Schizophrenia & Other Psychotic Disorders

The Food and Drug Administration wants updated boxed warnings on benzodiazepines to reflect the “serious” risks of abuse, misuse, addiction, physical dependence, and withdrawal reactions associated with these medications.

“The current prescribing information for benzodiazepines does not provide adequate warnings about these serious risks and harms associated with these medicines so they may be prescribed and used inappropriately,” the FDA said in a safety communication.

The FDA also wants revisions to the patient medication guides for benzodiazepines to help educate patients and caregivers about these risks.

“While benzodiazepines are important therapies for many Americans, they are also commonly abused and misused, often together with opioid pain relievers and other medicines, alcohol, and illicit drugs,” FDA Commissioner Stephen M. Hahn, MD, said in a statement.

“We are taking measures and requiring new labeling information to help health care professionals and patients better understand that, while benzodiazepines have many treatment benefits, they also carry with them an increased risk of abuse, misuse, addiction, and dependence,” said Dr. Hahn.
 

Ninety-two million prescriptions in 2019

Benzodiazepines are widely used to treat anxiety, insomnia, seizures, and other conditions, often for extended periods of time.

According to the FDA, in 2019, an estimated 92 million benzodiazepine prescriptions were dispensed from U.S. outpatient pharmacies, most commonly alprazolam, clonazepam, and lorazepam.

Data from 2018 show that roughly 5.4 million people in the United States 12 years and older abused or misused benzodiazepines in the previous year.

Although the precise risk of benzodiazepine addiction remains unclear, population data “clearly indicate that both primary benzodiazepine use disorders and polysubstance addiction involving benzodiazepines do occur,” the FDA said.

Data from the National Survey on Drug Use and Health from 2015-2016 suggest that half million community-dwelling U.S. adults were estimated to have a benzodiazepine use disorder.
 

Jump in overdose deaths

Overdose deaths involving benzodiazepines jumped from 1,298 in 2010 to 11,537 in 2017 – an increase of more 780%. Most of these deaths involved benzodiazepines taken with prescription opioids.

Before prescribing a benzodiazepine and during treatment, a patient’s risk for abuse, misuse, and addiction should be assessed, the FDA said.

The agency urged particular caution when prescribing benzodiazepines with opioids and other central nervous system depressants, which has resulted in serious adverse events including severe respiratory depression and death.

The FDA also says patients and caregivers should be warned about the risks of abuse, misuse, addiction, dependence, and withdrawal with benzodiazepines and the associated signs and symptoms.

Physicians are encouraged to report adverse events involving benzodiazepines or other medicines to the FDA’s MedWatch program.
 

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

The Food and Drug Administration wants updated boxed warnings on benzodiazepines to reflect the “serious” risks of abuse, misuse, addiction, physical dependence, and withdrawal reactions associated with these medications.

“The current prescribing information for benzodiazepines does not provide adequate warnings about these serious risks and harms associated with these medicines so they may be prescribed and used inappropriately,” the FDA said in a safety communication.

The FDA also wants revisions to the patient medication guides for benzodiazepines to help educate patients and caregivers about these risks.

“While benzodiazepines are important therapies for many Americans, they are also commonly abused and misused, often together with opioid pain relievers and other medicines, alcohol, and illicit drugs,” FDA Commissioner Stephen M. Hahn, MD, said in a statement.

“We are taking measures and requiring new labeling information to help health care professionals and patients better understand that, while benzodiazepines have many treatment benefits, they also carry with them an increased risk of abuse, misuse, addiction, and dependence,” said Dr. Hahn.
 

Ninety-two million prescriptions in 2019

Benzodiazepines are widely used to treat anxiety, insomnia, seizures, and other conditions, often for extended periods of time.

According to the FDA, in 2019, an estimated 92 million benzodiazepine prescriptions were dispensed from U.S. outpatient pharmacies, most commonly alprazolam, clonazepam, and lorazepam.

Data from 2018 show that roughly 5.4 million people in the United States 12 years and older abused or misused benzodiazepines in the previous year.

Although the precise risk of benzodiazepine addiction remains unclear, population data “clearly indicate that both primary benzodiazepine use disorders and polysubstance addiction involving benzodiazepines do occur,” the FDA said.

Data from the National Survey on Drug Use and Health from 2015-2016 suggest that half million community-dwelling U.S. adults were estimated to have a benzodiazepine use disorder.
 

Jump in overdose deaths

Overdose deaths involving benzodiazepines jumped from 1,298 in 2010 to 11,537 in 2017 – an increase of more 780%. Most of these deaths involved benzodiazepines taken with prescription opioids.

Before prescribing a benzodiazepine and during treatment, a patient’s risk for abuse, misuse, and addiction should be assessed, the FDA said.

The agency urged particular caution when prescribing benzodiazepines with opioids and other central nervous system depressants, which has resulted in serious adverse events including severe respiratory depression and death.

The FDA also says patients and caregivers should be warned about the risks of abuse, misuse, addiction, dependence, and withdrawal with benzodiazepines and the associated signs and symptoms.

Physicians are encouraged to report adverse events involving benzodiazepines or other medicines to the FDA’s MedWatch program.
 

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

The Food and Drug Administration wants updated boxed warnings on benzodiazepines to reflect the “serious” risks of abuse, misuse, addiction, physical dependence, and withdrawal reactions associated with these medications.

“The current prescribing information for benzodiazepines does not provide adequate warnings about these serious risks and harms associated with these medicines so they may be prescribed and used inappropriately,” the FDA said in a safety communication.

The FDA also wants revisions to the patient medication guides for benzodiazepines to help educate patients and caregivers about these risks.

“While benzodiazepines are important therapies for many Americans, they are also commonly abused and misused, often together with opioid pain relievers and other medicines, alcohol, and illicit drugs,” FDA Commissioner Stephen M. Hahn, MD, said in a statement.

“We are taking measures and requiring new labeling information to help health care professionals and patients better understand that, while benzodiazepines have many treatment benefits, they also carry with them an increased risk of abuse, misuse, addiction, and dependence,” said Dr. Hahn.
 

Ninety-two million prescriptions in 2019

Benzodiazepines are widely used to treat anxiety, insomnia, seizures, and other conditions, often for extended periods of time.

According to the FDA, in 2019, an estimated 92 million benzodiazepine prescriptions were dispensed from U.S. outpatient pharmacies, most commonly alprazolam, clonazepam, and lorazepam.

Data from 2018 show that roughly 5.4 million people in the United States 12 years and older abused or misused benzodiazepines in the previous year.

Although the precise risk of benzodiazepine addiction remains unclear, population data “clearly indicate that both primary benzodiazepine use disorders and polysubstance addiction involving benzodiazepines do occur,” the FDA said.

Data from the National Survey on Drug Use and Health from 2015-2016 suggest that half million community-dwelling U.S. adults were estimated to have a benzodiazepine use disorder.
 

Jump in overdose deaths

Overdose deaths involving benzodiazepines jumped from 1,298 in 2010 to 11,537 in 2017 – an increase of more 780%. Most of these deaths involved benzodiazepines taken with prescription opioids.

Before prescribing a benzodiazepine and during treatment, a patient’s risk for abuse, misuse, and addiction should be assessed, the FDA said.

The agency urged particular caution when prescribing benzodiazepines with opioids and other central nervous system depressants, which has resulted in serious adverse events including severe respiratory depression and death.

The FDA also says patients and caregivers should be warned about the risks of abuse, misuse, addiction, dependence, and withdrawal with benzodiazepines and the associated signs and symptoms.

Physicians are encouraged to report adverse events involving benzodiazepines or other medicines to the FDA’s MedWatch program.
 

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

Suicidality appears to have increased sharply in Israel during the initial nationwide lockdown implemented in response to the COVID-19 pandemic, Gil Zalsman, MD, MHA, reported at the virtual congress of the European College of Neuropsychopharmacology.

He presented highlights from a soon-to-be-published analysis of the content of online chat sessions fielded by a national crisis hotline (Sahar.org.il) during the first 6 months of 2020, compared with January through June 2019, in the pre-COVID-19 era.

It’s far too early to say whether actual deaths tied to suicide rose significantly during the spring lockdown, since medical examiners often take a long time before ruling suicide as cause of death. But this much is clear: The number of suicide-related chat sessions recorded at the volunteer-staffed national hotline during April 2020 was two-and-a-half times greater than in April 2019, and threefold greater in May 2020 than a year earlier, according to Dr. Zalsman, professor of psychiatry at Tel Aviv University and director of the Geha Mental Health Center in Petach Tikva, Israel, where he also directs an adolescent day unit.

The proportion of chats handled at the crisis hotline, many of them concerned with the standard topics – relationships, stress, fears, anxiety, and other non–suicide-related issues – was 48% greater in the first half of 2020, compared with a year earlier. Indeed, the pandemic is putting an enormous strain on crisis hotlines the world over.

“Everybody who is working hotlines knows that they’re falling apart. There are too many calls, too many chats. They need to multiply their volunteers,” Dr. Zalsman said.

The number of suicide-related online chats jumped the week of March 12, when schools closed across Israel and a partial lockdown began. The peak in suicide-related chats occurred beginning the week of April 17, when the forced total lockdown was declared.

“Everything was closed. You couldn’t go out or the police would arrest you,” Dr. Zalsman recalled.

The suicide-related chat count started to drop off in mid-May, when schools reopened, and continued to decline through the end of June.

Only a small percentage of suicide-related chats were deemed by crisis hotline volunteers and their supervisors to be truly life-threatening situations necessitating a call to the police. But the number of such exchanges was significantly greater in April and May 2020 than in January and February, or in April and May 2019.

Use of the crisis hotline is ordinarily skewed toward tech-savvy young people, or as Dr. Zalsman called them, “kids who live inside their computers.” He note that the psychological impact of the pandemic on children and adolescents is largely unexplored research territory to date.

“For some young kids, the fear that they will contaminate their parents or grandparents is horrifying. You can kill your grandfather by coughing,” Dr. Zalsman said.
 

Older people also seek help

A finding that he and his coinvestigators didn’t anticipate was the significantly increased use of the service by individuals aged 65 and older during the pandemic. This underscores the increased vulnerability of older people, which stems in part from their heightened risk for severe infection and consequent need for prolonged physical isolation, he said.

The conventional thinking among suicidologists is that during times of crisis – wars, natural disasters – suicidality plunges, then rises quickly afterward.

“People withhold themselves. When there’s a big danger from outside they ignore the danger from inside. And once the danger from outside is gone, they’re left with emptiness, unemployment, economic crisis, and they start” taking their own lives, Dr. Zalsman explained. He expects suicidality to increase after the pandemic, or as the Israeli crisis hotline data suggest, perhaps even during it, for multiple reasons. Patients with preexisting psychiatric disorders are often going untreated. The prolonged physical isolation causes emotional difficulties for some people, especially when accompanied by social isolation and loneliness. There is grief over the loss of friends and relatives because of COVID-19. And there is an expectation of looming economic hardship, with mounting unemployment and bankruptcies.

Dr. Zalsman reported having no financial conflicts regarding his study, conducted free of commercial support.

[email protected]

SOURCE: Zalsman G. ECNP 2020, Session TP.06.

Suicidality appears to have increased sharply in Israel during the initial nationwide lockdown implemented in response to the COVID-19 pandemic, Gil Zalsman, MD, MHA, reported at the virtual congress of the European College of Neuropsychopharmacology.

He presented highlights from a soon-to-be-published analysis of the content of online chat sessions fielded by a national crisis hotline (Sahar.org.il) during the first 6 months of 2020, compared with January through June 2019, in the pre-COVID-19 era.

It’s far too early to say whether actual deaths tied to suicide rose significantly during the spring lockdown, since medical examiners often take a long time before ruling suicide as cause of death. But this much is clear: The number of suicide-related chat sessions recorded at the volunteer-staffed national hotline during April 2020 was two-and-a-half times greater than in April 2019, and threefold greater in May 2020 than a year earlier, according to Dr. Zalsman, professor of psychiatry at Tel Aviv University and director of the Geha Mental Health Center in Petach Tikva, Israel, where he also directs an adolescent day unit.

The proportion of chats handled at the crisis hotline, many of them concerned with the standard topics – relationships, stress, fears, anxiety, and other non–suicide-related issues – was 48% greater in the first half of 2020, compared with a year earlier. Indeed, the pandemic is putting an enormous strain on crisis hotlines the world over.

“Everybody who is working hotlines knows that they’re falling apart. There are too many calls, too many chats. They need to multiply their volunteers,” Dr. Zalsman said.

The number of suicide-related online chats jumped the week of March 12, when schools closed across Israel and a partial lockdown began. The peak in suicide-related chats occurred beginning the week of April 17, when the forced total lockdown was declared.

“Everything was closed. You couldn’t go out or the police would arrest you,” Dr. Zalsman recalled.

The suicide-related chat count started to drop off in mid-May, when schools reopened, and continued to decline through the end of June.

Only a small percentage of suicide-related chats were deemed by crisis hotline volunteers and their supervisors to be truly life-threatening situations necessitating a call to the police. But the number of such exchanges was significantly greater in April and May 2020 than in January and February, or in April and May 2019.

Use of the crisis hotline is ordinarily skewed toward tech-savvy young people, or as Dr. Zalsman called them, “kids who live inside their computers.” He note that the psychological impact of the pandemic on children and adolescents is largely unexplored research territory to date.

“For some young kids, the fear that they will contaminate their parents or grandparents is horrifying. You can kill your grandfather by coughing,” Dr. Zalsman said.
 

Older people also seek help

A finding that he and his coinvestigators didn’t anticipate was the significantly increased use of the service by individuals aged 65 and older during the pandemic. This underscores the increased vulnerability of older people, which stems in part from their heightened risk for severe infection and consequent need for prolonged physical isolation, he said.

The conventional thinking among suicidologists is that during times of crisis – wars, natural disasters – suicidality plunges, then rises quickly afterward.

“People withhold themselves. When there’s a big danger from outside they ignore the danger from inside. And once the danger from outside is gone, they’re left with emptiness, unemployment, economic crisis, and they start” taking their own lives, Dr. Zalsman explained. He expects suicidality to increase after the pandemic, or as the Israeli crisis hotline data suggest, perhaps even during it, for multiple reasons. Patients with preexisting psychiatric disorders are often going untreated. The prolonged physical isolation causes emotional difficulties for some people, especially when accompanied by social isolation and loneliness. There is grief over the loss of friends and relatives because of COVID-19. And there is an expectation of looming economic hardship, with mounting unemployment and bankruptcies.

Dr. Zalsman reported having no financial conflicts regarding his study, conducted free of commercial support.

[email protected]

SOURCE: Zalsman G. ECNP 2020, Session TP.06.

Suicidality appears to have increased sharply in Israel during the initial nationwide lockdown implemented in response to the COVID-19 pandemic, Gil Zalsman, MD, MHA, reported at the virtual congress of the European College of Neuropsychopharmacology.

He presented highlights from a soon-to-be-published analysis of the content of online chat sessions fielded by a national crisis hotline (Sahar.org.il) during the first 6 months of 2020, compared with January through June 2019, in the pre-COVID-19 era.

It’s far too early to say whether actual deaths tied to suicide rose significantly during the spring lockdown, since medical examiners often take a long time before ruling suicide as cause of death. But this much is clear: The number of suicide-related chat sessions recorded at the volunteer-staffed national hotline during April 2020 was two-and-a-half times greater than in April 2019, and threefold greater in May 2020 than a year earlier, according to Dr. Zalsman, professor of psychiatry at Tel Aviv University and director of the Geha Mental Health Center in Petach Tikva, Israel, where he also directs an adolescent day unit.

The proportion of chats handled at the crisis hotline, many of them concerned with the standard topics – relationships, stress, fears, anxiety, and other non–suicide-related issues – was 48% greater in the first half of 2020, compared with a year earlier. Indeed, the pandemic is putting an enormous strain on crisis hotlines the world over.

“Everybody who is working hotlines knows that they’re falling apart. There are too many calls, too many chats. They need to multiply their volunteers,” Dr. Zalsman said.

The number of suicide-related online chats jumped the week of March 12, when schools closed across Israel and a partial lockdown began. The peak in suicide-related chats occurred beginning the week of April 17, when the forced total lockdown was declared.

“Everything was closed. You couldn’t go out or the police would arrest you,” Dr. Zalsman recalled.

The suicide-related chat count started to drop off in mid-May, when schools reopened, and continued to decline through the end of June.

Only a small percentage of suicide-related chats were deemed by crisis hotline volunteers and their supervisors to be truly life-threatening situations necessitating a call to the police. But the number of such exchanges was significantly greater in April and May 2020 than in January and February, or in April and May 2019.

Use of the crisis hotline is ordinarily skewed toward tech-savvy young people, or as Dr. Zalsman called them, “kids who live inside their computers.” He note that the psychological impact of the pandemic on children and adolescents is largely unexplored research territory to date.

“For some young kids, the fear that they will contaminate their parents or grandparents is horrifying. You can kill your grandfather by coughing,” Dr. Zalsman said.
 

Older people also seek help

A finding that he and his coinvestigators didn’t anticipate was the significantly increased use of the service by individuals aged 65 and older during the pandemic. This underscores the increased vulnerability of older people, which stems in part from their heightened risk for severe infection and consequent need for prolonged physical isolation, he said.

The conventional thinking among suicidologists is that during times of crisis – wars, natural disasters – suicidality plunges, then rises quickly afterward.

“People withhold themselves. When there’s a big danger from outside they ignore the danger from inside. And once the danger from outside is gone, they’re left with emptiness, unemployment, economic crisis, and they start” taking their own lives, Dr. Zalsman explained. He expects suicidality to increase after the pandemic, or as the Israeli crisis hotline data suggest, perhaps even during it, for multiple reasons. Patients with preexisting psychiatric disorders are often going untreated. The prolonged physical isolation causes emotional difficulties for some people, especially when accompanied by social isolation and loneliness. There is grief over the loss of friends and relatives because of COVID-19. And there is an expectation of looming economic hardship, with mounting unemployment and bankruptcies.

Dr. Zalsman reported having no financial conflicts regarding his study, conducted free of commercial support.

[email protected]

SOURCE: Zalsman G. ECNP 2020, Session TP.06.

The American Psychiatric Association has released a new evidence-based practice guideline for the treatment of schizophrenia.

The guideline focuses on assessment and treatment planning, which are integral to patient-centered care, and includes recommendations regarding pharmacotherapy, with particular focus on clozapine, as well as previously recommended and new psychosocial interventions.

“Our intention was to make recommendations to treat the whole person and take into account their family and other significant people in their lives,” George Keepers, MD, chair of the guideline writing group, said in an interview.
 

‘State-of-the-art methodology’

Dr. Keepers, professor of psychiatry at Oregon Health and Science University, Portland, explained the rigorous process that informs the current guideline, which was “based not solely on expert consensus but was preceded by an evidence-based review of the literature that was then discussed, digested, and distilled into specific recommendations.”

Many current recommendations are “similar to previous recommendations, but there are a few important differences,” he said.

Two experts in schizophrenia who were not involved in guideline authorship praised it for its usefulness and methodology.

Philip D. Harvey, PhD, Leonard M. Miller Professor of Psychiatry and Behavioral Sciences, University of Miami, said in an interview that the guideline “clarified the typical treatment algorithm from first episode to treatment resistance [which is] very clearly laid out for the first time.”

Christoph Correll, MD, professor of psychiatry and molecular medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, N.Y., said in an interview that the guideline “followed state-of-the-art methodology.”
 

First steps

The guideline recommends beginning with assessment of the patient and determination of the treatment plan.

Patients should be “treated with an antipsychotic medication and monitored for effectiveness and side effects.” Even after the patient’s symptoms have improved, antipsychotic treatment should continue.

For patients whose symptoms have improved, treatment should continue with the same antipsychotic and should not be switched.

“The problem we’re addressing in this recommendation is that patients are often treated with an effective medication and then forced, by circumstances or their insurance company, to switch to another that may not be effective for them, resulting in unnecessary relapses of the illness,” said Dr. Keepers.

“All we can do is recommend appropriate treatment and hope that the decision makers of the insurance companies will heed these recommendations and do what’s in the best interest of the patient,” he said.

“The guideline called out that antipsychotics that are effective and tolerated should be continued, without specifying a duration of treatment, thereby indicating indirectly that there is no clear end of the recommendation for ongoing maintenance treatment in individuals with schizophrenia,” said Dr. Correll.
 

Clozapine underutilized

The guideline highlights the role of clozapine and recommends its use for patients with treatment-resistant schizophrenia and those at risk for suicide. Clozapine is also recommended for patients at “substantial” risk for aggressive behavior, regardless of other treatments.

“Clozapine is underutilized for treatment of schizophrenia in the U.S. and a number of other countries, but it is a really important treatment for patients who don’t respond to other antipsychotic agents,” said Dr. Keepers.

“With this recommendation, we hope that more patients will wind up receiving the medication and benefiting from it,” he added.

In addition, patients should receive treatment with a long-acting injectable antipsychotic “if they prefer such treatment or if they have a history of poor or uncertain adherence” (level of evidence, 2B).

The guideline authors “are recommending long-acting injectable medications for people who want them, not just people with poor prior adherence, which is a critical step,” said Dr. Harvey, director of the division of psychology at the University of Miami.
 

Managing antipsychotic side effects

The guideline offers recommendations for patients experiencing antipsychotic-induced side effects. 

VMAT2s, which represent a “class of drugs that have become available since the last schizophrenia guidelines, are effective in tardive dyskinesia. It is important that patients with tardive dyskinesia have access to these drugs because they do work,” Dr. Keepers said.
 

Adequate funding needed

Recommended psychosocial interventions include treatment in a specialty care program for patients with schizophrenia who are experiencing a first episode of psychosis, use of cognitive-behavioral therapy for psychosis, psychoeducation, and supported employment services (2B).

“We reviewed very good data showing that patients who receive these services are more likely to be able to be employed and less likely to be rehospitalized or have a relapse,” Dr. Keepers observed.

In addition, patients with schizophrenia should receive assertive community treatment interventions if there is a “history of poor engagement with services leading to frequent relapse or social disruption.”

Family interventions are recommended for patients who have ongoing contact with their families (2B), and patients should also receive interventions “aimed at developing self-management skills and enhancing person-oriented recovery.” They should receive cognitive remediation, social skills training, and supportive psychotherapy.

Dr. Keepers pointed to “major barriers” to providing some of these psychosocial treatments. “They are beyond the scope of someone in an individual private practice situation, so they need to be delivered within the context of treatment programs that are either publicly or privately based,” he said.

“Psychiatrists can and do work closely with community and mental health centers, psychologists, and social workers who can provide these kinds of treatments,” but “many [treatments] require specialized skills and training before they can be offered, and there is a shortage of personnel to deliver them,” he noted.

“Both the national and state governments have not provided adequate funding for treatment of individuals with this condition [schizophrenia],” he added.

Dr. Keepers reports no relevant financial relationships. The other authors’ disclosures are listed in the original article. Dr. Harvey reports no relevant financial relationships. Dr. Correll disclosed ties to Acadia, Alkermes, Allergan, Angelini, Axsome, Gedeon Richter, Gerson Lehrman Group, Indivior, IntraCellular Therapies, Janssen/J&J, LB Pharma, Lundbeck, MedAvante-ProPhase, Medscape, Merck, Mylan, Neurocrine, Noven, Otsuka, Pfizer, Recordati, Rovi, Servier, Sumitomo Dainippon, Sunovion, Supernus, Takeda, and Teva. He has received grant support from Janssen and Takeda. He is also a stock option holder of LB Pharma.
 

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

The American Psychiatric Association has released a new evidence-based practice guideline for the treatment of schizophrenia.

The guideline focuses on assessment and treatment planning, which are integral to patient-centered care, and includes recommendations regarding pharmacotherapy, with particular focus on clozapine, as well as previously recommended and new psychosocial interventions.

“Our intention was to make recommendations to treat the whole person and take into account their family and other significant people in their lives,” George Keepers, MD, chair of the guideline writing group, said in an interview.
 

‘State-of-the-art methodology’

Dr. Keepers, professor of psychiatry at Oregon Health and Science University, Portland, explained the rigorous process that informs the current guideline, which was “based not solely on expert consensus but was preceded by an evidence-based review of the literature that was then discussed, digested, and distilled into specific recommendations.”

Many current recommendations are “similar to previous recommendations, but there are a few important differences,” he said.

Two experts in schizophrenia who were not involved in guideline authorship praised it for its usefulness and methodology.

Philip D. Harvey, PhD, Leonard M. Miller Professor of Psychiatry and Behavioral Sciences, University of Miami, said in an interview that the guideline “clarified the typical treatment algorithm from first episode to treatment resistance [which is] very clearly laid out for the first time.”

Christoph Correll, MD, professor of psychiatry and molecular medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, N.Y., said in an interview that the guideline “followed state-of-the-art methodology.”
 

First steps

The guideline recommends beginning with assessment of the patient and determination of the treatment plan.

Patients should be “treated with an antipsychotic medication and monitored for effectiveness and side effects.” Even after the patient’s symptoms have improved, antipsychotic treatment should continue.

For patients whose symptoms have improved, treatment should continue with the same antipsychotic and should not be switched.

“The problem we’re addressing in this recommendation is that patients are often treated with an effective medication and then forced, by circumstances or their insurance company, to switch to another that may not be effective for them, resulting in unnecessary relapses of the illness,” said Dr. Keepers.

“All we can do is recommend appropriate treatment and hope that the decision makers of the insurance companies will heed these recommendations and do what’s in the best interest of the patient,” he said.

“The guideline called out that antipsychotics that are effective and tolerated should be continued, without specifying a duration of treatment, thereby indicating indirectly that there is no clear end of the recommendation for ongoing maintenance treatment in individuals with schizophrenia,” said Dr. Correll.
 

Clozapine underutilized

The guideline highlights the role of clozapine and recommends its use for patients with treatment-resistant schizophrenia and those at risk for suicide. Clozapine is also recommended for patients at “substantial” risk for aggressive behavior, regardless of other treatments.

“Clozapine is underutilized for treatment of schizophrenia in the U.S. and a number of other countries, but it is a really important treatment for patients who don’t respond to other antipsychotic agents,” said Dr. Keepers.

“With this recommendation, we hope that more patients will wind up receiving the medication and benefiting from it,” he added.

In addition, patients should receive treatment with a long-acting injectable antipsychotic “if they prefer such treatment or if they have a history of poor or uncertain adherence” (level of evidence, 2B).

The guideline authors “are recommending long-acting injectable medications for people who want them, not just people with poor prior adherence, which is a critical step,” said Dr. Harvey, director of the division of psychology at the University of Miami.
 

