Schizophrenia & Other Psychotic Disorders

Images generated by photographic computer software are the first to depict accurate images of facial distortions experienced by patients with prosopometamorphopsia (PMO), a rare visual disorder that is often mistaken for mental illness.

PMO is a rare, often misdiagnosed, visual disorder in which human faces appear distorted in shape, texture, position, or color. Most patients with PMO see these distorted facial features all the time, whether they are looking at a face in person, on a screen, or paper.

For this study, investigators worked with a single patient, a 58-year-old man with a 31-month history of seeing what he describes as “demonic”-looking human faces. Unlike most cases of PMO, the patient reported seeing the distortions only when encountering someone in person but not on a screen or on paper.

This allowed researchers to use editing software to create an image on a computer screen that matched the patient’s distorted view.

“This new information should help healthcare professionals grasp the intensity of facial distortions experienced by people with PMO,” study investigator Brad Duchaine, PhD, professor, Department of Psychological and Brain Sciences, Dartmouth College, Hanover, New Hampshire, told this news organization.

“A substantial number of people we have worked with have been misdiagnosed, often with schizophrenia or some sort of psychotic episode, and some have been put on antipsychotics despite the fact they’ve just had some little tweak in their visual system,” he added.

The report was published online on March 23 in The Lancet.
 

Prevalence Underestimated?

Although fewer than 100 cases of PMO have been reported in the literature, Dr. Duchaine said this is likely an underestimate. Based on a response to a website his team created to recruit affected patients, he said he believes “there are far more cases out there that we realize.”

PMO might be caused by a neurologic event that leads to a lesion in the right temporal lobe, near areas of facial processing, but in many cases, the cause is unclear.

PMO can occur in the context of head trauma, as well as cerebral infarction, epilepsy, migraine, and hallucinogen-persisting perception disorder, researchers noted. The condition can also manifest without detectable structural brain changes.

“We’re hearing from a lot of people through our website who haven’t had, or aren’t aware of having had, a neurologic event that coincided with the onset of face distortions,” Dr. Duchaine noted.

The patient in this study had a significant head injury at age 43 that led to hospitalization. He was exposed to high levels of carbon monoxide about 4 months before his symptoms began, but it’s not clear if the PMO and the incident are related.

He was not prescribed any medications and reported no history of illicit substance use.

The patient also had a history of bipolar affective disorder and posttraumatic stress disorder. His visions of distorted faces were not accompanied by delusional beliefs about the people he encountered, the investigators reported.

Neuropsychological tests were normal, and there were no deficits of visual acuity or color vision. Computer-based face perception tests indicated mild impairment in recognition of facial identity but normal recognition of facial expression.

The patient did not typically see distortions when looking at objects, such as a coffee mug or computer. However, said Dr. Duchaine, “if you get enough text together, the text will start to swirl for him.”
 

Eye-Opening Findings

The patient described the visual facial distortions as “severely stretched features, with deep grooves on the forehead, cheeks, and chin.” Even though these faces were distorted, he was able to recognize the people he saw.

Because the patient reported no distortion when viewing facial images on a screen, researchers asked him to compare what he saw when he looked at the face of a person in the room to a photograph of the same person on a computer screen.

The patient alternated between observing the in-person face, which he perceived as distorted, and the photo on the screen, which he perceived as normal.

Researchers used real-time feedback from the patient and photo-editing software to manipulate the photo on the screen until the photo and the patient’s visual perception of the person in the room matched.

“This is the first time we have actually been able to have a visualization where we are really confident that that’s what someone with PMO is experiencing,” said Dr. Duchaine. “If he were a typical PMO case, he would look at the face in real life and look at the face on the screen and the face on the screen would be distorting as well.”

The researchers discovered that the patient’s distortions are influenced by color; if he looks at faces through a red filter, the distortions are greatly intensified, but if he looks at them through a green filter, the distortions are greatly reduced. He now wears green-filtered glasses in certain situations.

Dr. Duchaine hopes this case will open the eyes of clinicians. “These sorts of visual distortions that your patient is telling you about are probably real, and they’re not a sign of broader mental illness; it’s a problem limited to the visual system,” he said.

The research was funded by the Hitchcock Foundation. The authors reported no relevant conflicts of interest.
 

A version of this article appeared on Medscape.com.

Images generated by photographic computer software are the first to depict accurate images of facial distortions experienced by patients with prosopometamorphopsia (PMO), a rare visual disorder that is often mistaken for mental illness.

PMO is a rare, often misdiagnosed, visual disorder in which human faces appear distorted in shape, texture, position, or color. Most patients with PMO see these distorted facial features all the time, whether they are looking at a face in person, on a screen, or paper.

For this study, investigators worked with a single patient, a 58-year-old man with a 31-month history of seeing what he describes as “demonic”-looking human faces. Unlike most cases of PMO, the patient reported seeing the distortions only when encountering someone in person but not on a screen or on paper.

This allowed researchers to use editing software to create an image on a computer screen that matched the patient’s distorted view.

“This new information should help healthcare professionals grasp the intensity of facial distortions experienced by people with PMO,” study investigator Brad Duchaine, PhD, professor, Department of Psychological and Brain Sciences, Dartmouth College, Hanover, New Hampshire, told this news organization.

“A substantial number of people we have worked with have been misdiagnosed, often with schizophrenia or some sort of psychotic episode, and some have been put on antipsychotics despite the fact they’ve just had some little tweak in their visual system,” he added.

The report was published online on March 23 in The Lancet.
 

Prevalence Underestimated?

Although fewer than 100 cases of PMO have been reported in the literature, Dr. Duchaine said this is likely an underestimate. Based on a response to a website his team created to recruit affected patients, he said he believes “there are far more cases out there that we realize.”

PMO might be caused by a neurologic event that leads to a lesion in the right temporal lobe, near areas of facial processing, but in many cases, the cause is unclear.

PMO can occur in the context of head trauma, as well as cerebral infarction, epilepsy, migraine, and hallucinogen-persisting perception disorder, researchers noted. The condition can also manifest without detectable structural brain changes.

“We’re hearing from a lot of people through our website who haven’t had, or aren’t aware of having had, a neurologic event that coincided with the onset of face distortions,” Dr. Duchaine noted.

The patient in this study had a significant head injury at age 43 that led to hospitalization. He was exposed to high levels of carbon monoxide about 4 months before his symptoms began, but it’s not clear if the PMO and the incident are related.

He was not prescribed any medications and reported no history of illicit substance use.

The patient also had a history of bipolar affective disorder and posttraumatic stress disorder. His visions of distorted faces were not accompanied by delusional beliefs about the people he encountered, the investigators reported.

Neuropsychological tests were normal, and there were no deficits of visual acuity or color vision. Computer-based face perception tests indicated mild impairment in recognition of facial identity but normal recognition of facial expression.

The patient did not typically see distortions when looking at objects, such as a coffee mug or computer. However, said Dr. Duchaine, “if you get enough text together, the text will start to swirl for him.”
 

Eye-Opening Findings

The patient described the visual facial distortions as “severely stretched features, with deep grooves on the forehead, cheeks, and chin.” Even though these faces were distorted, he was able to recognize the people he saw.

Because the patient reported no distortion when viewing facial images on a screen, researchers asked him to compare what he saw when he looked at the face of a person in the room to a photograph of the same person on a computer screen.

The patient alternated between observing the in-person face, which he perceived as distorted, and the photo on the screen, which he perceived as normal.

Researchers used real-time feedback from the patient and photo-editing software to manipulate the photo on the screen until the photo and the patient’s visual perception of the person in the room matched.

“This is the first time we have actually been able to have a visualization where we are really confident that that’s what someone with PMO is experiencing,” said Dr. Duchaine. “If he were a typical PMO case, he would look at the face in real life and look at the face on the screen and the face on the screen would be distorting as well.”

The researchers discovered that the patient’s distortions are influenced by color; if he looks at faces through a red filter, the distortions are greatly intensified, but if he looks at them through a green filter, the distortions are greatly reduced. He now wears green-filtered glasses in certain situations.

Dr. Duchaine hopes this case will open the eyes of clinicians. “These sorts of visual distortions that your patient is telling you about are probably real, and they’re not a sign of broader mental illness; it’s a problem limited to the visual system,” he said.

The research was funded by the Hitchcock Foundation. The authors reported no relevant conflicts of interest.
 

A version of this article appeared on Medscape.com.

Images generated by photographic computer software are the first to depict accurate images of facial distortions experienced by patients with prosopometamorphopsia (PMO), a rare visual disorder that is often mistaken for mental illness.

PMO is a rare, often misdiagnosed, visual disorder in which human faces appear distorted in shape, texture, position, or color. Most patients with PMO see these distorted facial features all the time, whether they are looking at a face in person, on a screen, or paper.

For this study, investigators worked with a single patient, a 58-year-old man with a 31-month history of seeing what he describes as “demonic”-looking human faces. Unlike most cases of PMO, the patient reported seeing the distortions only when encountering someone in person but not on a screen or on paper.

This allowed researchers to use editing software to create an image on a computer screen that matched the patient’s distorted view.

“This new information should help healthcare professionals grasp the intensity of facial distortions experienced by people with PMO,” study investigator Brad Duchaine, PhD, professor, Department of Psychological and Brain Sciences, Dartmouth College, Hanover, New Hampshire, told this news organization.

“A substantial number of people we have worked with have been misdiagnosed, often with schizophrenia or some sort of psychotic episode, and some have been put on antipsychotics despite the fact they’ve just had some little tweak in their visual system,” he added.

The report was published online on March 23 in The Lancet.
 

Prevalence Underestimated?

Although fewer than 100 cases of PMO have been reported in the literature, Dr. Duchaine said this is likely an underestimate. Based on a response to a website his team created to recruit affected patients, he said he believes “there are far more cases out there that we realize.”

PMO might be caused by a neurologic event that leads to a lesion in the right temporal lobe, near areas of facial processing, but in many cases, the cause is unclear.

PMO can occur in the context of head trauma, as well as cerebral infarction, epilepsy, migraine, and hallucinogen-persisting perception disorder, researchers noted. The condition can also manifest without detectable structural brain changes.

“We’re hearing from a lot of people through our website who haven’t had, or aren’t aware of having had, a neurologic event that coincided with the onset of face distortions,” Dr. Duchaine noted.

The patient in this study had a significant head injury at age 43 that led to hospitalization. He was exposed to high levels of carbon monoxide about 4 months before his symptoms began, but it’s not clear if the PMO and the incident are related.

He was not prescribed any medications and reported no history of illicit substance use.

The patient also had a history of bipolar affective disorder and posttraumatic stress disorder. His visions of distorted faces were not accompanied by delusional beliefs about the people he encountered, the investigators reported.

Neuropsychological tests were normal, and there were no deficits of visual acuity or color vision. Computer-based face perception tests indicated mild impairment in recognition of facial identity but normal recognition of facial expression.

The patient did not typically see distortions when looking at objects, such as a coffee mug or computer. However, said Dr. Duchaine, “if you get enough text together, the text will start to swirl for him.”
 

Eye-Opening Findings

The patient described the visual facial distortions as “severely stretched features, with deep grooves on the forehead, cheeks, and chin.” Even though these faces were distorted, he was able to recognize the people he saw.

Because the patient reported no distortion when viewing facial images on a screen, researchers asked him to compare what he saw when he looked at the face of a person in the room to a photograph of the same person on a computer screen.

The patient alternated between observing the in-person face, which he perceived as distorted, and the photo on the screen, which he perceived as normal.

Researchers used real-time feedback from the patient and photo-editing software to manipulate the photo on the screen until the photo and the patient’s visual perception of the person in the room matched.

“This is the first time we have actually been able to have a visualization where we are really confident that that’s what someone with PMO is experiencing,” said Dr. Duchaine. “If he were a typical PMO case, he would look at the face in real life and look at the face on the screen and the face on the screen would be distorting as well.”

The researchers discovered that the patient’s distortions are influenced by color; if he looks at faces through a red filter, the distortions are greatly intensified, but if he looks at them through a green filter, the distortions are greatly reduced. He now wears green-filtered glasses in certain situations.

Dr. Duchaine hopes this case will open the eyes of clinicians. “These sorts of visual distortions that your patient is telling you about are probably real, and they’re not a sign of broader mental illness; it’s a problem limited to the visual system,” he said.

The research was funded by the Hitchcock Foundation. The authors reported no relevant conflicts of interest.
 

A version of this article appeared on Medscape.com.

