⁵ Hyperhidrosis may be categorized as primary (idiopathic) or secondary (also termed diaphoresis), and either focal or generalized.⁶ Many treatment recommendations focus on primary or focal hyperhidrosis and prioritize topical therapies.⁵ Because medication-induced hyperhidrosis most commonly presents as generalized³ and thus affects a large body surface area, the use of topical therapies is precluded. Topical therapy for psychotropic-induced hyperhidrosis should be pursued only if the patient’s sweating is localized.

Treating medication-induced hyperhidrosis becomes more complicated if it is not possible to alter the inciting medication (ie, because the medication is effective or the patient is resistant to change). In such scenarios, discontinuing the medication and initiating an alternative therapy may not be effective or feasible.² For generalized presentations of medication-induced hyperhidrosis, if the inciting medication cannot be altered, initiating an oral systemic therapy is the preferred treatment.^3,5

Oral anticholinergic medications (eg, benztropine, glycopyrrolate, and oxybutynin),^4-6 act directly on muscarinic receptors within the eccrine sweat glands to decrease or stop sweating. They are considered first-line for generalized hyperhidrosis but may be inappropriate for psychotropic-induced hyperhidrosis because many psychotropics (eg, tricyclic antidepressants, paroxetine, olanzapine, quetiapine, and clozapine) have anticholinergic properties. Adding an anticholinergic medication to these patients’ regimens may increase the adverse effect burden and worsen cognitive deficits. Additionally, approximately one-third of patients discontinue anticholinergic medications due to tolerability issues (eg, dry mouth).

Continue to: However, anticholinergic medications...

However, anticholinergic medications may still have a role in treating psychotropic-induced hyperhidrosis. Benztropine^3,7,8 and cyproheptadine^2,3,9 may be effective options, though their role in treating psychotropic-induced hyperhidrosis should be limited and reserved for patients who have another compelling indication for these medications (eg, extrapyramidal symptoms) or when other treatment options are ineffective or intolerable.

Avoiding anticholinergic medications can also be justified based on the proposed mechanism of psychotropic-induced hyperhidrosis as an extension of the medication’s toxic effects. Conceptualizing psychotropic-induced hyperhidrosis as similar to the diaphoresis and hyperthermia observed in neuroleptic malignant syndrome and serotonin syndrome offers a clearer target for treatment. Though the specifics of the mechanisms remain unknown,² many medications that cause hyperhidrosis do so by increasing sweat gland secretions, either directly by increasing cholinergic activity or indirectly via increased sympathetic transmission.

Considering this pathophysiology, another target for psychotropic-induced hyperhidrosis may be altered and/or excessive catecholamine activity. The use of medications such as clonidine,^3-6 propranolol,^4-6 or terazosin^2,3,10 should be considered given their beneficial effects on the activation of the sympathetic nervous system, although clonidine also possesses anticholinergic activity. The calcium channel blocker diltiazem can improve hyperhidrosis symptoms by interfering with the calcium signaling necessary for normal sweat gland function.^4,5 Comorbid cardiovascular diseases and tachycardia, an adverse effect of many psychotropic medications, may also be managed with these treatment options. Some research suggests using benzodiazepines to treat psychotropic-induced hyperhidrosis.^4-6 As is the case for anticholinergic medications, the use of benzodiazepines would require another compelling indication for long-term use.

Table 2^3,4,6-8,10 provides recommended dosing and caveats for the use of these medications and other potentially appropriate medications.

CP02211033_t2.png

Research of investigational treatments for generalized hyperhidrosis is ongoing. It is possible some of these medications may have a future role in the treatment of psychotropic-induced hyperhidrosis, with improved efficacy and better tolerability.

Continue to: CASE CONTINUED

CASE CONTINUED

Because Ms. K’s medication-induced hyperhidrosis is generalized and therefore ineligible for topical therapies, and because the inciting medication (paroxetine) cannot be switched to an alternative, the treatment team considers adding an oral medication. Treatment with an anticholinergic medication, such as benztropine, is not preferred due to the anticholinergic activity associated with paroxetine and Ms. K’s history of constipation. After discussing other oral treatment options with Ms. K, the team ultimately decides to initiate propranolol at a low dose (5 mg twice daily) to minimize the chances of an interaction with paroxetine, and titrate based on efficacy and tolerability.

Related Resources

• International Hyperhidrosis Society. Hyperhidrosis treatment overview. www.sweathelp.org/hyperhidrosis-treatments/treatment-overview.html