Managing antipsychotic side effects

The guideline offers recommendations for patients experiencing antipsychotic-induced side effects. 

VMAT2s, which represent a “class of drugs that have become available since the last schizophrenia guidelines, are effective in tardive dyskinesia. It is important that patients with tardive dyskinesia have access to these drugs because they do work,” Dr. Keepers said.
 

Adequate funding needed

Recommended psychosocial interventions include treatment in a specialty care program for patients with schizophrenia who are experiencing a first episode of psychosis, use of cognitive-behavioral therapy for psychosis, psychoeducation, and supported employment services (2B).

“We reviewed very good data showing that patients who receive these services are more likely to be able to be employed and less likely to be rehospitalized or have a relapse,” Dr. Keepers observed.

In addition, patients with schizophrenia should receive assertive community treatment interventions if there is a “history of poor engagement with services leading to frequent relapse or social disruption.”

Family interventions are recommended for patients who have ongoing contact with their families (2B), and patients should also receive interventions “aimed at developing self-management skills and enhancing person-oriented recovery.” They should receive cognitive remediation, social skills training, and supportive psychotherapy.

Dr. Keepers pointed to “major barriers” to providing some of these psychosocial treatments. “They are beyond the scope of someone in an individual private practice situation, so they need to be delivered within the context of treatment programs that are either publicly or privately based,” he said.

“Psychiatrists can and do work closely with community and mental health centers, psychologists, and social workers who can provide these kinds of treatments,” but “many [treatments] require specialized skills and training before they can be offered, and there is a shortage of personnel to deliver them,” he noted.

“Both the national and state governments have not provided adequate funding for treatment of individuals with this condition [schizophrenia],” he added.

Dr. Keepers reports no relevant financial relationships. The other authors’ disclosures are listed in the original article. Dr. Harvey reports no relevant financial relationships. Dr. Correll disclosed ties to Acadia, Alkermes, Allergan, Angelini, Axsome, Gedeon Richter, Gerson Lehrman Group, Indivior, IntraCellular Therapies, Janssen/J&J, LB Pharma, Lundbeck, MedAvante-ProPhase, Medscape, Merck, Mylan, Neurocrine, Noven, Otsuka, Pfizer, Recordati, Rovi, Servier, Sumitomo Dainippon, Sunovion, Supernus, Takeda, and Teva. He has received grant support from Janssen and Takeda. He is also a stock option holder of LB Pharma.
 

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

The American Psychiatric Association has released a new evidence-based practice guideline for the treatment of schizophrenia.

The guideline focuses on assessment and treatment planning, which are integral to patient-centered care, and includes recommendations regarding pharmacotherapy, with particular focus on clozapine, as well as previously recommended and new psychosocial interventions.

“Our intention was to make recommendations to treat the whole person and take into account their family and other significant people in their lives,” George Keepers, MD, chair of the guideline writing group, said in an interview.
 

‘State-of-the-art methodology’

Dr. Keepers, professor of psychiatry at Oregon Health and Science University, Portland, explained the rigorous process that informs the current guideline, which was “based not solely on expert consensus but was preceded by an evidence-based review of the literature that was then discussed, digested, and distilled into specific recommendations.”

Many current recommendations are “similar to previous recommendations, but there are a few important differences,” he said.

Two experts in schizophrenia who were not involved in guideline authorship praised it for its usefulness and methodology.

Philip D. Harvey, PhD, Leonard M. Miller Professor of Psychiatry and Behavioral Sciences, University of Miami, said in an interview that the guideline “clarified the typical treatment algorithm from first episode to treatment resistance [which is] very clearly laid out for the first time.”

Christoph Correll, MD, professor of psychiatry and molecular medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, N.Y., said in an interview that the guideline “followed state-of-the-art methodology.”
 

First steps

The guideline recommends beginning with assessment of the patient and determination of the treatment plan.

Patients should be “treated with an antipsychotic medication and monitored for effectiveness and side effects.” Even after the patient’s symptoms have improved, antipsychotic treatment should continue.

For patients whose symptoms have improved, treatment should continue with the same antipsychotic and should not be switched.

“The problem we’re addressing in this recommendation is that patients are often treated with an effective medication and then forced, by circumstances or their insurance company, to switch to another that may not be effective for them, resulting in unnecessary relapses of the illness,” said Dr. Keepers.

“All we can do is recommend appropriate treatment and hope that the decision makers of the insurance companies will heed these recommendations and do what’s in the best interest of the patient,” he said.

“The guideline called out that antipsychotics that are effective and tolerated should be continued, without specifying a duration of treatment, thereby indicating indirectly that there is no clear end of the recommendation for ongoing maintenance treatment in individuals with schizophrenia,” said Dr. Correll.
 

Clozapine underutilized

The guideline highlights the role of clozapine and recommends its use for patients with treatment-resistant schizophrenia and those at risk for suicide. Clozapine is also recommended for patients at “substantial” risk for aggressive behavior, regardless of other treatments.

“Clozapine is underutilized for treatment of schizophrenia in the U.S. and a number of other countries, but it is a really important treatment for patients who don’t respond to other antipsychotic agents,” said Dr. Keepers.

“With this recommendation, we hope that more patients will wind up receiving the medication and benefiting from it,” he added.

In addition, patients should receive treatment with a long-acting injectable antipsychotic “if they prefer such treatment or if they have a history of poor or uncertain adherence” (level of evidence, 2B).

The guideline authors “are recommending long-acting injectable medications for people who want them, not just people with poor prior adherence, which is a critical step,” said Dr. Harvey, director of the division of psychology at the University of Miami.
 

Managing antipsychotic side effects

The guideline offers recommendations for patients experiencing antipsychotic-induced side effects. 

VMAT2s, which represent a “class of drugs that have become available since the last schizophrenia guidelines, are effective in tardive dyskinesia. It is important that patients with tardive dyskinesia have access to these drugs because they do work,” Dr. Keepers said.
 

Adequate funding needed

Recommended psychosocial interventions include treatment in a specialty care program for patients with schizophrenia who are experiencing a first episode of psychosis, use of cognitive-behavioral therapy for psychosis, psychoeducation, and supported employment services (2B).

“We reviewed very good data showing that patients who receive these services are more likely to be able to be employed and less likely to be rehospitalized or have a relapse,” Dr. Keepers observed.

In addition, patients with schizophrenia should receive assertive community treatment interventions if there is a “history of poor engagement with services leading to frequent relapse or social disruption.”

Family interventions are recommended for patients who have ongoing contact with their families (2B), and patients should also receive interventions “aimed at developing self-management skills and enhancing person-oriented recovery.” They should receive cognitive remediation, social skills training, and supportive psychotherapy.

Dr. Keepers pointed to “major barriers” to providing some of these psychosocial treatments. “They are beyond the scope of someone in an individual private practice situation, so they need to be delivered within the context of treatment programs that are either publicly or privately based,” he said.

“Psychiatrists can and do work closely with community and mental health centers, psychologists, and social workers who can provide these kinds of treatments,” but “many [treatments] require specialized skills and training before they can be offered, and there is a shortage of personnel to deliver them,” he noted.

“Both the national and state governments have not provided adequate funding for treatment of individuals with this condition [schizophrenia],” he added.

Dr. Keepers reports no relevant financial relationships. The other authors’ disclosures are listed in the original article. Dr. Harvey reports no relevant financial relationships. Dr. Correll disclosed ties to Acadia, Alkermes, Allergan, Angelini, Axsome, Gedeon Richter, Gerson Lehrman Group, Indivior, IntraCellular Therapies, Janssen/J&J, LB Pharma, Lundbeck, MedAvante-ProPhase, Medscape, Merck, Mylan, Neurocrine, Noven, Otsuka, Pfizer, Recordati, Rovi, Servier, Sumitomo Dainippon, Sunovion, Supernus, Takeda, and Teva. He has received grant support from Janssen and Takeda. He is also a stock option holder of LB Pharma.
 

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

“This whole thing is not about heroism. It’s about decency. It may seem a ridiculous idea, but the only way to fight the plague is with decency . ”

– Albert Camus, La Peste (1947)¹

Severe acute respiratory syndrome (SARS), H1N1 swine flu, Ebola, Zika, and Middle East respiratory syndrome (MERS): the 21st century has already been witness to several serious infectious outbreaks and pandemics,² but none has been as deadly and consequential as the current one. The ongoing SARS-coronavirus-2 (SARS-CoV-2) pandemic is shaping not only current psychiatric care but the future of psychiatry. Now that we are beyond the initial stages of the coronavirus disease 2019 (COVID-19) pandemic, when psychiatrists had a crash course in disaster psychiatry, our attention must shift to rebuilding and managing disillusionment and other psychological fallout of the intense early days.³

In this article, we offer guidance to psychiatrists caring for patients with serious mental illness (SMI) during the SARS-CoV-2 pandemic. Patients with SMI are easily forgotten as other issues (eg, preserving ICU capacity) overshadow the already historically neglected needs of this impoverished group.⁴ From both human and public-health perspectives, this inattention is a mistake. Assuring psychiatric stability is critically important to prevent the spread of COVID-19 in marginalized communities comprised of individuals who are poor, members of racial minorities, and others who already experience health disparities.⁵ Without controlling transmission in these groups, the pandemic will not be sufficiently contained.

We begin by highlighting general principles of pandemic management because caring for patients with SMI does not occur in a vacuum. Infectious outbreaks require not only helping those who need direct medical care because they are infected, but also managing populations that are at risk of getting infected, including health care and other essential workers.

Principles of pandemic management

Delivery of medical care during a pandemic differs from routine care. An effective disaster response requires collaboration and coordination among public-health, treatment, and emergency systems. Many institutions shift to an incident management system and crisis leadership, with clear lines of authority to coordinate responders and build medical surge capacity. Such a top-down leadership approach must plan and allow for the emergence of other credible leaders and for the restoration of people’s agency.

Unfortunately, adaptive capacity may be limited, especially in the public sector and psychiatric care system, where resources are already poor. Particularly early in a pandemic, services considered non-essential—which includes most psychiatric outpatient care—can become unavailable. A major effort is needed to prevent the psychiatric care system from contracting further, as happened during 9/11.⁶ Additionally, “essential” cannot be conflated with “emergent,” as can easily occur in extreme circumstances. Early and sustained efforts are required to ensure that patients with SMI who may be teetering on the edge of emergency status do not slip off that edge, especially when the emergency medical system is operating over capacity.

A comprehensive outbreak response must consider that a pandemic is not only a medical crisis but a mental health crisis and a communication emergency.⁷ Mental health clinicians need to provide accurate information and help patients cope with their fears.

Continue to: Psychological aspects of pandemics

Psychological aspects of pandemics. Previous infectious outbreaks have reaffirmed that mental health plays an outsized role during epidemics. Chaos, uncertainty, fear of death, and loss of income and housing cause prolonged stress and exact a psychological toll.

Adverse psychological impacts include expectable, normal reactions such as stress-induced anxiety or insomnia. In addition, new-onset psychiatric illnesses or exacerbations of existing ones may emerge.⁸ As disillusionment and demoralization appear in the wake of the acute phase, with persistently high unemployment, suicide prevention becomes an important goal.⁹

Pandemics lead to expectable behavioral responses (eg, increases in substance use and interpersonal conflict). Fear-based decisions may result in unhelpful behavior, such as hoarding medications (which may result in shortages) or dangerous, unsupervised use of unproven medications (eg, hydroxychloroquine). Trust is needed to accept public-health measures, and recommendations (eg, wearing masks) must be culturally informed to be credible and effective.

Because people are affected differently, at individual, cultural, and socioeconomic levels, they will view the situation differently. For many people, secondary stressors (eg, job loss) may be more disastrous than the primary medical event (ie, the pandemic). This distinction is critical because concrete financial help, not psychiatric care, is needed. Sometimes, even when a psychiatric disorder such as SMI or major neurocognitive disorder is present, the illusion of an acute decompensation can be created by the loss of social and structural supports that previously scaffolded a person’s life.

Mental illness prevention. Community mental-health surveillance is important to monitor for distress, psychiatric symptoms, health-risk behaviors, risk and safety perception, and preparedness. Clinicians must be ready to normalize expectable and temporary distress, while recognizing when that distress becomes pathological. This may be difficult in patients with SMI who often already have reduced stress tolerance or problem-based coping skills.¹⁰

Continue to: Psychological first aid...

Psychological first aid (PFA) is a standard intervention recommended by the World Health Organization for most individuals following a disaster; it is evidence-informed and has face validity.¹¹ Intended to relieve distress by creating an environment that is safe, calm, and connected, PFA fosters self-efficacy and hope. While PFA is a form of universal prevention, it is not designed for patients with SMI, is not a psychiatric intervention, and is not provided by clinicians. Its principles, however, can easily be applied to patients with SMI to prevent distressing symptoms from becoming a relapse.

Communication. Good risk and crisis communication are critical because individual and population behavior will be governed by the perception of risk and fear, and not by facts. Failure to manage the “infodemic”⁷—with its misinformation, contradictory messages, and rumors—jeopardizes infection control if patients become paralyzed by uncertainty and fear. Scapegoating occurs easily during times of threat, and society must contain the parallel epidemic of xenophobia based on stigma and misinformation.¹²

Decision-making under uncertainty is not perfect and subject to revision as better information becomes available. Pointing this out to the public is delicate but essential to curtail skepticism and mistrust when policies are adjusted in response to new circumstances and knowledge.

Mistrust of an authority’s legitimacy and fear-based decisions lead to lack of cooperation with public-health measures, which can undermine an effective response to the pandemic. Travel restrictions or quarantine measures will not be followed if individuals question their importance. Like the general public, patients need education and clear communication to address their fear of contagion, dangers posed to family (and pets), and mistrust of authority and government. A lack of appreciation of the seriousness of the pandemic and individual responsibility may need to be addressed. Two important measures to accomplish this are steering patients to reputable sources of information and advising that they limit media exposure.

Resilience-building. Community and workplace resilience are important aspects of making it through a disaster as best as possible. Resilience is not innate and fixed; it must be deliberately built.¹³ Choosing an attitude of post-traumatic growth over the victim narrative is a helpful stance. Practicing self-care (rest, nutrition, exercise) and self-compassion (self-kindness, common humanity, mindfulness) is good advice for patients and caregivers alike.

Continue to: Workforce protection

Workforce protection. Compared to other disasters, infectious outbreaks disproportionally affect the medical community, and care delivery is at stake. While psychological and psychiatric needs may increase during a pandemic, services often contract, day programs and clinics close, teams are reduced to skeleton crews, and only emergency psychiatric care is available. Workforce protection is critical to avoid illness or simple absenteeism due to mistrust of protective measures.

Only a well-briefed, well-led, well-supported, and adequately resourced workforce is going to be effective in managing this public-health emergency. Burnout and moral injury are feared long-term consequences for health care workers that need to be proactively addressed.¹⁴ As opposed to other forms of disasters, managing your own fears about safety is important. Clinicians and their patients sit in the proverbial same boat.

Ethics. The anticipated need to ration life-saving care (eg, ventilators) has been at the forefront of ethical concerns.¹⁵ In psychiatry, the question of involuntary public-health interventions for uncooperative psychiatric patients sits uncomfortably between public-health ethics and human rights, and is an opportunity for collaboration with public-health and infectious-disease colleagues.

Redeployed clinicians and those working under substandard conditions may be concerned about civil liability due to a modified standard of care during a crisis. Some clinicians may ask if their duty to care must override their natural instinct to protect themselves. There is a lot of room for resentment in these circumstances. Redeployed or otherwise “conscripted” clinicians may resent administrators, especially those administering from the safety of their homes. Those “left behind” to work in potentially precarious circumstances may resent their absent colleagues. Moreover, these front-line clinicians may have been forced to make ethical decisions for which they were not prepared.¹⁶ Maintaining morale is far from trivial, not just during the pandemic, but afterward, when (and if) the entire workforce is reunited. All parties need to be mindful of how their actions and decisions impact and are perceived by others, both in the hospital and at home.

Managing patients with SMI during COVID-19

Patients with SMI are potentially hard hit by COVID-19 due to a “tragic” epidemiologic triad of agent-host-environment: SARS-CoV-2 is a highly infectious agent affecting patients with SMI who are vulnerable hosts in permissive environments (Figure).

Continue to: While not as infectious as measles...

While not as infectious as measles, COVID-19 is more infectious than the seasonal flu virus.¹⁷ It can lead to uncontrolled infection within a short period of time, particularly in enclosed settings. Outbreaks have occurred readily on cruise ships and aircraft carriers as well as in nursing homes, homeless shelters, prisons, and group homes.

Patients with SMI are vulnerable hosts because they have many of the medical risk factors¹⁸ that portend a poor prognosis if they become infected, including pre-existing lung conditions and heart disease¹⁹ as well as diabetes and obesity.²⁰ Obesity likely creates a hyperinflammatory state and a decrease in vital capacity. Patient-related behavioral factors include poor early-symptom reporting and ineffective infection control.

Unfavorable social determinants of health include not only poverty but crowded housing that is a perfect incubator for COVID-19.

Priority treatment goals. The overarching goal during a pandemic is to keep patients with SMI in psychiatric treatment and prevent them from disengaging from care in the service of infection control. Urgent tasks include infection control, relapse prevention, and preventing treatment disengagement and loneliness.

Infection control. As trusted sources of information, psychiatrists can play an important role in infection control in several important ways:

• educating patients about infection-control measures and public-health recommendations
• helping patients understand what testing can accomplish and when to pursue it
• encouraging protective health behaviors (eg, hand washing, mask wearing, physical distancing)
• assessing patients’ risk appreciation
• assessing for and addressing obstacles to implementing and complying with infection-control measures
• explaining contact tracing
• providing reassurance.

Continue to: Materials and explanations...

Materials and explanations must be adapted for patient understanding.

Patients with disorganization or cognitive disturbances may have difficulties cooperating or problem-solving. Patients with negative symptoms may be inappropriately unconcerned and also inaccurately report symptoms that suggest COVID-19. Acute psychosis or mania can prevent patients from complying with public-health efforts. Some measures may be difficult to implement if the means are simply not there (eg, physical distancing in a crowded apartment). Previously open settings (eg, group homes) have had to develop new mechanisms under the primacy of infection control. Inpatient units—traditionally places where community, shared healing, and group therapy are prized—have had to decrease maximum occupancy, limit the number of patients attending groups, and discourage or outrightly prohibit social interaction (eg, dining together).

Relapse prevention. Patients who take maintenance medications need to be supported. A manic or psychotic relapse during a pandemic puts patients at risk of acquiring and spreading COVID-19. “Treatment as prevention” is a slogan from human immunodeficiency virus (HIV) care that captures the importance of antiretroviral treatment to prevent medical complications from HIV, and also to reduce infecting other people. By analogy, psychiatric treatment for patients with SMI can prevent psychiatric instability and thereby control viral transmission. Avoiding sending psychiatric patients to a potentially stressed acute-care system is important.

Psychosocial support. Clinics need to ensure that patients continue to engage in care beyond medication-taking to proactively prevent psychiatric exacerbations. Healthful, resilience-building behaviors should be encouraged while monitoring and counseling against maladaptive ones (eg, increased substance use). Supporting patients emotionally and helping them solve problems are critical, particularly for those who are subjected to quarantine or isolation. Obviously, in these latter situations, outreach will be necessary and may require creative delivery systems and dedicated clinicians for patients who lack access to the technology necessary for virtual visits. Havens and Ghaemi²¹ have suggested that a good therapeutic alliance can be viewed as a mood stabilizer. Helping patients grieve losses (loved ones, jobs, sense of safety) may be an important part of support.

Even before COVID-19, loneliness was a major factor for patients with schizophrenia.²² A psychiatric clinic is one aspect of a person with SMI’s social network; during the initial phase of the pandemic, many clinics and treatment programs closed. Patients for whom clinics structure and anchor their activities are at high risk of disconnecting from treatment, staying at home, and becoming lonely.

Continue to: Caregivers are always important...

Caregivers are always important to SMI patients, but they may assume an even bigger role during this pandemic. Some patients may have moved in with a relative, after years of living on their own. In other cases, stable caregiver relationships may be disrupted due to COVID-19–related sickness in the caregiver; if not addressed, this can result in a patient’s clinical decompensation. Clinicians should take the opportunity to understand who a patient’s caregivers are (group home staff, families) and rekindle clinical contact with them. Relationships with caregivers that may have been on “autopilot” during normal times are opportunities for welcome support and guidance, to the benefit of both patients and caregivers.

Table 1 summarizes clinical tasks that need to be kept in mind when conducting clinic visits during COVID-19 in order to achieve the high-priority treatment goals of infection control, relapse prevention, and psychosocial support.

Differential diagnosis. Neuropsychiatric syndromes have long been observed in influenza pandemics,²³ due both to direct viral effects and to the effects of critical illness on the brain. Two core symptoms of COVID-19—anosmia and ageusia—suggest that COVID-19 can directly affect the brain. While neurologic manifestations are common,²⁴ it remains unclear to what extent COVID-19 can directly “cause” psychiatric symptoms, or if such symptoms are the result of cytokines²⁵ or other medical processes (eg, thromboembolism).²⁶ Psychosis due to COVID-19 may, in some cases, represent a stress-related brief psychotic disorder.²⁷

Hospitalized patients who have recovered from COVID-19 may have experienced prolonged sedation and severe delirium in an ICU.²⁸ Complications such as posttraumatic stress disorder,²⁹ hypoperfusion-related brain injuries, or other long-term cognitive difficulties may result. In previous flu epidemics, patients developed serious neurologic complications such as post-encephalitic Parkinson’s disease.³⁰

Any person subjected to isolation or quarantine is at risk for psychiatric complications.³¹ Patients with SMI who live in group homes may be particularly susceptible to new rules, including no-visitor policies.

Continue to: Outpatients whose primary disorder...

Outpatients whose primary disorder is well controlled may, like anyone else, struggle with the effects of the pandemic. It is necessary to carefully differentiate non-specific symptoms associated with stress from the emergence of a new disorder resulting from stress.³² For some patients, grief or adjustment disorders should be considered. Prolonged stress and uncertainty may eventually lead to an exacerbation of a primary disorder, particularly if the situation (eg, financial loss) does not improve or worsens. Demoralization and suicidal thinking need to be monitored. Relapse or increased use of alcohol or other substances as a response to stress may also complicate the clinical picture.³³ Last, smoking cessation as a major treatment goal in general should be re-emphasized and not ignored during the ongoing pandemic.³⁴

Table 2 summarizes psychiatric symptoms that need to be considered when managing a patient with SMI during this pandemic.

Treatment tools

Psychopharmacology. Even though crisis-mode prescribing may be necessary, the safe use of psychotropics remains the goal of psychiatric prescribing. Access to medications becomes a larger consideration; for many patients, a 90-day supply may be indicated. Review of polypharmacy, including for pneumonia risk, should be undertaken. Preventing drooling (eg, from sedation, clozapine, extrapyramidal symptoms [EPS]) will decrease aspiration risk.

In general, treatment of psychiatric symptoms in a patient with COVID-19 follows usual guidelines. The best treatment for COVID-19 patients with delirium, however, remains to be established, particularly how to manage severe agitation.²⁸ Pharmacodynamic and pharmacokinetic drug–drug interactions between psychotropics and antiviral treatments for COVID-19 (eg, QTc prolongation) can be expected and need to be reviewed.³⁵ For stress-related anxiety, judicious pharmacotherapy can be helpful. Diazepam given at the earliest signs of a psychotic relapse may stave off a relapse for patients with schizophrenia.³⁶ Even if permitted under relaxed prescribing rules during a public-health emergency, prescribing controlled substances without seeing patients in person requires additional thought. In some cases, adjusting the primary medication to buffer against stress may be preferred (eg, adjusting an antipsychotic in a patient on maintenance treatment for schizophrenia, particularly if a low-dose strategy is pursued).

Clozapine requires registry-based prescribing and bloodwork (“no blood, no drug”). The use of clozapine during this public-health emergency has been made easier because of FDA guidance that allows clozapine to be dispensed without blood work if obtaining blood work is not possible (eg, a patient is quarantined) or can be accomplished only at substantial risk to patients and the population at large. Under certain conditions, clozapine can be dispensed safely and in a way that is consistent with infection prevention. Clozapine-treated patients admitted with COVID-19 should be monitored for clozapine toxicity and the clozapine dose adjusted.³⁷ A consensus statement consistent with the FDA and clinical considerations for using clozapine during COVID-19 is summarized in Table 3.³⁸

Continue to: Long-acting injectable antipsychotics...

Long-acting injectable antipsychotics (LAIs) pose a problem because they require in-person visits. Ideally, during a pandemic, patients should be seen in person as frequently as medically necessary but as infrequently as possible to limit exposure of both patients and staff. Table 4 provides some clinical recommendations on how to use LAIs during the pandemic.³⁹

Supportive psychotherapy may be the most important tool we have in helping patients with loss and uncertainty during these challenging months.⁴⁰ Simply staying in contact with patients plays a major role in preventing care discontinuity. Even routine interactions have become stressful, with everyone wearing a mask that partially obscures the face. People with impaired hearing may find it even more difficult to understand you.

Education, problem-solving, and a directive, encouraging style are major tools of supportive psychotherapy to reduce symptoms and increase adaptive skills. Clarify that social distancing refers to physical, not emotional, distancing. The judicious and temporary use of anxiolytics is appropriate to reduce anxiety. Concrete help and problem-solving (eg, filling out forms) are examples of proactive crisis intervention.

Telepsychiatry emerged in the pandemic’s early days as the default mode of practice in order to limit in-person contacts.⁴¹ Like all new technology, telepsychiatry brings progress and peril.⁴² While it has gone surprisingly well for most, the “digital divide” does not afford all patients access to the needed technology. The long-term effectiveness and acceptance of telehealth remain to be seen. (Editor’s Note: For more about this topic, see “Telepsychiatry: What you need to know.” Current Psychiatry. 2020;19[6]:16-23.)

Lessons learned and outlook

Infectious outbreaks have historically inflicted long-term disruptions on societies and altered the course of history. However, each disaster is unique, and lessons from previous disasters may only partially apply.⁴³ We do not yet know how this one will end, including how long it will take for the world’s economies to recover. If nothing else, the current public-health emergency has brought to the forefront what psychiatrists have always known: health disparities are partially responsible for different disease risks (in this case, the risk of getting infected with SARS-CoV-2).⁵ It may not be a coincidence that the Black Lives Matter movement is becoming a major impetus for social change at a time when the pandemic is exposing health-care inequalities.

Continue to: Some areas of the country...