Patients receiving long-acting injectable (LAI) antipsychotics upon hospital discharge were 75% less likely to be readmitted 30 days later compared with those who received an oral antipsychotic, new research showed.

Investigators reported the findings support the use of LAI antipsychotics over oral medication following a hospital stay for schizophrenia or schizoaffective disorder.

“I suspect the lower readmission rate that has been observed with long-acting injections has more to do with people forgetting to take a pill each and every day than with any inherent superiority of the injectable medication,” lead author Daniel Greer, PharmD, BCPP, clinical assistant professor at Rutgers University Ernest Mario School of Pharmacy, Piscataway, New Jersey, said in a news release.

“Other studies on the use of antipsychotic medication have found that roughly three fourths of patients do not take oral medications exactly as directed, and it’s much easier to get a shot every few months than it is to take a pill every day, even though the shot requires a trip to the doctor,” Dr. Greer added.

The study was published online on January 17, 2024, in the Journal of Clinical Psychopharmacology.
 

Fewer Repeat Stays

Investigators compared 30-day readmission rates for all 343 patients with schizophrenia or schizoaffective disorder who were discharged from an inpatient psychiatric unit between August 2019 and June 2022.

A total of 240 patients (70%) were discharged on an oral antipsychotic, most commonly risperidone or olanzapine, and 103 (30%) were sent home on an LAI antipsychotic, most commonly aripiprazole lauroxil or haloperidol decanoate.

Within 30 days of discharge, 22 patients (6.4%) were readmitted for a schizophrenic or schizoaffective exacerbation — two in the LAI antipsychotic group and 20 in the oral antipsychotic group (1.9% vs 8.3%; P = .03).

The LAI antipsychotic group had a higher average daily chlorpromazine equivalent antipsychotic dose than the oral group (477.3 mg vs 278.6 mg; P < .001), which investigators said may indicate a difference in illness severity between the patient groups.

There was no significant between-group difference in the use of anticholinergic medications to treat extrapyramidal symptoms (22% in the LAI group and 31% in the oral group) despite the LAI group receiving greater doses.

That suggests “that both formulations may be equally as likely to cause these adverse effects,” the researchers noted.

Thirty-day readmission rates are important both medically and financially, investigators noted. In schizophrenia, access to medications and nonadherence are “significant problems.” LAI antipsychotic medications may alleviate some of these burdens but come with a high up-front cost.

“Medication access through pharmaceutical company free trial replacement programs may be an option for facilities with restricted formularies or limited medication funding to decrease 30-day readmissions,” investigators wrote.

“The cost of the injections is far lower than the cost of hospital treatments,” Dr. Greer added in the news release. “And each additional visit to the hospital increases the odds that there will be more visits in the future. Every time someone experiences psychosis, they lose gray matter, and they suffer damage that never heals. That’s why it’s so vital to minimize psychotic episodes.”

Chief limitations of the study included its single-center, retrospective chart review design and small sample size. Also, complete patient medication history was not obtained.

The study had no specific funding. The authors declared no relevant conflicts of interest.
 

A version of this article appeared on Medscape.com.

Patients receiving long-acting injectable (LAI) antipsychotics upon hospital discharge were 75% less likely to be readmitted 30 days later compared with those who received an oral antipsychotic, new research showed.

Investigators reported the findings support the use of LAI antipsychotics over oral medication following a hospital stay for schizophrenia or schizoaffective disorder.

“I suspect the lower readmission rate that has been observed with long-acting injections has more to do with people forgetting to take a pill each and every day than with any inherent superiority of the injectable medication,” lead author Daniel Greer, PharmD, BCPP, clinical assistant professor at Rutgers University Ernest Mario School of Pharmacy, Piscataway, New Jersey, said in a news release.

“Other studies on the use of antipsychotic medication have found that roughly three fourths of patients do not take oral medications exactly as directed, and it’s much easier to get a shot every few months than it is to take a pill every day, even though the shot requires a trip to the doctor,” Dr. Greer added.

The study was published online on January 17, 2024, in the Journal of Clinical Psychopharmacology.
 

Fewer Repeat Stays

Investigators compared 30-day readmission rates for all 343 patients with schizophrenia or schizoaffective disorder who were discharged from an inpatient psychiatric unit between August 2019 and June 2022.

A total of 240 patients (70%) were discharged on an oral antipsychotic, most commonly risperidone or olanzapine, and 103 (30%) were sent home on an LAI antipsychotic, most commonly aripiprazole lauroxil or haloperidol decanoate.

Within 30 days of discharge, 22 patients (6.4%) were readmitted for a schizophrenic or schizoaffective exacerbation — two in the LAI antipsychotic group and 20 in the oral antipsychotic group (1.9% vs 8.3%; P = .03).

The LAI antipsychotic group had a higher average daily chlorpromazine equivalent antipsychotic dose than the oral group (477.3 mg vs 278.6 mg; P < .001), which investigators said may indicate a difference in illness severity between the patient groups.

There was no significant between-group difference in the use of anticholinergic medications to treat extrapyramidal symptoms (22% in the LAI group and 31% in the oral group) despite the LAI group receiving greater doses.

That suggests “that both formulations may be equally as likely to cause these adverse effects,” the researchers noted.

Thirty-day readmission rates are important both medically and financially, investigators noted. In schizophrenia, access to medications and nonadherence are “significant problems.” LAI antipsychotic medications may alleviate some of these burdens but come with a high up-front cost.

“Medication access through pharmaceutical company free trial replacement programs may be an option for facilities with restricted formularies or limited medication funding to decrease 30-day readmissions,” investigators wrote.

“The cost of the injections is far lower than the cost of hospital treatments,” Dr. Greer added in the news release. “And each additional visit to the hospital increases the odds that there will be more visits in the future. Every time someone experiences psychosis, they lose gray matter, and they suffer damage that never heals. That’s why it’s so vital to minimize psychotic episodes.”

Chief limitations of the study included its single-center, retrospective chart review design and small sample size. Also, complete patient medication history was not obtained.

The study had no specific funding. The authors declared no relevant conflicts of interest.
 

A version of this article appeared on Medscape.com.

Patients receiving long-acting injectable (LAI) antipsychotics upon hospital discharge were 75% less likely to be readmitted 30 days later compared with those who received an oral antipsychotic, new research showed.

Investigators reported the findings support the use of LAI antipsychotics over oral medication following a hospital stay for schizophrenia or schizoaffective disorder.

“I suspect the lower readmission rate that has been observed with long-acting injections has more to do with people forgetting to take a pill each and every day than with any inherent superiority of the injectable medication,” lead author Daniel Greer, PharmD, BCPP, clinical assistant professor at Rutgers University Ernest Mario School of Pharmacy, Piscataway, New Jersey, said in a news release.

“Other studies on the use of antipsychotic medication have found that roughly three fourths of patients do not take oral medications exactly as directed, and it’s much easier to get a shot every few months than it is to take a pill every day, even though the shot requires a trip to the doctor,” Dr. Greer added.

The study was published online on January 17, 2024, in the Journal of Clinical Psychopharmacology.
 

Fewer Repeat Stays

Investigators compared 30-day readmission rates for all 343 patients with schizophrenia or schizoaffective disorder who were discharged from an inpatient psychiatric unit between August 2019 and June 2022.

A total of 240 patients (70%) were discharged on an oral antipsychotic, most commonly risperidone or olanzapine, and 103 (30%) were sent home on an LAI antipsychotic, most commonly aripiprazole lauroxil or haloperidol decanoate.

Within 30 days of discharge, 22 patients (6.4%) were readmitted for a schizophrenic or schizoaffective exacerbation — two in the LAI antipsychotic group and 20 in the oral antipsychotic group (1.9% vs 8.3%; P = .03).

The LAI antipsychotic group had a higher average daily chlorpromazine equivalent antipsychotic dose than the oral group (477.3 mg vs 278.6 mg; P < .001), which investigators said may indicate a difference in illness severity between the patient groups.

There was no significant between-group difference in the use of anticholinergic medications to treat extrapyramidal symptoms (22% in the LAI group and 31% in the oral group) despite the LAI group receiving greater doses.

That suggests “that both formulations may be equally as likely to cause these adverse effects,” the researchers noted.

Thirty-day readmission rates are important both medically and financially, investigators noted. In schizophrenia, access to medications and nonadherence are “significant problems.” LAI antipsychotic medications may alleviate some of these burdens but come with a high up-front cost.

“Medication access through pharmaceutical company free trial replacement programs may be an option for facilities with restricted formularies or limited medication funding to decrease 30-day readmissions,” investigators wrote.

“The cost of the injections is far lower than the cost of hospital treatments,” Dr. Greer added in the news release. “And each additional visit to the hospital increases the odds that there will be more visits in the future. Every time someone experiences psychosis, they lose gray matter, and they suffer damage that never heals. That’s why it’s so vital to minimize psychotic episodes.”

Chief limitations of the study included its single-center, retrospective chart review design and small sample size. Also, complete patient medication history was not obtained.

The study had no specific funding. The authors declared no relevant conflicts of interest.
 

A version of this article appeared on Medscape.com.

The number of state psychiatric hospital beds has hit a historic low with about 11 beds per 100,000 population, a new report showed.

More than half of those beds (52%) were occupied by forensic patients, individuals with serious mental illness (SMI) who were committed to the state hospital through the criminal legal system to help establish competency for trial.

“The shortage of psychiatric beds has real consequences for people with SMI — some will wait months in jail despite not yet being found guilty of a crime, others will be denied admission despite being critically ill, and others still will be discharged prematurely onto the streets to free up beds, where they may grow sicker and be at an elevated risk of mortality,” wrote report coauthors Shanti Silver of the Treatment Advocacy Center (TAC) in Arlington and Elizabeth Sinclair Hanq of the National Association of State Mental Health Program Directors in Alexandria, Virginia.

Published online on January 24, Prevention Over Punishment: Finding the Right Balance of Civil and Forensic State Psychiatric Hospital Beds recommends that state and local governments work together to open additional state psychiatric hospital beds for civil and forensic patients with SMI.

To obtain data about the availability of state psychiatric hospital beds, TAC surveyed state officials from April to August 2023. Official responses were provided by 41 states and the District of Columbia.

Information for the remaining states was gathered from state websites, media articles, preexisting reports, hospital admission staff, or personal contacts living in those states.

The median occupancy rate for state-run hospitals in the new report was 90%, well above the 85% level investigators say usually signals a bed shortage. Overall, 73% of states reported occupancy rates above that level, with 11 states operating at 95% capacity.

The proportion of state psychiatric beds occupied by forensic patients has increased by 12% since 2016, largely driven by the growing number of individuals awaiting a competency determination to stand trial. Before they occupy these beds, however, people with SMI can languish in jail for months or even years, waiting for a bed to open.

About 15% of all state hospital beds and 31% of forensic beds across 34 states were occupied by individuals who had been found not guilty of a crime by reasons of insanity.

“The prioritization of admission of forensic patients has effectively created a system where someone must be arrested to access a state hospital bed,” report coauthor Lisa Dailey, TAC executive director, told this news organization. “But there are not enough beds for forensic patients either; thousands of inmates are waiting in jail on any given day for a bed to open up.”

There are several factors contributing to the scarcity of beds, including an existing hospital staffing shortage made worse by the COVID-19 pandemic and a lack of appropriate discharge facilities.

Report authors offered a number of recommendations to federal, state, and local officials to increase the availability of state-run psychiatric hospital beds, including infrastructure changes involving recruiting and retaining staff for state hospitals and funding new discharge or step-down facilities so that patients have a place to recover when they leave the hospital.

Policy changes could also help, the report noted. Policymakers should consider “dismiss and transfer” procedures to address the backlog of nearly 6000 people with SMI waiting for a state hospital bed to achieve competency to stand trial. With “dismiss and transfer,” criminal charges are dismissed or suspended while an application for civil commitment is filed in the probate court. Once a civil commitment order has been issued, the individual is released to an outpatient commitment program for treatment.

“States must strive for prevention over punishment,” the report concluded.

There was no study funding reported, nor were disclosures available.
 

A version of this article appeared on Medscape.com.

The number of state psychiatric hospital beds has hit a historic low with about 11 beds per 100,000 population, a new report showed.

More than half of those beds (52%) were occupied by forensic patients, individuals with serious mental illness (SMI) who were committed to the state hospital through the criminal legal system to help establish competency for trial.