Drug Brand Names

Acamprosate • Campral
Aripiprazole • Abilify
Buprenorphine • Sublocade
Buprenorphine/naloxone • Zubsolv
Bupropion • Wellbutrin
Carbamazepine • Tegretol
Citalopram • Celexa
Clomipramine • Anafranil
Clonidine • Catapres
Clozapine • Clozaril
Desipramine • Norpramin
Desvenlafaxine • Pristiq
Dextroamphetamine/amphetamine • Adderall
Diltiazem • Cardizem
Divalproex • Depakote
Donepezil • Aricept
Doxepin • Silenor
Duloxetine • Cymbalta
Escitalopram • Lexapro
Eszopiclone • Lunesta
Fluoxetine • Prozac
Fluvoxamine • Luvox
Guanfacine • Intuniv
Glycopyrrolate • Cuvposa
Hydroxyzine • Vistaril
Imipramine • Tofranil
Levomilnacipran • Fetzima
Lisdexamfetamine • Vyvanse
Methadone • Dolophine, Methadose
Modafinil • Provigil
Nortriptyline • Pamelor
Olanzapine • Zyprexa
Paliperidone palmitate • Invega Sustenna
Paroxetine • Paxil
Phenelzine • Nardil
Pimozide • Orap
Protriptyline • Vivactil
Quetiapine • Seroquel
Rivastigmine • Exelon
Selegiline transdermal • Emsam
Sertraline • Zoloft
Temazepam • Restoril
Thiothixene • Navane
Tiagabine • Gabitril
Topiramate • Topamax
Tranylcypromine • Parnate
Vilazodone • Viibryd
Vortioxetine • Trintellix
Zaleplon • Sonata
Ziprasidone • Geodon
Zolpidem • Ambien
Zonisamide • Zonegran

CP02211033_pp.png

Ms. K, age 32, presents to the psychiatric clinic for a routine follow-up. Her history includes agoraphobia, attention-deficit/hyperactivity disorder, and schizoaffective disorder. Ms. K’s current medications are oral hydroxyzine 50 mg 4 times daily as needed for anxiety and paliperidone palmitate 234 mg IM monthly. Since her last follow-up, she has been switched from oral sertraline 150 mg/d to oral paroxetine 20 mg/d. Ms. K reports having constipation (which improves by taking oral docusate 100 mg twice daily) and generalized hyperhidrosis. She wants to alleviate the hyperhidrosis without changing her paroxetine because that medication improved her symptoms.

Hyperhidrosis—excessive sweating not need­ed to maintain a normal body temperature—is an uncommon and uncomfortable adverse effect of many medications, including psychotropics.¹ This long-term adverse effect typically is not dose-related and does not remit with continued therapy.²Table 1^1-3 lists psychotropic medications associated with hyperhidrosis as well as postulated mechanisms.

CP02211033_t1.png

The incidence of medication-induced hyperhidrosis is unknown,but for psychotropic medications it is estimated to be 5% to 20%.³ Patients may not report hyperhidrosis due to embarrassment; in clinical trials, reporting measures may be inconsistent and, in some cases, misleading. For example, it is possible hyperhidrosis that appears to be associated with buprenorphine is actually a symptom of the withdrawal syndrome rather than a direct effect of the medication. Also, some medications, including certain psychotropics (eg, paroxetine⁴ and topiramate³) may cause either hyperhidrosis or hypohidrosis (decreased sweating). Few medications carry labeled warnings for hypohidrosis; the condition generally is not of clinical concern unless patients experience heat intolerance or hyperthermia.³

Psychotropic-induced hyperhidrosis is likely an idiopathic effect. There are few known predisposing factors, but some medications carry a greater risk than others. In a meta-analysis, Beyer et al² found certain selective serotonin reuptake inhibitors (SSRIs), such as sertraline and paroxetine, had a higher risk of causing hyperhidrosis. Fluvoxamine, bupropion, and vortioxetine had the lowest risk. The class risk for SSRIs was comparable to that of serotonin-norepinephrine reuptake inhibitors (SNRIs), which all carried a comparable risk. In this analysis, neither indication nor dose were reliable indicators of risk of causing hyperhidrosis. However, the study found that for both SSRIs and SNRIs, increased affinity for the dopamine transporter was correlated with an increased risk of hyperhidrosis.²

Treatment

Treatment of hyperhidrosis depends on its cause and presentation.⁵ Hyperhidrosis may be categorized as primary (idiopathic) or secondary (also termed diaphoresis), and either focal or generalized.⁶ Many treatment recommendations focus on primary or focal hyperhidrosis and prioritize topical therapies.⁵ Because medication-induced hyperhidrosis most commonly presents as generalized³ and thus affects a large body surface area, the use of topical therapies is precluded. Topical therapy for psychotropic-induced hyperhidrosis should be pursued only if the patient’s sweating is localized.

Treating medication-induced hyperhidrosis becomes more complicated if it is not possible to alter the inciting medication (ie, because the medication is effective or the patient is resistant to change). In such scenarios, discontinuing the medication and initiating an alternative therapy may not be effective or feasible.² For generalized presentations of medication-induced hyperhidrosis, if the inciting medication cannot be altered, initiating an oral systemic therapy is the preferred treatment.^3,5

Oral anticholinergic medications (eg, benztropine, glycopyrrolate, and oxybutynin),^4-6 act directly on muscarinic receptors within the eccrine sweat glands to decrease or stop sweating. They are considered first-line for generalized hyperhidrosis but may be inappropriate for psychotropic-induced hyperhidrosis because many psychotropics (eg, tricyclic antidepressants, paroxetine, olanzapine, quetiapine, and clozapine) have anticholinergic properties. Adding an anticholinergic medication to these patients’ regimens may increase the adverse effect burden and worsen cognitive deficits. Additionally, approximately one-third of patients discontinue anticholinergic medications due to tolerability issues (eg, dry mouth).

Continue to: However, anticholinergic medications...