Some areas of the country succeeded in reducing infections and limiting community spread, which ushered in an uneasy sense of normalcy even while the pandemic continues. At least for now, these locales can focus on rebuilding and preparing for expectable fluctuations in disease activity, including the arrival of the annual flu season on top of COVID-19.⁴⁴ Recovery is not a return to the status quo ante but building stronger communities—“building back better.”⁴⁵ Unless there is a continuum of care, shortcomings in one sector will have ripple effects through the entire system, particularly for psychiatric care for patients with SMI, which was inadequate before the pandemic.

Ensuring access to critical care was a priority during the pandemic’s early phase but came at the price of deferring other types of care, such as routine primary care; the coming months will see the downstream consequences of this approach,⁴⁶ including for patients with SMI.

In the meantime, doing our job as clinicians, as Camus’s fictitious Dr. Bernard Rieux from the epigraph responds when asked how to define decency, may be the best we can do in these times. This includes contributing to and molding our field’s future and fostering a sense of agency in our patients and in ourselves. Major goals will be to preserve lessons learned, maintain flexibility, and avoid a return to unhelpful overregulation and payment models that do not reflect the flexible, person-centered care so important for patients with SMI.⁴⁷

Bottom Line

During a pandemic, patients with serious mental illness may be easily forgotten as other issues overshadow the needs of this impoverished group. During a pandemic, the priority treatment goals for these patients are infection control, relapse prevention, and preventing treatment disengagement and loneliness. A pandemic requires changes in how patients with serious mental illness will receive psychopharmacology and psychotherapy.

Related Resources

• Huremović D (ed). Psychiatry of pandemics: a mental health response to infection outbreak. Cham, Switzerland: Springer Nature Switzerland AG; 2019.
• Ursano RJ, Fullerton CS, Weisaeth L, et al (eds). Textbook of disaster psychiatry. 2nd ed. Cambridge, UK: Cambridge University Press; 2017.
• Centers for Disease Control and Prevention. Coronavirus (COVID-19). https://www.cdc.gov/coronavirus/2019-ncov/index.html.
• American Psychiatric Association. Coronavirus resources. https://www.psychiatry.org/psychiatrists/covid-19-coronavirus.
• SMI Adviser. Make informed decisions related to COVID-19 and mental health. https://smiadviser.org/about/covid.

Drug Brand Names

Clozapine • Clozaril
Diazepam • Valium
Hydroxychloroquine • Plaquenil

“This whole thing is not about heroism. It’s about decency. It may seem a ridiculous idea, but the only way to fight the plague is with decency . ”

– Albert Camus, La Peste (1947)¹

Severe acute respiratory syndrome (SARS), H1N1 swine flu, Ebola, Zika, and Middle East respiratory syndrome (MERS): the 21st century has already been witness to several serious infectious outbreaks and pandemics,² but none has been as deadly and consequential as the current one. The ongoing SARS-coronavirus-2 (SARS-CoV-2) pandemic is shaping not only current psychiatric care but the future of psychiatry. Now that we are beyond the initial stages of the coronavirus disease 2019 (COVID-19) pandemic, when psychiatrists had a crash course in disaster psychiatry, our attention must shift to rebuilding and managing disillusionment and other psychological fallout of the intense early days.³

In this article, we offer guidance to psychiatrists caring for patients with serious mental illness (SMI) during the SARS-CoV-2 pandemic. Patients with SMI are easily forgotten as other issues (eg, preserving ICU capacity) overshadow the already historically neglected needs of this impoverished group.⁴ From both human and public-health perspectives, this inattention is a mistake. Assuring psychiatric stability is critically important to prevent the spread of COVID-19 in marginalized communities comprised of individuals who are poor, members of racial minorities, and others who already experience health disparities.⁵ Without controlling transmission in these groups, the pandemic will not be sufficiently contained.

We begin by highlighting general principles of pandemic management because caring for patients with SMI does not occur in a vacuum. Infectious outbreaks require not only helping those who need direct medical care because they are infected, but also managing populations that are at risk of getting infected, including health care and other essential workers.

Principles of pandemic management

Delivery of medical care during a pandemic differs from routine care. An effective disaster response requires collaboration and coordination among public-health, treatment, and emergency systems. Many institutions shift to an incident management system and crisis leadership, with clear lines of authority to coordinate responders and build medical surge capacity. Such a top-down leadership approach must plan and allow for the emergence of other credible leaders and for the restoration of people’s agency.

Unfortunately, adaptive capacity may be limited, especially in the public sector and psychiatric care system, where resources are already poor. Particularly early in a pandemic, services considered non-essential—which includes most psychiatric outpatient care—can become unavailable. A major effort is needed to prevent the psychiatric care system from contracting further, as happened during 9/11.⁶ Additionally, “essential” cannot be conflated with “emergent,” as can easily occur in extreme circumstances. Early and sustained efforts are required to ensure that patients with SMI who may be teetering on the edge of emergency status do not slip off that edge, especially when the emergency medical system is operating over capacity.

A comprehensive outbreak response must consider that a pandemic is not only a medical crisis but a mental health crisis and a communication emergency.⁷ Mental health clinicians need to provide accurate information and help patients cope with their fears.

Continue to: Psychological aspects of pandemics

Psychological aspects of pandemics. Previous infectious outbreaks have reaffirmed that mental health plays an outsized role during epidemics. Chaos, uncertainty, fear of death, and loss of income and housing cause prolonged stress and exact a psychological toll.

Adverse psychological impacts include expectable, normal reactions such as stress-induced anxiety or insomnia. In addition, new-onset psychiatric illnesses or exacerbations of existing ones may emerge.⁸ As disillusionment and demoralization appear in the wake of the acute phase, with persistently high unemployment, suicide prevention becomes an important goal.⁹

Pandemics lead to expectable behavioral responses (eg, increases in substance use and interpersonal conflict). Fear-based decisions may result in unhelpful behavior, such as hoarding medications (which may result in shortages) or dangerous, unsupervised use of unproven medications (eg, hydroxychloroquine). Trust is needed to accept public-health measures, and recommendations (eg, wearing masks) must be culturally informed to be credible and effective.

Because people are affected differently, at individual, cultural, and socioeconomic levels, they will view the situation differently. For many people, secondary stressors (eg, job loss) may be more disastrous than the primary medical event (ie, the pandemic). This distinction is critical because concrete financial help, not psychiatric care, is needed. Sometimes, even when a psychiatric disorder such as SMI or major neurocognitive disorder is present, the illusion of an acute decompensation can be created by the loss of social and structural supports that previously scaffolded a person’s life.

Mental illness prevention. Community mental-health surveillance is important to monitor for distress, psychiatric symptoms, health-risk behaviors, risk and safety perception, and preparedness. Clinicians must be ready to normalize expectable and temporary distress, while recognizing when that distress becomes pathological. This may be difficult in patients with SMI who often already have reduced stress tolerance or problem-based coping skills.¹⁰

Continue to: Psychological first aid...

Psychological first aid (PFA) is a standard intervention recommended by the World Health Organization for most individuals following a disaster; it is evidence-informed and has face validity.¹¹ Intended to relieve distress by creating an environment that is safe, calm, and connected, PFA fosters self-efficacy and hope. While PFA is a form of universal prevention, it is not designed for patients with SMI, is not a psychiatric intervention, and is not provided by clinicians. Its principles, however, can easily be applied to patients with SMI to prevent distressing symptoms from becoming a relapse.

Communication. Good risk and crisis communication are critical because individual and population behavior will be governed by the perception of risk and fear, and not by facts. Failure to manage the “infodemic”⁷—with its misinformation, contradictory messages, and rumors—jeopardizes infection control if patients become paralyzed by uncertainty and fear. Scapegoating occurs easily during times of threat, and society must contain the parallel epidemic of xenophobia based on stigma and misinformation.¹²

Decision-making under uncertainty is not perfect and subject to revision as better information becomes available. Pointing this out to the public is delicate but essential to curtail skepticism and mistrust when policies are adjusted in response to new circumstances and knowledge.

Mistrust of an authority’s legitimacy and fear-based decisions lead to lack of cooperation with public-health measures, which can undermine an effective response to the pandemic. Travel restrictions or quarantine measures will not be followed if individuals question their importance. Like the general public, patients need education and clear communication to address their fear of contagion, dangers posed to family (and pets), and mistrust of authority and government. A lack of appreciation of the seriousness of the pandemic and individual responsibility may need to be addressed. Two important measures to accomplish this are steering patients to reputable sources of information and advising that they limit media exposure.

Resilience-building. Community and workplace resilience are important aspects of making it through a disaster as best as possible. Resilience is not innate and fixed; it must be deliberately built.¹³ Choosing an attitude of post-traumatic growth over the victim narrative is a helpful stance. Practicing self-care (rest, nutrition, exercise) and self-compassion (self-kindness, common humanity, mindfulness) is good advice for patients and caregivers alike.

Continue to: Workforce protection

Workforce protection. Compared to other disasters, infectious outbreaks disproportionally affect the medical community, and care delivery is at stake. While psychological and psychiatric needs may increase during a pandemic, services often contract, day programs and clinics close, teams are reduced to skeleton crews, and only emergency psychiatric care is available. Workforce protection is critical to avoid illness or simple absenteeism due to mistrust of protective measures.

Only a well-briefed, well-led, well-supported, and adequately resourced workforce is going to be effective in managing this public-health emergency. Burnout and moral injury are feared long-term consequences for health care workers that need to be proactively addressed.¹⁴ As opposed to other forms of disasters, managing your own fears about safety is important. Clinicians and their patients sit in the proverbial same boat.

Ethics. The anticipated need to ration life-saving care (eg, ventilators) has been at the forefront of ethical concerns.¹⁵ In psychiatry, the question of involuntary public-health interventions for uncooperative psychiatric patients sits uncomfortably between public-health ethics and human rights, and is an opportunity for collaboration with public-health and infectious-disease colleagues.

Redeployed clinicians and those working under substandard conditions may be concerned about civil liability due to a modified standard of care during a crisis. Some clinicians may ask if their duty to care must override their natural instinct to protect themselves. There is a lot of room for resentment in these circumstances. Redeployed or otherwise “conscripted” clinicians may resent administrators, especially those administering from the safety of their homes. Those “left behind” to work in potentially precarious circumstances may resent their absent colleagues. Moreover, these front-line clinicians may have been forced to make ethical decisions for which they were not prepared.¹⁶ Maintaining morale is far from trivial, not just during the pandemic, but afterward, when (and if) the entire workforce is reunited. All parties need to be mindful of how their actions and decisions impact and are perceived by others, both in the hospital and at home.

Managing patients with SMI during COVID-19

Patients with SMI are potentially hard hit by COVID-19 due to a “tragic” epidemiologic triad of agent-host-environment: SARS-CoV-2 is a highly infectious agent affecting patients with SMI who are vulnerable hosts in permissive environments (Figure).

Continue to: While not as infectious as measles...

While not as infectious as measles, COVID-19 is more infectious than the seasonal flu virus.¹⁷ It can lead to uncontrolled infection within a short period of time, particularly in enclosed settings. Outbreaks have occurred readily on cruise ships and aircraft carriers as well as in nursing homes, homeless shelters, prisons, and group homes.

Patients with SMI are vulnerable hosts because they have many of the medical risk factors¹⁸ that portend a poor prognosis if they become infected, including pre-existing lung conditions and heart disease¹⁹ as well as diabetes and obesity.²⁰ Obesity likely creates a hyperinflammatory state and a decrease in vital capacity. Patient-related behavioral factors include poor early-symptom reporting and ineffective infection control.

Unfavorable social determinants of health include not only poverty but crowded housing that is a perfect incubator for COVID-19.

Priority treatment goals. The overarching goal during a pandemic is to keep patients with SMI in psychiatric treatment and prevent them from disengaging from care in the service of infection control. Urgent tasks include infection control, relapse prevention, and preventing treatment disengagement and loneliness.

Infection control. As trusted sources of information, psychiatrists can play an important role in infection control in several important ways:

• educating patients about infection-control measures and public-health recommendations
• helping patients understand what testing can accomplish and when to pursue it
• encouraging protective health behaviors (eg, hand washing, mask wearing, physical distancing)
• assessing patients’ risk appreciation
• assessing for and addressing obstacles to implementing and complying with infection-control measures
• explaining contact tracing
• providing reassurance.

Continue to: Materials and explanations...

Materials and explanations must be adapted for patient understanding.

Patients with disorganization or cognitive disturbances may have difficulties cooperating or problem-solving. Patients with negative symptoms may be inappropriately unconcerned and also inaccurately report symptoms that suggest COVID-19. Acute psychosis or mania can prevent patients from complying with public-health efforts. Some measures may be difficult to implement if the means are simply not there (eg, physical distancing in a crowded apartment). Previously open settings (eg, group homes) have had to develop new mechanisms under the primacy of infection control. Inpatient units—traditionally places where community, shared healing, and group therapy are prized—have had to decrease maximum occupancy, limit the number of patients attending groups, and discourage or outrightly prohibit social interaction (eg, dining together).

Relapse prevention. Patients who take maintenance medications need to be supported. A manic or psychotic relapse during a pandemic puts patients at risk of acquiring and spreading COVID-19. “Treatment as prevention” is a slogan from human immunodeficiency virus (HIV) care that captures the importance of antiretroviral treatment to prevent medical complications from HIV, and also to reduce infecting other people. By analogy, psychiatric treatment for patients with SMI can prevent psychiatric instability and thereby control viral transmission. Avoiding sending psychiatric patients to a potentially stressed acute-care system is important.

Psychosocial support. Clinics need to ensure that patients continue to engage in care beyond medication-taking to proactively prevent psychiatric exacerbations. Healthful, resilience-building behaviors should be encouraged while monitoring and counseling against maladaptive ones (eg, increased substance use). Supporting patients emotionally and helping them solve problems are critical, particularly for those who are subjected to quarantine or isolation. Obviously, in these latter situations, outreach will be necessary and may require creative delivery systems and dedicated clinicians for patients who lack access to the technology necessary for virtual visits. Havens and Ghaemi²¹ have suggested that a good therapeutic alliance can be viewed as a mood stabilizer. Helping patients grieve losses (loved ones, jobs, sense of safety) may be an important part of support.

Even before COVID-19, loneliness was a major factor for patients with schizophrenia.²² A psychiatric clinic is one aspect of a person with SMI’s social network; during the initial phase of the pandemic, many clinics and treatment programs closed. Patients for whom clinics structure and anchor their activities are at high risk of disconnecting from treatment, staying at home, and becoming lonely.

Continue to: Caregivers are always important...

Caregivers are always important to SMI patients, but they may assume an even bigger role during this pandemic. Some patients may have moved in with a relative, after years of living on their own. In other cases, stable caregiver relationships may be disrupted due to COVID-19–related sickness in the caregiver; if not addressed, this can result in a patient’s clinical decompensation. Clinicians should take the opportunity to understand who a patient’s caregivers are (group home staff, families) and rekindle clinical contact with them. Relationships with caregivers that may have been on “autopilot” during normal times are opportunities for welcome support and guidance, to the benefit of both patients and caregivers.

Table 1 summarizes clinical tasks that need to be kept in mind when conducting clinic visits during COVID-19 in order to achieve the high-priority treatment goals of infection control, relapse prevention, and psychosocial support.

Differential diagnosis. Neuropsychiatric syndromes have long been observed in influenza pandemics,²³ due both to direct viral effects and to the effects of critical illness on the brain. Two core symptoms of COVID-19—anosmia and ageusia—suggest that COVID-19 can directly affect the brain. While neurologic manifestations are common,²⁴ it remains unclear to what extent COVID-19 can directly “cause” psychiatric symptoms, or if such symptoms are the result of cytokines²⁵ or other medical processes (eg, thromboembolism).²⁶ Psychosis due to COVID-19 may, in some cases, represent a stress-related brief psychotic disorder.²⁷

Hospitalized patients who have recovered from COVID-19 may have experienced prolonged sedation and severe delirium in an ICU.²⁸ Complications such as posttraumatic stress disorder,²⁹ hypoperfusion-related brain injuries, or other long-term cognitive difficulties may result. In previous flu epidemics, patients developed serious neurologic complications such as post-encephalitic Parkinson’s disease.³⁰

Any person subjected to isolation or quarantine is at risk for psychiatric complications.³¹ Patients with SMI who live in group homes may be particularly susceptible to new rules, including no-visitor policies.

Continue to: Outpatients whose primary disorder...

Outpatients whose primary disorder is well controlled may, like anyone else, struggle with the effects of the pandemic. It is necessary to carefully differentiate non-specific symptoms associated with stress from the emergence of a new disorder resulting from stress.³² For some patients, grief or adjustment disorders should be considered. Prolonged stress and uncertainty may eventually lead to an exacerbation of a primary disorder, particularly if the situation (eg, financial loss) does not improve or worsens. Demoralization and suicidal thinking need to be monitored. Relapse or increased use of alcohol or other substances as a response to stress may also complicate the clinical picture.³³ Last, smoking cessation as a major treatment goal in general should be re-emphasized and not ignored during the ongoing pandemic.³⁴

Table 2 summarizes psychiatric symptoms that need to be considered when managing a patient with SMI during this pandemic.

Treatment tools

Psychopharmacology. Even though crisis-mode prescribing may be necessary, the safe use of psychotropics remains the goal of psychiatric prescribing. Access to medications becomes a larger consideration; for many patients, a 90-day supply may be indicated. Review of polypharmacy, including for pneumonia risk, should be undertaken. Preventing drooling (eg, from sedation, clozapine, extrapyramidal symptoms [EPS]) will decrease aspiration risk.

In general, treatment of psychiatric symptoms in a patient with COVID-19 follows usual guidelines. The best treatment for COVID-19 patients with delirium, however, remains to be established, particularly how to manage severe agitation.²⁸ Pharmacodynamic and pharmacokinetic drug–drug interactions between psychotropics and antiviral treatments for COVID-19 (eg, QTc prolongation) can be expected and need to be reviewed.³⁵ For stress-related anxiety, judicious pharmacotherapy can be helpful. Diazepam given at the earliest signs of a psychotic relapse may stave off a relapse for patients with schizophrenia.³⁶ Even if permitted under relaxed prescribing rules during a public-health emergency, prescribing controlled substances without seeing patients in person requires additional thought. In some cases, adjusting the primary medication to buffer against stress may be preferred (eg, adjusting an antipsychotic in a patient on maintenance treatment for schizophrenia, particularly if a low-dose strategy is pursued).

Clozapine requires registry-based prescribing and bloodwork (“no blood, no drug”). The use of clozapine during this public-health emergency has been made easier because of FDA guidance that allows clozapine to be dispensed without blood work if obtaining blood work is not possible (eg, a patient is quarantined) or can be accomplished only at substantial risk to patients and the population at large. Under certain conditions, clozapine can be dispensed safely and in a way that is consistent with infection prevention. Clozapine-treated patients admitted with COVID-19 should be monitored for clozapine toxicity and the clozapine dose adjusted.³⁷ A consensus statement consistent with the FDA and clinical considerations for using clozapine during COVID-19 is summarized in Table 3.³⁸

Continue to: Long-acting injectable antipsychotics...

Long-acting injectable antipsychotics (LAIs) pose a problem because they require in-person visits. Ideally, during a pandemic, patients should be seen in person as frequently as medically necessary but as infrequently as possible to limit exposure of both patients and staff. Table 4 provides some clinical recommendations on how to use LAIs during the pandemic.³⁹

Supportive psychotherapy may be the most important tool we have in helping patients with loss and uncertainty during these challenging months.⁴⁰ Simply staying in contact with patients plays a major role in preventing care discontinuity. Even routine interactions have become stressful, with everyone wearing a mask that partially obscures the face. People with impaired hearing may find it even more difficult to understand you.

Education, problem-solving, and a directive, encouraging style are major tools of supportive psychotherapy to reduce symptoms and increase adaptive skills. Clarify that social distancing refers to physical, not emotional, distancing. The judicious and temporary use of anxiolytics is appropriate to reduce anxiety. Concrete help and problem-solving (eg, filling out forms) are examples of proactive crisis intervention.

Telepsychiatry emerged in the pandemic’s early days as the default mode of practice in order to limit in-person contacts.⁴¹ Like all new technology, telepsychiatry brings progress and peril.⁴² While it has gone surprisingly well for most, the “digital divide” does not afford all patients access to the needed technology. The long-term effectiveness and acceptance of telehealth remain to be seen. (Editor’s Note: For more about this topic, see “Telepsychiatry: What you need to know.” Current Psychiatry. 2020;19[6]:16-23.)

Lessons learned and outlook

Infectious outbreaks have historically inflicted long-term disruptions on societies and altered the course of history. However, each disaster is unique, and lessons from previous disasters may only partially apply.⁴³ We do not yet know how this one will end, including how long it will take for the world’s economies to recover. If nothing else, the current public-health emergency has brought to the forefront what psychiatrists have always known: health disparities are partially responsible for different disease risks (in this case, the risk of getting infected with SARS-CoV-2).⁵ It may not be a coincidence that the Black Lives Matter movement is becoming a major impetus for social change at a time when the pandemic is exposing health-care inequalities.

Continue to: Some areas of the country...

Some areas of the country succeeded in reducing infections and limiting community spread, which ushered in an uneasy sense of normalcy even while the pandemic continues. At least for now, these locales can focus on rebuilding and preparing for expectable fluctuations in disease activity, including the arrival of the annual flu season on top of COVID-19.⁴⁴ Recovery is not a return to the status quo ante but building stronger communities—“building back better.”⁴⁵ Unless there is a continuum of care, shortcomings in one sector will have ripple effects through the entire system, particularly for psychiatric care for patients with SMI, which was inadequate before the pandemic.

Ensuring access to critical care was a priority during the pandemic’s early phase but came at the price of deferring other types of care, such as routine primary care; the coming months will see the downstream consequences of this approach,⁴⁶ including for patients with SMI.

In the meantime, doing our job as clinicians, as Camus’s fictitious Dr. Bernard Rieux from the epigraph responds when asked how to define decency, may be the best we can do in these times. This includes contributing to and molding our field’s future and fostering a sense of agency in our patients and in ourselves. Major goals will be to preserve lessons learned, maintain flexibility, and avoid a return to unhelpful overregulation and payment models that do not reflect the flexible, person-centered care so important for patients with SMI.⁴⁷

Bottom Line

During a pandemic, patients with serious mental illness may be easily forgotten as other issues overshadow the needs of this impoverished group. During a pandemic, the priority treatment goals for these patients are infection control, relapse prevention, and preventing treatment disengagement and loneliness. A pandemic requires changes in how patients with serious mental illness will receive psychopharmacology and psychotherapy.

Related Resources

• Huremović D (ed). Psychiatry of pandemics: a mental health response to infection outbreak. Cham, Switzerland: Springer Nature Switzerland AG; 2019.
• Ursano RJ, Fullerton CS, Weisaeth L, et al (eds). Textbook of disaster psychiatry. 2nd ed. Cambridge, UK: Cambridge University Press; 2017.
• Centers for Disease Control and Prevention. Coronavirus (COVID-19). https://www.cdc.gov/coronavirus/2019-ncov/index.html.
• American Psychiatric Association. Coronavirus resources. https://www.psychiatry.org/psychiatrists/covid-19-coronavirus.
• SMI Adviser. Make informed decisions related to COVID-19 and mental health. https://smiadviser.org/about/covid.

Drug Brand Names

Clozapine • Clozaril
Diazepam • Valium
Hydroxychloroquine • Plaquenil

“This whole thing is not about heroism. It’s about decency. It may seem a ridiculous idea, but the only way to fight the plague is with decency . ”

– Albert Camus, La Peste (1947)¹

Severe acute respiratory syndrome (SARS), H1N1 swine flu, Ebola, Zika, and Middle East respiratory syndrome (MERS): the 21st century has already been witness to several serious infectious outbreaks and pandemics,² but none has been as deadly and consequential as the current one. The ongoing SARS-coronavirus-2 (SARS-CoV-2) pandemic is shaping not only current psychiatric care but the future of psychiatry. Now that we are beyond the initial stages of the coronavirus disease 2019 (COVID-19) pandemic, when psychiatrists had a crash course in disaster psychiatry, our attention must shift to rebuilding and managing disillusionment and other psychological fallout of the intense early days.³

In this article, we offer guidance to psychiatrists caring for patients with serious mental illness (SMI) during the SARS-CoV-2 pandemic. Patients with SMI are easily forgotten as other issues (eg, preserving ICU capacity) overshadow the already historically neglected needs of this impoverished group.⁴ From both human and public-health perspectives, this inattention is a mistake. Assuring psychiatric stability is critically important to prevent the spread of COVID-19 in marginalized communities comprised of individuals who are poor, members of racial minorities, and others who already experience health disparities.⁵ Without controlling transmission in these groups, the pandemic will not be sufficiently contained.

We begin by highlighting general principles of pandemic management because caring for patients with SMI does not occur in a vacuum. Infectious outbreaks require not only helping those who need direct medical care because they are infected, but also managing populations that are at risk of getting infected, including health care and other essential workers.

Principles of pandemic management

Delivery of medical care during a pandemic differs from routine care. An effective disaster response requires collaboration and coordination among public-health, treatment, and emergency systems. Many institutions shift to an incident management system and crisis leadership, with clear lines of authority to coordinate responders and build medical surge capacity. Such a top-down leadership approach must plan and allow for the emergence of other credible leaders and for the restoration of people’s agency.

Unfortunately, adaptive capacity may be limited, especially in the public sector and psychiatric care system, where resources are already poor. Particularly early in a pandemic, services considered non-essential—which includes most psychiatric outpatient care—can become unavailable. A major effort is needed to prevent the psychiatric care system from contracting further, as happened during 9/11.⁶ Additionally, “essential” cannot be conflated with “emergent,” as can easily occur in extreme circumstances. Early and sustained efforts are required to ensure that patients with SMI who may be teetering on the edge of emergency status do not slip off that edge, especially when the emergency medical system is operating over capacity.

A comprehensive outbreak response must consider that a pandemic is not only a medical crisis but a mental health crisis and a communication emergency.⁷ Mental health clinicians need to provide accurate information and help patients cope with their fears.

Continue to: Psychological aspects of pandemics

Psychological aspects of pandemics. Previous infectious outbreaks have reaffirmed that mental health plays an outsized role during epidemics. Chaos, uncertainty, fear of death, and loss of income and housing cause prolonged stress and exact a psychological toll.

Adverse psychological impacts include expectable, normal reactions such as stress-induced anxiety or insomnia. In addition, new-onset psychiatric illnesses or exacerbations of existing ones may emerge.⁸ As disillusionment and demoralization appear in the wake of the acute phase, with persistently high unemployment, suicide prevention becomes an important goal.⁹

Pandemics lead to expectable behavioral responses (eg, increases in substance use and interpersonal conflict). Fear-based decisions may result in unhelpful behavior, such as hoarding medications (which may result in shortages) or dangerous, unsupervised use of unproven medications (eg, hydroxychloroquine). Trust is needed to accept public-health measures, and recommendations (eg, wearing masks) must be culturally informed to be credible and effective.