“The shortage of psychiatric beds has real consequences for people with SMI — some will wait months in jail despite not yet being found guilty of a crime, others will be denied admission despite being critically ill, and others still will be discharged prematurely onto the streets to free up beds, where they may grow sicker and be at an elevated risk of mortality,” wrote report coauthors Shanti Silver of the Treatment Advocacy Center (TAC) in Arlington and Elizabeth Sinclair Hanq of the National Association of State Mental Health Program Directors in Alexandria, Virginia.

Published online on January 24, Prevention Over Punishment: Finding the Right Balance of Civil and Forensic State Psychiatric Hospital Beds recommends that state and local governments work together to open additional state psychiatric hospital beds for civil and forensic patients with SMI.

To obtain data about the availability of state psychiatric hospital beds, TAC surveyed state officials from April to August 2023. Official responses were provided by 41 states and the District of Columbia.

Information for the remaining states was gathered from state websites, media articles, preexisting reports, hospital admission staff, or personal contacts living in those states.

The median occupancy rate for state-run hospitals in the new report was 90%, well above the 85% level investigators say usually signals a bed shortage. Overall, 73% of states reported occupancy rates above that level, with 11 states operating at 95% capacity.

The proportion of state psychiatric beds occupied by forensic patients has increased by 12% since 2016, largely driven by the growing number of individuals awaiting a competency determination to stand trial. Before they occupy these beds, however, people with SMI can languish in jail for months or even years, waiting for a bed to open.

About 15% of all state hospital beds and 31% of forensic beds across 34 states were occupied by individuals who had been found not guilty of a crime by reasons of insanity.

“The prioritization of admission of forensic patients has effectively created a system where someone must be arrested to access a state hospital bed,” report coauthor Lisa Dailey, TAC executive director, told this news organization. “But there are not enough beds for forensic patients either; thousands of inmates are waiting in jail on any given day for a bed to open up.”

There are several factors contributing to the scarcity of beds, including an existing hospital staffing shortage made worse by the COVID-19 pandemic and a lack of appropriate discharge facilities.

Report authors offered a number of recommendations to federal, state, and local officials to increase the availability of state-run psychiatric hospital beds, including infrastructure changes involving recruiting and retaining staff for state hospitals and funding new discharge or step-down facilities so that patients have a place to recover when they leave the hospital.

Policy changes could also help, the report noted. Policymakers should consider “dismiss and transfer” procedures to address the backlog of nearly 6000 people with SMI waiting for a state hospital bed to achieve competency to stand trial. With “dismiss and transfer,” criminal charges are dismissed or suspended while an application for civil commitment is filed in the probate court. Once a civil commitment order has been issued, the individual is released to an outpatient commitment program for treatment.

“States must strive for prevention over punishment,” the report concluded.

There was no study funding reported, nor were disclosures available.
 

A version of this article appeared on Medscape.com.

The number of state psychiatric hospital beds has hit a historic low with about 11 beds per 100,000 population, a new report showed.

More than half of those beds (52%) were occupied by forensic patients, individuals with serious mental illness (SMI) who were committed to the state hospital through the criminal legal system to help establish competency for trial.

“The shortage of psychiatric beds has real consequences for people with SMI — some will wait months in jail despite not yet being found guilty of a crime, others will be denied admission despite being critically ill, and others still will be discharged prematurely onto the streets to free up beds, where they may grow sicker and be at an elevated risk of mortality,” wrote report coauthors Shanti Silver of the Treatment Advocacy Center (TAC) in Arlington and Elizabeth Sinclair Hanq of the National Association of State Mental Health Program Directors in Alexandria, Virginia.

Published online on January 24, Prevention Over Punishment: Finding the Right Balance of Civil and Forensic State Psychiatric Hospital Beds recommends that state and local governments work together to open additional state psychiatric hospital beds for civil and forensic patients with SMI.

To obtain data about the availability of state psychiatric hospital beds, TAC surveyed state officials from April to August 2023. Official responses were provided by 41 states and the District of Columbia.

Information for the remaining states was gathered from state websites, media articles, preexisting reports, hospital admission staff, or personal contacts living in those states.

The median occupancy rate for state-run hospitals in the new report was 90%, well above the 85% level investigators say usually signals a bed shortage. Overall, 73% of states reported occupancy rates above that level, with 11 states operating at 95% capacity.

The proportion of state psychiatric beds occupied by forensic patients has increased by 12% since 2016, largely driven by the growing number of individuals awaiting a competency determination to stand trial. Before they occupy these beds, however, people with SMI can languish in jail for months or even years, waiting for a bed to open.

About 15% of all state hospital beds and 31% of forensic beds across 34 states were occupied by individuals who had been found not guilty of a crime by reasons of insanity.

“The prioritization of admission of forensic patients has effectively created a system where someone must be arrested to access a state hospital bed,” report coauthor Lisa Dailey, TAC executive director, told this news organization. “But there are not enough beds for forensic patients either; thousands of inmates are waiting in jail on any given day for a bed to open up.”

There are several factors contributing to the scarcity of beds, including an existing hospital staffing shortage made worse by the COVID-19 pandemic and a lack of appropriate discharge facilities.

Report authors offered a number of recommendations to federal, state, and local officials to increase the availability of state-run psychiatric hospital beds, including infrastructure changes involving recruiting and retaining staff for state hospitals and funding new discharge or step-down facilities so that patients have a place to recover when they leave the hospital.

Policy changes could also help, the report noted. Policymakers should consider “dismiss and transfer” procedures to address the backlog of nearly 6000 people with SMI waiting for a state hospital bed to achieve competency to stand trial. With “dismiss and transfer,” criminal charges are dismissed or suspended while an application for civil commitment is filed in the probate court. Once a civil commitment order has been issued, the individual is released to an outpatient commitment program for treatment.

“States must strive for prevention over punishment,” the report concluded.

There was no study funding reported, nor were disclosures available.
 

A version of this article appeared on Medscape.com.

Iloperidone, a second-generation antipsychotic used to treat schizophrenia, appears to be safe and effective in the treatment of bipolar mania, new research suggested.

Results of the phase 3 randomized double-blind placebo-controlled trial show patients with bipolar mania who received iloperidone had significantly greater change from baseline to 4 weeks on the Young Mania Rating Scale (YMRS) compared with placebo, an improvement detected as early as 14 days from the initial dose.

The incidence of akathisia and extrapyramidal symptoms (EPS) was low in the treatment group, and the medication was well-tolerated.

“This study provides evidence that iloperidone improves the symptoms of bipolar mania in adults and can be a useful treatment option for people with bipolar disorder,” the investigators, led by Rosarelis Torres, PhD, of Vanda Pharmaceuticals, and colleagues wrote.

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

Early Improvement

Iloperidone was first approved by the US Food and Drug Administration in 2009 for treatment of schizophrenia.

The current study included 414 participants (mean age, 43 years; 56% male) across 17 US and international sites. Patients with psychotic features received a fixed daily dose of 24 mg of iloperidone (n = 206) or placebo (n = 208).

Participants completed a screening period of up to 7 days before randomization, followed by a 1-day baseline evaluation period and a 28-day treatment phase.

The primary efficacy endpoint was change from baseline to week 4 on the YMRS (vs placebo), while secondary efficacy endpoints included change from baseline on the Clinical Global Impressions-Severity and Clinical Global Impression of Change scales (CGI-S and CGI-C, respectively).

Compared with placebo, iloperidone was associated with significant improvement of mania symptoms at week 4, with a mean reduction on the YMRS scale of −4.0 (P = .000008), and significant decreases on the CGI-S (mean, −0.4; P = .0005) and CGI-C scales (mean, −0.5; P = .0002).

Statistically significant differences between iloperidone and placebo were observed as early as day 14 and continued through days 21 and 28.

Post hoc analyses found no difference in efficacy even when patients who had received benzodiazepines were excluded, regardless of the presence or absence of psychotic features at baseline.
 

Favorable Akathisia Profile

As for safety, 68% of patients in the iloperidone group experienced at least one adverse event, compared with 49% of patients in the placebo group.

Patients in the treatment group had a higher rate of withdrawal from the study than those in the placebo group (32.9% vs 27.1%), and more patients in the iloperidone group experienced treatment-emergent adverse events (TEAEs) leading to study drug discontinuation (8.7% vs 5.3%). However, no TEAEs associated with discontinuation occurred in more than two patients in either group, and none of the participants experienced any AE leading to death.

The most common adverse events (AEs) were tachycardia (18%), dizziness (11%), dry mouth (9%), increased alanine aminotransferase (7%), nasal congestion (6%), weight gain (6%), and somnolence (5%).

Five serious AEs were reported in four participants in the treatment group and one in the placebo group. Two were identified as related to the study medication. These included sedation and spontaneous penile erection.

Changes from baseline in clinical laboratory parameters were not largely different between the groups, but there were post-randomization changes in QT interval in three iloperidone patients. The incidence of orthostatic response was also higher for iloperidone vs placebo.

Although “much improved compared to early antipsychotics, SGAs can still cause considerable adverse motor side effects,” the authors wrote. “However, among all SGAs, iloperidone’s akathisia profile is favorable.”

Antipsychotic-induced akathisia has been reported more frequently in patients with bipolar disorder than in those with schizophrenia treated with the same medication, investigators noted.

One study limitation is the fact that long-term efficacy in the prevention of manic or depressive episodes was not assessed.
 

Potential Second-Line Treatment

Commenting on the study, Richard Louis Price, MD, assistant professor of psychiatry, at Weill Cornell Medical College, New York City, said the findings suggest iloperidone may be “modestly effective” for patients with bipolar 1 mania or mixed episodes.

“It’s helpful to have new treatment options, especially for patients who have difficulty tolerating other agents,” said Dr. Price, who was not involved with the study.

Also commenting on the research, Roger S. McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, Toronto, Ontario, Canada, noted iloperidone’s “interesting antipsychotic pharmacodynamic,” highlighting the drug’s high-binding affinity for serotonin 5HT_2A and dopamine D₂ and D₃ receptors, as well as the noradrenergic α₁ receptors.

The drug’s profile “suggests benefit in manic features and agitation, perhaps with a lower propensity to EPS, which is especially important in persons at higher risk, like persons living with bipolar disorder,” Dr. McIntyre said.

Dr. McIntyre, who was not involved with the study, added iloperidone could be a second-line therapy because of its tolerability profile, provided the study results can be replicated.

“When considering alternatives with similar efficacy, absence of titration (or simple titration) minimal to no weight gain, no orthostatic hypotension, and no potential concerns with QT, those alternatives would have to be considered first-line, assuming that the study results are replicated,” he said.

This study was funded by Vanda Pharmaceuticals. The authors’ disclosures are listed in the original paper. Dr. McIntyre had received research grant support from CIHR/GACD/National Natural Science Foundation of China and the Milken Institute; speaker/consultation fees from Lundbeck, Janssen, Alkermes, Neumora Therapeutics, Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine Biosciences, Sunovion, Bausch Health, Axsome Therapeutics, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular Therapies Inc., NewBridge Pharmaceuticals, Viatris, Abbvie, and Atai Life Sciences. McIntyre is the CEO of Braxia Scientific Corp. Dr. Price had received honoraria from AbbVie, Alkermes, Allergan, Intra-Cellular Therapies, Janssen, Jazz, Lundbeck, Neuronetics, Otsuka, and Supernus.

A version of this article appeared on Medscape.com.

Iloperidone, a second-generation antipsychotic used to treat schizophrenia, appears to be safe and effective in the treatment of bipolar mania, new research suggested.

Results of the phase 3 randomized double-blind placebo-controlled trial show patients with bipolar mania who received iloperidone had significantly greater change from baseline to 4 weeks on the Young Mania Rating Scale (YMRS) compared with placebo, an improvement detected as early as 14 days from the initial dose.

The incidence of akathisia and extrapyramidal symptoms (EPS) was low in the treatment group, and the medication was well-tolerated.

“This study provides evidence that iloperidone improves the symptoms of bipolar mania in adults and can be a useful treatment option for people with bipolar disorder,” the investigators, led by Rosarelis Torres, PhD, of Vanda Pharmaceuticals, and colleagues wrote.

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

Early Improvement

Iloperidone was first approved by the US Food and Drug Administration in 2009 for treatment of schizophrenia.

The current study included 414 participants (mean age, 43 years; 56% male) across 17 US and international sites. Patients with psychotic features received a fixed daily dose of 24 mg of iloperidone (n = 206) or placebo (n = 208).