However, anticholinergic medications may still have a role in treating psychotropic-induced hyperhidrosis. Benztropine^3,7,8 and cyproheptadine^2,3,9 may be effective options, though their role in treating psychotropic-induced hyperhidrosis should be limited and reserved for patients who have another compelling indication for these medications (eg, extrapyramidal symptoms) or when other treatment options are ineffective or intolerable.

Avoiding anticholinergic medications can also be justified based on the proposed mechanism of psychotropic-induced hyperhidrosis as an extension of the medication’s toxic effects. Conceptualizing psychotropic-induced hyperhidrosis as similar to the diaphoresis and hyperthermia observed in neuroleptic malignant syndrome and serotonin syndrome offers a clearer target for treatment. Though the specifics of the mechanisms remain unknown,² many medications that cause hyperhidrosis do so by increasing sweat gland secretions, either directly by increasing cholinergic activity or indirectly via increased sympathetic transmission.

Considering this pathophysiology, another target for psychotropic-induced hyperhidrosis may be altered and/or excessive catecholamine activity. The use of medications such as clonidine,^3-6 propranolol,^4-6 or terazosin^2,3,10 should be considered given their beneficial effects on the activation of the sympathetic nervous system, although clonidine also possesses anticholinergic activity. The calcium channel blocker diltiazem can improve hyperhidrosis symptoms by interfering with the calcium signaling necessary for normal sweat gland function.^4,5 Comorbid cardiovascular diseases and tachycardia, an adverse effect of many psychotropic medications, may also be managed with these treatment options. Some research suggests using benzodiazepines to treat psychotropic-induced hyperhidrosis.^4-6 As is the case for anticholinergic medications, the use of benzodiazepines would require another compelling indication for long-term use.

Table 2^3,4,6-8,10 provides recommended dosing and caveats for the use of these medications and other potentially appropriate medications.

CP02211033_t2.png

Research of investigational treatments for generalized hyperhidrosis is ongoing. It is possible some of these medications may have a future role in the treatment of psychotropic-induced hyperhidrosis, with improved efficacy and better tolerability.

Continue to: CASE CONTINUED

CASE CONTINUED

Because Ms. K’s medication-induced hyperhidrosis is generalized and therefore ineligible for topical therapies, and because the inciting medication (paroxetine) cannot be switched to an alternative, the treatment team considers adding an oral medication. Treatment with an anticholinergic medication, such as benztropine, is not preferred due to the anticholinergic activity associated with paroxetine and Ms. K’s history of constipation. After discussing other oral treatment options with Ms. K, the team ultimately decides to initiate propranolol at a low dose (5 mg twice daily) to minimize the chances of an interaction with paroxetine, and titrate based on efficacy and tolerability.

Related Resources

• International Hyperhidrosis Society. Hyperhidrosis treatment overview. www.sweathelp.org/hyperhidrosis-treatments/treatment-overview.html

Drug Brand Names

Acamprosate • Campral
Aripiprazole • Abilify
Buprenorphine • Sublocade
Buprenorphine/naloxone • Zubsolv
Bupropion • Wellbutrin
Carbamazepine • Tegretol
Citalopram • Celexa
Clomipramine • Anafranil
Clonidine • Catapres
Clozapine • Clozaril
Desipramine • Norpramin
Desvenlafaxine • Pristiq
Dextroamphetamine/amphetamine • Adderall
Diltiazem • Cardizem
Divalproex • Depakote
Donepezil • Aricept
Doxepin • Silenor
Duloxetine • Cymbalta
Escitalopram • Lexapro
Eszopiclone • Lunesta
Fluoxetine • Prozac
Fluvoxamine • Luvox
Guanfacine • Intuniv
Glycopyrrolate • Cuvposa
Hydroxyzine • Vistaril
Imipramine • Tofranil
Levomilnacipran • Fetzima
Lisdexamfetamine • Vyvanse
Methadone • Dolophine, Methadose
Modafinil • Provigil
Nortriptyline • Pamelor
Olanzapine • Zyprexa
Paliperidone palmitate • Invega Sustenna
Paroxetine • Paxil
Phenelzine • Nardil
Pimozide • Orap
Protriptyline • Vivactil
Quetiapine • Seroquel
Rivastigmine • Exelon
Selegiline transdermal • Emsam
Sertraline • Zoloft
Temazepam • Restoril
Thiothixene • Navane
Tiagabine • Gabitril
Topiramate • Topamax
Tranylcypromine • Parnate
Vilazodone • Viibryd
Vortioxetine • Trintellix
Zaleplon • Sonata
Ziprasidone • Geodon
Zolpidem • Ambien
Zonisamide • Zonegran

Clinicians of all experience levels, particularly trainees, may struggle when interviewing an individual experiencing psychosis. Many clinicians feel unsure what to say when a patient expresses fixed beliefs that are not amenable to change despite conflicting evidence, or worry about inadvertently affirming these beliefs. Supporting and empathizing with a person experiencing psychosis while avoiding reinforcing delusional beliefs is an important skillset for clinicians to have. While there is no single “correct” approach to interviewing individuals with psychosis, key principles include:

1. Do not begin by challenging delusions

People experiencing delusions often feel strongly about the validity of their beliefs and find evidence to support them. Directly challenging these beliefs from the beginning may alienate them. Instead, explore with neutral questioning: “Can you tell me more about X?” “What did you notice that made you believe Y?” Later, when rapport is established, it may be appropriate to explore discrepancies that provide insight into their delusions, a technique used in cognitive-behavioral therapy for psychosis.