Because people are affected differently, at individual, cultural, and socioeconomic levels, they will view the situation differently. For many people, secondary stressors (eg, job loss) may be more disastrous than the primary medical event (ie, the pandemic). This distinction is critical because concrete financial help, not psychiatric care, is needed. Sometimes, even when a psychiatric disorder such as SMI or major neurocognitive disorder is present, the illusion of an acute decompensation can be created by the loss of social and structural supports that previously scaffolded a person’s life.

Mental illness prevention. Community mental-health surveillance is important to monitor for distress, psychiatric symptoms, health-risk behaviors, risk and safety perception, and preparedness. Clinicians must be ready to normalize expectable and temporary distress, while recognizing when that distress becomes pathological. This may be difficult in patients with SMI who often already have reduced stress tolerance or problem-based coping skills.¹⁰

Continue to: Psychological first aid...

Psychological first aid (PFA) is a standard intervention recommended by the World Health Organization for most individuals following a disaster; it is evidence-informed and has face validity.¹¹ Intended to relieve distress by creating an environment that is safe, calm, and connected, PFA fosters self-efficacy and hope. While PFA is a form of universal prevention, it is not designed for patients with SMI, is not a psychiatric intervention, and is not provided by clinicians. Its principles, however, can easily be applied to patients with SMI to prevent distressing symptoms from becoming a relapse.

Communication. Good risk and crisis communication are critical because individual and population behavior will be governed by the perception of risk and fear, and not by facts. Failure to manage the “infodemic”⁷—with its misinformation, contradictory messages, and rumors—jeopardizes infection control if patients become paralyzed by uncertainty and fear. Scapegoating occurs easily during times of threat, and society must contain the parallel epidemic of xenophobia based on stigma and misinformation.¹²

Decision-making under uncertainty is not perfect and subject to revision as better information becomes available. Pointing this out to the public is delicate but essential to curtail skepticism and mistrust when policies are adjusted in response to new circumstances and knowledge.

Mistrust of an authority’s legitimacy and fear-based decisions lead to lack of cooperation with public-health measures, which can undermine an effective response to the pandemic. Travel restrictions or quarantine measures will not be followed if individuals question their importance. Like the general public, patients need education and clear communication to address their fear of contagion, dangers posed to family (and pets), and mistrust of authority and government. A lack of appreciation of the seriousness of the pandemic and individual responsibility may need to be addressed. Two important measures to accomplish this are steering patients to reputable sources of information and advising that they limit media exposure.

Resilience-building. Community and workplace resilience are important aspects of making it through a disaster as best as possible. Resilience is not innate and fixed; it must be deliberately built.¹³ Choosing an attitude of post-traumatic growth over the victim narrative is a helpful stance. Practicing self-care (rest, nutrition, exercise) and self-compassion (self-kindness, common humanity, mindfulness) is good advice for patients and caregivers alike.

Continue to: Workforce protection

Workforce protection. Compared to other disasters, infectious outbreaks disproportionally affect the medical community, and care delivery is at stake. While psychological and psychiatric needs may increase during a pandemic, services often contract, day programs and clinics close, teams are reduced to skeleton crews, and only emergency psychiatric care is available. Workforce protection is critical to avoid illness or simple absenteeism due to mistrust of protective measures.

Only a well-briefed, well-led, well-supported, and adequately resourced workforce is going to be effective in managing this public-health emergency. Burnout and moral injury are feared long-term consequences for health care workers that need to be proactively addressed.¹⁴ As opposed to other forms of disasters, managing your own fears about safety is important. Clinicians and their patients sit in the proverbial same boat.

Ethics. The anticipated need to ration life-saving care (eg, ventilators) has been at the forefront of ethical concerns.¹⁵ In psychiatry, the question of involuntary public-health interventions for uncooperative psychiatric patients sits uncomfortably between public-health ethics and human rights, and is an opportunity for collaboration with public-health and infectious-disease colleagues.

Redeployed clinicians and those working under substandard conditions may be concerned about civil liability due to a modified standard of care during a crisis. Some clinicians may ask if their duty to care must override their natural instinct to protect themselves. There is a lot of room for resentment in these circumstances. Redeployed or otherwise “conscripted” clinicians may resent administrators, especially those administering from the safety of their homes. Those “left behind” to work in potentially precarious circumstances may resent their absent colleagues. Moreover, these front-line clinicians may have been forced to make ethical decisions for which they were not prepared.¹⁶ Maintaining morale is far from trivial, not just during the pandemic, but afterward, when (and if) the entire workforce is reunited. All parties need to be mindful of how their actions and decisions impact and are perceived by others, both in the hospital and at home.

Managing patients with SMI during COVID-19

Patients with SMI are potentially hard hit by COVID-19 due to a “tragic” epidemiologic triad of agent-host-environment: SARS-CoV-2 is a highly infectious agent affecting patients with SMI who are vulnerable hosts in permissive environments (Figure).

Continue to: While not as infectious as measles...

While not as infectious as measles, COVID-19 is more infectious than the seasonal flu virus.¹⁷ It can lead to uncontrolled infection within a short period of time, particularly in enclosed settings. Outbreaks have occurred readily on cruise ships and aircraft carriers as well as in nursing homes, homeless shelters, prisons, and group homes.

Patients with SMI are vulnerable hosts because they have many of the medical risk factors¹⁸ that portend a poor prognosis if they become infected, including pre-existing lung conditions and heart disease¹⁹ as well as diabetes and obesity.²⁰ Obesity likely creates a hyperinflammatory state and a decrease in vital capacity. Patient-related behavioral factors include poor early-symptom reporting and ineffective infection control.

Unfavorable social determinants of health include not only poverty but crowded housing that is a perfect incubator for COVID-19.

Priority treatment goals. The overarching goal during a pandemic is to keep patients with SMI in psychiatric treatment and prevent them from disengaging from care in the service of infection control. Urgent tasks include infection control, relapse prevention, and preventing treatment disengagement and loneliness.

Infection control. As trusted sources of information, psychiatrists can play an important role in infection control in several important ways:

• educating patients about infection-control measures and public-health recommendations
• helping patients understand what testing can accomplish and when to pursue it
• encouraging protective health behaviors (eg, hand washing, mask wearing, physical distancing)
• assessing patients’ risk appreciation
• assessing for and addressing obstacles to implementing and complying with infection-control measures
• explaining contact tracing
• providing reassurance.

Continue to: Materials and explanations...

Materials and explanations must be adapted for patient understanding.

Patients with disorganization or cognitive disturbances may have difficulties cooperating or problem-solving. Patients with negative symptoms may be inappropriately unconcerned and also inaccurately report symptoms that suggest COVID-19. Acute psychosis or mania can prevent patients from complying with public-health efforts. Some measures may be difficult to implement if the means are simply not there (eg, physical distancing in a crowded apartment). Previously open settings (eg, group homes) have had to develop new mechanisms under the primacy of infection control. Inpatient units—traditionally places where community, shared healing, and group therapy are prized—have had to decrease maximum occupancy, limit the number of patients attending groups, and discourage or outrightly prohibit social interaction (eg, dining together).

Relapse prevention. Patients who take maintenance medications need to be supported. A manic or psychotic relapse during a pandemic puts patients at risk of acquiring and spreading COVID-19. “Treatment as prevention” is a slogan from human immunodeficiency virus (HIV) care that captures the importance of antiretroviral treatment to prevent medical complications from HIV, and also to reduce infecting other people. By analogy, psychiatric treatment for patients with SMI can prevent psychiatric instability and thereby control viral transmission. Avoiding sending psychiatric patients to a potentially stressed acute-care system is important.

Psychosocial support. Clinics need to ensure that patients continue to engage in care beyond medication-taking to proactively prevent psychiatric exacerbations. Healthful, resilience-building behaviors should be encouraged while monitoring and counseling against maladaptive ones (eg, increased substance use). Supporting patients emotionally and helping them solve problems are critical, particularly for those who are subjected to quarantine or isolation. Obviously, in these latter situations, outreach will be necessary and may require creative delivery systems and dedicated clinicians for patients who lack access to the technology necessary for virtual visits. Havens and Ghaemi²¹ have suggested that a good therapeutic alliance can be viewed as a mood stabilizer. Helping patients grieve losses (loved ones, jobs, sense of safety) may be an important part of support.

Even before COVID-19, loneliness was a major factor for patients with schizophrenia.²² A psychiatric clinic is one aspect of a person with SMI’s social network; during the initial phase of the pandemic, many clinics and treatment programs closed. Patients for whom clinics structure and anchor their activities are at high risk of disconnecting from treatment, staying at home, and becoming lonely.

Continue to: Caregivers are always important...

Caregivers are always important to SMI patients, but they may assume an even bigger role during this pandemic. Some patients may have moved in with a relative, after years of living on their own. In other cases, stable caregiver relationships may be disrupted due to COVID-19–related sickness in the caregiver; if not addressed, this can result in a patient’s clinical decompensation. Clinicians should take the opportunity to understand who a patient’s caregivers are (group home staff, families) and rekindle clinical contact with them. Relationships with caregivers that may have been on “autopilot” during normal times are opportunities for welcome support and guidance, to the benefit of both patients and caregivers.

Table 1 summarizes clinical tasks that need to be kept in mind when conducting clinic visits during COVID-19 in order to achieve the high-priority treatment goals of infection control, relapse prevention, and psychosocial support.

Differential diagnosis. Neuropsychiatric syndromes have long been observed in influenza pandemics,²³ due both to direct viral effects and to the effects of critical illness on the brain. Two core symptoms of COVID-19—anosmia and ageusia—suggest that COVID-19 can directly affect the brain. While neurologic manifestations are common,²⁴ it remains unclear to what extent COVID-19 can directly “cause” psychiatric symptoms, or if such symptoms are the result of cytokines²⁵ or other medical processes (eg, thromboembolism).²⁶ Psychosis due to COVID-19 may, in some cases, represent a stress-related brief psychotic disorder.²⁷

Hospitalized patients who have recovered from COVID-19 may have experienced prolonged sedation and severe delirium in an ICU.²⁸ Complications such as posttraumatic stress disorder,²⁹ hypoperfusion-related brain injuries, or other long-term cognitive difficulties may result. In previous flu epidemics, patients developed serious neurologic complications such as post-encephalitic Parkinson’s disease.³⁰

Any person subjected to isolation or quarantine is at risk for psychiatric complications.³¹ Patients with SMI who live in group homes may be particularly susceptible to new rules, including no-visitor policies.

Continue to: Outpatients whose primary disorder...

Outpatients whose primary disorder is well controlled may, like anyone else, struggle with the effects of the pandemic. It is necessary to carefully differentiate non-specific symptoms associated with stress from the emergence of a new disorder resulting from stress.³² For some patients, grief or adjustment disorders should be considered. Prolonged stress and uncertainty may eventually lead to an exacerbation of a primary disorder, particularly if the situation (eg, financial loss) does not improve or worsens. Demoralization and suicidal thinking need to be monitored. Relapse or increased use of alcohol or other substances as a response to stress may also complicate the clinical picture.³³ Last, smoking cessation as a major treatment goal in general should be re-emphasized and not ignored during the ongoing pandemic.³⁴

Table 2 summarizes psychiatric symptoms that need to be considered when managing a patient with SMI during this pandemic.

Treatment tools

Psychopharmacology. Even though crisis-mode prescribing may be necessary, the safe use of psychotropics remains the goal of psychiatric prescribing. Access to medications becomes a larger consideration; for many patients, a 90-day supply may be indicated. Review of polypharmacy, including for pneumonia risk, should be undertaken. Preventing drooling (eg, from sedation, clozapine, extrapyramidal symptoms [EPS]) will decrease aspiration risk.

In general, treatment of psychiatric symptoms in a patient with COVID-19 follows usual guidelines. The best treatment for COVID-19 patients with delirium, however, remains to be established, particularly how to manage severe agitation.²⁸ Pharmacodynamic and pharmacokinetic drug–drug interactions between psychotropics and antiviral treatments for COVID-19 (eg, QTc prolongation) can be expected and need to be reviewed.³⁵ For stress-related anxiety, judicious pharmacotherapy can be helpful. Diazepam given at the earliest signs of a psychotic relapse may stave off a relapse for patients with schizophrenia.³⁶ Even if permitted under relaxed prescribing rules during a public-health emergency, prescribing controlled substances without seeing patients in person requires additional thought. In some cases, adjusting the primary medication to buffer against stress may be preferred (eg, adjusting an antipsychotic in a patient on maintenance treatment for schizophrenia, particularly if a low-dose strategy is pursued).

Clozapine requires registry-based prescribing and bloodwork (“no blood, no drug”). The use of clozapine during this public-health emergency has been made easier because of FDA guidance that allows clozapine to be dispensed without blood work if obtaining blood work is not possible (eg, a patient is quarantined) or can be accomplished only at substantial risk to patients and the population at large. Under certain conditions, clozapine can be dispensed safely and in a way that is consistent with infection prevention. Clozapine-treated patients admitted with COVID-19 should be monitored for clozapine toxicity and the clozapine dose adjusted.³⁷ A consensus statement consistent with the FDA and clinical considerations for using clozapine during COVID-19 is summarized in Table 3.³⁸

Continue to: Long-acting injectable antipsychotics...

Long-acting injectable antipsychotics (LAIs) pose a problem because they require in-person visits. Ideally, during a pandemic, patients should be seen in person as frequently as medically necessary but as infrequently as possible to limit exposure of both patients and staff. Table 4 provides some clinical recommendations on how to use LAIs during the pandemic.³⁹

Supportive psychotherapy may be the most important tool we have in helping patients with loss and uncertainty during these challenging months.⁴⁰ Simply staying in contact with patients plays a major role in preventing care discontinuity. Even routine interactions have become stressful, with everyone wearing a mask that partially obscures the face. People with impaired hearing may find it even more difficult to understand you.

Education, problem-solving, and a directive, encouraging style are major tools of supportive psychotherapy to reduce symptoms and increase adaptive skills. Clarify that social distancing refers to physical, not emotional, distancing. The judicious and temporary use of anxiolytics is appropriate to reduce anxiety. Concrete help and problem-solving (eg, filling out forms) are examples of proactive crisis intervention.

Telepsychiatry emerged in the pandemic’s early days as the default mode of practice in order to limit in-person contacts.⁴¹ Like all new technology, telepsychiatry brings progress and peril.⁴² While it has gone surprisingly well for most, the “digital divide” does not afford all patients access to the needed technology. The long-term effectiveness and acceptance of telehealth remain to be seen. (Editor’s Note: For more about this topic, see “Telepsychiatry: What you need to know.” Current Psychiatry. 2020;19[6]:16-23.)

Lessons learned and outlook

Infectious outbreaks have historically inflicted long-term disruptions on societies and altered the course of history. However, each disaster is unique, and lessons from previous disasters may only partially apply.⁴³ We do not yet know how this one will end, including how long it will take for the world’s economies to recover. If nothing else, the current public-health emergency has brought to the forefront what psychiatrists have always known: health disparities are partially responsible for different disease risks (in this case, the risk of getting infected with SARS-CoV-2).⁵ It may not be a coincidence that the Black Lives Matter movement is becoming a major impetus for social change at a time when the pandemic is exposing health-care inequalities.

Continue to: Some areas of the country...

Some areas of the country succeeded in reducing infections and limiting community spread, which ushered in an uneasy sense of normalcy even while the pandemic continues. At least for now, these locales can focus on rebuilding and preparing for expectable fluctuations in disease activity, including the arrival of the annual flu season on top of COVID-19.⁴⁴ Recovery is not a return to the status quo ante but building stronger communities—“building back better.”⁴⁵ Unless there is a continuum of care, shortcomings in one sector will have ripple effects through the entire system, particularly for psychiatric care for patients with SMI, which was inadequate before the pandemic.

Ensuring access to critical care was a priority during the pandemic’s early phase but came at the price of deferring other types of care, such as routine primary care; the coming months will see the downstream consequences of this approach,⁴⁶ including for patients with SMI.

In the meantime, doing our job as clinicians, as Camus’s fictitious Dr. Bernard Rieux from the epigraph responds when asked how to define decency, may be the best we can do in these times. This includes contributing to and molding our field’s future and fostering a sense of agency in our patients and in ourselves. Major goals will be to preserve lessons learned, maintain flexibility, and avoid a return to unhelpful overregulation and payment models that do not reflect the flexible, person-centered care so important for patients with SMI.⁴⁷

Bottom Line

During a pandemic, patients with serious mental illness may be easily forgotten as other issues overshadow the needs of this impoverished group. During a pandemic, the priority treatment goals for these patients are infection control, relapse prevention, and preventing treatment disengagement and loneliness. A pandemic requires changes in how patients with serious mental illness will receive psychopharmacology and psychotherapy.

Related Resources

• Huremović D (ed). Psychiatry of pandemics: a mental health response to infection outbreak. Cham, Switzerland: Springer Nature Switzerland AG; 2019.
• Ursano RJ, Fullerton CS, Weisaeth L, et al (eds). Textbook of disaster psychiatry. 2nd ed. Cambridge, UK: Cambridge University Press; 2017.
• Centers for Disease Control and Prevention. Coronavirus (COVID-19). https://www.cdc.gov/coronavirus/2019-ncov/index.html.
• American Psychiatric Association. Coronavirus resources. https://www.psychiatry.org/psychiatrists/covid-19-coronavirus.
• SMI Adviser. Make informed decisions related to COVID-19 and mental health. https://smiadviser.org/about/covid.

Drug Brand Names

Clozapine • Clozaril
Diazepam • Valium
Hydroxychloroquine • Plaquenil

CASE Perseverating on nonexistent sexual assaults

Mr. R, age 17, who has been diagnosed with obsessive-compulsive disorder (OCD), presents to the emergency department (ED) because he thinks that he is being sexually assaulted and is concerned that he is sexually assaulting other people. His family reports that Mr. R has perseverated over these thoughts for months, although there is no evidence to suggest these events have occurred. In order to ameliorate his distress, he performs rituals of looking upwards and repeatedly saying, “It didn’t happen.”

Mr. R is admitted to the inpatient psychiatry unit for further evaluation.

HISTORY Decompensation while attending a PHP

Mr. R had been diagnosed with bipolar disorder and attention-deficit/hyperactivity disorder when he was 13. During that time, he was treated with divalproex sodium and dextroamphetamine. At age 15, Mr. R’s diagnosis was changed to OCD. Seven months before coming to the ED, his symptoms had been getting worse. On one occasion, Mr. R was talking in a nonsensical fashion at school, and the police were called. Mr. R became physically aggressive with the police and was subsequently hospitalized, after which he attended a partial hospitalization program (PHP). At the PHP, Mr. R received exposure and response prevention therapy for OCD, but did not improve, and his symptoms deteriorated until he was unable to brush his teeth or shower regularly. While attending the PHP, Mr. R also developed disorganized speech. The PHP clinicians became concerned that Mr. R’s symptoms may have been prodromal symptoms of schizophrenia because he did not respond to the OCD treatment and his symptoms had worsened over the 3 months he attended the PHP.

EVALUATION Normal laboratory results

Upon admission to the inpatient psychiatric unit, Mr. R is restarted on his home medications, which include fluvoxamine, 150 mg in the morning and 200 mg at bedtime; methylfolate, 2,000 mcg/d; risperidone, 3 mg nightly; and hydroxyzine, 25 mg as needed for anxiety.

His laboratory workup, including a complete blood count, comprehensive metabolic panel, urine drug screen, and blood ethanol, are all within normal limits. Previous laboratory results, including a thyroid function panel, vitamin D level, and various autoimmune panels, were also within normal limits.

His family reports that Mr. R’s symptoms seem to worsen when he is under increased stress from school and prepping for standardized college admission examinations. The family also says that while he is playing tennis, Mr. R will posture himself in a crouched down position and at times will remain in this position for 30 minutes.

Mr. R says he eventually wants to go to college and have a professional career.

[polldaddy:10600530]

Continue to: The authors' observations

 

 

The authors’ observations

When considering Mr. R’s diagnosis, our treatment team considered the possibility of OCD with absent insight/delusional beliefs, OCD with comorbid schizophrenia, bipolar disorder, and psychotic disorder due to another medical condition.

Overlap between OCD and schizophrenia

There appears to be both an epidemiologic and biologic overlap between OCD and schizophrenia. The Table¹ summarizes the DSM-5 criteria for OCD and for schizophrenia. Schirmbeck et al² reported that the estimated prevalence of OCD in patients with schizophrenia is 12%, which is higher than in the general population. Obsessive-compulsive symptoms (OCS) in patients with schizophrenia have been reported to be even more prevalent (30.7%).² In a prospective cohort study, de Haan et al³ assessed 172 patients with first-episode schizophrenia, schizophreniform disorder, or schizoaffective disorder for the development of OCS over a 5-year follow-up period. Symptoms were tracked over time and included OCS on first assessment, persistent OCS, subsequent emergence of OCS, and intermittent OCS. A striking 51.1% of the patient sample screened positive.³ Obsessions and delusions are similar because they are both irrational thoughts, the former with insight and the latter without insight. The fact that OCS were present in up to 14% of drug-naïve patients with schizophrenia in this study suggests that this was not merely an adverse effect of antipsychotic medication.

Much of the literature about OCD examines its functional impairment in adults, with findings extrapolated to pediatric patients. Children differ from adults in a variety of meaningful ways. Baytunca et al⁴ examined adolescents with early-onset schizophrenia, with and without comorbid OCD. Patients with comorbid OCD required higher doses of antipsychotic medication to treat acute psychotic symptoms and maintain a reduction in symptoms. The study controlled for the severity of schizophrenia, and its findings suggest that schizophrenia with comorbid OCD is more treatment-resistant than schizophrenia alone.⁴

Some researchers have theorized that in adolescents, OCD and psychosis are integrally related such that one disorder could represent a prodrome or a cause of the other disorder. Niendam et al⁵ studied OCS in the psychosis prodrome. They found that OCS can present as a part of the prodromal picture in youth at high risk for psychosis. However, because none of the patients experiencing OCS converted to full-blown psychosis, these results suggest that OCS may not represent a prodrome to psychosis per se. Instead, these individuals may represent a subset of false positives over the follow-up period.⁵ Another possible explanation for the increased emergence of pre-psychotic symptoms in adolescents with OCD could be a difference in their threshold of perception. OCS compels adolescents with OCD to self-analyze more critically and frequently. As a result, these patients may more often report depressive symptoms, distress, and exacerbations of pre-psychotic symptoms. These findings highlight that comorbid OCD can amplify the psychosocial distress among higher-risk youth. It is therefore essential for physicians to perform a thorough interview in this population because subtle psychotic symptoms may be present.

[polldaddy:10600532]

Continue to: TREATMENT Improvement after switching to haloperidol

 

 

TREATMENT Improvement after switching to haloperidol

The treatment team decides to change Mr. R’s medications by cross-titrating risperidone to lurasidone and increasing hydroxyzine from 25 to 50 mg every 6 hours as needed for anxiety. Over the next several days, Mr. R reports some improvement in symptoms. However, according to staff on the unit, he continues to display disorganized behavior, respond to internal stimuli, and posture in his room. It is unclear if these symptoms are due to a psychotic illness or part of his OCD rituals. Due to worsening of symptoms, the team decides to taper lurasidone and switch to haloperidol. Mr. R starts haloperidol, 1 mg twice a day, and this is titrated to 7.5 mg three times a day. Soon after, his thoughts become more organized, he has fewer delusional thoughts, his concentration is improved, and he no longer appears to respond to internal stimuli.

The treatment team obtains a consultation on whether electroconvulsive therapy would be appropriate, but this treatment is not recommended. Instead, the team considers switching Mr. R to clozapine if the current treatment fails. Because Mr. R’s psychotic symptoms continue to improve while he is receiving haloperidol, clozapine is not added. To address Mr. R’s persistent, severe OCD symptoms, fluvoxamine is cross-tapered to sertraline, started at 50 mg/d and titrated to 100 mg/d. Mr. R shows significant improvement in the days that follow.

Throughout admission, Mr. R focuses on his lack of improvement and how this episode is negatively impacting his grades and his dream of going to college and having a professional career.

OUTCOME Relief at last

Mr. R improves with the addition of sertraline and tolerates rapid titration well. He continues haloperidol without adverse effects, and is discharged home with close follow-up in a PHP and outpatient psychiatry.

However, after discharge, Mr. R’s symptoms get worse, and he is admitted to a different inpatient facility. At this facility, he continues sertraline, but haloperidol is cross-titrated to olanzapine.

Continue to: Currently...

Currently, Mr. R has greatly improved and is able to function in school. He takes sertraline, 100 mg twice a day, and olanzapine, 7.5 mg twice a day. Mr. R reports his rituals have reduced in frequency to less than 15 minutes each day. His thought processes are organized, and he is confident he will be able to achieve his goals.

The authors’ observations

Given Mr. R’s rapid improvement once an effective pharmacologic regimen was established, we concluded that he had a severe case of OCD with absent insight/delusional beliefs, and that he did not have schizophrenia. Mr. R’s case highlights how a psychiatric diagnosis can produce anxiety as a result of the psychosocial stressors and limitations associated with that diagnosis.

Bottom Line

There is both an epidemiologic and biologic overlap between obsessive-compulsive disorder and schizophrenia. In adolescents, either disorder could represent a prodrome or a cause of the other. It is essential to perform a thorough assessment of individuals with obsessive-compulsive disorder because these patients may exhibit subtle psychotic symptoms.

Related Resources

• Cunill R, Castells X, Simeon D. Relationships between obsessivecompulsive symptomatology and severity of psychosis in schizophrenia: a systematic review and meta-analysis. J Clin Psychiatry. 2009;70(1):70-82.
• Harris E, Delgado SV. Treatment-resistant OCD: there’s more we can do. Current Psychiatry. 2018;17(11):10-12,14-18,51.

Drug Brand Names

Clozapine • Clozaril
Dextroamphetamine • Dexedrine
Divalproex sodium • Depakote
Fluvoxamine • Luvox
Haloperidol • Haldol
Hydroxyzine • Atarax, Vistaril
Lurasidone • Latuda
Olanzapine • Zyprexa
Risperidone • Risperdal
Sertraline • Zoloft

CASE Perseverating on nonexistent sexual assaults

Mr. R, age 17, who has been diagnosed with obsessive-compulsive disorder (OCD), presents to the emergency department (ED) because he thinks that he is being sexually assaulted and is concerned that he is sexually assaulting other people. His family reports that Mr. R has perseverated over these thoughts for months, although there is no evidence to suggest these events have occurred. In order to ameliorate his distress, he performs rituals of looking upwards and repeatedly saying, “It didn’t happen.”