Participants completed a screening period of up to 7 days before randomization, followed by a 1-day baseline evaluation period and a 28-day treatment phase.

The primary efficacy endpoint was change from baseline to week 4 on the YMRS (vs placebo), while secondary efficacy endpoints included change from baseline on the Clinical Global Impressions-Severity and Clinical Global Impression of Change scales (CGI-S and CGI-C, respectively).

Compared with placebo, iloperidone was associated with significant improvement of mania symptoms at week 4, with a mean reduction on the YMRS scale of −4.0 (P = .000008), and significant decreases on the CGI-S (mean, −0.4; P = .0005) and CGI-C scales (mean, −0.5; P = .0002).

Statistically significant differences between iloperidone and placebo were observed as early as day 14 and continued through days 21 and 28.

Post hoc analyses found no difference in efficacy even when patients who had received benzodiazepines were excluded, regardless of the presence or absence of psychotic features at baseline.
 

Favorable Akathisia Profile

As for safety, 68% of patients in the iloperidone group experienced at least one adverse event, compared with 49% of patients in the placebo group.

Patients in the treatment group had a higher rate of withdrawal from the study than those in the placebo group (32.9% vs 27.1%), and more patients in the iloperidone group experienced treatment-emergent adverse events (TEAEs) leading to study drug discontinuation (8.7% vs 5.3%). However, no TEAEs associated with discontinuation occurred in more than two patients in either group, and none of the participants experienced any AE leading to death.

The most common adverse events (AEs) were tachycardia (18%), dizziness (11%), dry mouth (9%), increased alanine aminotransferase (7%), nasal congestion (6%), weight gain (6%), and somnolence (5%).

Five serious AEs were reported in four participants in the treatment group and one in the placebo group. Two were identified as related to the study medication. These included sedation and spontaneous penile erection.

Changes from baseline in clinical laboratory parameters were not largely different between the groups, but there were post-randomization changes in QT interval in three iloperidone patients. The incidence of orthostatic response was also higher for iloperidone vs placebo.

Although “much improved compared to early antipsychotics, SGAs can still cause considerable adverse motor side effects,” the authors wrote. “However, among all SGAs, iloperidone’s akathisia profile is favorable.”

Antipsychotic-induced akathisia has been reported more frequently in patients with bipolar disorder than in those with schizophrenia treated with the same medication, investigators noted.

One study limitation is the fact that long-term efficacy in the prevention of manic or depressive episodes was not assessed.
 

Potential Second-Line Treatment

Commenting on the study, Richard Louis Price, MD, assistant professor of psychiatry, at Weill Cornell Medical College, New York City, said the findings suggest iloperidone may be “modestly effective” for patients with bipolar 1 mania or mixed episodes.

“It’s helpful to have new treatment options, especially for patients who have difficulty tolerating other agents,” said Dr. Price, who was not involved with the study.

Also commenting on the research, Roger S. McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, Toronto, Ontario, Canada, noted iloperidone’s “interesting antipsychotic pharmacodynamic,” highlighting the drug’s high-binding affinity for serotonin 5HT_2A and dopamine D₂ and D₃ receptors, as well as the noradrenergic α₁ receptors.

The drug’s profile “suggests benefit in manic features and agitation, perhaps with a lower propensity to EPS, which is especially important in persons at higher risk, like persons living with bipolar disorder,” Dr. McIntyre said.

Dr. McIntyre, who was not involved with the study, added iloperidone could be a second-line therapy because of its tolerability profile, provided the study results can be replicated.

“When considering alternatives with similar efficacy, absence of titration (or simple titration) minimal to no weight gain, no orthostatic hypotension, and no potential concerns with QT, those alternatives would have to be considered first-line, assuming that the study results are replicated,” he said.

This study was funded by Vanda Pharmaceuticals. The authors’ disclosures are listed in the original paper. Dr. McIntyre had received research grant support from CIHR/GACD/National Natural Science Foundation of China and the Milken Institute; speaker/consultation fees from Lundbeck, Janssen, Alkermes, Neumora Therapeutics, Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine Biosciences, Sunovion, Bausch Health, Axsome Therapeutics, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular Therapies Inc., NewBridge Pharmaceuticals, Viatris, Abbvie, and Atai Life Sciences. McIntyre is the CEO of Braxia Scientific Corp. Dr. Price had received honoraria from AbbVie, Alkermes, Allergan, Intra-Cellular Therapies, Janssen, Jazz, Lundbeck, Neuronetics, Otsuka, and Supernus.

A version of this article appeared on Medscape.com.

Iloperidone, a second-generation antipsychotic used to treat schizophrenia, appears to be safe and effective in the treatment of bipolar mania, new research suggested.

Results of the phase 3 randomized double-blind placebo-controlled trial show patients with bipolar mania who received iloperidone had significantly greater change from baseline to 4 weeks on the Young Mania Rating Scale (YMRS) compared with placebo, an improvement detected as early as 14 days from the initial dose.

The incidence of akathisia and extrapyramidal symptoms (EPS) was low in the treatment group, and the medication was well-tolerated.

“This study provides evidence that iloperidone improves the symptoms of bipolar mania in adults and can be a useful treatment option for people with bipolar disorder,” the investigators, led by Rosarelis Torres, PhD, of Vanda Pharmaceuticals, and colleagues wrote.

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

Early Improvement

Iloperidone was first approved by the US Food and Drug Administration in 2009 for treatment of schizophrenia.

The current study included 414 participants (mean age, 43 years; 56% male) across 17 US and international sites. Patients with psychotic features received a fixed daily dose of 24 mg of iloperidone (n = 206) or placebo (n = 208).

Participants completed a screening period of up to 7 days before randomization, followed by a 1-day baseline evaluation period and a 28-day treatment phase.

The primary efficacy endpoint was change from baseline to week 4 on the YMRS (vs placebo), while secondary efficacy endpoints included change from baseline on the Clinical Global Impressions-Severity and Clinical Global Impression of Change scales (CGI-S and CGI-C, respectively).

Compared with placebo, iloperidone was associated with significant improvement of mania symptoms at week 4, with a mean reduction on the YMRS scale of −4.0 (P = .000008), and significant decreases on the CGI-S (mean, −0.4; P = .0005) and CGI-C scales (mean, −0.5; P = .0002).

Statistically significant differences between iloperidone and placebo were observed as early as day 14 and continued through days 21 and 28.

Post hoc analyses found no difference in efficacy even when patients who had received benzodiazepines were excluded, regardless of the presence or absence of psychotic features at baseline.
 

Favorable Akathisia Profile

As for safety, 68% of patients in the iloperidone group experienced at least one adverse event, compared with 49% of patients in the placebo group.

Patients in the treatment group had a higher rate of withdrawal from the study than those in the placebo group (32.9% vs 27.1%), and more patients in the iloperidone group experienced treatment-emergent adverse events (TEAEs) leading to study drug discontinuation (8.7% vs 5.3%). However, no TEAEs associated with discontinuation occurred in more than two patients in either group, and none of the participants experienced any AE leading to death.

The most common adverse events (AEs) were tachycardia (18%), dizziness (11%), dry mouth (9%), increased alanine aminotransferase (7%), nasal congestion (6%), weight gain (6%), and somnolence (5%).

Five serious AEs were reported in four participants in the treatment group and one in the placebo group. Two were identified as related to the study medication. These included sedation and spontaneous penile erection.

Changes from baseline in clinical laboratory parameters were not largely different between the groups, but there were post-randomization changes in QT interval in three iloperidone patients. The incidence of orthostatic response was also higher for iloperidone vs placebo.

Although “much improved compared to early antipsychotics, SGAs can still cause considerable adverse motor side effects,” the authors wrote. “However, among all SGAs, iloperidone’s akathisia profile is favorable.”

Antipsychotic-induced akathisia has been reported more frequently in patients with bipolar disorder than in those with schizophrenia treated with the same medication, investigators noted.

One study limitation is the fact that long-term efficacy in the prevention of manic or depressive episodes was not assessed.
 

Potential Second-Line Treatment

Commenting on the study, Richard Louis Price, MD, assistant professor of psychiatry, at Weill Cornell Medical College, New York City, said the findings suggest iloperidone may be “modestly effective” for patients with bipolar 1 mania or mixed episodes.

“It’s helpful to have new treatment options, especially for patients who have difficulty tolerating other agents,” said Dr. Price, who was not involved with the study.

Also commenting on the research, Roger S. McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, Toronto, Ontario, Canada, noted iloperidone’s “interesting antipsychotic pharmacodynamic,” highlighting the drug’s high-binding affinity for serotonin 5HT_2A and dopamine D₂ and D₃ receptors, as well as the noradrenergic α₁ receptors.

The drug’s profile “suggests benefit in manic features and agitation, perhaps with a lower propensity to EPS, which is especially important in persons at higher risk, like persons living with bipolar disorder,” Dr. McIntyre said.

Dr. McIntyre, who was not involved with the study, added iloperidone could be a second-line therapy because of its tolerability profile, provided the study results can be replicated.

“When considering alternatives with similar efficacy, absence of titration (or simple titration) minimal to no weight gain, no orthostatic hypotension, and no potential concerns with QT, those alternatives would have to be considered first-line, assuming that the study results are replicated,” he said.

This study was funded by Vanda Pharmaceuticals. The authors’ disclosures are listed in the original paper. Dr. McIntyre had received research grant support from CIHR/GACD/National Natural Science Foundation of China and the Milken Institute; speaker/consultation fees from Lundbeck, Janssen, Alkermes, Neumora Therapeutics, Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine Biosciences, Sunovion, Bausch Health, Axsome Therapeutics, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular Therapies Inc., NewBridge Pharmaceuticals, Viatris, Abbvie, and Atai Life Sciences. McIntyre is the CEO of Braxia Scientific Corp. Dr. Price had received honoraria from AbbVie, Alkermes, Allergan, Intra-Cellular Therapies, Janssen, Jazz, Lundbeck, Neuronetics, Otsuka, and Supernus.

A version of this article appeared on Medscape.com.

Xanomeline-trospium (KarXT) — a novel therapy that combines a muscarinic receptor agonist with an anticholinergic agent — led to statistically significant and clinically meaningful improvements in positive and negative symptoms of schizophrenia compared with placebo in the phase 3 EMERGENT-2 trial, a new study shows.

Xanomeline-trospium treatment was not associated with weight gain compared with placebo, and the incidences of extrapyramidal motor symptoms or akathisia were low and similar between treatment groups.

The EMERGENT-2 results “support the potential for KarXT to represent a new class of effective and well-tolerated antipsychotic medicines based on activating muscarinic receptors, not the D2 dopamine receptor-blocking mechanism of all current antipsychotic medications,” write the authors, led by Inder Kaul, MD, with Karuna Therapeutics, Boston, Massachusetts.

The US Food and Drug Administration has accepted the company’s new drug application for KarXT for the treatment of schizophrenia in adults. The Prescription Drug User Fee Act action date is September 26, 2024.

Results of the EMERGENT-2 trial were published online on December 14, 2023, in The Lancet.
 

Beyond the Dopamine System

Evidence suggests the muscarinic cholinergic system is involved in the pathophysiology of schizophrenia.

Xanomeline is an oral muscarinic cholinergic receptor agonist that does not have direct effects on the dopamine receptor. Combining it with trospium chloride, an oral pan-muscarinic receptor antagonist, is thought to reduce side effects associated with xanomeline’s activation of peripheral muscarinic receptors in peripheral tissues.

EMERGENT-2 was a multicenter, double-blind, placebo-controlled trial that enrolled 252 adults with schizophrenia who recently experienced a worsening of psychotic symptoms warranting hospitalization.

Patients were treated for 5 weeks, with xanomeline-trospium titrated from 50 mg/20 mg twice daily to 125 mg/30 mg twice daily. Efficacy and safety analyses were conducted in those who had received at least one dose of the study drug.

The primary endpoint was change in baseline to week 5 in Positive and Negative Syndrome Scale (PANSS) total score (range, 30-210, with higher scores indicating more severe symptoms).

At the end of the treatment period, xanomeline-trospium was associated with a significant 9.6-point reduction in PANSS total scores relative to placebo. PANSS total scores fell by 21.2 points with xanomeline-trospium vs 11.6 points with placebo (P < .0001; Cohen d effect size, 0.61).

All secondary endpoints were also met, with active treatment demonstrating statistically significant reductions compared with placebo at week 5 (P < .05).