2. Validate the emotion, not the psychosis

Many interviewers worry that talking about a patient’s delusions or voices will inadvertently reinforce them. Instead of agreeing with the content, listen for and empathize with the emotion (which is often fear): “That sounds frightening.” If the emotion is unclear, ask: “How did you feel when that happened?” When unsure what to say, sometimes a neutral “mmm” conveys listening without reinforcing the psychosis.

3. Explicitly state emotions and intentions

People with psychosis may have difficulty processing others’ emotions and facial expressions.¹ We recommend using verbal cues to assist them in recognizing emotions and intentions: “It makes me sad to hear how alone you felt,” or “I’m here to help you.” The interviewer may mildly “amplify” their facial expressions so that the person experiencing psychosis can more clearly identify the expressed emotion, though not all individuals with psychosis respond well to this.

4. Reflect the patient’s own words

We recommend using the patient’s exact (typically nonclinical) words in referring to their experiences to build rapport and a shared understanding of their subjective experience.² Avoid introducing clinical jargon, such as “delusion” or “hallucination.” For example, the interviewer might follow a patient’s explanation of their experiences by asking: “You heard voices in the walls—what did they say?” If the patient uses clinical jargon, the interviewer should clarify their meaning: “When you say ‘paranoid,’ what does that mean to you?”

5. Be intentional with gestures and positioning

People with schizophrenia-spectrum disorders may have difficulty interpreting gestures and are more likely to perceive gestures as self-referential.¹ We recommend minimizing gestures or using simple, neutral-to-positive movements appropriate to cultural context. For example, in the United States, hands with palms up in front of the body generally convey openness, whereas arms crossed over the chest may convey anger. We recommend that to avoid appearing confrontational, interviewers do not position themselves directly in front of the patient, instead positioning themselves at an angle. Consider mirroring patients’ gestures or postures to convey empathy and build rapport.³

Clinicians of all experience levels, particularly trainees, may struggle when interviewing an individual experiencing psychosis. Many clinicians feel unsure what to say when a patient expresses fixed beliefs that are not amenable to change despite conflicting evidence, or worry about inadvertently affirming these beliefs. Supporting and empathizing with a person experiencing psychosis while avoiding reinforcing delusional beliefs is an important skillset for clinicians to have. While there is no single “correct” approach to interviewing individuals with psychosis, key principles include:

1. Do not begin by challenging delusions

People experiencing delusions often feel strongly about the validity of their beliefs and find evidence to support them. Directly challenging these beliefs from the beginning may alienate them. Instead, explore with neutral questioning: “Can you tell me more about X?” “What did you notice that made you believe Y?” Later, when rapport is established, it may be appropriate to explore discrepancies that provide insight into their delusions, a technique used in cognitive-behavioral therapy for psychosis.

2. Validate the emotion, not the psychosis

Many interviewers worry that talking about a patient’s delusions or voices will inadvertently reinforce them. Instead of agreeing with the content, listen for and empathize with the emotion (which is often fear): “That sounds frightening.” If the emotion is unclear, ask: “How did you feel when that happened?” When unsure what to say, sometimes a neutral “mmm” conveys listening without reinforcing the psychosis.

3. Explicitly state emotions and intentions

People with psychosis may have difficulty processing others’ emotions and facial expressions.¹ We recommend using verbal cues to assist them in recognizing emotions and intentions: “It makes me sad to hear how alone you felt,” or “I’m here to help you.” The interviewer may mildly “amplify” their facial expressions so that the person experiencing psychosis can more clearly identify the expressed emotion, though not all individuals with psychosis respond well to this.

4. Reflect the patient’s own words

We recommend using the patient’s exact (typically nonclinical) words in referring to their experiences to build rapport and a shared understanding of their subjective experience.² Avoid introducing clinical jargon, such as “delusion” or “hallucination.” For example, the interviewer might follow a patient’s explanation of their experiences by asking: “You heard voices in the walls—what did they say?” If the patient uses clinical jargon, the interviewer should clarify their meaning: “When you say ‘paranoid,’ what does that mean to you?”

5. Be intentional with gestures and positioning

People with schizophrenia-spectrum disorders may have difficulty interpreting gestures and are more likely to perceive gestures as self-referential.¹ We recommend minimizing gestures or using simple, neutral-to-positive movements appropriate to cultural context. For example, in the United States, hands with palms up in front of the body generally convey openness, whereas arms crossed over the chest may convey anger. We recommend that to avoid appearing confrontational, interviewers do not position themselves directly in front of the patient, instead positioning themselves at an angle. Consider mirroring patients’ gestures or postures to convey empathy and build rapport.³

Clinicians of all experience levels, particularly trainees, may struggle when interviewing an individual experiencing psychosis. Many clinicians feel unsure what to say when a patient expresses fixed beliefs that are not amenable to change despite conflicting evidence, or worry about inadvertently affirming these beliefs. Supporting and empathizing with a person experiencing psychosis while avoiding reinforcing delusional beliefs is an important skillset for clinicians to have. While there is no single “correct” approach to interviewing individuals with psychosis, key principles include:

1. Do not begin by challenging delusions

People experiencing delusions often feel strongly about the validity of their beliefs and find evidence to support them. Directly challenging these beliefs from the beginning may alienate them. Instead, explore with neutral questioning: “Can you tell me more about X?” “What did you notice that made you believe Y?” Later, when rapport is established, it may be appropriate to explore discrepancies that provide insight into their delusions, a technique used in cognitive-behavioral therapy for psychosis.