Mr. R is admitted to the inpatient psychiatry unit for further evaluation.

HISTORY Decompensation while attending a PHP

Mr. R had been diagnosed with bipolar disorder and attention-deficit/hyperactivity disorder when he was 13. During that time, he was treated with divalproex sodium and dextroamphetamine. At age 15, Mr. R’s diagnosis was changed to OCD. Seven months before coming to the ED, his symptoms had been getting worse. On one occasion, Mr. R was talking in a nonsensical fashion at school, and the police were called. Mr. R became physically aggressive with the police and was subsequently hospitalized, after which he attended a partial hospitalization program (PHP). At the PHP, Mr. R received exposure and response prevention therapy for OCD, but did not improve, and his symptoms deteriorated until he was unable to brush his teeth or shower regularly. While attending the PHP, Mr. R also developed disorganized speech. The PHP clinicians became concerned that Mr. R’s symptoms may have been prodromal symptoms of schizophrenia because he did not respond to the OCD treatment and his symptoms had worsened over the 3 months he attended the PHP.

EVALUATION Normal laboratory results

Upon admission to the inpatient psychiatric unit, Mr. R is restarted on his home medications, which include fluvoxamine, 150 mg in the morning and 200 mg at bedtime; methylfolate, 2,000 mcg/d; risperidone, 3 mg nightly; and hydroxyzine, 25 mg as needed for anxiety.

His laboratory workup, including a complete blood count, comprehensive metabolic panel, urine drug screen, and blood ethanol, are all within normal limits. Previous laboratory results, including a thyroid function panel, vitamin D level, and various autoimmune panels, were also within normal limits.

His family reports that Mr. R’s symptoms seem to worsen when he is under increased stress from school and prepping for standardized college admission examinations. The family also says that while he is playing tennis, Mr. R will posture himself in a crouched down position and at times will remain in this position for 30 minutes.

Mr. R says he eventually wants to go to college and have a professional career.

[polldaddy:10600530]

Continue to: The authors' observations

 

 

The authors’ observations

When considering Mr. R’s diagnosis, our treatment team considered the possibility of OCD with absent insight/delusional beliefs, OCD with comorbid schizophrenia, bipolar disorder, and psychotic disorder due to another medical condition.

Overlap between OCD and schizophrenia

There appears to be both an epidemiologic and biologic overlap between OCD and schizophrenia. The Table¹ summarizes the DSM-5 criteria for OCD and for schizophrenia. Schirmbeck et al² reported that the estimated prevalence of OCD in patients with schizophrenia is 12%, which is higher than in the general population. Obsessive-compulsive symptoms (OCS) in patients with schizophrenia have been reported to be even more prevalent (30.7%).² In a prospective cohort study, de Haan et al³ assessed 172 patients with first-episode schizophrenia, schizophreniform disorder, or schizoaffective disorder for the development of OCS over a 5-year follow-up period. Symptoms were tracked over time and included OCS on first assessment, persistent OCS, subsequent emergence of OCS, and intermittent OCS. A striking 51.1% of the patient sample screened positive.³ Obsessions and delusions are similar because they are both irrational thoughts, the former with insight and the latter without insight. The fact that OCS were present in up to 14% of drug-naïve patients with schizophrenia in this study suggests that this was not merely an adverse effect of antipsychotic medication.

Much of the literature about OCD examines its functional impairment in adults, with findings extrapolated to pediatric patients. Children differ from adults in a variety of meaningful ways. Baytunca et al⁴ examined adolescents with early-onset schizophrenia, with and without comorbid OCD. Patients with comorbid OCD required higher doses of antipsychotic medication to treat acute psychotic symptoms and maintain a reduction in symptoms. The study controlled for the severity of schizophrenia, and its findings suggest that schizophrenia with comorbid OCD is more treatment-resistant than schizophrenia alone.⁴

Some researchers have theorized that in adolescents, OCD and psychosis are integrally related such that one disorder could represent a prodrome or a cause of the other disorder. Niendam et al⁵ studied OCS in the psychosis prodrome. They found that OCS can present as a part of the prodromal picture in youth at high risk for psychosis. However, because none of the patients experiencing OCS converted to full-blown psychosis, these results suggest that OCS may not represent a prodrome to psychosis per se. Instead, these individuals may represent a subset of false positives over the follow-up period.⁵ Another possible explanation for the increased emergence of pre-psychotic symptoms in adolescents with OCD could be a difference in their threshold of perception. OCS compels adolescents with OCD to self-analyze more critically and frequently. As a result, these patients may more often report depressive symptoms, distress, and exacerbations of pre-psychotic symptoms. These findings highlight that comorbid OCD can amplify the psychosocial distress among higher-risk youth. It is therefore essential for physicians to perform a thorough interview in this population because subtle psychotic symptoms may be present.

[polldaddy:10600532]

Continue to: TREATMENT Improvement after switching to haloperidol

 

 

TREATMENT Improvement after switching to haloperidol

The treatment team decides to change Mr. R’s medications by cross-titrating risperidone to lurasidone and increasing hydroxyzine from 25 to 50 mg every 6 hours as needed for anxiety. Over the next several days, Mr. R reports some improvement in symptoms. However, according to staff on the unit, he continues to display disorganized behavior, respond to internal stimuli, and posture in his room. It is unclear if these symptoms are due to a psychotic illness or part of his OCD rituals. Due to worsening of symptoms, the team decides to taper lurasidone and switch to haloperidol. Mr. R starts haloperidol, 1 mg twice a day, and this is titrated to 7.5 mg three times a day. Soon after, his thoughts become more organized, he has fewer delusional thoughts, his concentration is improved, and he no longer appears to respond to internal stimuli.

The treatment team obtains a consultation on whether electroconvulsive therapy would be appropriate, but this treatment is not recommended. Instead, the team considers switching Mr. R to clozapine if the current treatment fails. Because Mr. R’s psychotic symptoms continue to improve while he is receiving haloperidol, clozapine is not added. To address Mr. R’s persistent, severe OCD symptoms, fluvoxamine is cross-tapered to sertraline, started at 50 mg/d and titrated to 100 mg/d. Mr. R shows significant improvement in the days that follow.

Throughout admission, Mr. R focuses on his lack of improvement and how this episode is negatively impacting his grades and his dream of going to college and having a professional career.

OUTCOME Relief at last

Mr. R improves with the addition of sertraline and tolerates rapid titration well. He continues haloperidol without adverse effects, and is discharged home with close follow-up in a PHP and outpatient psychiatry.

However, after discharge, Mr. R’s symptoms get worse, and he is admitted to a different inpatient facility. At this facility, he continues sertraline, but haloperidol is cross-titrated to olanzapine.

Continue to: Currently...

Currently, Mr. R has greatly improved and is able to function in school. He takes sertraline, 100 mg twice a day, and olanzapine, 7.5 mg twice a day. Mr. R reports his rituals have reduced in frequency to less than 15 minutes each day. His thought processes are organized, and he is confident he will be able to achieve his goals.

The authors’ observations

Given Mr. R’s rapid improvement once an effective pharmacologic regimen was established, we concluded that he had a severe case of OCD with absent insight/delusional beliefs, and that he did not have schizophrenia. Mr. R’s case highlights how a psychiatric diagnosis can produce anxiety as a result of the psychosocial stressors and limitations associated with that diagnosis.

Bottom Line

There is both an epidemiologic and biologic overlap between obsessive-compulsive disorder and schizophrenia. In adolescents, either disorder could represent a prodrome or a cause of the other. It is essential to perform a thorough assessment of individuals with obsessive-compulsive disorder because these patients may exhibit subtle psychotic symptoms.

Related Resources

• Cunill R, Castells X, Simeon D. Relationships between obsessivecompulsive symptomatology and severity of psychosis in schizophrenia: a systematic review and meta-analysis. J Clin Psychiatry. 2009;70(1):70-82.
• Harris E, Delgado SV. Treatment-resistant OCD: there’s more we can do. Current Psychiatry. 2018;17(11):10-12,14-18,51.

Drug Brand Names

Clozapine • Clozaril
Dextroamphetamine • Dexedrine
Divalproex sodium • Depakote
Fluvoxamine • Luvox
Haloperidol • Haldol
Hydroxyzine • Atarax, Vistaril
Lurasidone • Latuda
Olanzapine • Zyprexa
Risperidone • Risperdal
Sertraline • Zoloft

CASE Perseverating on nonexistent sexual assaults

Mr. R, age 17, who has been diagnosed with obsessive-compulsive disorder (OCD), presents to the emergency department (ED) because he thinks that he is being sexually assaulted and is concerned that he is sexually assaulting other people. His family reports that Mr. R has perseverated over these thoughts for months, although there is no evidence to suggest these events have occurred. In order to ameliorate his distress, he performs rituals of looking upwards and repeatedly saying, “It didn’t happen.”

Mr. R is admitted to the inpatient psychiatry unit for further evaluation.

HISTORY Decompensation while attending a PHP

Mr. R had been diagnosed with bipolar disorder and attention-deficit/hyperactivity disorder when he was 13. During that time, he was treated with divalproex sodium and dextroamphetamine. At age 15, Mr. R’s diagnosis was changed to OCD. Seven months before coming to the ED, his symptoms had been getting worse. On one occasion, Mr. R was talking in a nonsensical fashion at school, and the police were called. Mr. R became physically aggressive with the police and was subsequently hospitalized, after which he attended a partial hospitalization program (PHP). At the PHP, Mr. R received exposure and response prevention therapy for OCD, but did not improve, and his symptoms deteriorated until he was unable to brush his teeth or shower regularly. While attending the PHP, Mr. R also developed disorganized speech. The PHP clinicians became concerned that Mr. R’s symptoms may have been prodromal symptoms of schizophrenia because he did not respond to the OCD treatment and his symptoms had worsened over the 3 months he attended the PHP.

EVALUATION Normal laboratory results

Upon admission to the inpatient psychiatric unit, Mr. R is restarted on his home medications, which include fluvoxamine, 150 mg in the morning and 200 mg at bedtime; methylfolate, 2,000 mcg/d; risperidone, 3 mg nightly; and hydroxyzine, 25 mg as needed for anxiety.

His laboratory workup, including a complete blood count, comprehensive metabolic panel, urine drug screen, and blood ethanol, are all within normal limits. Previous laboratory results, including a thyroid function panel, vitamin D level, and various autoimmune panels, were also within normal limits.

His family reports that Mr. R’s symptoms seem to worsen when he is under increased stress from school and prepping for standardized college admission examinations. The family also says that while he is playing tennis, Mr. R will posture himself in a crouched down position and at times will remain in this position for 30 minutes.

Mr. R says he eventually wants to go to college and have a professional career.

[polldaddy:10600530]

Continue to: The authors' observations

 

 

The authors’ observations

When considering Mr. R’s diagnosis, our treatment team considered the possibility of OCD with absent insight/delusional beliefs, OCD with comorbid schizophrenia, bipolar disorder, and psychotic disorder due to another medical condition.

Overlap between OCD and schizophrenia

There appears to be both an epidemiologic and biologic overlap between OCD and schizophrenia. The Table¹ summarizes the DSM-5 criteria for OCD and for schizophrenia. Schirmbeck et al² reported that the estimated prevalence of OCD in patients with schizophrenia is 12%, which is higher than in the general population. Obsessive-compulsive symptoms (OCS) in patients with schizophrenia have been reported to be even more prevalent (30.7%).² In a prospective cohort study, de Haan et al³ assessed 172 patients with first-episode schizophrenia, schizophreniform disorder, or schizoaffective disorder for the development of OCS over a 5-year follow-up period. Symptoms were tracked over time and included OCS on first assessment, persistent OCS, subsequent emergence of OCS, and intermittent OCS. A striking 51.1% of the patient sample screened positive.³ Obsessions and delusions are similar because they are both irrational thoughts, the former with insight and the latter without insight. The fact that OCS were present in up to 14% of drug-naïve patients with schizophrenia in this study suggests that this was not merely an adverse effect of antipsychotic medication.

Much of the literature about OCD examines its functional impairment in adults, with findings extrapolated to pediatric patients. Children differ from adults in a variety of meaningful ways. Baytunca et al⁴ examined adolescents with early-onset schizophrenia, with and without comorbid OCD. Patients with comorbid OCD required higher doses of antipsychotic medication to treat acute psychotic symptoms and maintain a reduction in symptoms. The study controlled for the severity of schizophrenia, and its findings suggest that schizophrenia with comorbid OCD is more treatment-resistant than schizophrenia alone.⁴

Some researchers have theorized that in adolescents, OCD and psychosis are integrally related such that one disorder could represent a prodrome or a cause of the other disorder. Niendam et al⁵ studied OCS in the psychosis prodrome. They found that OCS can present as a part of the prodromal picture in youth at high risk for psychosis. However, because none of the patients experiencing OCS converted to full-blown psychosis, these results suggest that OCS may not represent a prodrome to psychosis per se. Instead, these individuals may represent a subset of false positives over the follow-up period.⁵ Another possible explanation for the increased emergence of pre-psychotic symptoms in adolescents with OCD could be a difference in their threshold of perception. OCS compels adolescents with OCD to self-analyze more critically and frequently. As a result, these patients may more often report depressive symptoms, distress, and exacerbations of pre-psychotic symptoms. These findings highlight that comorbid OCD can amplify the psychosocial distress among higher-risk youth. It is therefore essential for physicians to perform a thorough interview in this population because subtle psychotic symptoms may be present.

[polldaddy:10600532]

Continue to: TREATMENT Improvement after switching to haloperidol

 

 

TREATMENT Improvement after switching to haloperidol

The treatment team decides to change Mr. R’s medications by cross-titrating risperidone to lurasidone and increasing hydroxyzine from 25 to 50 mg every 6 hours as needed for anxiety. Over the next several days, Mr. R reports some improvement in symptoms. However, according to staff on the unit, he continues to display disorganized behavior, respond to internal stimuli, and posture in his room. It is unclear if these symptoms are due to a psychotic illness or part of his OCD rituals. Due to worsening of symptoms, the team decides to taper lurasidone and switch to haloperidol. Mr. R starts haloperidol, 1 mg twice a day, and this is titrated to 7.5 mg three times a day. Soon after, his thoughts become more organized, he has fewer delusional thoughts, his concentration is improved, and he no longer appears to respond to internal stimuli.

The treatment team obtains a consultation on whether electroconvulsive therapy would be appropriate, but this treatment is not recommended. Instead, the team considers switching Mr. R to clozapine if the current treatment fails. Because Mr. R’s psychotic symptoms continue to improve while he is receiving haloperidol, clozapine is not added. To address Mr. R’s persistent, severe OCD symptoms, fluvoxamine is cross-tapered to sertraline, started at 50 mg/d and titrated to 100 mg/d. Mr. R shows significant improvement in the days that follow.

Throughout admission, Mr. R focuses on his lack of improvement and how this episode is negatively impacting his grades and his dream of going to college and having a professional career.

OUTCOME Relief at last

Mr. R improves with the addition of sertraline and tolerates rapid titration well. He continues haloperidol without adverse effects, and is discharged home with close follow-up in a PHP and outpatient psychiatry.

However, after discharge, Mr. R’s symptoms get worse, and he is admitted to a different inpatient facility. At this facility, he continues sertraline, but haloperidol is cross-titrated to olanzapine.

Continue to: Currently...

Currently, Mr. R has greatly improved and is able to function in school. He takes sertraline, 100 mg twice a day, and olanzapine, 7.5 mg twice a day. Mr. R reports his rituals have reduced in frequency to less than 15 minutes each day. His thought processes are organized, and he is confident he will be able to achieve his goals.

The authors’ observations

Given Mr. R’s rapid improvement once an effective pharmacologic regimen was established, we concluded that he had a severe case of OCD with absent insight/delusional beliefs, and that he did not have schizophrenia. Mr. R’s case highlights how a psychiatric diagnosis can produce anxiety as a result of the psychosocial stressors and limitations associated with that diagnosis.

Bottom Line

There is both an epidemiologic and biologic overlap between obsessive-compulsive disorder and schizophrenia. In adolescents, either disorder could represent a prodrome or a cause of the other. It is essential to perform a thorough assessment of individuals with obsessive-compulsive disorder because these patients may exhibit subtle psychotic symptoms.

Related Resources

• Cunill R, Castells X, Simeon D. Relationships between obsessivecompulsive symptomatology and severity of psychosis in schizophrenia: a systematic review and meta-analysis. J Clin Psychiatry. 2009;70(1):70-82.
• Harris E, Delgado SV. Treatment-resistant OCD: there’s more we can do. Current Psychiatry. 2018;17(11):10-12,14-18,51.

Drug Brand Names

Clozapine • Clozaril
Dextroamphetamine • Dexedrine
Divalproex sodium • Depakote
Fluvoxamine • Luvox
Haloperidol • Haldol
Hydroxyzine • Atarax, Vistaril
Lurasidone • Latuda
Olanzapine • Zyprexa
Risperidone • Risperdal
Sertraline • Zoloft

Psychiatric emergencies—such as a patient who is agitated, self-destructive, or suicidal—may arise in a variety of settings, including emergency departments and inpatient units.¹ Before emergently prescribing psychotropic medications to address acute psychiatric symptoms, there are numerous factors a clinician needs to consider.^1-3 Asking the following questions may help you quickly obtain important clinical information to determine which medication to use during a psychiatric emergency:

Age. Is the patient a child, adolescent, adult, or older adult?

Allergies. Does the patient have any medication allergies or sensitivities?

Behaviors. What are the imminent dangerous behaviors that warrant emergent medication use

Collateral information. If the patient was brought by police or family, how was he/she behaving in the community or at home? If brought from a correctional facility or other institution, how did he/she behave in that setting?

Concurrent diagnoses/interventions. Does the patient have a psychiatric or medical diagnosis? Is the patient receiving any pharmacologic or nonpharmacologic treatments?

First visit. Is this the patient’s first visit to your facility? Or has the patient been to the facility previously and/or repeatedly? Has the patient ever been prescribed psychotropic medications? If the patient has received emergent medications before, which medications were used, and were they helpful?

Continue to: Legal status

Legal status. Is the patient voluntary for treatment or involuntary for treatment? If voluntary, is involuntary treatment needed?

Street. Was this patient evaluated in a medical setting before presenting to your facility? Or did this patient arrive directly from the community/street?

Substance use. Has the patient been using any licit and/or illicit substances?

In my experience with psychiatric emergencies, asking these questions has helped guide my decision-making during these situations. They have helped me to determine the appropriate medication, route of administration, dose, and monitoring requirements. Although other factors can impact clinicians’ decision-making in these situations, I have found these questions to be a good starting point.

Psychiatric emergencies—such as a patient who is agitated, self-destructive, or suicidal—may arise in a variety of settings, including emergency departments and inpatient units.¹ Before emergently prescribing psychotropic medications to address acute psychiatric symptoms, there are numerous factors a clinician needs to consider.^1-3 Asking the following questions may help you quickly obtain important clinical information to determine which medication to use during a psychiatric emergency:

Age. Is the patient a child, adolescent, adult, or older adult?

Allergies. Does the patient have any medication allergies or sensitivities?

Behaviors. What are the imminent dangerous behaviors that warrant emergent medication use

Collateral information. If the patient was brought by police or family, how was he/she behaving in the community or at home? If brought from a correctional facility or other institution, how did he/she behave in that setting?

Concurrent diagnoses/interventions. Does the patient have a psychiatric or medical diagnosis? Is the patient receiving any pharmacologic or nonpharmacologic treatments?

First visit. Is this the patient’s first visit to your facility? Or has the patient been to the facility previously and/or repeatedly? Has the patient ever been prescribed psychotropic medications? If the patient has received emergent medications before, which medications were used, and were they helpful?

Continue to: Legal status

Legal status. Is the patient voluntary for treatment or involuntary for treatment? If voluntary, is involuntary treatment needed?

Street. Was this patient evaluated in a medical setting before presenting to your facility? Or did this patient arrive directly from the community/street?

Substance use. Has the patient been using any licit and/or illicit substances?

In my experience with psychiatric emergencies, asking these questions has helped guide my decision-making during these situations. They have helped me to determine the appropriate medication, route of administration, dose, and monitoring requirements. Although other factors can impact clinicians’ decision-making in these situations, I have found these questions to be a good starting point.

Psychiatric emergencies—such as a patient who is agitated, self-destructive, or suicidal—may arise in a variety of settings, including emergency departments and inpatient units.¹ Before emergently prescribing psychotropic medications to address acute psychiatric symptoms, there are numerous factors a clinician needs to consider.^1-3 Asking the following questions may help you quickly obtain important clinical information to determine which medication to use during a psychiatric emergency:

Age. Is the patient a child, adolescent, adult, or older adult?

Allergies. Does the patient have any medication allergies or sensitivities?

Behaviors. What are the imminent dangerous behaviors that warrant emergent medication use

Collateral information. If the patient was brought by police or family, how was he/she behaving in the community or at home? If brought from a correctional facility or other institution, how did he/she behave in that setting?

Concurrent diagnoses/interventions. Does the patient have a psychiatric or medical diagnosis? Is the patient receiving any pharmacologic or nonpharmacologic treatments?

First visit. Is this the patient’s first visit to your facility? Or has the patient been to the facility previously and/or repeatedly? Has the patient ever been prescribed psychotropic medications? If the patient has received emergent medications before, which medications were used, and were they helpful?

Continue to: Legal status

Legal status. Is the patient voluntary for treatment or involuntary for treatment? If voluntary, is involuntary treatment needed?

Street. Was this patient evaluated in a medical setting before presenting to your facility? Or did this patient arrive directly from the community/street?

Substance use. Has the patient been using any licit and/or illicit substances?

In my experience with psychiatric emergencies, asking these questions has helped guide my decision-making during these situations. They have helped me to determine the appropriate medication, route of administration, dose, and monitoring requirements. Although other factors can impact clinicians’ decision-making in these situations, I have found these questions to be a good starting point.

Two new studies highlight the importance of early intervention in first-episode psychosis (FEP).

In the first study, Australian investigators conclude that, for some FEP patients, early psychosocial interventions may fend off the need for immediate treatment with antipsychotic medications.

In the second study, UK researchers show that long duration of untreated psychosis (DUP) is linked to a significantly reduced treatment response.

For both studies, the findings highlight the importance of rapid access to a comprehensive range of treatments in the first weeks after FEP onset.

“In a select group of people with first-episode psychosis, we found there was no difference in symptoms and functioning between those who had antipsychotic medication and those who didn’t,” lead author Shona M. Francey, PhD, clinical psychologist at Orygen, the National Center of Excellence in Youth Mental Health, Parkville, Australia, told Medscape Medical News.

“These findings supported our idea that, in the early phases of psychosis, with close monitoring and good psychosocial intervention, antipsychotic medication can be delayed,” Francey said.

The Australian study was published in Schizophrenia Bulletin Open. The British study was published in Lancet Psychiatry.
 

Adverse effects

Francey and colleagues note that, in comparison with standard treatment, early interventions produce superior outcomes for patients with psychosis. Although there are a variety of treatment options, low-dose second-generation antipsychotics typically play a central role.

However, atypical antipsychotics have rapid metabolic side effects, including weight gain and altered glucose metabolism, that increase the risk for cardiovascular disease and premature mortality. Importantly, such adverse effects are amplified among patients with FEP, who tend to be younger and treatment naive.

On the other hand, a growing body of evidence shows the benefit of nonpharmacologic interventions for patients with FEP, the investigators note. In addition, clinical staging models appear to support the use of less aggressive treatment early in the disease course.

“We have been working in early intervention for psychosis for a number of years and have found it’s possible to intervene early with young people and either prevent the onset of psychosis or ameliorate its impact,” said Francey.

“Since we can see some improvement in people in the prepsychotic phase, we wanted to know if we can also see some benefit without medication after the onset of what we would call full-threshold psychosis,” she added.

Staged Treatment and Acceptability Guidelines in Early Psychosis (STAGES) was a 6-month, triple-blind, randomized controlled noninferiority study that included 90 participants between the ages of 15 and 25 years who had FEP.

To maximize safety, patients were required to have low levels of suicidality and aggression, a DUP of less than 6 months, and to be living in stable accommodation with social support.

Participants were randomly assigned to two groups – one in which patients underwent intensive psychosocial therapy and received low-dose antipsychotic medication (n = 44), and one in which patients underwent intensive psychosocial therapy and were given placebo (n = 46).

Depending on the timing of study enrollment, those in the medication group received risperidone 1 mg or paliperidone 3 mg.

The psychosocial intervention consisted of cognitive-behavioral case management (CBCM), an intervention developed specifically for patients with early psychosis that is strongly focused on therapeutic engagement.

CBCM delivers formulation-driven cognitive-behavioral therapy and psychoeducation within a therapeutic case management framework, Francey said.

The primary outcome was level of functioning at 6, 12, and 24 months, as measured by the Social and Occupational Functioning Scale (SOFAS). The primary prespecified endpoint was outcome at 6 months. A noninferiority margin of 10.5 on the SOFAS was used as the smallest value representing a clinically important effect.

Other assessment tools included the BPRS-4 to test for positive psychotic symptoms, the Scale for the Assessment of Negative Symptoms (SANS), the Hamilton Rating Scale for Depression, and the Hamilton Rating Scale for Anxiety.

At baseline, the two treatment groups were comparable with respect to all measures of functioning and psychopathology.

The study’s discontinuation rate was high. At 6 months, only 16 patients in the psychosocial group had completed therapy, compared with 11 in the antipsychotic group.

At this point, the two groups were comparable in terms of psychopathology and functioning ratings. Both groups had lower symptoms, higher functioning scores, and higher Quality of Life Scale (QLS) scores than at baseline.

SOFAS scores were not significantly different between the groups at this time point. The mean score was 61.7 ± 16.8 in the psychosocial group and 61.5 ± 13.4 in the medication group.

The researchers note that, because the upper limit of the confidence interval (CI) was less than the study’s a priori inferiority margin of 10.5, psychosocial therapy was not inferior to medication at the 6-month assessment point.
 

Antipsychotics: Use with caution

Although between-group differences in SOFAS scores were not significant at 12 and 24 months, noninferiority of psychosocial therapy alone could not be confirmed because the CIs included the inferiority margin at each time point.

The two groups were statistically comparable at 6 months with respect to all other measures of psychopathology and the QLS. Similar results were found at 12 and 24 months.

The lone exception was with SANS at 12 months, on which patients in the placebo group had significantly higher negative symptom scores than the patients in the medication group.

There were no significant differences between study groups with respect to the number of adverse events.

Francey noted that the findings are important because they suggest that some young people with early-stage FEP and short DUP may be able to achieve symptom remission and function better without antipsychotic medication, provided they receive psychological interventions and comprehensive case management.