These secondary endpoints included change in PANSS positive subscale, PANSS negative subscale, PANSS Marder negative factor, Clinical Global Impression-Severity score, and percentage of participants achieving at least a 30% reduction from baseline to week 5 in PANSS total score.

Rates of discontinuation related to side effects were similar with active treatment and placebo (7% and 6%, respectively). The most common side effects with xanomeline-trospium were constipation (21%), dyspepsia (19%), nausea (19%), vomiting (14%), headache (14%), hypertension (10%), dizziness (9%), and gastroesophageal reflux disease (6%).

Xanomeline-trospium demonstrated a “distinctive safety and tolerability profile and was not associated with many of the adverse events typically associated with current antipsychotic treatments, including extrapyramidal motor symptoms, weight gain, changes in lipid and glucose parameters, and somnolence,” the authors report.
 

Potential ‘Game-Changer’

Xanomeline-trospium is a potential “game-changer” for patients with schizophrenia, Ann Shinn, MD, MPH, director of clinical research, Schizophrenia and Bipolar Disorder Research Program, McLean Hospital, and assistant professor of psychiatry, Harvard Medical School, told this news organization.

There was a “clear separation between the people who were randomized to KarXT vs placebo. It’s not just a statistically significant but also a clinically significant difference in the reduction in symptoms of psychosis,” said Dr. Shinn, who wasn’t involved in the study.

“What’s really exciting” is that the drug did not cause weight gain or extrapyramidal symptoms compared with placebo. “Both from an efficacy and side-effect perspective, I think more patients with schizophrenia are going to be willing to take medication,” Dr. Shinn noted.

Also commenting on this research for this news organization, René Kahn, MD, PhD, professor and chair of psychiatry at the Icahn School of Medicine at Mount Sinai in New York, noted that current antipsychotic medications for schizophrenia work “directly on the dopamine system — either as dopamine antagonists or partial agonist.”

Xanomeline-trospium provides a “new mechanism of action, a new system that’s being targeted in the treatment of schizophrenia, and the effect size was rather large, so the drug didn’t just squeak by,” Dr. Kahn said.

Nonetheless, “we’ll have to wait and see whether it’s as effective or more effective than drugs currently on the market. The proof of the pudding will come when it’s marketed and used on thousands and thousands of patients,” Dr. Kahn added.

The coauthors of an accompanying commentary say the EMERGENT-2 findings “strongly support the possibility that agonism of muscarinic receptors provides the first viable antipsychotic alternative to blocking the dopamine D2 receptor for more than 70 years, and as such encourage further research.”

However, as a regulatory trial, EMERGENT-2 does not provide comparative data on the benefits and harms of KarXT with existing alternatives.

This represents a “missed opportunity to provide patients and clinicians with the information that is clinically needed — what is the treatment of choice for a patient?” writes Andrea Cipriani, MD, PhD, with the Department of Psychiatry, University of Oxford, United Kingdom, and co-authors.

The study was funded by Karuna Therapeutics. Several authors disclosed relationships with the company. Dr. Kahn disclosed various relationships with Boehringer Ingelheim International GmbH. Dr. Cipriani received research, educational, and consultancy fees from the Italian Network for Paediatric Trials, the CARIPLO Foundation, Lundbeck, and Angelini Pharma and was chief investigator of one trial about seltorexant in adolescent depression, sponsored by Janssen. Dr. Shinn had no relevant disclosures.

A version of this article appeared on Medscape.com.

Xanomeline-trospium (KarXT) — a novel therapy that combines a muscarinic receptor agonist with an anticholinergic agent — led to statistically significant and clinically meaningful improvements in positive and negative symptoms of schizophrenia compared with placebo in the phase 3 EMERGENT-2 trial, a new study shows.

Xanomeline-trospium treatment was not associated with weight gain compared with placebo, and the incidences of extrapyramidal motor symptoms or akathisia were low and similar between treatment groups.

The EMERGENT-2 results “support the potential for KarXT to represent a new class of effective and well-tolerated antipsychotic medicines based on activating muscarinic receptors, not the D2 dopamine receptor-blocking mechanism of all current antipsychotic medications,” write the authors, led by Inder Kaul, MD, with Karuna Therapeutics, Boston, Massachusetts.

The US Food and Drug Administration has accepted the company’s new drug application for KarXT for the treatment of schizophrenia in adults. The Prescription Drug User Fee Act action date is September 26, 2024.

Results of the EMERGENT-2 trial were published online on December 14, 2023, in The Lancet.
 

Beyond the Dopamine System

Evidence suggests the muscarinic cholinergic system is involved in the pathophysiology of schizophrenia.

Xanomeline is an oral muscarinic cholinergic receptor agonist that does not have direct effects on the dopamine receptor. Combining it with trospium chloride, an oral pan-muscarinic receptor antagonist, is thought to reduce side effects associated with xanomeline’s activation of peripheral muscarinic receptors in peripheral tissues.

EMERGENT-2 was a multicenter, double-blind, placebo-controlled trial that enrolled 252 adults with schizophrenia who recently experienced a worsening of psychotic symptoms warranting hospitalization.

Patients were treated for 5 weeks, with xanomeline-trospium titrated from 50 mg/20 mg twice daily to 125 mg/30 mg twice daily. Efficacy and safety analyses were conducted in those who had received at least one dose of the study drug.

The primary endpoint was change in baseline to week 5 in Positive and Negative Syndrome Scale (PANSS) total score (range, 30-210, with higher scores indicating more severe symptoms).

At the end of the treatment period, xanomeline-trospium was associated with a significant 9.6-point reduction in PANSS total scores relative to placebo. PANSS total scores fell by 21.2 points with xanomeline-trospium vs 11.6 points with placebo (P < .0001; Cohen d effect size, 0.61).

All secondary endpoints were also met, with active treatment demonstrating statistically significant reductions compared with placebo at week 5 (P < .05).

These secondary endpoints included change in PANSS positive subscale, PANSS negative subscale, PANSS Marder negative factor, Clinical Global Impression-Severity score, and percentage of participants achieving at least a 30% reduction from baseline to week 5 in PANSS total score.

Rates of discontinuation related to side effects were similar with active treatment and placebo (7% and 6%, respectively). The most common side effects with xanomeline-trospium were constipation (21%), dyspepsia (19%), nausea (19%), vomiting (14%), headache (14%), hypertension (10%), dizziness (9%), and gastroesophageal reflux disease (6%).

Xanomeline-trospium demonstrated a “distinctive safety and tolerability profile and was not associated with many of the adverse events typically associated with current antipsychotic treatments, including extrapyramidal motor symptoms, weight gain, changes in lipid and glucose parameters, and somnolence,” the authors report.
 

Potential ‘Game-Changer’

Xanomeline-trospium is a potential “game-changer” for patients with schizophrenia, Ann Shinn, MD, MPH, director of clinical research, Schizophrenia and Bipolar Disorder Research Program, McLean Hospital, and assistant professor of psychiatry, Harvard Medical School, told this news organization.

There was a “clear separation between the people who were randomized to KarXT vs placebo. It’s not just a statistically significant but also a clinically significant difference in the reduction in symptoms of psychosis,” said Dr. Shinn, who wasn’t involved in the study.

“What’s really exciting” is that the drug did not cause weight gain or extrapyramidal symptoms compared with placebo. “Both from an efficacy and side-effect perspective, I think more patients with schizophrenia are going to be willing to take medication,” Dr. Shinn noted.

Also commenting on this research for this news organization, René Kahn, MD, PhD, professor and chair of psychiatry at the Icahn School of Medicine at Mount Sinai in New York, noted that current antipsychotic medications for schizophrenia work “directly on the dopamine system — either as dopamine antagonists or partial agonist.”

Xanomeline-trospium provides a “new mechanism of action, a new system that’s being targeted in the treatment of schizophrenia, and the effect size was rather large, so the drug didn’t just squeak by,” Dr. Kahn said.

Nonetheless, “we’ll have to wait and see whether it’s as effective or more effective than drugs currently on the market. The proof of the pudding will come when it’s marketed and used on thousands and thousands of patients,” Dr. Kahn added.

The coauthors of an accompanying commentary say the EMERGENT-2 findings “strongly support the possibility that agonism of muscarinic receptors provides the first viable antipsychotic alternative to blocking the dopamine D2 receptor for more than 70 years, and as such encourage further research.”

However, as a regulatory trial, EMERGENT-2 does not provide comparative data on the benefits and harms of KarXT with existing alternatives.

This represents a “missed opportunity to provide patients and clinicians with the information that is clinically needed — what is the treatment of choice for a patient?” writes Andrea Cipriani, MD, PhD, with the Department of Psychiatry, University of Oxford, United Kingdom, and co-authors.

The study was funded by Karuna Therapeutics. Several authors disclosed relationships with the company. Dr. Kahn disclosed various relationships with Boehringer Ingelheim International GmbH. Dr. Cipriani received research, educational, and consultancy fees from the Italian Network for Paediatric Trials, the CARIPLO Foundation, Lundbeck, and Angelini Pharma and was chief investigator of one trial about seltorexant in adolescent depression, sponsored by Janssen. Dr. Shinn had no relevant disclosures.

A version of this article appeared on Medscape.com.

Xanomeline-trospium (KarXT) — a novel therapy that combines a muscarinic receptor agonist with an anticholinergic agent — led to statistically significant and clinically meaningful improvements in positive and negative symptoms of schizophrenia compared with placebo in the phase 3 EMERGENT-2 trial, a new study shows.

Xanomeline-trospium treatment was not associated with weight gain compared with placebo, and the incidences of extrapyramidal motor symptoms or akathisia were low and similar between treatment groups.

The EMERGENT-2 results “support the potential for KarXT to represent a new class of effective and well-tolerated antipsychotic medicines based on activating muscarinic receptors, not the D2 dopamine receptor-blocking mechanism of all current antipsychotic medications,” write the authors, led by Inder Kaul, MD, with Karuna Therapeutics, Boston, Massachusetts.

The US Food and Drug Administration has accepted the company’s new drug application for KarXT for the treatment of schizophrenia in adults. The Prescription Drug User Fee Act action date is September 26, 2024.

Results of the EMERGENT-2 trial were published online on December 14, 2023, in The Lancet.
 

Beyond the Dopamine System

Evidence suggests the muscarinic cholinergic system is involved in the pathophysiology of schizophrenia.

Xanomeline is an oral muscarinic cholinergic receptor agonist that does not have direct effects on the dopamine receptor. Combining it with trospium chloride, an oral pan-muscarinic receptor antagonist, is thought to reduce side effects associated with xanomeline’s activation of peripheral muscarinic receptors in peripheral tissues.

EMERGENT-2 was a multicenter, double-blind, placebo-controlled trial that enrolled 252 adults with schizophrenia who recently experienced a worsening of psychotic symptoms warranting hospitalization.

Patients were treated for 5 weeks, with xanomeline-trospium titrated from 50 mg/20 mg twice daily to 125 mg/30 mg twice daily. Efficacy and safety analyses were conducted in those who had received at least one dose of the study drug.

The primary endpoint was change in baseline to week 5 in Positive and Negative Syndrome Scale (PANSS) total score (range, 30-210, with higher scores indicating more severe symptoms).

At the end of the treatment period, xanomeline-trospium was associated with a significant 9.6-point reduction in PANSS total scores relative to placebo. PANSS total scores fell by 21.2 points with xanomeline-trospium vs 11.6 points with placebo (P < .0001; Cohen d effect size, 0.61).

All secondary endpoints were also met, with active treatment demonstrating statistically significant reductions compared with placebo at week 5 (P < .05).

These secondary endpoints included change in PANSS positive subscale, PANSS negative subscale, PANSS Marder negative factor, Clinical Global Impression-Severity score, and percentage of participants achieving at least a 30% reduction from baseline to week 5 in PANSS total score.

Rates of discontinuation related to side effects were similar with active treatment and placebo (7% and 6%, respectively). The most common side effects with xanomeline-trospium were constipation (21%), dyspepsia (19%), nausea (19%), vomiting (14%), headache (14%), hypertension (10%), dizziness (9%), and gastroesophageal reflux disease (6%).

Xanomeline-trospium demonstrated a “distinctive safety and tolerability profile and was not associated with many of the adverse events typically associated with current antipsychotic treatments, including extrapyramidal motor symptoms, weight gain, changes in lipid and glucose parameters, and somnolence,” the authors report.
 