2. Validate the emotion, not the psychosis

Many interviewers worry that talking about a patient’s delusions or voices will inadvertently reinforce them. Instead of agreeing with the content, listen for and empathize with the emotion (which is often fear): “That sounds frightening.” If the emotion is unclear, ask: “How did you feel when that happened?” When unsure what to say, sometimes a neutral “mmm” conveys listening without reinforcing the psychosis.

3. Explicitly state emotions and intentions

People with psychosis may have difficulty processing others’ emotions and facial expressions.¹ We recommend using verbal cues to assist them in recognizing emotions and intentions: “It makes me sad to hear how alone you felt,” or “I’m here to help you.” The interviewer may mildly “amplify” their facial expressions so that the person experiencing psychosis can more clearly identify the expressed emotion, though not all individuals with psychosis respond well to this.

4. Reflect the patient’s own words

We recommend using the patient’s exact (typically nonclinical) words in referring to their experiences to build rapport and a shared understanding of their subjective experience.² Avoid introducing clinical jargon, such as “delusion” or “hallucination.” For example, the interviewer might follow a patient’s explanation of their experiences by asking: “You heard voices in the walls—what did they say?” If the patient uses clinical jargon, the interviewer should clarify their meaning: “When you say ‘paranoid,’ what does that mean to you?”

5. Be intentional with gestures and positioning

People with schizophrenia-spectrum disorders may have difficulty interpreting gestures and are more likely to perceive gestures as self-referential.¹ We recommend minimizing gestures or using simple, neutral-to-positive movements appropriate to cultural context. For example, in the United States, hands with palms up in front of the body generally convey openness, whereas arms crossed over the chest may convey anger. We recommend that to avoid appearing confrontational, interviewers do not position themselves directly in front of the patient, instead positioning themselves at an angle. Consider mirroring patients’ gestures or postures to convey empathy and build rapport.³

TOPLINE:

Individuals who visited the ER for substance-induced psychosis had a 160% greater risk of developing a schizophrenia spectrum disorder (SSD), compared with the general population, new research shows. Three years after an initial ER visit, 18.5% of those with substance-induced psychosis were diagnosed with an SSD. Cannabis-induced psychosis was associated with the greatest risk.

METHODOLOGY:

• In this retrospective, population-based cohort study, investigators evaluated the risk of transition to a diagnosis of SSD for individuals with an ER visit for substance use versus the general population.
• Investigators at The Ottawa Hospital and the Institute for Clinical Evaluative Sciences, both in Ontario, analyzed data from six linked databases containing health information on nearly 10 million Ontario residents aged 14-65 years eligible for medical coverage.
• Investigators collected the health data between January 2008 and March 2022 on residents with substance use–related ER visits with, and without, psychosis.

TAKEAWAY:

• There were nearly 408,000 individuals with an ER visit for substance use, of which 13,800 (3.4%) of the visits were for substance-induced psychosis.
• Individuals with substance-induced psychosis were at a 163-fold (age- and sex-adjusted hazard ratio, 163.2; 95% confidence interval, 156.1-170.5) increased risk of transitioning to an SSD, relative to the general population (3-year risk, 18.5% vs. 0.1%).
• Individuals with an ER visit for substance use without psychosis had a lower relative risk of transitioning (aHR, 9.8; 95% CI, 9.5-10.2; 3-year risk, 1.4%) but incurred more than three times the absolute number of transitions (9,969 vs. 3,029).
• ER visits related to cannabis use had the highest transition risk among visits with psychosis (aHR, 241.6; 95% CI, 225.5-258.9) and the third-highest risk among visits without psychosis (aHR, 14.3; 95% CI, 13.5-15.2).
• Younger age and male sex were associated with a higher risk of transition, and the risk of male sex was greater in younger, compared with older, individuals particularly for cannabis use.

IN PRACTICE:

“Primary prevention efforts aimed at reducing substance use and substance use disorders could substantially reduce the population-level burden of chronic psychoses,” the investigators write. “Our findings also highlight the need for targeted secondary prevention providing early intervention and reducing substance use in the highest-risk groups, which may delay or prevent transition to schizophrenia spectrum disorders.”

SOURCE:

Daniel T. Myran, MD, MPH, of the Ottawa Hospital Research Institute, led the study, which was funded by the Canadian Institutes of Health Research and the University of Ottawa department of family medicine. The study was published online in JAMA Psychiatry.

LIMITATIONS:

Investigators did not have access to detailed data on substance-related outpatient visits or patterns of substance use, which could provide additional prognostic information.

DISCLOSURES:

Dr. Myran reported receiving grants from the Canadian Institutes of Health Research during the conduct of the study. Dr. Solmi reported receiving honoraria for participation on advisory boards or presentations from AbbVie, Angelini, Lundbeck, and Otsuka outside the submitted work. The remaining authors have disclosed no relevant financial relationships.