This challenges conventional wisdom that antipsychotic medications should be used for all patients who experience psychosis, she added.

However, managing FEP with psychosocial interventions should only be considered when it is safe to do so, Francey noted. In addition, the benefits of psychosocial interventions in these patients are less clear at 12 and 24 months.

Given these caveats, she noted that antipsychotics still play an important role in the treatment of these patients.

“I think there is definitely a place for medications. But I think they should be used cautiously, and you need a good, strong relationship between your treating team and your [patient] to work out what is needed and when it’s needed,” said Francey.

In addition, “when we do use medications, we should use the smallest possible dose that we can and also incorporate psychological support. I think that’s a really important part of it as well,” she said.
 

Timing matters

In the Lancet Psychiatry study, the researchers note that prolonged DUP is associated with worse outcomes, including increased symptoms, diminished social functioning, and poorer quality of life. The mechanism by which delayed treatment causes more harm remains unclear.

It is possible that symptoms simply accumulate over time, thereby worsening presentation. Another possibility is that continued psychosis after an initial critical period may cause long-term harm, they write.

They hypothesize that untreated psychosis can cause general treatment resistance by exacerbating underlying disease processes and that such damage progresses faster in the early stages of illness and then slows over time.

In addition, socially disruptive symptoms that are evident prior to FEP presentation may have a confounding effect, thereby leading to earlier presentation.

The investigators used data from two longitudinal cohort studies – the National Evaluation of Development of Early Intervention Network (NEDEN) study and the Outlook study.

In the NEDEN trial, 290 of 901 FEP patients (32%) were assessed within 3 weeks of presentation. In Outlook, 69 of 332 patients (21%) were assessed within 3 weeks of presentation.

In both studies, patients were examined at baseline, 6 months, and 12 months using the Positive and Negative Syndrome Scale (PANSS), the Calgary Depression Scale for Schizophrenia, the Mania Rating Scale, the Insight Scale, and SOFAS. The latter two measures were used only at baseline and 12-month follow-up. Logistic regression analyses were used to determine the association between DUP and outcomes.

In the NEDEN study, 751 patients were assessed at 6 months, and 719 were assessed at 12 months. In the Outlook study, 238 and 220 were assessed at the same two time points, respectively.

Results showed a curvilinear relationship between DUP and symptom severity. Longer DUP was predictive of reduced treatment response. However, patient response worsened more slowly as DUP lengthened.

For example, increasing DUP by ten times was predictive of less improvement in PANSS total score by 7.34 (95% CI, 5.76 – 8.92; P < .0001) in NEDEN and by 3.85 (95% CI, 1.69 – 600; P =. 0005) in Outlook. Nevertheless, longer DUP was not associated with worse presentation for any symptoms except depression in NEDEN.

The findings seem to support that the potential harm incurred by delaying treatment among patients with FEP is greatest in the early weeks of psychosis and then levels off, the investigators note.

Given these insights, mental health professionals might consider focusing their efforts on the early detection and treatment of patients for whom DUP is short.

Similarly, because DUP was directly associated with all symptoms, early access to comprehensive treatment “might be preferable to early delivery of particular treatments with particular effects (eg, dopamine antagonists),” they write.
 

“A pragmatic call”

Commenting on the British study in an accompanying editorial, Lena K. Palaniyappan, MD, University of Western Ontario, London, Canada, and Rajeev Krishnadas, MD, University of Glasgow, Scotland, write that any illness left untreated can become more challenging to treat, including psychosis.

“This should make early intervention in psychosis a pragmatic call with no prima facie argument against it,” they write. A reduction in DUP “underpins the rationale behind early detection and intervention in psychosis.”

The editorialists note that the relationship between DUP and successful treatment in early psychosis “strengthens the argument for more proactive early assessment and intervention to shorten treatment delay.

“As we have learnt over the past two decades, even punctual treatment when symptoms first arise continues to be too late when it comes to psychosis,” they write.

Francey also recognizes the value of early intervention in FEP. However, she noted that comprehensive psychosocial therapy might well prove effective enough to stave off antipsychotic therapy in a certain subset of patients.

“For some people, antipsychotics may never need to be introduced,” she said. “Some people recover from their first episode of psychosis and don’t go on to have any more, while others have an episodic illness,” she said.

If another episode develops and the symptoms come back, further psychosocial interventions could then be tried “or you might want to move on” to psychotic medication “because trying to get people better and functioning as well as they can is our primary aim,” Francey said.

The STAGES study was supported by the Australian National Health and Medical Research Council. The British study was funded by the UK Department of Health, the National Institute of Health Research, and the Medical Research Council. Francey and Krishnadas have reported no relevant financial relationships. Palaniyappan has received grants and personal fees from Janssen Canada and Otsuka Canada, grants from Sunovion, and personal fees from SPMM Course UK and the Canadian Psychiatric Association.
 

This article first appeared on Medscape.com.

Two new studies highlight the importance of early intervention in first-episode psychosis (FEP).

In the first study, Australian investigators conclude that, for some FEP patients, early psychosocial interventions may fend off the need for immediate treatment with antipsychotic medications.

In the second study, UK researchers show that long duration of untreated psychosis (DUP) is linked to a significantly reduced treatment response.

For both studies, the findings highlight the importance of rapid access to a comprehensive range of treatments in the first weeks after FEP onset.

“In a select group of people with first-episode psychosis, we found there was no difference in symptoms and functioning between those who had antipsychotic medication and those who didn’t,” lead author Shona M. Francey, PhD, clinical psychologist at Orygen, the National Center of Excellence in Youth Mental Health, Parkville, Australia, told Medscape Medical News.

“These findings supported our idea that, in the early phases of psychosis, with close monitoring and good psychosocial intervention, antipsychotic medication can be delayed,” Francey said.

The Australian study was published in Schizophrenia Bulletin Open. The British study was published in Lancet Psychiatry.
 

Adverse effects

Francey and colleagues note that, in comparison with standard treatment, early interventions produce superior outcomes for patients with psychosis. Although there are a variety of treatment options, low-dose second-generation antipsychotics typically play a central role.

However, atypical antipsychotics have rapid metabolic side effects, including weight gain and altered glucose metabolism, that increase the risk for cardiovascular disease and premature mortality. Importantly, such adverse effects are amplified among patients with FEP, who tend to be younger and treatment naive.

On the other hand, a growing body of evidence shows the benefit of nonpharmacologic interventions for patients with FEP, the investigators note. In addition, clinical staging models appear to support the use of less aggressive treatment early in the disease course.

“We have been working in early intervention for psychosis for a number of years and have found it’s possible to intervene early with young people and either prevent the onset of psychosis or ameliorate its impact,” said Francey.

“Since we can see some improvement in people in the prepsychotic phase, we wanted to know if we can also see some benefit without medication after the onset of what we would call full-threshold psychosis,” she added.

Staged Treatment and Acceptability Guidelines in Early Psychosis (STAGES) was a 6-month, triple-blind, randomized controlled noninferiority study that included 90 participants between the ages of 15 and 25 years who had FEP.

To maximize safety, patients were required to have low levels of suicidality and aggression, a DUP of less than 6 months, and to be living in stable accommodation with social support.

Participants were randomly assigned to two groups – one in which patients underwent intensive psychosocial therapy and received low-dose antipsychotic medication (n = 44), and one in which patients underwent intensive psychosocial therapy and were given placebo (n = 46).

Depending on the timing of study enrollment, those in the medication group received risperidone 1 mg or paliperidone 3 mg.

The psychosocial intervention consisted of cognitive-behavioral case management (CBCM), an intervention developed specifically for patients with early psychosis that is strongly focused on therapeutic engagement.

CBCM delivers formulation-driven cognitive-behavioral therapy and psychoeducation within a therapeutic case management framework, Francey said.

The primary outcome was level of functioning at 6, 12, and 24 months, as measured by the Social and Occupational Functioning Scale (SOFAS). The primary prespecified endpoint was outcome at 6 months. A noninferiority margin of 10.5 on the SOFAS was used as the smallest value representing a clinically important effect.

Other assessment tools included the BPRS-4 to test for positive psychotic symptoms, the Scale for the Assessment of Negative Symptoms (SANS), the Hamilton Rating Scale for Depression, and the Hamilton Rating Scale for Anxiety.

At baseline, the two treatment groups were comparable with respect to all measures of functioning and psychopathology.

The study’s discontinuation rate was high. At 6 months, only 16 patients in the psychosocial group had completed therapy, compared with 11 in the antipsychotic group.

At this point, the two groups were comparable in terms of psychopathology and functioning ratings. Both groups had lower symptoms, higher functioning scores, and higher Quality of Life Scale (QLS) scores than at baseline.

SOFAS scores were not significantly different between the groups at this time point. The mean score was 61.7 ± 16.8 in the psychosocial group and 61.5 ± 13.4 in the medication group.

The researchers note that, because the upper limit of the confidence interval (CI) was less than the study’s a priori inferiority margin of 10.5, psychosocial therapy was not inferior to medication at the 6-month assessment point.
 

Antipsychotics: Use with caution

Although between-group differences in SOFAS scores were not significant at 12 and 24 months, noninferiority of psychosocial therapy alone could not be confirmed because the CIs included the inferiority margin at each time point.

The two groups were statistically comparable at 6 months with respect to all other measures of psychopathology and the QLS. Similar results were found at 12 and 24 months.

The lone exception was with SANS at 12 months, on which patients in the placebo group had significantly higher negative symptom scores than the patients in the medication group.

There were no significant differences between study groups with respect to the number of adverse events.

Francey noted that the findings are important because they suggest that some young people with early-stage FEP and short DUP may be able to achieve symptom remission and function better without antipsychotic medication, provided they receive psychological interventions and comprehensive case management.

This challenges conventional wisdom that antipsychotic medications should be used for all patients who experience psychosis, she added.

However, managing FEP with psychosocial interventions should only be considered when it is safe to do so, Francey noted. In addition, the benefits of psychosocial interventions in these patients are less clear at 12 and 24 months.

Given these caveats, she noted that antipsychotics still play an important role in the treatment of these patients.

“I think there is definitely a place for medications. But I think they should be used cautiously, and you need a good, strong relationship between your treating team and your [patient] to work out what is needed and when it’s needed,” said Francey.

In addition, “when we do use medications, we should use the smallest possible dose that we can and also incorporate psychological support. I think that’s a really important part of it as well,” she said.
 

Timing matters

In the Lancet Psychiatry study, the researchers note that prolonged DUP is associated with worse outcomes, including increased symptoms, diminished social functioning, and poorer quality of life. The mechanism by which delayed treatment causes more harm remains unclear.

It is possible that symptoms simply accumulate over time, thereby worsening presentation. Another possibility is that continued psychosis after an initial critical period may cause long-term harm, they write.

They hypothesize that untreated psychosis can cause general treatment resistance by exacerbating underlying disease processes and that such damage progresses faster in the early stages of illness and then slows over time.

In addition, socially disruptive symptoms that are evident prior to FEP presentation may have a confounding effect, thereby leading to earlier presentation.

The investigators used data from two longitudinal cohort studies – the National Evaluation of Development of Early Intervention Network (NEDEN) study and the Outlook study.

In the NEDEN trial, 290 of 901 FEP patients (32%) were assessed within 3 weeks of presentation. In Outlook, 69 of 332 patients (21%) were assessed within 3 weeks of presentation.

In both studies, patients were examined at baseline, 6 months, and 12 months using the Positive and Negative Syndrome Scale (PANSS), the Calgary Depression Scale for Schizophrenia, the Mania Rating Scale, the Insight Scale, and SOFAS. The latter two measures were used only at baseline and 12-month follow-up. Logistic regression analyses were used to determine the association between DUP and outcomes.

In the NEDEN study, 751 patients were assessed at 6 months, and 719 were assessed at 12 months. In the Outlook study, 238 and 220 were assessed at the same two time points, respectively.

Results showed a curvilinear relationship between DUP and symptom severity. Longer DUP was predictive of reduced treatment response. However, patient response worsened more slowly as DUP lengthened.

For example, increasing DUP by ten times was predictive of less improvement in PANSS total score by 7.34 (95% CI, 5.76 – 8.92; P < .0001) in NEDEN and by 3.85 (95% CI, 1.69 – 600; P =. 0005) in Outlook. Nevertheless, longer DUP was not associated with worse presentation for any symptoms except depression in NEDEN.

The findings seem to support that the potential harm incurred by delaying treatment among patients with FEP is greatest in the early weeks of psychosis and then levels off, the investigators note.

Given these insights, mental health professionals might consider focusing their efforts on the early detection and treatment of patients for whom DUP is short.

Similarly, because DUP was directly associated with all symptoms, early access to comprehensive treatment “might be preferable to early delivery of particular treatments with particular effects (eg, dopamine antagonists),” they write.
 

“A pragmatic call”

Commenting on the British study in an accompanying editorial, Lena K. Palaniyappan, MD, University of Western Ontario, London, Canada, and Rajeev Krishnadas, MD, University of Glasgow, Scotland, write that any illness left untreated can become more challenging to treat, including psychosis.

“This should make early intervention in psychosis a pragmatic call with no prima facie argument against it,” they write. A reduction in DUP “underpins the rationale behind early detection and intervention in psychosis.”

The editorialists note that the relationship between DUP and successful treatment in early psychosis “strengthens the argument for more proactive early assessment and intervention to shorten treatment delay.

“As we have learnt over the past two decades, even punctual treatment when symptoms first arise continues to be too late when it comes to psychosis,” they write.

Francey also recognizes the value of early intervention in FEP. However, she noted that comprehensive psychosocial therapy might well prove effective enough to stave off antipsychotic therapy in a certain subset of patients.

“For some people, antipsychotics may never need to be introduced,” she said. “Some people recover from their first episode of psychosis and don’t go on to have any more, while others have an episodic illness,” she said.

If another episode develops and the symptoms come back, further psychosocial interventions could then be tried “or you might want to move on” to psychotic medication “because trying to get people better and functioning as well as they can is our primary aim,” Francey said.

The STAGES study was supported by the Australian National Health and Medical Research Council. The British study was funded by the UK Department of Health, the National Institute of Health Research, and the Medical Research Council. Francey and Krishnadas have reported no relevant financial relationships. Palaniyappan has received grants and personal fees from Janssen Canada and Otsuka Canada, grants from Sunovion, and personal fees from SPMM Course UK and the Canadian Psychiatric Association.
 

This article first appeared on Medscape.com.

Two new studies highlight the importance of early intervention in first-episode psychosis (FEP).

In the first study, Australian investigators conclude that, for some FEP patients, early psychosocial interventions may fend off the need for immediate treatment with antipsychotic medications.

In the second study, UK researchers show that long duration of untreated psychosis (DUP) is linked to a significantly reduced treatment response.

For both studies, the findings highlight the importance of rapid access to a comprehensive range of treatments in the first weeks after FEP onset.

“In a select group of people with first-episode psychosis, we found there was no difference in symptoms and functioning between those who had antipsychotic medication and those who didn’t,” lead author Shona M. Francey, PhD, clinical psychologist at Orygen, the National Center of Excellence in Youth Mental Health, Parkville, Australia, told Medscape Medical News.

“These findings supported our idea that, in the early phases of psychosis, with close monitoring and good psychosocial intervention, antipsychotic medication can be delayed,” Francey said.

The Australian study was published in Schizophrenia Bulletin Open. The British study was published in Lancet Psychiatry.
 

Adverse effects

Francey and colleagues note that, in comparison with standard treatment, early interventions produce superior outcomes for patients with psychosis. Although there are a variety of treatment options, low-dose second-generation antipsychotics typically play a central role.

However, atypical antipsychotics have rapid metabolic side effects, including weight gain and altered glucose metabolism, that increase the risk for cardiovascular disease and premature mortality. Importantly, such adverse effects are amplified among patients with FEP, who tend to be younger and treatment naive.

On the other hand, a growing body of evidence shows the benefit of nonpharmacologic interventions for patients with FEP, the investigators note. In addition, clinical staging models appear to support the use of less aggressive treatment early in the disease course.

“We have been working in early intervention for psychosis for a number of years and have found it’s possible to intervene early with young people and either prevent the onset of psychosis or ameliorate its impact,” said Francey.

“Since we can see some improvement in people in the prepsychotic phase, we wanted to know if we can also see some benefit without medication after the onset of what we would call full-threshold psychosis,” she added.

Staged Treatment and Acceptability Guidelines in Early Psychosis (STAGES) was a 6-month, triple-blind, randomized controlled noninferiority study that included 90 participants between the ages of 15 and 25 years who had FEP.

To maximize safety, patients were required to have low levels of suicidality and aggression, a DUP of less than 6 months, and to be living in stable accommodation with social support.

Participants were randomly assigned to two groups – one in which patients underwent intensive psychosocial therapy and received low-dose antipsychotic medication (n = 44), and one in which patients underwent intensive psychosocial therapy and were given placebo (n = 46).

Depending on the timing of study enrollment, those in the medication group received risperidone 1 mg or paliperidone 3 mg.

The psychosocial intervention consisted of cognitive-behavioral case management (CBCM), an intervention developed specifically for patients with early psychosis that is strongly focused on therapeutic engagement.

CBCM delivers formulation-driven cognitive-behavioral therapy and psychoeducation within a therapeutic case management framework, Francey said.

The primary outcome was level of functioning at 6, 12, and 24 months, as measured by the Social and Occupational Functioning Scale (SOFAS). The primary prespecified endpoint was outcome at 6 months. A noninferiority margin of 10.5 on the SOFAS was used as the smallest value representing a clinically important effect.

Other assessment tools included the BPRS-4 to test for positive psychotic symptoms, the Scale for the Assessment of Negative Symptoms (SANS), the Hamilton Rating Scale for Depression, and the Hamilton Rating Scale for Anxiety.

At baseline, the two treatment groups were comparable with respect to all measures of functioning and psychopathology.

The study’s discontinuation rate was high. At 6 months, only 16 patients in the psychosocial group had completed therapy, compared with 11 in the antipsychotic group.

At this point, the two groups were comparable in terms of psychopathology and functioning ratings. Both groups had lower symptoms, higher functioning scores, and higher Quality of Life Scale (QLS) scores than at baseline.

SOFAS scores were not significantly different between the groups at this time point. The mean score was 61.7 ± 16.8 in the psychosocial group and 61.5 ± 13.4 in the medication group.

The researchers note that, because the upper limit of the confidence interval (CI) was less than the study’s a priori inferiority margin of 10.5, psychosocial therapy was not inferior to medication at the 6-month assessment point.
 

Antipsychotics: Use with caution

Although between-group differences in SOFAS scores were not significant at 12 and 24 months, noninferiority of psychosocial therapy alone could not be confirmed because the CIs included the inferiority margin at each time point.

The two groups were statistically comparable at 6 months with respect to all other measures of psychopathology and the QLS. Similar results were found at 12 and 24 months.

The lone exception was with SANS at 12 months, on which patients in the placebo group had significantly higher negative symptom scores than the patients in the medication group.

There were no significant differences between study groups with respect to the number of adverse events.

Francey noted that the findings are important because they suggest that some young people with early-stage FEP and short DUP may be able to achieve symptom remission and function better without antipsychotic medication, provided they receive psychological interventions and comprehensive case management.

This challenges conventional wisdom that antipsychotic medications should be used for all patients who experience psychosis, she added.

However, managing FEP with psychosocial interventions should only be considered when it is safe to do so, Francey noted. In addition, the benefits of psychosocial interventions in these patients are less clear at 12 and 24 months.

Given these caveats, she noted that antipsychotics still play an important role in the treatment of these patients.

“I think there is definitely a place for medications. But I think they should be used cautiously, and you need a good, strong relationship between your treating team and your [patient] to work out what is needed and when it’s needed,” said Francey.

In addition, “when we do use medications, we should use the smallest possible dose that we can and also incorporate psychological support. I think that’s a really important part of it as well,” she said.
 

Timing matters

In the Lancet Psychiatry study, the researchers note that prolonged DUP is associated with worse outcomes, including increased symptoms, diminished social functioning, and poorer quality of life. The mechanism by which delayed treatment causes more harm remains unclear.

It is possible that symptoms simply accumulate over time, thereby worsening presentation. Another possibility is that continued psychosis after an initial critical period may cause long-term harm, they write.

They hypothesize that untreated psychosis can cause general treatment resistance by exacerbating underlying disease processes and that such damage progresses faster in the early stages of illness and then slows over time.

In addition, socially disruptive symptoms that are evident prior to FEP presentation may have a confounding effect, thereby leading to earlier presentation.

The investigators used data from two longitudinal cohort studies – the National Evaluation of Development of Early Intervention Network (NEDEN) study and the Outlook study.

In the NEDEN trial, 290 of 901 FEP patients (32%) were assessed within 3 weeks of presentation. In Outlook, 69 of 332 patients (21%) were assessed within 3 weeks of presentation.

In both studies, patients were examined at baseline, 6 months, and 12 months using the Positive and Negative Syndrome Scale (PANSS), the Calgary Depression Scale for Schizophrenia, the Mania Rating Scale, the Insight Scale, and SOFAS. The latter two measures were used only at baseline and 12-month follow-up. Logistic regression analyses were used to determine the association between DUP and outcomes.

In the NEDEN study, 751 patients were assessed at 6 months, and 719 were assessed at 12 months. In the Outlook study, 238 and 220 were assessed at the same two time points, respectively.

Results showed a curvilinear relationship between DUP and symptom severity. Longer DUP was predictive of reduced treatment response. However, patient response worsened more slowly as DUP lengthened.

For example, increasing DUP by ten times was predictive of less improvement in PANSS total score by 7.34 (95% CI, 5.76 – 8.92; P < .0001) in NEDEN and by 3.85 (95% CI, 1.69 – 600; P =. 0005) in Outlook. Nevertheless, longer DUP was not associated with worse presentation for any symptoms except depression in NEDEN.

The findings seem to support that the potential harm incurred by delaying treatment among patients with FEP is greatest in the early weeks of psychosis and then levels off, the investigators note.

Given these insights, mental health professionals might consider focusing their efforts on the early detection and treatment of patients for whom DUP is short.

Similarly, because DUP was directly associated with all symptoms, early access to comprehensive treatment “might be preferable to early delivery of particular treatments with particular effects (eg, dopamine antagonists),” they write.
 

“A pragmatic call”

Commenting on the British study in an accompanying editorial, Lena K. Palaniyappan, MD, University of Western Ontario, London, Canada, and Rajeev Krishnadas, MD, University of Glasgow, Scotland, write that any illness left untreated can become more challenging to treat, including psychosis.

“This should make early intervention in psychosis a pragmatic call with no prima facie argument against it,” they write. A reduction in DUP “underpins the rationale behind early detection and intervention in psychosis.”

The editorialists note that the relationship between DUP and successful treatment in early psychosis “strengthens the argument for more proactive early assessment and intervention to shorten treatment delay.

“As we have learnt over the past two decades, even punctual treatment when symptoms first arise continues to be too late when it comes to psychosis,” they write.

Francey also recognizes the value of early intervention in FEP. However, she noted that comprehensive psychosocial therapy might well prove effective enough to stave off antipsychotic therapy in a certain subset of patients.

“For some people, antipsychotics may never need to be introduced,” she said. “Some people recover from their first episode of psychosis and don’t go on to have any more, while others have an episodic illness,” she said.

If another episode develops and the symptoms come back, further psychosocial interventions could then be tried “or you might want to move on” to psychotic medication “because trying to get people better and functioning as well as they can is our primary aim,” Francey said.

The STAGES study was supported by the Australian National Health and Medical Research Council. The British study was funded by the UK Department of Health, the National Institute of Health Research, and the Medical Research Council. Francey and Krishnadas have reported no relevant financial relationships. Palaniyappan has received grants and personal fees from Janssen Canada and Otsuka Canada, grants from Sunovion, and personal fees from SPMM Course UK and the Canadian Psychiatric Association.
 

This article first appeared on Medscape.com.

The COVID-19 pandemic has, like it or not, made experimental labs rats out of us all.

Since the U.S. “shutdown” began in March, we have all had to adjust to a situation in which we are home more, stuck seeing less of our friends, exercising less, often eating and drinking more, or using recreational substances more – in part because of the severe stress. We have been ripped away from many of the social “anchors” of our weeks; that is, the spiritual, social and physical, and tactile supports that sustain and motivate us in our lives.

And yet, many of us, of all ages, stripes, and colors are thriving. Why is that so? Without necessarily being fully fledged, card carrying misanthropes, many of us are actually not bereft when forced to spend some alone time.

CANCER CIFTCI/Getty Images

We may be self-starters and have hobbies and interests that we may have neglected but can fall back on with alacrity. Activities such as gardening, cooking, reading, working at our day jobs, listening to music, streaming TV, and so on are now more available to us.

The pandemic has produced unforeseen side effects, such as decreased pollution, less seismic “noise” on our planet, increasingly bold activity by wild life, and we can actually hear bird songs in our yards. Likewise, the social isolation has enabled us to focus more on “back burner” projects and to motivate us toward accessing and achieving other internally driven goals.

Also, to many, it has provided a surprising and unexpected privilege to meaningfully connect while in close quarters with spouses, children, and other loved ones, which has improved and cemented relationships under some level of duress, perhaps.

Similarly, and perhaps surprisingly, in addition to the above reasons, many of our patients with chronic mental illness may be functioning reasonably well, too, even better than their “walking wounded” loved ones and peers. They may be reaping the rewards of many years of consistent biopsychosocial support in strong mental health programs.

But another reason might be the lowered expectations. As one stable patient with schizophrenia said, “No one is hassling me now; no one is aggravating me to go to this group or that, to leave the house to volunteer, to get a job. I’m just so much more relaxed; I’ve got this.” And certainly the Freudian “schadenfreude” defense has something to do with this as well. Seeing family members lose their jobs, become financially vulnerable, being unable to or stymied from demonstrating mastery in many different situations and skill sets elicit the empathy and galvanizes the support of well-managed patients with mental illness – already used to existential threats – for their generally higher functioning loved ones.

As one of my struggling patients said, “Welcome to my world!” Years of hardship, lack of intimate relationships because of social anxiety, and psychotic level obsessive-compulsive disorder have trained, indeed, inured her to the daily pain, constriction, and misery of social isolation. Her life, despite working full time, has remained static, while younger siblings have married, started a family, moved away. She is still living at home with her elderly parents. They now worry about catching COVID-19, while she is now their protector with roles reversed, doing their shopping, and providing moral support and encouragement for the whole family.