Potential ‘Game-Changer’

Xanomeline-trospium is a potential “game-changer” for patients with schizophrenia, Ann Shinn, MD, MPH, director of clinical research, Schizophrenia and Bipolar Disorder Research Program, McLean Hospital, and assistant professor of psychiatry, Harvard Medical School, told this news organization.

There was a “clear separation between the people who were randomized to KarXT vs placebo. It’s not just a statistically significant but also a clinically significant difference in the reduction in symptoms of psychosis,” said Dr. Shinn, who wasn’t involved in the study.

“What’s really exciting” is that the drug did not cause weight gain or extrapyramidal symptoms compared with placebo. “Both from an efficacy and side-effect perspective, I think more patients with schizophrenia are going to be willing to take medication,” Dr. Shinn noted.

Also commenting on this research for this news organization, René Kahn, MD, PhD, professor and chair of psychiatry at the Icahn School of Medicine at Mount Sinai in New York, noted that current antipsychotic medications for schizophrenia work “directly on the dopamine system — either as dopamine antagonists or partial agonist.”

Xanomeline-trospium provides a “new mechanism of action, a new system that’s being targeted in the treatment of schizophrenia, and the effect size was rather large, so the drug didn’t just squeak by,” Dr. Kahn said.

Nonetheless, “we’ll have to wait and see whether it’s as effective or more effective than drugs currently on the market. The proof of the pudding will come when it’s marketed and used on thousands and thousands of patients,” Dr. Kahn added.

The coauthors of an accompanying commentary say the EMERGENT-2 findings “strongly support the possibility that agonism of muscarinic receptors provides the first viable antipsychotic alternative to blocking the dopamine D2 receptor for more than 70 years, and as such encourage further research.”

However, as a regulatory trial, EMERGENT-2 does not provide comparative data on the benefits and harms of KarXT with existing alternatives.

This represents a “missed opportunity to provide patients and clinicians with the information that is clinically needed — what is the treatment of choice for a patient?” writes Andrea Cipriani, MD, PhD, with the Department of Psychiatry, University of Oxford, United Kingdom, and co-authors.

The study was funded by Karuna Therapeutics. Several authors disclosed relationships with the company. Dr. Kahn disclosed various relationships with Boehringer Ingelheim International GmbH. Dr. Cipriani received research, educational, and consultancy fees from the Italian Network for Paediatric Trials, the CARIPLO Foundation, Lundbeck, and Angelini Pharma and was chief investigator of one trial about seltorexant in adolescent depression, sponsored by Janssen. Dr. Shinn had no relevant disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

Emergency department (ED) visits for schizophrenia spectrum disorders increased by 15% in the early phase of the COVID-19 pandemic, a new study showed. Researchers said the findings suggested a need for social policies that strengthen mental health prevention systems.

METHODOLOGY:

Investigators obtained data from the University of California (UC) Health Data Warehouse on ED visits at five large UC health systems.

They captured the ICD-10 codes relating to schizophrenia spectrum disorders for ED visits from January 2016 to December 2021 for patients aged 18 years and older.

TAKEAWAY:

Between January 2016 and December 2021, there were 377,800 psychiatric ED visits, 10% of which involved schizophrenia spectrum disorders.

The mean number of visits per month for schizophrenia spectrum disorders rose from 520 before the pandemic to 558 visits per month after March 2020.

Compared to prepandemic numbers and after controlling for visits for other psychiatric disorders, there were 70.5 additional visits (P = .02) for schizophrenia spectrum disorders at 1 month and 74.9 additional visits (P = .005) at 3 months following the initial phase of the COVID-19 pandemic in California.

Investigators noted that prior studies indicated that COVID-19 infections may induce psychosis in some individuals, which could have been one underlying factor in the spike in cases.

IN PRACTICE:

“The COVID-19 pandemic draws attention to the vulnerability of patients with schizophrenia to macrosocial shocks, underscoring the importance of social policies related to income support, housing, and health insurance for future emergency preparedness and the need to strengthen mental healthcare systems,” the authors wrote.

SOURCE:

Parvita Singh, PhD, of The Ohio State University in Columbus, led the study, which was published online in JAMA Network Open.

LIMITATIONS:

Data used in the study excluded patients younger than 18 years. In addition, there was no analysis for trends by age or sex, which could have added valuable information to the study, the authors wrote. There was also no way to identify patients with newly diagnosed schizophrenia.

DISCLOSURES:

The study was funded through the Coronavirus Response and Relief Supplemental Appropriations Act and the Ohio Department of Mental Health and Addiction Services. Study disclosures are noted in the original study.

A version of this article appeared on Medscape.com.

TOPLINE:

Emergency department (ED) visits for schizophrenia spectrum disorders increased by 15% in the early phase of the COVID-19 pandemic, a new study showed. Researchers said the findings suggested a need for social policies that strengthen mental health prevention systems.

METHODOLOGY:

Investigators obtained data from the University of California (UC) Health Data Warehouse on ED visits at five large UC health systems.

They captured the ICD-10 codes relating to schizophrenia spectrum disorders for ED visits from January 2016 to December 2021 for patients aged 18 years and older.

TAKEAWAY:

Between January 2016 and December 2021, there were 377,800 psychiatric ED visits, 10% of which involved schizophrenia spectrum disorders.

The mean number of visits per month for schizophrenia spectrum disorders rose from 520 before the pandemic to 558 visits per month after March 2020.

Compared to prepandemic numbers and after controlling for visits for other psychiatric disorders, there were 70.5 additional visits (P = .02) for schizophrenia spectrum disorders at 1 month and 74.9 additional visits (P = .005) at 3 months following the initial phase of the COVID-19 pandemic in California.

Investigators noted that prior studies indicated that COVID-19 infections may induce psychosis in some individuals, which could have been one underlying factor in the spike in cases.

IN PRACTICE:

“The COVID-19 pandemic draws attention to the vulnerability of patients with schizophrenia to macrosocial shocks, underscoring the importance of social policies related to income support, housing, and health insurance for future emergency preparedness and the need to strengthen mental healthcare systems,” the authors wrote.

SOURCE:

Parvita Singh, PhD, of The Ohio State University in Columbus, led the study, which was published online in JAMA Network Open.

LIMITATIONS:

Data used in the study excluded patients younger than 18 years. In addition, there was no analysis for trends by age or sex, which could have added valuable information to the study, the authors wrote. There was also no way to identify patients with newly diagnosed schizophrenia.

DISCLOSURES:

The study was funded through the Coronavirus Response and Relief Supplemental Appropriations Act and the Ohio Department of Mental Health and Addiction Services. Study disclosures are noted in the original study.

A version of this article appeared on Medscape.com.

TOPLINE:

Emergency department (ED) visits for schizophrenia spectrum disorders increased by 15% in the early phase of the COVID-19 pandemic, a new study showed. Researchers said the findings suggested a need for social policies that strengthen mental health prevention systems.

METHODOLOGY:

Investigators obtained data from the University of California (UC) Health Data Warehouse on ED visits at five large UC health systems.

They captured the ICD-10 codes relating to schizophrenia spectrum disorders for ED visits from January 2016 to December 2021 for patients aged 18 years and older.

TAKEAWAY:

Between January 2016 and December 2021, there were 377,800 psychiatric ED visits, 10% of which involved schizophrenia spectrum disorders.

The mean number of visits per month for schizophrenia spectrum disorders rose from 520 before the pandemic to 558 visits per month after March 2020.

Compared to prepandemic numbers and after controlling for visits for other psychiatric disorders, there were 70.5 additional visits (P = .02) for schizophrenia spectrum disorders at 1 month and 74.9 additional visits (P = .005) at 3 months following the initial phase of the COVID-19 pandemic in California.

Investigators noted that prior studies indicated that COVID-19 infections may induce psychosis in some individuals, which could have been one underlying factor in the spike in cases.

IN PRACTICE:

“The COVID-19 pandemic draws attention to the vulnerability of patients with schizophrenia to macrosocial shocks, underscoring the importance of social policies related to income support, housing, and health insurance for future emergency preparedness and the need to strengthen mental healthcare systems,” the authors wrote.

SOURCE:

Parvita Singh, PhD, of The Ohio State University in Columbus, led the study, which was published online in JAMA Network Open.

LIMITATIONS:

Data used in the study excluded patients younger than 18 years. In addition, there was no analysis for trends by age or sex, which could have added valuable information to the study, the authors wrote. There was also no way to identify patients with newly diagnosed schizophrenia.

DISCLOSURES:

The study was funded through the Coronavirus Response and Relief Supplemental Appropriations Act and the Ohio Department of Mental Health and Addiction Services. Study disclosures are noted in the original study.

A version of this article appeared on Medscape.com.

High doses of a second-generation antipsychotic are associated with a significantly increased risk for death in young adults, adding to longstanding safety concerns regarding the use of higher doses of antipsychotic medication in this age group.

In a large cohort study, people aged 18-24 years had a significantly higher risk for death when starting a second-generation antipsychotic at doses greater than 100-mg chlorpromazine equivalents, but no increased mortality risk with lower doses.

There was no association with mortality risk in children aged 5-17 years with either dose.

“This finding suggests that antipsychotic medication–related fatalities are rare in healthy children without psychosis,” lead investigator Wayne Ray, PhD, from Vanderbilt University School of Medicine in Nashville, Tennessee, and colleagues wrote in a recent study that was published online in JAMA Psychiatry.

“In contrast, young adults aged 18-24 years treated with doses greater than 100-mg chlorpromazine equivalents had 127.5 additional deaths for every 100,000 person-years of exposure, suggesting further investigations of antipsychotic medication safety in this population are needed.”
 

Large, Retrospective Study

The researchers compared mortality for more than 2 million Medicaid patients aged 5-24 years (mean age, 13 years; 51% men) starting treatment with a second-generation antipsychotic vs control psychiatric medications. None of them had a diagnosis of severe somatic illness, schizophrenia, or related psychosis.

From January 2004 through September 2013, more than 21 million prescriptions were filled — roughly 5.4 million for antipsychotic doses of 100 mg or less, 2.8 million for doses greater than 100 mg, and 13.5 million for control medications.

The most commonly prescribed antipsychotic medication was risperidone, followed by aripiprazole, quetiapine, ziprasidone, and olanzapine. The most commonly prescribed control medication was clonidine, followed by atomoxetine, guanfacine, and sertraline.

In the overall study population, there was no significant association with risk for death for antipsychotic doses less than or equal to 100-mg chlorpromazine equivalents (hazard ratio [HR], 1.08; 95% CI, 0.89-1.32). However, mortality risk was increased at doses greater than 100 mg (HR, 1.37; 95% CI, 1.11-1.70).

Looking at mortality risk by age, for children aged 5-17 years, there was no significant association with either antipsychotic dose, whereas young adults aged 18-24 years had increased risk for doses greater than 100 mg (HR, 1.68; 95% CI, 1.23-2.29).
 

Start Low, Go Slow

“Start low and go slow is always a good rule of thumb when it comes to the use of these and any medicines, especially among especially among children and adolescents,” Caleb Alexander, MD, codirector of the Center for Drug Safety and Effectiveness at Johns Hopkins University in Baltimore, Maryland, who wasn’t involved in the study, told this news organization.

Alexander_Caleb_MD_web.jpg

Higher-dose antipsychotic treatment was significantly associated with overdose deaths (HR, 1.57; 95% CI, 1.02-2.42) and other unintentional injury deaths (HR, 1.57; 95% CI, 1.12-2.22), but not with nonoverdose suicide deaths or cardiovascular/metabolic deaths.

Death certificates listed opioid involvement in more than half of overdose deaths in those taking higher antipsychotic doses as well as those taking control medications.

“That’s a good reminder that the risk of these medicines may increase markedly when they’re combined with other treatments, such as prescription opioids,” Dr. Alexander said.

Also weighing in on the research, Anish Dube, MD, chair of the American Psychiatric Association’s Council on Children, Adolescents, and their Families, said the study is “notable for both the increased risk of death among young adults 18-24 prescribed treatment with antipsychotics at doses greater than 100-mg chlorpromazine equivalents, but also for the absence of such a finding with antipsychotic use in younger age groups,” he said.

“This suggests an interaction between other factors more common to young adults, such as substance use as mentioned by the authors, and concurrent treatment with antipsychotic medications at doses greater than 100-mg chlorpromazine equivalents,” said Dr. Dube.

“As the authors point out, additional research is needed to help clarify the observed increased risk of death at this developmental juncture so as to allow us to better predict which young adults may be especially vulnerable,” Dr. Dube said.