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

TOPLINE:

Individuals who visited the ER for substance-induced psychosis had a 160% greater risk of developing a schizophrenia spectrum disorder (SSD), compared with the general population, new research shows. Three years after an initial ER visit, 18.5% of those with substance-induced psychosis were diagnosed with an SSD. Cannabis-induced psychosis was associated with the greatest risk.

METHODOLOGY:

• In this retrospective, population-based cohort study, investigators evaluated the risk of transition to a diagnosis of SSD for individuals with an ER visit for substance use versus the general population.
• Investigators at The Ottawa Hospital and the Institute for Clinical Evaluative Sciences, both in Ontario, analyzed data from six linked databases containing health information on nearly 10 million Ontario residents aged 14-65 years eligible for medical coverage.
• Investigators collected the health data between January 2008 and March 2022 on residents with substance use–related ER visits with, and without, psychosis.

TAKEAWAY:

• There were nearly 408,000 individuals with an ER visit for substance use, of which 13,800 (3.4%) of the visits were for substance-induced psychosis.
• Individuals with substance-induced psychosis were at a 163-fold (age- and sex-adjusted hazard ratio, 163.2; 95% confidence interval, 156.1-170.5) increased risk of transitioning to an SSD, relative to the general population (3-year risk, 18.5% vs. 0.1%).
• Individuals with an ER visit for substance use without psychosis had a lower relative risk of transitioning (aHR, 9.8; 95% CI, 9.5-10.2; 3-year risk, 1.4%) but incurred more than three times the absolute number of transitions (9,969 vs. 3,029).
• ER visits related to cannabis use had the highest transition risk among visits with psychosis (aHR, 241.6; 95% CI, 225.5-258.9) and the third-highest risk among visits without psychosis (aHR, 14.3; 95% CI, 13.5-15.2).
• Younger age and male sex were associated with a higher risk of transition, and the risk of male sex was greater in younger, compared with older, individuals particularly for cannabis use.

IN PRACTICE:

“Primary prevention efforts aimed at reducing substance use and substance use disorders could substantially reduce the population-level burden of chronic psychoses,” the investigators write. “Our findings also highlight the need for targeted secondary prevention providing early intervention and reducing substance use in the highest-risk groups, which may delay or prevent transition to schizophrenia spectrum disorders.”

SOURCE:

Daniel T. Myran, MD, MPH, of the Ottawa Hospital Research Institute, led the study, which was funded by the Canadian Institutes of Health Research and the University of Ottawa department of family medicine. The study was published online in JAMA Psychiatry.

LIMITATIONS:

Investigators did not have access to detailed data on substance-related outpatient visits or patterns of substance use, which could provide additional prognostic information.

DISCLOSURES:

Dr. Myran reported receiving grants from the Canadian Institutes of Health Research during the conduct of the study. Dr. Solmi reported receiving honoraria for participation on advisory boards or presentations from AbbVie, Angelini, Lundbeck, and Otsuka outside the submitted work. The remaining authors have disclosed no relevant financial relationships.

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

TOPLINE:

Individuals who visited the ER for substance-induced psychosis had a 160% greater risk of developing a schizophrenia spectrum disorder (SSD), compared with the general population, new research shows. Three years after an initial ER visit, 18.5% of those with substance-induced psychosis were diagnosed with an SSD. Cannabis-induced psychosis was associated with the greatest risk.

METHODOLOGY:

• In this retrospective, population-based cohort study, investigators evaluated the risk of transition to a diagnosis of SSD for individuals with an ER visit for substance use versus the general population.
• Investigators at The Ottawa Hospital and the Institute for Clinical Evaluative Sciences, both in Ontario, analyzed data from six linked databases containing health information on nearly 10 million Ontario residents aged 14-65 years eligible for medical coverage.
• Investigators collected the health data between January 2008 and March 2022 on residents with substance use–related ER visits with, and without, psychosis.

TAKEAWAY:

• There were nearly 408,000 individuals with an ER visit for substance use, of which 13,800 (3.4%) of the visits were for substance-induced psychosis.
• Individuals with substance-induced psychosis were at a 163-fold (age- and sex-adjusted hazard ratio, 163.2; 95% confidence interval, 156.1-170.5) increased risk of transitioning to an SSD, relative to the general population (3-year risk, 18.5% vs. 0.1%).
• Individuals with an ER visit for substance use without psychosis had a lower relative risk of transitioning (aHR, 9.8; 95% CI, 9.5-10.2; 3-year risk, 1.4%) but incurred more than three times the absolute number of transitions (9,969 vs. 3,029).
• ER visits related to cannabis use had the highest transition risk among visits with psychosis (aHR, 241.6; 95% CI, 225.5-258.9) and the third-highest risk among visits without psychosis (aHR, 14.3; 95% CI, 13.5-15.2).
• Younger age and male sex were associated with a higher risk of transition, and the risk of male sex was greater in younger, compared with older, individuals particularly for cannabis use.

IN PRACTICE:

“Primary prevention efforts aimed at reducing substance use and substance use disorders could substantially reduce the population-level burden of chronic psychoses,” the investigators write. “Our findings also highlight the need for targeted secondary prevention providing early intervention and reducing substance use in the highest-risk groups, which may delay or prevent transition to schizophrenia spectrum disorders.”