Many of us have lost jobs, been furloughed, seen our dreams disappear, and are unable to pay rent or mortgages. Those with chronic mental illness, especially those living in states with a strong social safety net, are continuing to receive their Social Security disability checks, and maintain their in-home health and family supports. They also have continued their adherence with the mental health system structure by continuing with telemedicine therapy and regular medications or monthly intramuscular shots. Their families are especially cognizant of the need for ongoing structure and stability, which is now easier to provide. And what of those patients who endured severe anxiety and panic disorders in their prepandemic states? It is true that many do require higher doses of their anxiolytics, especially benzodiazepines. They do know how to “roll with the punches” with their lifetime experience, as opposed to the “newbies” whose incipient anxiety is brought to the forefront and who might not even recognize these debilitating symptoms and are not keen, for reasons of stigma, to be seen by a mental health expert unless compelled to.

It is up to us as psychiatrists and other mental health clinicians to minimize dependence on those medications by using alternative non–dependence-forming anxiolytics and encouraging our patients to hone and develop the skills from cognitive-behavioral therapy. COVID-19 is just one more stressor, superimposed on many others, and unlikely to precipitate any “tipping point” in functioning, even if there are significant losses among loved ones to the virus.

How about our child and adolescent patients? As a rule of thumb, those with anxiety disorders, social anxiety, selective mutism – and those experiencing challenges and bullying in the rough and tumble world of schools – are doing significantly better. Those with ADHD and impulse control disorders, however, might be struggling with school, especially with Zoom calls and very high distractibility, boredom, and motivational challenges. They may need their doses of medications adjusted up, and their parents are struggling. The risk for unwitnessed and unmonitored abuse in home situations is higher.

Those with chronic mental illness often do have increased risk factors for COVID-19 that might be compounded by their psychopharmacologic treatment for conditions/behaviors such as diabetes, obesity, cardiovascular disease, and substance use. By proactively monitoring those comorbid disorders in a multimodal treatment program, we can help mitigate those baseline challenges.

This aspect of the COVID-19 pandemic is, alas, likely to prove to be an illusory positive “blip” on the radar screen for many with chronic mental illness. Nevertheless, the self-knowledge and awareness of hidden strengths rather than weakness, resilience rather than shrinking from challenges, is not insignificant. This “flight into normality” may be a change that can be internalized and nurtured once vaccines are available and life on planet Earth returns to a new normal.
 

Dr. Tofler is affiliated with Kaiser Permanente Psychiatry in Los Angeles. He also is a visiting faculty member in the department of psychiatry and biobehavioral sciences at the University of California, Los Angeles. Dr. Tofler has no conflicts of interest.

The COVID-19 pandemic has, like it or not, made experimental labs rats out of us all.

Since the U.S. “shutdown” began in March, we have all had to adjust to a situation in which we are home more, stuck seeing less of our friends, exercising less, often eating and drinking more, or using recreational substances more – in part because of the severe stress. We have been ripped away from many of the social “anchors” of our weeks; that is, the spiritual, social and physical, and tactile supports that sustain and motivate us in our lives.

And yet, many of us, of all ages, stripes, and colors are thriving. Why is that so? Without necessarily being fully fledged, card carrying misanthropes, many of us are actually not bereft when forced to spend some alone time.

CANCER CIFTCI/Getty Images

We may be self-starters and have hobbies and interests that we may have neglected but can fall back on with alacrity. Activities such as gardening, cooking, reading, working at our day jobs, listening to music, streaming TV, and so on are now more available to us.

The pandemic has produced unforeseen side effects, such as decreased pollution, less seismic “noise” on our planet, increasingly bold activity by wild life, and we can actually hear bird songs in our yards. Likewise, the social isolation has enabled us to focus more on “back burner” projects and to motivate us toward accessing and achieving other internally driven goals.

Also, to many, it has provided a surprising and unexpected privilege to meaningfully connect while in close quarters with spouses, children, and other loved ones, which has improved and cemented relationships under some level of duress, perhaps.

Similarly, and perhaps surprisingly, in addition to the above reasons, many of our patients with chronic mental illness may be functioning reasonably well, too, even better than their “walking wounded” loved ones and peers. They may be reaping the rewards of many years of consistent biopsychosocial support in strong mental health programs.

But another reason might be the lowered expectations. As one stable patient with schizophrenia said, “No one is hassling me now; no one is aggravating me to go to this group or that, to leave the house to volunteer, to get a job. I’m just so much more relaxed; I’ve got this.” And certainly the Freudian “schadenfreude” defense has something to do with this as well. Seeing family members lose their jobs, become financially vulnerable, being unable to or stymied from demonstrating mastery in many different situations and skill sets elicit the empathy and galvanizes the support of well-managed patients with mental illness – already used to existential threats – for their generally higher functioning loved ones.

As one of my struggling patients said, “Welcome to my world!” Years of hardship, lack of intimate relationships because of social anxiety, and psychotic level obsessive-compulsive disorder have trained, indeed, inured her to the daily pain, constriction, and misery of social isolation. Her life, despite working full time, has remained static, while younger siblings have married, started a family, moved away. She is still living at home with her elderly parents. They now worry about catching COVID-19, while she is now their protector with roles reversed, doing their shopping, and providing moral support and encouragement for the whole family.

Many of us have lost jobs, been furloughed, seen our dreams disappear, and are unable to pay rent or mortgages. Those with chronic mental illness, especially those living in states with a strong social safety net, are continuing to receive their Social Security disability checks, and maintain their in-home health and family supports. They also have continued their adherence with the mental health system structure by continuing with telemedicine therapy and regular medications or monthly intramuscular shots. Their families are especially cognizant of the need for ongoing structure and stability, which is now easier to provide. And what of those patients who endured severe anxiety and panic disorders in their prepandemic states? It is true that many do require higher doses of their anxiolytics, especially benzodiazepines. They do know how to “roll with the punches” with their lifetime experience, as opposed to the “newbies” whose incipient anxiety is brought to the forefront and who might not even recognize these debilitating symptoms and are not keen, for reasons of stigma, to be seen by a mental health expert unless compelled to.

It is up to us as psychiatrists and other mental health clinicians to minimize dependence on those medications by using alternative non–dependence-forming anxiolytics and encouraging our patients to hone and develop the skills from cognitive-behavioral therapy. COVID-19 is just one more stressor, superimposed on many others, and unlikely to precipitate any “tipping point” in functioning, even if there are significant losses among loved ones to the virus.

How about our child and adolescent patients? As a rule of thumb, those with anxiety disorders, social anxiety, selective mutism – and those experiencing challenges and bullying in the rough and tumble world of schools – are doing significantly better. Those with ADHD and impulse control disorders, however, might be struggling with school, especially with Zoom calls and very high distractibility, boredom, and motivational challenges. They may need their doses of medications adjusted up, and their parents are struggling. The risk for unwitnessed and unmonitored abuse in home situations is higher.

Those with chronic mental illness often do have increased risk factors for COVID-19 that might be compounded by their psychopharmacologic treatment for conditions/behaviors such as diabetes, obesity, cardiovascular disease, and substance use. By proactively monitoring those comorbid disorders in a multimodal treatment program, we can help mitigate those baseline challenges.

This aspect of the COVID-19 pandemic is, alas, likely to prove to be an illusory positive “blip” on the radar screen for many with chronic mental illness. Nevertheless, the self-knowledge and awareness of hidden strengths rather than weakness, resilience rather than shrinking from challenges, is not insignificant. This “flight into normality” may be a change that can be internalized and nurtured once vaccines are available and life on planet Earth returns to a new normal.
 

Dr. Tofler is affiliated with Kaiser Permanente Psychiatry in Los Angeles. He also is a visiting faculty member in the department of psychiatry and biobehavioral sciences at the University of California, Los Angeles. Dr. Tofler has no conflicts of interest.

The COVID-19 pandemic has, like it or not, made experimental labs rats out of us all.

Since the U.S. “shutdown” began in March, we have all had to adjust to a situation in which we are home more, stuck seeing less of our friends, exercising less, often eating and drinking more, or using recreational substances more – in part because of the severe stress. We have been ripped away from many of the social “anchors” of our weeks; that is, the spiritual, social and physical, and tactile supports that sustain and motivate us in our lives.

And yet, many of us, of all ages, stripes, and colors are thriving. Why is that so? Without necessarily being fully fledged, card carrying misanthropes, many of us are actually not bereft when forced to spend some alone time.

CANCER CIFTCI/Getty Images

We may be self-starters and have hobbies and interests that we may have neglected but can fall back on with alacrity. Activities such as gardening, cooking, reading, working at our day jobs, listening to music, streaming TV, and so on are now more available to us.

The pandemic has produced unforeseen side effects, such as decreased pollution, less seismic “noise” on our planet, increasingly bold activity by wild life, and we can actually hear bird songs in our yards. Likewise, the social isolation has enabled us to focus more on “back burner” projects and to motivate us toward accessing and achieving other internally driven goals.

Also, to many, it has provided a surprising and unexpected privilege to meaningfully connect while in close quarters with spouses, children, and other loved ones, which has improved and cemented relationships under some level of duress, perhaps.

Similarly, and perhaps surprisingly, in addition to the above reasons, many of our patients with chronic mental illness may be functioning reasonably well, too, even better than their “walking wounded” loved ones and peers. They may be reaping the rewards of many years of consistent biopsychosocial support in strong mental health programs.

But another reason might be the lowered expectations. As one stable patient with schizophrenia said, “No one is hassling me now; no one is aggravating me to go to this group or that, to leave the house to volunteer, to get a job. I’m just so much more relaxed; I’ve got this.” And certainly the Freudian “schadenfreude” defense has something to do with this as well. Seeing family members lose their jobs, become financially vulnerable, being unable to or stymied from demonstrating mastery in many different situations and skill sets elicit the empathy and galvanizes the support of well-managed patients with mental illness – already used to existential threats – for their generally higher functioning loved ones.

As one of my struggling patients said, “Welcome to my world!” Years of hardship, lack of intimate relationships because of social anxiety, and psychotic level obsessive-compulsive disorder have trained, indeed, inured her to the daily pain, constriction, and misery of social isolation. Her life, despite working full time, has remained static, while younger siblings have married, started a family, moved away. She is still living at home with her elderly parents. They now worry about catching COVID-19, while she is now their protector with roles reversed, doing their shopping, and providing moral support and encouragement for the whole family.

Many of us have lost jobs, been furloughed, seen our dreams disappear, and are unable to pay rent or mortgages. Those with chronic mental illness, especially those living in states with a strong social safety net, are continuing to receive their Social Security disability checks, and maintain their in-home health and family supports. They also have continued their adherence with the mental health system structure by continuing with telemedicine therapy and regular medications or monthly intramuscular shots. Their families are especially cognizant of the need for ongoing structure and stability, which is now easier to provide. And what of those patients who endured severe anxiety and panic disorders in their prepandemic states? It is true that many do require higher doses of their anxiolytics, especially benzodiazepines. They do know how to “roll with the punches” with their lifetime experience, as opposed to the “newbies” whose incipient anxiety is brought to the forefront and who might not even recognize these debilitating symptoms and are not keen, for reasons of stigma, to be seen by a mental health expert unless compelled to.

It is up to us as psychiatrists and other mental health clinicians to minimize dependence on those medications by using alternative non–dependence-forming anxiolytics and encouraging our patients to hone and develop the skills from cognitive-behavioral therapy. COVID-19 is just one more stressor, superimposed on many others, and unlikely to precipitate any “tipping point” in functioning, even if there are significant losses among loved ones to the virus.

How about our child and adolescent patients? As a rule of thumb, those with anxiety disorders, social anxiety, selective mutism – and those experiencing challenges and bullying in the rough and tumble world of schools – are doing significantly better. Those with ADHD and impulse control disorders, however, might be struggling with school, especially with Zoom calls and very high distractibility, boredom, and motivational challenges. They may need their doses of medications adjusted up, and their parents are struggling. The risk for unwitnessed and unmonitored abuse in home situations is higher.

Those with chronic mental illness often do have increased risk factors for COVID-19 that might be compounded by their psychopharmacologic treatment for conditions/behaviors such as diabetes, obesity, cardiovascular disease, and substance use. By proactively monitoring those comorbid disorders in a multimodal treatment program, we can help mitigate those baseline challenges.

This aspect of the COVID-19 pandemic is, alas, likely to prove to be an illusory positive “blip” on the radar screen for many with chronic mental illness. Nevertheless, the self-knowledge and awareness of hidden strengths rather than weakness, resilience rather than shrinking from challenges, is not insignificant. This “flight into normality” may be a change that can be internalized and nurtured once vaccines are available and life on planet Earth returns to a new normal.
 

Dr. Tofler is affiliated with Kaiser Permanente Psychiatry in Los Angeles. He also is a visiting faculty member in the department of psychiatry and biobehavioral sciences at the University of California, Los Angeles. Dr. Tofler has no conflicts of interest.

Aggression in individuals is influenced by genetic and environmental factors, but can be reduced with treatment, according to Emil F. Coccaro, MD.

“It actually is a complex triad of emotion, cognition, and behavior. The emotion is anger, the cognition is hostility, and the behavior is aggression. And they sort of go in that order,” Dr. Coccaro said at Focus on Neuropsychiatry presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.

Although aggression can be thought of in a numerous ways, premeditated and impulsive aggression are most relevant to behavioral studies in psychiatry, Dr. Coccaro explained. Premeditated aggression is goal oriented, while impulsive aggression comes from frustration or a response to a threat. Impulsive aggression is “typically social or frustrative in nature, and studies that we’ve done that show that individuals move toward a threat while nonaggressives move away it,” he said. Both types of aggression can be seen in the same individuals at different times.

Aggression also can be considered using a threshold model. Calm individuals, for example, might have a low baseline of aggression and a high threshold before they act out. An aggressive person, on the other hand, has a lower threshold and a higher baseline level. “Their delta to get to the point where they’re going to explode is much shorter, much lower than it is in someone who is healthy,” Dr. Coccaro said.

“What we think is that the threshold to explode is probably regulated by various neurobiological features. The baseline state of aggression also may be related to baseline neurobiological features, but also what’s going on in the environment, because the neurobiological features that send someone to exploding aggression are there all the time,” he explained.

Individuals with secondary aggression are likely to have an underlying condition, such as a primary disease of the brain, systemic or metabolic disorder, or a psychiatric disorder such as schizophrenia. “If someone’s schizophrenic and they’ve got voices telling them to hurt somebody, or delusions that someone’s going to hurt them, that’s not primary aggression, that’s secondary to the psychosis,” Dr. Coccaro noted.

An individual with primary aggression is likely to have intermittent explosive disorder (IED). IED is not a new diagnosis and has been listed in the DSM since the DSM-I as “passive-aggressive personality.” It was relisted in the DSM-II as “explosive personality,” then changed to IED in the DSM-3 as a diagnosis of exclusion that was poorly operationalized, according to Dr. Coccaro. The criteria for IED under the DSM-III did not define the number of recurrent outbursts needed, what they looked like, the time frame, and excluded people who were generally impulsive.

“That’s not really what these people look like and it’s not what impulsive aggression looks like,” he said. Although the DSM-IV removed the exclusion criteria for general impulsivity and aggression, “it was still purely operational.”

The DSM-5 criteria define IED as “verbal and physical aggression without destruction or assault, twice equally on average for 3 months, or three or more episodes of physical destruction/assault over a 1-year period. These individuals have outbursts “grossly out of proportion to provocation,” the aggression is generally impulsive, and it causes stress and impairment with an age of onset at older than 6 years.

“It’s not better accounted for a whole variety of things, but we actually made some of those exclusion criteria a little less stringent,” compared with criteria in the DSM-IV, Dr. Coccaro said. “That’s because it turns out that it doesn’t really matter much of the time what the comorbidity is. If you have this aggressiveness in the absence of those other conditions, it’s IED.”

According to a reanalysis of the National Comorbidity Survey, 11.7% of adolescents displayed aggressiveness within the last year and 17.3% over a lifetime, compared with 5.1% of adults within the last year and 8.0% within a lifetime. Under DSM-5 criteria, 6.4% of adolescents within the last year and 8.9% over a lifetime currently have IED, compared with 2.6% of adults within the last year and 4.0% over a lifetime, but “could go as high” as the percentage of individuals diagnosed with aggressiveness, Dr. Coccaro noted.

“People who are not called IED many times are not called IED because we didn’t have all the information we needed to actually make the diagnosis,” he said.

Individuals with DSM-5 IED can have as many as 30 episodes in 1 year, compared with those who are nonaggressive and are also more likely to damage property. “These are the big episodes, not simply the episodes where people are getting irritable and snapping at people. These are the big ones, where they’re really destroying objects and pushing or hitting people,” Dr. Coccaro said. About one-fourth of individuals with IED hurt victims badly enough that they require medical attention, one-fifth exhibit aggression toward a partner, and one-fourth receive aggression from their own partner.

In terms of comorbidity with other psychiatric disorders, “IEDs don’t have more comorbidity in general than other disorders,” Dr. Coccaro noted. Personality disorders such as paranoid, antisocial, borderline narcissistic, and obsessive-compulsive disorders are more common in individuals with IED. Aggression in these people present differently depending on the personality disorder. “Someone who’s paranoid might blow up at you if you get in their face. For an antisocial, they’ll blow up at you if you’re preventing them from doing what they want to do. Borderlines, you reject them or you abandon them, they’re going to blow up. Narcissists will blow up when you reject. OCD will also blow up when you mess around with their sense of order,” Dr. Coccaro said.

Genetics also play a role in whether a person may have IED. There is a “clear signal” in families, with about one-fourth of individuals with IED having a relative with IED, compared with 8% of nonaggressive individuals. These percentages were consistent, regardless of whether the individual had a comorbid condition, history of alcohol or drug use, or history of suicide, he said. Other factors that influence likelihood of IED are environment, behaviors such as smoking, and conditions such as traumatic brain injury. Experiencing aggression as a child is another factor.

“IED is the categorical expression of impulsive aggression, and it’s far more common than once thought,” Dr. Coccaro said. “And IED is totally unrecognized in its role in societal violence.”
 

Treatment can suppress, but not cure aggression

Medications used to treat aggression and impulsive aggression include lithium, SSRIs, mood stabilizers, neuroleptics, and beta-blockers. However, the treatments are not a “magic bullet,” Dr. Coccaro noted. “The meds tend to suppress aggressiveness, but not cure it.”

Timing of treatment is also a factor for medication. In studies of patients taking lithium for aggression, for example, “when they gave the drug to people who liked being aggressive, they didn’t like being on these drugs because it made them feel unprotected. It just was at odds with who they thought they were,” Dr. Coccaro said. “The people who took the drug and did well and really liked being on the drug with people who didn’t like that they were aggressive.”

Neurorehabilitation and cognitive-behavioral therapy specific to aggression, called cognitive relaxation and coping skills therapy, are nonpsychotropic approaches to treating aggression. “These therapeutic approaches are working not only to reduce progression, but also to reduce the social information processing problems that aggressive individuals have,” Dr. Coccaro said.

Another approach, known as interpretation bias training, teaches individuals with aggression to judge slightly angry-looking photos of people as not being angry. After 7-14 days of training, aggressive behavior in adolescents has been shown to be reduced. The changes were also visible on functional MRI.

“What they found was that when you treated them, the change in the amygdala went down when you looked at the angry faces and in the left lateral, post training, they became happier,” Dr. Coccaro said.

Global Academy and this news organization are owned by the same parent company. Dr. Coccaro reported serving as a consultant for Avanir, Azevan, and Bracket. He also reported receiving research grants from the National Institute of Mental Health, the National Institute on Alcohol Abuse and Alcoholism, and the Pritzker Pucker Family Foundation.

Aggression in individuals is influenced by genetic and environmental factors, but can be reduced with treatment, according to Emil F. Coccaro, MD.

“It actually is a complex triad of emotion, cognition, and behavior. The emotion is anger, the cognition is hostility, and the behavior is aggression. And they sort of go in that order,” Dr. Coccaro said at Focus on Neuropsychiatry presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.

Although aggression can be thought of in a numerous ways, premeditated and impulsive aggression are most relevant to behavioral studies in psychiatry, Dr. Coccaro explained. Premeditated aggression is goal oriented, while impulsive aggression comes from frustration or a response to a threat. Impulsive aggression is “typically social or frustrative in nature, and studies that we’ve done that show that individuals move toward a threat while nonaggressives move away it,” he said. Both types of aggression can be seen in the same individuals at different times.

Aggression also can be considered using a threshold model. Calm individuals, for example, might have a low baseline of aggression and a high threshold before they act out. An aggressive person, on the other hand, has a lower threshold and a higher baseline level. “Their delta to get to the point where they’re going to explode is much shorter, much lower than it is in someone who is healthy,” Dr. Coccaro said.

“What we think is that the threshold to explode is probably regulated by various neurobiological features. The baseline state of aggression also may be related to baseline neurobiological features, but also what’s going on in the environment, because the neurobiological features that send someone to exploding aggression are there all the time,” he explained.

Individuals with secondary aggression are likely to have an underlying condition, such as a primary disease of the brain, systemic or metabolic disorder, or a psychiatric disorder such as schizophrenia. “If someone’s schizophrenic and they’ve got voices telling them to hurt somebody, or delusions that someone’s going to hurt them, that’s not primary aggression, that’s secondary to the psychosis,” Dr. Coccaro noted.

An individual with primary aggression is likely to have intermittent explosive disorder (IED). IED is not a new diagnosis and has been listed in the DSM since the DSM-I as “passive-aggressive personality.” It was relisted in the DSM-II as “explosive personality,” then changed to IED in the DSM-3 as a diagnosis of exclusion that was poorly operationalized, according to Dr. Coccaro. The criteria for IED under the DSM-III did not define the number of recurrent outbursts needed, what they looked like, the time frame, and excluded people who were generally impulsive.

“That’s not really what these people look like and it’s not what impulsive aggression looks like,” he said. Although the DSM-IV removed the exclusion criteria for general impulsivity and aggression, “it was still purely operational.”

The DSM-5 criteria define IED as “verbal and physical aggression without destruction or assault, twice equally on average for 3 months, or three or more episodes of physical destruction/assault over a 1-year period. These individuals have outbursts “grossly out of proportion to provocation,” the aggression is generally impulsive, and it causes stress and impairment with an age of onset at older than 6 years.

“It’s not better accounted for a whole variety of things, but we actually made some of those exclusion criteria a little less stringent,” compared with criteria in the DSM-IV, Dr. Coccaro said. “That’s because it turns out that it doesn’t really matter much of the time what the comorbidity is. If you have this aggressiveness in the absence of those other conditions, it’s IED.”

According to a reanalysis of the National Comorbidity Survey, 11.7% of adolescents displayed aggressiveness within the last year and 17.3% over a lifetime, compared with 5.1% of adults within the last year and 8.0% within a lifetime. Under DSM-5 criteria, 6.4% of adolescents within the last year and 8.9% over a lifetime currently have IED, compared with 2.6% of adults within the last year and 4.0% over a lifetime, but “could go as high” as the percentage of individuals diagnosed with aggressiveness, Dr. Coccaro noted.

“People who are not called IED many times are not called IED because we didn’t have all the information we needed to actually make the diagnosis,” he said.

Individuals with DSM-5 IED can have as many as 30 episodes in 1 year, compared with those who are nonaggressive and are also more likely to damage property. “These are the big episodes, not simply the episodes where people are getting irritable and snapping at people. These are the big ones, where they’re really destroying objects and pushing or hitting people,” Dr. Coccaro said. About one-fourth of individuals with IED hurt victims badly enough that they require medical attention, one-fifth exhibit aggression toward a partner, and one-fourth receive aggression from their own partner.

In terms of comorbidity with other psychiatric disorders, “IEDs don’t have more comorbidity in general than other disorders,” Dr. Coccaro noted. Personality disorders such as paranoid, antisocial, borderline narcissistic, and obsessive-compulsive disorders are more common in individuals with IED. Aggression in these people present differently depending on the personality disorder. “Someone who’s paranoid might blow up at you if you get in their face. For an antisocial, they’ll blow up at you if you’re preventing them from doing what they want to do. Borderlines, you reject them or you abandon them, they’re going to blow up. Narcissists will blow up when you reject. OCD will also blow up when you mess around with their sense of order,” Dr. Coccaro said.

Genetics also play a role in whether a person may have IED. There is a “clear signal” in families, with about one-fourth of individuals with IED having a relative with IED, compared with 8% of nonaggressive individuals. These percentages were consistent, regardless of whether the individual had a comorbid condition, history of alcohol or drug use, or history of suicide, he said. Other factors that influence likelihood of IED are environment, behaviors such as smoking, and conditions such as traumatic brain injury. Experiencing aggression as a child is another factor.

“IED is the categorical expression of impulsive aggression, and it’s far more common than once thought,” Dr. Coccaro said. “And IED is totally unrecognized in its role in societal violence.”
 

Treatment can suppress, but not cure aggression

Medications used to treat aggression and impulsive aggression include lithium, SSRIs, mood stabilizers, neuroleptics, and beta-blockers. However, the treatments are not a “magic bullet,” Dr. Coccaro noted. “The meds tend to suppress aggressiveness, but not cure it.”

Timing of treatment is also a factor for medication. In studies of patients taking lithium for aggression, for example, “when they gave the drug to people who liked being aggressive, they didn’t like being on these drugs because it made them feel unprotected. It just was at odds with who they thought they were,” Dr. Coccaro said. “The people who took the drug and did well and really liked being on the drug with people who didn’t like that they were aggressive.”

Neurorehabilitation and cognitive-behavioral therapy specific to aggression, called cognitive relaxation and coping skills therapy, are nonpsychotropic approaches to treating aggression. “These therapeutic approaches are working not only to reduce progression, but also to reduce the social information processing problems that aggressive individuals have,” Dr. Coccaro said.

Another approach, known as interpretation bias training, teaches individuals with aggression to judge slightly angry-looking photos of people as not being angry. After 7-14 days of training, aggressive behavior in adolescents has been shown to be reduced. The changes were also visible on functional MRI.

“What they found was that when you treated them, the change in the amygdala went down when you looked at the angry faces and in the left lateral, post training, they became happier,” Dr. Coccaro said.

Global Academy and this news organization are owned by the same parent company. Dr. Coccaro reported serving as a consultant for Avanir, Azevan, and Bracket. He also reported receiving research grants from the National Institute of Mental Health, the National Institute on Alcohol Abuse and Alcoholism, and the Pritzker Pucker Family Foundation.

Aggression in individuals is influenced by genetic and environmental factors, but can be reduced with treatment, according to Emil F. Coccaro, MD.

“It actually is a complex triad of emotion, cognition, and behavior. The emotion is anger, the cognition is hostility, and the behavior is aggression. And they sort of go in that order,” Dr. Coccaro said at Focus on Neuropsychiatry presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.