The findings also point to a need for caution when prescribing any antipsychotic medications off label, Dr. Dube added, especially among people aged 18-24 years, and other treatments should be considered when possible.

“Thankfully, with greater awareness and increased scrutiny, overall prescriptions for antipsychotic medications in the pediatric and young adult populations have likely decreased since the study period,” he said.

Limitations of the study include potential residual confounding, confining the study population to Medicaid recipients, restriction to second-generation antipsychotics, and exclusion of individuals with psychoses or severe somatic illness. Also, insufficient numbers of deaths from specific causes precluded an examination of individual antipsychotics or more detailed dose categories.

“No study is perfect,” said Dr. Alexander, “and some of the findings may be due to unmeasured differences between the groups that were being compared. That’s the elephant in the room.”

The study was funded by a grant from the National Institute for Child Health and Human Development. Dr. Ray, Dr. Alexander, and Dr. Dube have no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

High doses of a second-generation antipsychotic are associated with a significantly increased risk for death in young adults, adding to longstanding safety concerns regarding the use of higher doses of antipsychotic medication in this age group.

In a large cohort study, people aged 18-24 years had a significantly higher risk for death when starting a second-generation antipsychotic at doses greater than 100-mg chlorpromazine equivalents, but no increased mortality risk with lower doses.

There was no association with mortality risk in children aged 5-17 years with either dose.

“This finding suggests that antipsychotic medication–related fatalities are rare in healthy children without psychosis,” lead investigator Wayne Ray, PhD, from Vanderbilt University School of Medicine in Nashville, Tennessee, and colleagues wrote in a recent study that was published online in JAMA Psychiatry.

“In contrast, young adults aged 18-24 years treated with doses greater than 100-mg chlorpromazine equivalents had 127.5 additional deaths for every 100,000 person-years of exposure, suggesting further investigations of antipsychotic medication safety in this population are needed.”
 

Large, Retrospective Study

The researchers compared mortality for more than 2 million Medicaid patients aged 5-24 years (mean age, 13 years; 51% men) starting treatment with a second-generation antipsychotic vs control psychiatric medications. None of them had a diagnosis of severe somatic illness, schizophrenia, or related psychosis.

From January 2004 through September 2013, more than 21 million prescriptions were filled — roughly 5.4 million for antipsychotic doses of 100 mg or less, 2.8 million for doses greater than 100 mg, and 13.5 million for control medications.

The most commonly prescribed antipsychotic medication was risperidone, followed by aripiprazole, quetiapine, ziprasidone, and olanzapine. The most commonly prescribed control medication was clonidine, followed by atomoxetine, guanfacine, and sertraline.

In the overall study population, there was no significant association with risk for death for antipsychotic doses less than or equal to 100-mg chlorpromazine equivalents (hazard ratio [HR], 1.08; 95% CI, 0.89-1.32). However, mortality risk was increased at doses greater than 100 mg (HR, 1.37; 95% CI, 1.11-1.70).

Looking at mortality risk by age, for children aged 5-17 years, there was no significant association with either antipsychotic dose, whereas young adults aged 18-24 years had increased risk for doses greater than 100 mg (HR, 1.68; 95% CI, 1.23-2.29).
 

Start Low, Go Slow

“Start low and go slow is always a good rule of thumb when it comes to the use of these and any medicines, especially among especially among children and adolescents,” Caleb Alexander, MD, codirector of the Center for Drug Safety and Effectiveness at Johns Hopkins University in Baltimore, Maryland, who wasn’t involved in the study, told this news organization.

Alexander_Caleb_MD_web.jpg

Higher-dose antipsychotic treatment was significantly associated with overdose deaths (HR, 1.57; 95% CI, 1.02-2.42) and other unintentional injury deaths (HR, 1.57; 95% CI, 1.12-2.22), but not with nonoverdose suicide deaths or cardiovascular/metabolic deaths.

Death certificates listed opioid involvement in more than half of overdose deaths in those taking higher antipsychotic doses as well as those taking control medications.

“That’s a good reminder that the risk of these medicines may increase markedly when they’re combined with other treatments, such as prescription opioids,” Dr. Alexander said.

Also weighing in on the research, Anish Dube, MD, chair of the American Psychiatric Association’s Council on Children, Adolescents, and their Families, said the study is “notable for both the increased risk of death among young adults 18-24 prescribed treatment with antipsychotics at doses greater than 100-mg chlorpromazine equivalents, but also for the absence of such a finding with antipsychotic use in younger age groups,” he said.

“This suggests an interaction between other factors more common to young adults, such as substance use as mentioned by the authors, and concurrent treatment with antipsychotic medications at doses greater than 100-mg chlorpromazine equivalents,” said Dr. Dube.

“As the authors point out, additional research is needed to help clarify the observed increased risk of death at this developmental juncture so as to allow us to better predict which young adults may be especially vulnerable,” Dr. Dube said.

The findings also point to a need for caution when prescribing any antipsychotic medications off label, Dr. Dube added, especially among people aged 18-24 years, and other treatments should be considered when possible.

“Thankfully, with greater awareness and increased scrutiny, overall prescriptions for antipsychotic medications in the pediatric and young adult populations have likely decreased since the study period,” he said.

Limitations of the study include potential residual confounding, confining the study population to Medicaid recipients, restriction to second-generation antipsychotics, and exclusion of individuals with psychoses or severe somatic illness. Also, insufficient numbers of deaths from specific causes precluded an examination of individual antipsychotics or more detailed dose categories.

“No study is perfect,” said Dr. Alexander, “and some of the findings may be due to unmeasured differences between the groups that were being compared. That’s the elephant in the room.”

The study was funded by a grant from the National Institute for Child Health and Human Development. Dr. Ray, Dr. Alexander, and Dr. Dube have no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

High doses of a second-generation antipsychotic are associated with a significantly increased risk for death in young adults, adding to longstanding safety concerns regarding the use of higher doses of antipsychotic medication in this age group.

In a large cohort study, people aged 18-24 years had a significantly higher risk for death when starting a second-generation antipsychotic at doses greater than 100-mg chlorpromazine equivalents, but no increased mortality risk with lower doses.

There was no association with mortality risk in children aged 5-17 years with either dose.

“This finding suggests that antipsychotic medication–related fatalities are rare in healthy children without psychosis,” lead investigator Wayne Ray, PhD, from Vanderbilt University School of Medicine in Nashville, Tennessee, and colleagues wrote in a recent study that was published online in JAMA Psychiatry.

“In contrast, young adults aged 18-24 years treated with doses greater than 100-mg chlorpromazine equivalents had 127.5 additional deaths for every 100,000 person-years of exposure, suggesting further investigations of antipsychotic medication safety in this population are needed.”
 

Large, Retrospective Study

The researchers compared mortality for more than 2 million Medicaid patients aged 5-24 years (mean age, 13 years; 51% men) starting treatment with a second-generation antipsychotic vs control psychiatric medications. None of them had a diagnosis of severe somatic illness, schizophrenia, or related psychosis.

From January 2004 through September 2013, more than 21 million prescriptions were filled — roughly 5.4 million for antipsychotic doses of 100 mg or less, 2.8 million for doses greater than 100 mg, and 13.5 million for control medications.

The most commonly prescribed antipsychotic medication was risperidone, followed by aripiprazole, quetiapine, ziprasidone, and olanzapine. The most commonly prescribed control medication was clonidine, followed by atomoxetine, guanfacine, and sertraline.

In the overall study population, there was no significant association with risk for death for antipsychotic doses less than or equal to 100-mg chlorpromazine equivalents (hazard ratio [HR], 1.08; 95% CI, 0.89-1.32). However, mortality risk was increased at doses greater than 100 mg (HR, 1.37; 95% CI, 1.11-1.70).

Looking at mortality risk by age, for children aged 5-17 years, there was no significant association with either antipsychotic dose, whereas young adults aged 18-24 years had increased risk for doses greater than 100 mg (HR, 1.68; 95% CI, 1.23-2.29).
 

Start Low, Go Slow

“Start low and go slow is always a good rule of thumb when it comes to the use of these and any medicines, especially among especially among children and adolescents,” Caleb Alexander, MD, codirector of the Center for Drug Safety and Effectiveness at Johns Hopkins University in Baltimore, Maryland, who wasn’t involved in the study, told this news organization.

Alexander_Caleb_MD_web.jpg

Higher-dose antipsychotic treatment was significantly associated with overdose deaths (HR, 1.57; 95% CI, 1.02-2.42) and other unintentional injury deaths (HR, 1.57; 95% CI, 1.12-2.22), but not with nonoverdose suicide deaths or cardiovascular/metabolic deaths.

Death certificates listed opioid involvement in more than half of overdose deaths in those taking higher antipsychotic doses as well as those taking control medications.

“That’s a good reminder that the risk of these medicines may increase markedly when they’re combined with other treatments, such as prescription opioids,” Dr. Alexander said.

Also weighing in on the research, Anish Dube, MD, chair of the American Psychiatric Association’s Council on Children, Adolescents, and their Families, said the study is “notable for both the increased risk of death among young adults 18-24 prescribed treatment with antipsychotics at doses greater than 100-mg chlorpromazine equivalents, but also for the absence of such a finding with antipsychotic use in younger age groups,” he said.

“This suggests an interaction between other factors more common to young adults, such as substance use as mentioned by the authors, and concurrent treatment with antipsychotic medications at doses greater than 100-mg chlorpromazine equivalents,” said Dr. Dube.

“As the authors point out, additional research is needed to help clarify the observed increased risk of death at this developmental juncture so as to allow us to better predict which young adults may be especially vulnerable,” Dr. Dube said.

The findings also point to a need for caution when prescribing any antipsychotic medications off label, Dr. Dube added, especially among people aged 18-24 years, and other treatments should be considered when possible.

“Thankfully, with greater awareness and increased scrutiny, overall prescriptions for antipsychotic medications in the pediatric and young adult populations have likely decreased since the study period,” he said.

Limitations of the study include potential residual confounding, confining the study population to Medicaid recipients, restriction to second-generation antipsychotics, and exclusion of individuals with psychoses or severe somatic illness. Also, insufficient numbers of deaths from specific causes precluded an examination of individual antipsychotics or more detailed dose categories.

“No study is perfect,” said Dr. Alexander, “and some of the findings may be due to unmeasured differences between the groups that were being compared. That’s the elephant in the room.”

The study was funded by a grant from the National Institute for Child Health and Human Development. Dr. Ray, Dr. Alexander, and Dr. Dube have no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Stephen M. Strakowski, MD: Hello. Thank you all for joining us today. I’m very excited to have some great guests to talk about what I consider an active controversy. I’m Stephen M. Strakowski. I’m a professor and vice chair of psychiatry at Indiana University, and professor and associate vice president at University of Texas in Austin.

Today we’re going to talk about cannabis. As all of you are aware, everyone’s talking about cannabis. We hear constantly on social media and in interviews, particularly with relevance to psychiatric disorders, that everyone should be thinking about using cannabis. That seems to be the common conversation.

Last week, I had a patient who said, “All my friends tell me I need to be on cannabis.” That was their solution to her problems. With that in mind, let me introduce our guests, who are both experts on this, to talk about the role of cannabis in psychiatric disorders today.

First, I want to welcome Dr. Leslie Hulvershorn. Dr. Hulvershorn is an associate professor and chair at Indiana University in Indianapolis. Dr. Christopher Hammond is an assistant professor and the director of the co-occurring disorders program at Johns Hopkins. Welcome!

Leslie A. Hulvershorn, MD, MSc: Thank you.

Christopher J. Hammond, MD, PhD: Thank you.

Dr. Strakowski: Leslie, as I mentioned, many people are talking about how cannabis could be a good treatment for psychiatric disorders. Is that true?

Dr. Hulvershorn: If you look at what defines a good treatment, what you’re looking for is clinical trials, ideally randomized, placebo-controlled clinical trials.

When we look at research related to cannabis, we see very few of those trials, and we see that the cannabis plant is actually quite complicated and there are many different compounds that come from it. So we need to look at all the different compounds.

If you think about THC, delta 9 or delta 8, depending on the version, that’s the active ingredient that we most often think about when we say “cannabis.” If you look at THC studies, there really is no evidence that I could find that it helps psychiatric disorders.

What we do find is an enormous literature, many hunDr.eds of studies, actually, that show that THC actually worsens or even brings on psychiatric disorders. There’s a separate conversation about other compounds within the cannabis plant, like CBD, cannabidiol, where there’s maybe a signal that certain anxiety disorders might be improved by a compound like that.