SOURCE:

Daniel T. Myran, MD, MPH, of the Ottawa Hospital Research Institute, led the study, which was funded by the Canadian Institutes of Health Research and the University of Ottawa department of family medicine. The study was published online in JAMA Psychiatry.

LIMITATIONS:

Investigators did not have access to detailed data on substance-related outpatient visits or patterns of substance use, which could provide additional prognostic information.

DISCLOSURES:

Dr. Myran reported receiving grants from the Canadian Institutes of Health Research during the conduct of the study. Dr. Solmi reported receiving honoraria for participation on advisory boards or presentations from AbbVie, Angelini, Lundbeck, and Otsuka outside the submitted work. The remaining authors have disclosed no relevant financial relationships.

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

TOPLINE:

There is an extensive genetic overlap between schizophrenia and smoking, but there are also schizophrenia genes that may protect against obesity, illustrating the bidirectional effects of shared loci across cardiovascular disease (CVD) risk factors, results of new research suggest.

METHODOLOGY:

• Genome-wide association studies (GWAS) have detected several loci associated with CVD risk factors, including body mass index (BMI), waist-to-hip ratio, type 2 diabetes, lipids, and blood pressure, with increasing evidence suggesting genetic overlap between such risk factors and schizophrenia.
• Researchers obtained what they call an “unprecedentedly large” set of GWAS samples, including schizophrenia (53,386 patients and 77,258 controls) and various CVD risk factors.
• They used analytic approaches to identify genetic links between schizophrenia and CVD risk factors, including bivariate causal mixture model (MiXeR), which estimates the number of shared genetic variants between pairs of phenotypes, and conditional and conjunctional false discovery rate (condFDR and conjFDR), to identify specific genetic loci; these approaches can identify genetic overlap regardless of the effect directions.

TAKEAWAY:

• Using MiXeR, the study showed that several genetic variants underlying schizophrenia also influence CVD phenotypes, particularly risk factors of smoking and BMI.
• A total of 825 distinct loci were jointly associated with schizophrenia and CVD phenotypes at conjFDR < .05.
• Most of the loci shared with smoking were in line with positive genetic correlations; the authors noted individuals with schizophrenia are more nicotine dependent than the general population, and they experience greater reinforcing effects of nicotine and worse withdrawal symptoms during abstinence than the general population.
• The overlapping loci with BMI had effect directions consistent with negative genetic correlations, suggesting people with schizophrenia are genetically predisposed to lower BMI; this is in line with evidence of low BMI being a risk factor for schizophrenia, although obesity is more common in people with schizophrenia.
• There was a pattern of mixed effect directions among loci jointly associated with schizophrenia and lipids, blood pressure, type 2 diabetes, waist-to-hip ratio, and coronary artery disease, which may reflect variation in genetic susceptibility to CVD across subgroups of schizophrenia.

IN PRACTICE:

The new results “shed light” on biological pathways associated with comorbidity between CVD and schizophrenia, said the authors, adding future work could provide insights into mechanisms underlying the comorbidity and could facilitate development of antipsychotics with lower metabolic side effects, which could help prevent comorbid CVD, “thereby helping to mitigate a major clinical and health care problem.”

SOURCE:

The study was led by Linn Rødevand, PhD, Norwegian Center for Mental Disorders Research, Division of Mental Health and Addiction, Institute of Clinical Medicine, Oslo University Hospital, University of Oslo, and colleagues. It was published online in the American Journal of Psychiatry.

LIMITATIONS:

Methods used in the study are limited by uncertainties in translating genetic loci to causal variants, which restricts the biological interpretation of the shared genetic variants. Among other methodological limitations are that discrepancies between the linkage disequilibrium structure of the samples used for the GWAS and that of the reference panel may have biased estimates underlying MiXeR.

DISCLOSURES:

The study received support from the Research Council of Norway, Norwegian Health Association, South-East Norway Regional Health Authority, and the European Union. Dr. Rødevand reports no relevant financial relationships.

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

TOPLINE:

There is an extensive genetic overlap between schizophrenia and smoking, but there are also schizophrenia genes that may protect against obesity, illustrating the bidirectional effects of shared loci across cardiovascular disease (CVD) risk factors, results of new research suggest.

METHODOLOGY:

• Genome-wide association studies (GWAS) have detected several loci associated with CVD risk factors, including body mass index (BMI), waist-to-hip ratio, type 2 diabetes, lipids, and blood pressure, with increasing evidence suggesting genetic overlap between such risk factors and schizophrenia.
• Researchers obtained what they call an “unprecedentedly large” set of GWAS samples, including schizophrenia (53,386 patients and 77,258 controls) and various CVD risk factors.
• They used analytic approaches to identify genetic links between schizophrenia and CVD risk factors, including bivariate causal mixture model (MiXeR), which estimates the number of shared genetic variants between pairs of phenotypes, and conditional and conjunctional false discovery rate (condFDR and conjFDR), to identify specific genetic loci; these approaches can identify genetic overlap regardless of the effect directions.