Although aggression can be thought of in a numerous ways, premeditated and impulsive aggression are most relevant to behavioral studies in psychiatry, Dr. Coccaro explained. Premeditated aggression is goal oriented, while impulsive aggression comes from frustration or a response to a threat. Impulsive aggression is “typically social or frustrative in nature, and studies that we’ve done that show that individuals move toward a threat while nonaggressives move away it,” he said. Both types of aggression can be seen in the same individuals at different times.

Aggression also can be considered using a threshold model. Calm individuals, for example, might have a low baseline of aggression and a high threshold before they act out. An aggressive person, on the other hand, has a lower threshold and a higher baseline level. “Their delta to get to the point where they’re going to explode is much shorter, much lower than it is in someone who is healthy,” Dr. Coccaro said.

“What we think is that the threshold to explode is probably regulated by various neurobiological features. The baseline state of aggression also may be related to baseline neurobiological features, but also what’s going on in the environment, because the neurobiological features that send someone to exploding aggression are there all the time,” he explained.

Individuals with secondary aggression are likely to have an underlying condition, such as a primary disease of the brain, systemic or metabolic disorder, or a psychiatric disorder such as schizophrenia. “If someone’s schizophrenic and they’ve got voices telling them to hurt somebody, or delusions that someone’s going to hurt them, that’s not primary aggression, that’s secondary to the psychosis,” Dr. Coccaro noted.

An individual with primary aggression is likely to have intermittent explosive disorder (IED). IED is not a new diagnosis and has been listed in the DSM since the DSM-I as “passive-aggressive personality.” It was relisted in the DSM-II as “explosive personality,” then changed to IED in the DSM-3 as a diagnosis of exclusion that was poorly operationalized, according to Dr. Coccaro. The criteria for IED under the DSM-III did not define the number of recurrent outbursts needed, what they looked like, the time frame, and excluded people who were generally impulsive.

“That’s not really what these people look like and it’s not what impulsive aggression looks like,” he said. Although the DSM-IV removed the exclusion criteria for general impulsivity and aggression, “it was still purely operational.”

The DSM-5 criteria define IED as “verbal and physical aggression without destruction or assault, twice equally on average for 3 months, or three or more episodes of physical destruction/assault over a 1-year period. These individuals have outbursts “grossly out of proportion to provocation,” the aggression is generally impulsive, and it causes stress and impairment with an age of onset at older than 6 years.

“It’s not better accounted for a whole variety of things, but we actually made some of those exclusion criteria a little less stringent,” compared with criteria in the DSM-IV, Dr. Coccaro said. “That’s because it turns out that it doesn’t really matter much of the time what the comorbidity is. If you have this aggressiveness in the absence of those other conditions, it’s IED.”

According to a reanalysis of the National Comorbidity Survey, 11.7% of adolescents displayed aggressiveness within the last year and 17.3% over a lifetime, compared with 5.1% of adults within the last year and 8.0% within a lifetime. Under DSM-5 criteria, 6.4% of adolescents within the last year and 8.9% over a lifetime currently have IED, compared with 2.6% of adults within the last year and 4.0% over a lifetime, but “could go as high” as the percentage of individuals diagnosed with aggressiveness, Dr. Coccaro noted.

“People who are not called IED many times are not called IED because we didn’t have all the information we needed to actually make the diagnosis,” he said.

Individuals with DSM-5 IED can have as many as 30 episodes in 1 year, compared with those who are nonaggressive and are also more likely to damage property. “These are the big episodes, not simply the episodes where people are getting irritable and snapping at people. These are the big ones, where they’re really destroying objects and pushing or hitting people,” Dr. Coccaro said. About one-fourth of individuals with IED hurt victims badly enough that they require medical attention, one-fifth exhibit aggression toward a partner, and one-fourth receive aggression from their own partner.

In terms of comorbidity with other psychiatric disorders, “IEDs don’t have more comorbidity in general than other disorders,” Dr. Coccaro noted. Personality disorders such as paranoid, antisocial, borderline narcissistic, and obsessive-compulsive disorders are more common in individuals with IED. Aggression in these people present differently depending on the personality disorder. “Someone who’s paranoid might blow up at you if you get in their face. For an antisocial, they’ll blow up at you if you’re preventing them from doing what they want to do. Borderlines, you reject them or you abandon them, they’re going to blow up. Narcissists will blow up when you reject. OCD will also blow up when you mess around with their sense of order,” Dr. Coccaro said.

Genetics also play a role in whether a person may have IED. There is a “clear signal” in families, with about one-fourth of individuals with IED having a relative with IED, compared with 8% of nonaggressive individuals. These percentages were consistent, regardless of whether the individual had a comorbid condition, history of alcohol or drug use, or history of suicide, he said. Other factors that influence likelihood of IED are environment, behaviors such as smoking, and conditions such as traumatic brain injury. Experiencing aggression as a child is another factor.

“IED is the categorical expression of impulsive aggression, and it’s far more common than once thought,” Dr. Coccaro said. “And IED is totally unrecognized in its role in societal violence.”
 

Treatment can suppress, but not cure aggression

Medications used to treat aggression and impulsive aggression include lithium, SSRIs, mood stabilizers, neuroleptics, and beta-blockers. However, the treatments are not a “magic bullet,” Dr. Coccaro noted. “The meds tend to suppress aggressiveness, but not cure it.”

Timing of treatment is also a factor for medication. In studies of patients taking lithium for aggression, for example, “when they gave the drug to people who liked being aggressive, they didn’t like being on these drugs because it made them feel unprotected. It just was at odds with who they thought they were,” Dr. Coccaro said. “The people who took the drug and did well and really liked being on the drug with people who didn’t like that they were aggressive.”

Neurorehabilitation and cognitive-behavioral therapy specific to aggression, called cognitive relaxation and coping skills therapy, are nonpsychotropic approaches to treating aggression. “These therapeutic approaches are working not only to reduce progression, but also to reduce the social information processing problems that aggressive individuals have,” Dr. Coccaro said.

Another approach, known as interpretation bias training, teaches individuals with aggression to judge slightly angry-looking photos of people as not being angry. After 7-14 days of training, aggressive behavior in adolescents has been shown to be reduced. The changes were also visible on functional MRI.

“What they found was that when you treated them, the change in the amygdala went down when you looked at the angry faces and in the left lateral, post training, they became happier,” Dr. Coccaro said.

Global Academy and this news organization are owned by the same parent company. Dr. Coccaro reported serving as a consultant for Avanir, Azevan, and Bracket. He also reported receiving research grants from the National Institute of Mental Health, the National Institute on Alcohol Abuse and Alcoholism, and the Pritzker Pucker Family Foundation.

Chloroquine may be associated with serious psychiatric side effects, even in patients with no family or personal history of psychiatric disorders, a new review suggests.

In a letter to the editor published online July 28 in The Journal of Clinical Psychiatry, the authors summarize data from several studies published as far back as 1993 and as recently as May 2020.

“In addition to previously reported side effects, chloroquine could also induce psychiatric side effects which are polymorphic and can persist even after stopping the drug,” lead author Florence Gressier, MD, PhD, CESP, Inserm, department of psychiatry, Le Kremlin Bicêtre, France, said in an interview.

“In COVID-19 patients who may still be [undergoing treatment] with chloroquine, close psychiatric assessment and monitoring should be performed,” she said.
 

Heated controversy

Chloroquine and hydroxychloroquine have been at the center of heated controversy for their potential role in preventing or treating COVID-19.

Following findings of a small French study that suggested efficacy in lowering the viral load in patients with COVID-19, President Donald Trump expressed optimism regarding the role of hydroxychloroquine in treating COVID-19, calling it a “game changer”.

Other studies, however, have called into question both the efficacy and the safety of hydroxychloroquine in treating COVID-19. On June 15, the Food and Drug Administration revoked the emergency use authorization it had given in March to chloroquine and hydroxychloroquine for the treatment of COVID-19.

Nevertheless, hydroxychloroquine continues to be prescribed for COVID-19. For example, an article that appeared in Click2Houston on June 15 quoted the chief medical officer of Houston’s United Memorial Center as saying he plans to continue prescribing hydroxychloroquine for patients with COVID-19 until he finds a better alternative.

As discussed in a Medscape expert commentary, a group of physicians who held a “white coat summit” in front of the U.S. Supreme Court building promoted the use of hydroxychloroquine for the treatment of COVID-19. The video of their summit was retweeted by President Trump and garnered millions of views before it was taken down by Twitter, Facebook, and YouTube.
 

Sudden onset

For the new review, “we wanted to alert the public and practitioners on the potentially psychiatric risks induced by chloroquine, as it could be taken as self-medication or potentially still prescribed,” Dr. Gressier said.

“We think the format of the letter to the editor allows information to be provided in a concise and clear manner,” she added.

According to the FDA’s Adverse Event Reporting System database, 12% of reported adverse events (520 of 4,336) following the use of chloroquine that occurred between the fourth quarter of 2012 and the fourth quarter of 2019 were neuropsychiatric. These events included amnesia, delirium, hallucinations, depression, and loss of consciousness, the authors write.

The researchers acknowledged that the incidence of psychiatric adverse effects associated with the use of chloroquine is “unclear in the absence of high-quality, randomized placebo-controlled trials of its safety.” Nevertheless, they pointed out that there have been reports of insomnia and depression when the drug was used as prophylaxis against malaria .

Moreover, some case series or case reports describe symptoms such as depression, anxiety, agitation, violent outburst, suicidal ideation, and psychosis in patients who have been treated with chloroquine for malaria, lupus erythematosus, and rheumatoid arthritis .

“In contrast to many other psychoses, chloroquine psychosis may be more affective and include prominent visual hallucinations, symptoms of derealization, and disorders of thought, with preserved insight,” the authors wrote.

They noted that the frequency of symptoms does not appear to be connected to the cumulative dose or the duration of treatment, and the onset of psychosis or other adverse effects is usually “sudden.”

In addition, they warn that the drug’s psychiatric effects may go unnoticed, especially because COVID-19 itself has been associated with neuropsychiatric symptoms, making it hard to distinguish between symptoms caused by the illness and those caused by the drug.

Although the psychiatric symptoms typically occur early after treatment initiation, some “subtle” symptoms might persist after stopping the drug, possibly owing to its “extremely long” half-life, the authors stated.

Dr. Gressier noted that practicing clinicians should look up reports about self-medication with chloroquine “and warn their patients about the risk induced by chloroquine.”
 

Safe but ‘not benign’

Nilanjana Bose, MD, MBA, a rheumatologist at the Rheumatology Center of Houston, said she uses hydroxychloroquine “all the time” in clinical practice to treat patients with rheumatic conditions.

“I cannot comment on whether it [hydroxychloroquine or chloroquine] is a potential prophylactic or treatment for COVID-19, but I can say that, from a safety point of view, as a rheumatologist who uses hydroxychloroquine at a dose of 400 mg/day, I do not think we need to worry about serious [psychiatric] side effects,” Dr. Bose said in an interview.

Because clinicians are trying all types of possible treatments for COVID-19, “if this medication has possible efficacy, it is a great medicine from a rheumatologic perspective and is safe,” she added.

Nevertheless, the drug is “not benign, and regular side effects will be there, and of course, higher doses will cause more side effects,” said Dr. Bose, who was not involved in authoring the letter.

She counsels patients about potential psychiatric side effects of hydroxychloroquine because some of her patients have complained about irritability, worsening anxiety and depression, and difficulty sleeping.
 

Be wary

James “Jimmy” Potash, MD, MPH, Henry Phipps Professor of Psychiatry and Behavioral Sciences, Johns Hopkins Medicine, Baltimore, said in an interview that the “take-home message of this letter is that serious psychiatric effects, psychotic illness in particular,” can occur in individuals who take chloroquine and hydroxychloroquine.

In addition, “these are potentially very concerning side effects that psychiatrists should be aware of,” noted Dr. Potash, department director and psychiatrist-in-chief at Johns Hopkins.

He said that one of his patients who had been “completely psychiatrically healthy” took chloroquine prophylactically prior to traveling overseas. After she began taking the drug, she had an episode of mania that resolved once she discontinued the medication and received treatment for the mania.

“If you add potential psychiatric side effects to the other side effects that can result from these medications, that adds up to a pretty important reason to be wary of taking them, particularly for the indication of COVID-19, where the level of evidence that it helps in any way is still quite weak,” Dr. Potash said.

In an interview, Remington Nevin, MD, MPH, DrPH, executive director at the Quinism Foundation, White River Junction, Vt., a nonprofit organization that supports and promotes education and research on disorders caused by poisoning by quinoline drugs; and faculty associate in the department of mental health at Johns Hopkins Bloomberg School of Public Health, said that the authors of the letter “are to be commended for their efforts in raising awareness of the potentially lasting and disabling psychiatric effects of chloroquine and hydroxychloroquine, which, as with similar effects from other synthetic quinoline antimalarials, have occasionally been overlooked or misattributed to other conditions.”

He added: “I have proposed that the chronic neuropsychiatric effects of this class of drug are best considered not as side effects but as signs and symptoms of a disorder known as chronic quinoline encephalopathy caused by poisoning of the central nervous system.”

Dr. Gressier and the other letter authors, Dr. Bose, and Dr. Potash have reported no relevant financial relationships. Dr. Nevin has been retained as a consultant and expert witness in legal cases involving claims of adverse effects from quinoline antimalarial drugs.

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

Chloroquine may be associated with serious psychiatric side effects, even in patients with no family or personal history of psychiatric disorders, a new review suggests.

In a letter to the editor published online July 28 in The Journal of Clinical Psychiatry, the authors summarize data from several studies published as far back as 1993 and as recently as May 2020.

“In addition to previously reported side effects, chloroquine could also induce psychiatric side effects which are polymorphic and can persist even after stopping the drug,” lead author Florence Gressier, MD, PhD, CESP, Inserm, department of psychiatry, Le Kremlin Bicêtre, France, said in an interview.

“In COVID-19 patients who may still be [undergoing treatment] with chloroquine, close psychiatric assessment and monitoring should be performed,” she said.
 

Heated controversy

Chloroquine and hydroxychloroquine have been at the center of heated controversy for their potential role in preventing or treating COVID-19.

Following findings of a small French study that suggested efficacy in lowering the viral load in patients with COVID-19, President Donald Trump expressed optimism regarding the role of hydroxychloroquine in treating COVID-19, calling it a “game changer”.

Other studies, however, have called into question both the efficacy and the safety of hydroxychloroquine in treating COVID-19. On June 15, the Food and Drug Administration revoked the emergency use authorization it had given in March to chloroquine and hydroxychloroquine for the treatment of COVID-19.

Nevertheless, hydroxychloroquine continues to be prescribed for COVID-19. For example, an article that appeared in Click2Houston on June 15 quoted the chief medical officer of Houston’s United Memorial Center as saying he plans to continue prescribing hydroxychloroquine for patients with COVID-19 until he finds a better alternative.

As discussed in a Medscape expert commentary, a group of physicians who held a “white coat summit” in front of the U.S. Supreme Court building promoted the use of hydroxychloroquine for the treatment of COVID-19. The video of their summit was retweeted by President Trump and garnered millions of views before it was taken down by Twitter, Facebook, and YouTube.
 

Sudden onset

For the new review, “we wanted to alert the public and practitioners on the potentially psychiatric risks induced by chloroquine, as it could be taken as self-medication or potentially still prescribed,” Dr. Gressier said.

“We think the format of the letter to the editor allows information to be provided in a concise and clear manner,” she added.

According to the FDA’s Adverse Event Reporting System database, 12% of reported adverse events (520 of 4,336) following the use of chloroquine that occurred between the fourth quarter of 2012 and the fourth quarter of 2019 were neuropsychiatric. These events included amnesia, delirium, hallucinations, depression, and loss of consciousness, the authors write.

The researchers acknowledged that the incidence of psychiatric adverse effects associated with the use of chloroquine is “unclear in the absence of high-quality, randomized placebo-controlled trials of its safety.” Nevertheless, they pointed out that there have been reports of insomnia and depression when the drug was used as prophylaxis against malaria .

Moreover, some case series or case reports describe symptoms such as depression, anxiety, agitation, violent outburst, suicidal ideation, and psychosis in patients who have been treated with chloroquine for malaria, lupus erythematosus, and rheumatoid arthritis .

“In contrast to many other psychoses, chloroquine psychosis may be more affective and include prominent visual hallucinations, symptoms of derealization, and disorders of thought, with preserved insight,” the authors wrote.

They noted that the frequency of symptoms does not appear to be connected to the cumulative dose or the duration of treatment, and the onset of psychosis or other adverse effects is usually “sudden.”

In addition, they warn that the drug’s psychiatric effects may go unnoticed, especially because COVID-19 itself has been associated with neuropsychiatric symptoms, making it hard to distinguish between symptoms caused by the illness and those caused by the drug.

Although the psychiatric symptoms typically occur early after treatment initiation, some “subtle” symptoms might persist after stopping the drug, possibly owing to its “extremely long” half-life, the authors stated.

Dr. Gressier noted that practicing clinicians should look up reports about self-medication with chloroquine “and warn their patients about the risk induced by chloroquine.”
 

Safe but ‘not benign’

Nilanjana Bose, MD, MBA, a rheumatologist at the Rheumatology Center of Houston, said she uses hydroxychloroquine “all the time” in clinical practice to treat patients with rheumatic conditions.

“I cannot comment on whether it [hydroxychloroquine or chloroquine] is a potential prophylactic or treatment for COVID-19, but I can say that, from a safety point of view, as a rheumatologist who uses hydroxychloroquine at a dose of 400 mg/day, I do not think we need to worry about serious [psychiatric] side effects,” Dr. Bose said in an interview.

Because clinicians are trying all types of possible treatments for COVID-19, “if this medication has possible efficacy, it is a great medicine from a rheumatologic perspective and is safe,” she added.

Nevertheless, the drug is “not benign, and regular side effects will be there, and of course, higher doses will cause more side effects,” said Dr. Bose, who was not involved in authoring the letter.

She counsels patients about potential psychiatric side effects of hydroxychloroquine because some of her patients have complained about irritability, worsening anxiety and depression, and difficulty sleeping.
 

Be wary

James “Jimmy” Potash, MD, MPH, Henry Phipps Professor of Psychiatry and Behavioral Sciences, Johns Hopkins Medicine, Baltimore, said in an interview that the “take-home message of this letter is that serious psychiatric effects, psychotic illness in particular,” can occur in individuals who take chloroquine and hydroxychloroquine.

In addition, “these are potentially very concerning side effects that psychiatrists should be aware of,” noted Dr. Potash, department director and psychiatrist-in-chief at Johns Hopkins.

He said that one of his patients who had been “completely psychiatrically healthy” took chloroquine prophylactically prior to traveling overseas. After she began taking the drug, she had an episode of mania that resolved once she discontinued the medication and received treatment for the mania.

“If you add potential psychiatric side effects to the other side effects that can result from these medications, that adds up to a pretty important reason to be wary of taking them, particularly for the indication of COVID-19, where the level of evidence that it helps in any way is still quite weak,” Dr. Potash said.

In an interview, Remington Nevin, MD, MPH, DrPH, executive director at the Quinism Foundation, White River Junction, Vt., a nonprofit organization that supports and promotes education and research on disorders caused by poisoning by quinoline drugs; and faculty associate in the department of mental health at Johns Hopkins Bloomberg School of Public Health, said that the authors of the letter “are to be commended for their efforts in raising awareness of the potentially lasting and disabling psychiatric effects of chloroquine and hydroxychloroquine, which, as with similar effects from other synthetic quinoline antimalarials, have occasionally been overlooked or misattributed to other conditions.”

He added: “I have proposed that the chronic neuropsychiatric effects of this class of drug are best considered not as side effects but as signs and symptoms of a disorder known as chronic quinoline encephalopathy caused by poisoning of the central nervous system.”

Dr. Gressier and the other letter authors, Dr. Bose, and Dr. Potash have reported no relevant financial relationships. Dr. Nevin has been retained as a consultant and expert witness in legal cases involving claims of adverse effects from quinoline antimalarial drugs.

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

Chloroquine may be associated with serious psychiatric side effects, even in patients with no family or personal history of psychiatric disorders, a new review suggests.

In a letter to the editor published online July 28 in The Journal of Clinical Psychiatry, the authors summarize data from several studies published as far back as 1993 and as recently as May 2020.

“In addition to previously reported side effects, chloroquine could also induce psychiatric side effects which are polymorphic and can persist even after stopping the drug,” lead author Florence Gressier, MD, PhD, CESP, Inserm, department of psychiatry, Le Kremlin Bicêtre, France, said in an interview.

“In COVID-19 patients who may still be [undergoing treatment] with chloroquine, close psychiatric assessment and monitoring should be performed,” she said.
 

Heated controversy

Chloroquine and hydroxychloroquine have been at the center of heated controversy for their potential role in preventing or treating COVID-19.

Following findings of a small French study that suggested efficacy in lowering the viral load in patients with COVID-19, President Donald Trump expressed optimism regarding the role of hydroxychloroquine in treating COVID-19, calling it a “game changer”.

Other studies, however, have called into question both the efficacy and the safety of hydroxychloroquine in treating COVID-19. On June 15, the Food and Drug Administration revoked the emergency use authorization it had given in March to chloroquine and hydroxychloroquine for the treatment of COVID-19.

Nevertheless, hydroxychloroquine continues to be prescribed for COVID-19. For example, an article that appeared in Click2Houston on June 15 quoted the chief medical officer of Houston’s United Memorial Center as saying he plans to continue prescribing hydroxychloroquine for patients with COVID-19 until he finds a better alternative.

As discussed in a Medscape expert commentary, a group of physicians who held a “white coat summit” in front of the U.S. Supreme Court building promoted the use of hydroxychloroquine for the treatment of COVID-19. The video of their summit was retweeted by President Trump and garnered millions of views before it was taken down by Twitter, Facebook, and YouTube.
 

Sudden onset

For the new review, “we wanted to alert the public and practitioners on the potentially psychiatric risks induced by chloroquine, as it could be taken as self-medication or potentially still prescribed,” Dr. Gressier said.

“We think the format of the letter to the editor allows information to be provided in a concise and clear manner,” she added.

According to the FDA’s Adverse Event Reporting System database, 12% of reported adverse events (520 of 4,336) following the use of chloroquine that occurred between the fourth quarter of 2012 and the fourth quarter of 2019 were neuropsychiatric. These events included amnesia, delirium, hallucinations, depression, and loss of consciousness, the authors write.

The researchers acknowledged that the incidence of psychiatric adverse effects associated with the use of chloroquine is “unclear in the absence of high-quality, randomized placebo-controlled trials of its safety.” Nevertheless, they pointed out that there have been reports of insomnia and depression when the drug was used as prophylaxis against malaria .

Moreover, some case series or case reports describe symptoms such as depression, anxiety, agitation, violent outburst, suicidal ideation, and psychosis in patients who have been treated with chloroquine for malaria, lupus erythematosus, and rheumatoid arthritis .

“In contrast to many other psychoses, chloroquine psychosis may be more affective and include prominent visual hallucinations, symptoms of derealization, and disorders of thought, with preserved insight,” the authors wrote.

They noted that the frequency of symptoms does not appear to be connected to the cumulative dose or the duration of treatment, and the onset of psychosis or other adverse effects is usually “sudden.”

In addition, they warn that the drug’s psychiatric effects may go unnoticed, especially because COVID-19 itself has been associated with neuropsychiatric symptoms, making it hard to distinguish between symptoms caused by the illness and those caused by the drug.

Although the psychiatric symptoms typically occur early after treatment initiation, some “subtle” symptoms might persist after stopping the drug, possibly owing to its “extremely long” half-life, the authors stated.

Dr. Gressier noted that practicing clinicians should look up reports about self-medication with chloroquine “and warn their patients about the risk induced by chloroquine.”
 

Safe but ‘not benign’

Nilanjana Bose, MD, MBA, a rheumatologist at the Rheumatology Center of Houston, said she uses hydroxychloroquine “all the time” in clinical practice to treat patients with rheumatic conditions.

“I cannot comment on whether it [hydroxychloroquine or chloroquine] is a potential prophylactic or treatment for COVID-19, but I can say that, from a safety point of view, as a rheumatologist who uses hydroxychloroquine at a dose of 400 mg/day, I do not think we need to worry about serious [psychiatric] side effects,” Dr. Bose said in an interview.

Because clinicians are trying all types of possible treatments for COVID-19, “if this medication has possible efficacy, it is a great medicine from a rheumatologic perspective and is safe,” she added.

Nevertheless, the drug is “not benign, and regular side effects will be there, and of course, higher doses will cause more side effects,” said Dr. Bose, who was not involved in authoring the letter.

She counsels patients about potential psychiatric side effects of hydroxychloroquine because some of her patients have complained about irritability, worsening anxiety and depression, and difficulty sleeping.
 

Be wary

James “Jimmy” Potash, MD, MPH, Henry Phipps Professor of Psychiatry and Behavioral Sciences, Johns Hopkins Medicine, Baltimore, said in an interview that the “take-home message of this letter is that serious psychiatric effects, psychotic illness in particular,” can occur in individuals who take chloroquine and hydroxychloroquine.

In addition, “these are potentially very concerning side effects that psychiatrists should be aware of,” noted Dr. Potash, department director and psychiatrist-in-chief at Johns Hopkins.

He said that one of his patients who had been “completely psychiatrically healthy” took chloroquine prophylactically prior to traveling overseas. After she began taking the drug, she had an episode of mania that resolved once she discontinued the medication and received treatment for the mania.

“If you add potential psychiatric side effects to the other side effects that can result from these medications, that adds up to a pretty important reason to be wary of taking them, particularly for the indication of COVID-19, where the level of evidence that it helps in any way is still quite weak,” Dr. Potash said.

In an interview, Remington Nevin, MD, MPH, DrPH, executive director at the Quinism Foundation, White River Junction, Vt., a nonprofit organization that supports and promotes education and research on disorders caused by poisoning by quinoline drugs; and faculty associate in the department of mental health at Johns Hopkins Bloomberg School of Public Health, said that the authors of the letter “are to be commended for their efforts in raising awareness of the potentially lasting and disabling psychiatric effects of chloroquine and hydroxychloroquine, which, as with similar effects from other synthetic quinoline antimalarials, have occasionally been overlooked or misattributed to other conditions.”

He added: “I have proposed that the chronic neuropsychiatric effects of this class of drug are best considered not as side effects but as signs and symptoms of a disorder known as chronic quinoline encephalopathy caused by poisoning of the central nervous system.”

Dr. Gressier and the other letter authors, Dr. Bose, and Dr. Potash have reported no relevant financial relationships. Dr. Nevin has been retained as a consultant and expert witness in legal cases involving claims of adverse effects from quinoline antimalarial drugs.

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