TAKEAWAY:

• Using MiXeR, the study showed that several genetic variants underlying schizophrenia also influence CVD phenotypes, particularly risk factors of smoking and BMI.
• A total of 825 distinct loci were jointly associated with schizophrenia and CVD phenotypes at conjFDR < .05.
• Most of the loci shared with smoking were in line with positive genetic correlations; the authors noted individuals with schizophrenia are more nicotine dependent than the general population, and they experience greater reinforcing effects of nicotine and worse withdrawal symptoms during abstinence than the general population.
• The overlapping loci with BMI had effect directions consistent with negative genetic correlations, suggesting people with schizophrenia are genetically predisposed to lower BMI; this is in line with evidence of low BMI being a risk factor for schizophrenia, although obesity is more common in people with schizophrenia.
• There was a pattern of mixed effect directions among loci jointly associated with schizophrenia and lipids, blood pressure, type 2 diabetes, waist-to-hip ratio, and coronary artery disease, which may reflect variation in genetic susceptibility to CVD across subgroups of schizophrenia.

IN PRACTICE:

The new results “shed light” on biological pathways associated with comorbidity between CVD and schizophrenia, said the authors, adding future work could provide insights into mechanisms underlying the comorbidity and could facilitate development of antipsychotics with lower metabolic side effects, which could help prevent comorbid CVD, “thereby helping to mitigate a major clinical and health care problem.”

SOURCE:

The study was led by Linn Rødevand, PhD, Norwegian Center for Mental Disorders Research, Division of Mental Health and Addiction, Institute of Clinical Medicine, Oslo University Hospital, University of Oslo, and colleagues. It was published online in the American Journal of Psychiatry.

LIMITATIONS:

Methods used in the study are limited by uncertainties in translating genetic loci to causal variants, which restricts the biological interpretation of the shared genetic variants. Among other methodological limitations are that discrepancies between the linkage disequilibrium structure of the samples used for the GWAS and that of the reference panel may have biased estimates underlying MiXeR.

DISCLOSURES:

The study received support from the Research Council of Norway, Norwegian Health Association, South-East Norway Regional Health Authority, and the European Union. Dr. Rødevand reports no relevant financial relationships.

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

TOPLINE:

There is an extensive genetic overlap between schizophrenia and smoking, but there are also schizophrenia genes that may protect against obesity, illustrating the bidirectional effects of shared loci across cardiovascular disease (CVD) risk factors, results of new research suggest.

METHODOLOGY:

• Genome-wide association studies (GWAS) have detected several loci associated with CVD risk factors, including body mass index (BMI), waist-to-hip ratio, type 2 diabetes, lipids, and blood pressure, with increasing evidence suggesting genetic overlap between such risk factors and schizophrenia.
• Researchers obtained what they call an “unprecedentedly large” set of GWAS samples, including schizophrenia (53,386 patients and 77,258 controls) and various CVD risk factors.
• They used analytic approaches to identify genetic links between schizophrenia and CVD risk factors, including bivariate causal mixture model (MiXeR), which estimates the number of shared genetic variants between pairs of phenotypes, and conditional and conjunctional false discovery rate (condFDR and conjFDR), to identify specific genetic loci; these approaches can identify genetic overlap regardless of the effect directions.

TAKEAWAY:

• Using MiXeR, the study showed that several genetic variants underlying schizophrenia also influence CVD phenotypes, particularly risk factors of smoking and BMI.
• A total of 825 distinct loci were jointly associated with schizophrenia and CVD phenotypes at conjFDR < .05.
• Most of the loci shared with smoking were in line with positive genetic correlations; the authors noted individuals with schizophrenia are more nicotine dependent than the general population, and they experience greater reinforcing effects of nicotine and worse withdrawal symptoms during abstinence than the general population.
• The overlapping loci with BMI had effect directions consistent with negative genetic correlations, suggesting people with schizophrenia are genetically predisposed to lower BMI; this is in line with evidence of low BMI being a risk factor for schizophrenia, although obesity is more common in people with schizophrenia.
• There was a pattern of mixed effect directions among loci jointly associated with schizophrenia and lipids, blood pressure, type 2 diabetes, waist-to-hip ratio, and coronary artery disease, which may reflect variation in genetic susceptibility to CVD across subgroups of schizophrenia.

IN PRACTICE:

The new results “shed light” on biological pathways associated with comorbidity between CVD and schizophrenia, said the authors, adding future work could provide insights into mechanisms underlying the comorbidity and could facilitate development of antipsychotics with lower metabolic side effects, which could help prevent comorbid CVD, “thereby helping to mitigate a major clinical and health care problem.”

SOURCE:

The study was led by Linn Rødevand, PhD, Norwegian Center for Mental Disorders Research, Division of Mental Health and Addiction, Institute of Clinical Medicine, Oslo University Hospital, University of Oslo, and colleagues. It was published online in the American Journal of Psychiatry.

LIMITATIONS:

Methods used in the study are limited by uncertainties in translating genetic loci to causal variants, which restricts the biological interpretation of the shared genetic variants. Among other methodological limitations are that discrepancies between the linkage disequilibrium structure of the samples used for the GWAS and that of the reference panel may have biased estimates underlying MiXeR.

DISCLOSURES:

The study received support from the Research Council of Norway, Norwegian Health Association, South-East Norway Regional Health Authority, and the European Union. Dr. Rødevand reports no relevant financial relationships.

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