Certainly, rare forms of epilepsy have been found to be improved with that compound. It really depends on what you’re looking at within the cannabis plant, but if we’re thinking about THC, the answer really is no, this is not a helpful thing. In fact, it’s probably a harmful thing to be ingesting in terms of psychiatric disorders.

Dr. Strakowski: Thank you, Leslie. Chris, what would you add to that? Do we know anything about the use of cannabis in any psychiatric condition?

Dr. Hammond: I definitely would echo what Leslie said. The popular opinion, that the media and the state legislatures have really, in many ways, put the cart before the horse — they speak about cannabis as a medication for the treatment of psychiatric conditions before we have sufficient evidence to say that it’s safe or effective for these conditions. Most of the evidence that we have, particularly in regard to the cannabinoid compound, delta 9, tetrahyDr.ocannabinol, or THC, suggests that that cannabinoid is associated with adverse mental health outcomes across different categories.

Dr. Strakowski: Our group, a long time ago, conducted a study looking at first episode of mania, and found that regular cannabis use increases the risk for subsequent manic episodes. I’m not aware of many other studies like that.

You referred, Chris, to the safety aspect. If you look at social media, the press, and the conversations where cannabis is talked about, there’s no risk, right? This is something anybody can use. There are no negative consequences. Is that true? I mean, is it really risk free?

Dr. Hammond: Research shows that that’s an inaccurate framing of the safety profile of cannabis. Again, as Leslie put it very well, cannabis is many different compounds. Using this catchall phrase of «cannabis» is not very helpful.

In regard to the main bioactive compounds of the cannabis plant, THC and cannabidiol, or CBD, what we know from studies of THC administration and from medications that have been designed to mimic THC and act on receptors that THC acts on is that those medications have clear side effects and adverse events in a percentage of patients who take them, particularly in regard to precipitating panic attacks, dysphoric episodes, and psychosis in some individuals.

Dr. Hulvershorn: I would add that it really depends on the age of the person that you’re talking about and when they’re first exposed to cannabis. If you’re talking about a person, say, under the age of 14 who uses cannabis, there’s a large amount of concern about the worsening of psychosis and mental health symptoms, but also cognitive features like memory.

There’s a very good study that was conducted in New Zealand that followed a large number of kids over time and showed significant decreases in working memory capacity for kids who used quite heavily.

Then you think about pregnant women. That’s very interesting literature, where people are finding that cannabis not only affects brain development but also a host of other systems in the body. For example, I think the risk for asthma is increased. If you look at the genes in the placenta that are affected, it has much to do with the immune system.

Women who are using cannabis during pregnancy are really exposing their fetus to a range of potential risks that we certainly don’t understand well enough, but there’s enough science that suggests this is really concerning.

If you take a step back and look at animal models, even with things like CBD products, which, again, everybody seems to be buying and they’re viewed as very safe — it’s almost hard to find things without CBD these days.

There we find, for example, in developing rats that testicular development seems to be affected with high doses of CBD. There’s just a huge array of effects, even outside of the psychiatric world, that make me very nervous about anyone using, especially a pregnant woman or a young person.

Then there’s a whole separate literature on adults. It’s hard to find studies that suggest this is a great idea. You’re going to find on the mental health side of things, and the cognitive side of things, many effects as well.

I, personally, am agnostic one way or the other. If cannabis turns out to be helpful, great. We love things that are helpful in medicine. We don’t really care where they come from. I’m not biased politically one way or the other. It’s just when you look at the totality of the literature, it’s hard to feel excited about people using cannabis at any age.

Dr. Hammond: It’s difficult to interpret the literature because of some biases there. It speaks to the importance of thoughtful research being done in this space that takes a neutral approach to assessing cannabis and looking for evidence of both potential benefit and potential harm.

The other piece that I think is of value that builds off what Leslie mentioned is the effects of cannabis and THC. The risk for harm appears to be greater in pregnant women and in young people. For adults, I think, we’re also still trying to understand what the effects are.

The other way of parsing out effects and thinking about them is in terms of the acute effects and the acute response in the moment right after one ingests cannabis vs the long-term effects.

After acute ingestion of cannabis, it can precipitate a psychotic episode, dysphoria or severe depressive symptoms, or severe anxiety, and can cause one to be disoriented, have delayed response time, and affect the ability to Dr.ive. In that capacity, it is related to a higher risk for motor vehicle crashes.

Dr. Strakowski: That’s very interesting. In my practice, and maybe it’s atypical, but half to two thirds of my patients, particularly the younger ones, are using cannabis in some form or another. In my experience, if they’re under 21, they’re more likely to use cannabis than alcohol.

What do we tell our patients? Is there a safe level of use? Do we say to never touch it? How do we manage the social pressure and environment that our patients have to live in?

Dr. Hulvershorn: I think about what we call motivational interviewing and the substance use disorder field, which is a style of interacting with someone that’s very neutral to discuss the pros and the cons. In my practice, people are usually coming to us because of problems related to their substance use.

Not everyone is experiencing those, but for those people, it’s a pretty easy discussion. It sounds like you’re getting into trouble. Your athletic performance is suffering. Your scholastic performance is suffering.

You walk them toward understanding that, wait a minute, if I smoked less weed or no weed, I would probably be doing better in this or that domain of my life. That seems to be the most helpful thing, by allowing them to come to that conclusion.

I think it is a more difficult conversation for people who don’t identify any problems related to their use. What is the right answer? Again, I just go back to saying, “Is this good for you? It’s hard to find the literature that suggests that. Is it neutral for you? Maybe, for some people. Is it harmful for some people? Absolutely.”

I think, for me, the most impactful studies have been those that showed for certain people with certain genetic makeup, cannabis is an absolutely terrible idea. Their risk for psychosis development and things like that are so high. For other people, they could smoke weed all day and never have a problem, based on their genetics — maybe. We don’t know. It’s not like we’re doing blood tests to figure out who you are.

The safest advice, I think, is no use. That’s never going to be bad advice.

Dr. Hammond: I mostly agree with Leslie on this point but feel very, very strongly that — in this era, where in the context of popular media, celebrities and other people are stating that cannabis is good and should be put in everything — clinical providers, especially pediatric providers, need to be extremely grounded in the science, and not let popular media sway our approach and strategy for working with these young people.

There’s two decades worth of data from longitudinal studies that have followed individuals from birth or from preadolescence into their thirties and forties, that show us that, for this association between cannabis use and later adverse mental health outcomes, there is a dose effect there.

The earlier an individual starts using, the more frequent they use, and more persistent their use is over time, those individuals have poorer mental health outcomes compared with individuals who choose to abstain or individuals who use just a few times and stop.

There’s also a signal for higher-THC-potency products being associated with poorer mental health outcomes, particularly when used during adolescence.

I apply a motivational interviewing approach as well to disseminate this information to both the young people and their parents about the risks, and to communicate what the data clearly show in regard to using THC-based cannabinoid products, which is that we don’t have evidence that shows that any use is healthy to the developing brain.

There’s a large amount of evidence that suggests it’s harmful to the developing brain, so the recommendation is not to use, to delay the onset of use, if you want to use, until adulthood. Many youth choose to use. For those young people, we meet them where they’re at and try to work with them on cutting down.

Dr. Strakowski: Thank you both. There’s an interesting effort in different states, with lobbying by celebrities and legislators pushing insurance companies to fund cannabis use broadly, including in a number of psychiatric indications, with no FDA approval at this point. Do you support that? Is that a good idea?

Dr. Hammond: Absolutely not.

Dr. Strakowski: Thank you.

Dr. Hammond: I think that’s a very important statement to make. For the medical and healthcare profession to stand strong related to states requiring insurance companies to cover medical cannabis really opens the door to lawsuits that would force insurance companies to cover other undertested bioactive chemicals and health supplements.

There are insufficient safety data for medical cannabis for FDA approval for any condition right now. The FDA has approved cannabinoid-based medications. Those cannabinoid-based medications have really undergone rigorous safety and efficacy testing, and have been approved for very narrow indications, none of which are psychiatric conditions.

They’ve been approved for chemotherapy-associated nausea and vomiting, treatment-resistant seizures related to two rare seizure disorders that emerge during childhood, and related to tuberous sclerosis, and one related to treating multiple sclerosis–associated spasticity and central neuropathic pain.

Dr. Hulvershorn: Steve, I think it’s important for listeners to be aware that there is a process in place for any therapeutic to become tested and reviewed. We see an industry that stands to make an enormous amount of money, and that is really the motivation for this industry.

These are not folks who are, out of the kindness of their heart, just hoping for better treatments for people. There are many ways you could channel that desire that does not include cannabis making money.

It’s really a profit-motivated industry. They’re very effective at lobbying. The public, unfortunately, has been sort of manipulated by this industry to believe that these are healthy, safe, and natural just because they grow in the ground.

Unfortunately, that’s really the issue. I think people just need to keep that in mind. Someone stands to make a large amount of money off of this. This is a very calculated, strategic approach that goes state by state but is nationally organized, and is potentially, like Chris says, for many reasons, really harmful.

I see it as sort of a bullying approach. Like if your Dr.ug works, Medicaid will pay for it. Medicaid in each state will review the studies. The FDA obviously leads the way. To cut the line without the research is really not helpful — circumventing the process that’s been in place for a long time and works well.

Dr. Hammond: Yes, it sets a dangerous precedent.

Dr. Strakowski: I was going to add the same, that it’s potentially dangerous. Thank you both, Dr.s Hulvershorn and Hammond, for a really good, lively discussion. I know we could talk for a very long time about this situation.

I do think it’s clear for listeners, most of whom are practitioners, that at this point in time, there just really does not seem to be strong evidence for the use of cannabis-based products for any psychiatric condition.

I do think we have to approach the people we’re working with around their psychiatric conditions to manage use and abuse wisely, like we would with any other substance. I appreciate everyone who’s tuned in today to watch us. I hope this is useful for your practice. Thank you.

Stephen M. Strakowski, MD, has disclosed the following relevant financial relationships:

• Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Roche; Procter & Gamble; Novartis; Sunovion
• Received income in an amount equal to or greater than $250 from: Roche; Procter & Gamble; Novartis; Sunovion; Oxford University Press

Leslie A. Hulvershorn, MD, MSc, has disclosed the following relevant financial relationships:

• Received income in an amount equal to or greater than $250 from: Greenwich Biosciences, educational grant for Summit

Christopher J. Hammond, MD, PhD, has disclosed the following relevant financial relationships:

• Received research grant from National Institutes of Health Grants; Bench to Bench Award; Substance Abuse and Mental Health Services Administration; Doris Duke.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Stephen M. Strakowski, MD: Hello. Thank you all for joining us today. I’m very excited to have some great guests to talk about what I consider an active controversy. I’m Stephen M. Strakowski. I’m a professor and vice chair of psychiatry at Indiana University, and professor and associate vice president at University of Texas in Austin.

Today we’re going to talk about cannabis. As all of you are aware, everyone’s talking about cannabis. We hear constantly on social media and in interviews, particularly with relevance to psychiatric disorders, that everyone should be thinking about using cannabis. That seems to be the common conversation.

Last week, I had a patient who said, “All my friends tell me I need to be on cannabis.” That was their solution to her problems. With that in mind, let me introduce our guests, who are both experts on this, to talk about the role of cannabis in psychiatric disorders today.

First, I want to welcome Dr. Leslie Hulvershorn. Dr. Hulvershorn is an associate professor and chair at Indiana University in Indianapolis. Dr. Christopher Hammond is an assistant professor and the director of the co-occurring disorders program at Johns Hopkins. Welcome!

Leslie A. Hulvershorn, MD, MSc: Thank you.

Christopher J. Hammond, MD, PhD: Thank you.

Dr. Strakowski: Leslie, as I mentioned, many people are talking about how cannabis could be a good treatment for psychiatric disorders. Is that true?

Dr. Hulvershorn: If you look at what defines a good treatment, what you’re looking for is clinical trials, ideally randomized, placebo-controlled clinical trials.

When we look at research related to cannabis, we see very few of those trials, and we see that the cannabis plant is actually quite complicated and there are many different compounds that come from it. So we need to look at all the different compounds.

If you think about THC, delta 9 or delta 8, depending on the version, that’s the active ingredient that we most often think about when we say “cannabis.” If you look at THC studies, there really is no evidence that I could find that it helps psychiatric disorders.

What we do find is an enormous literature, many hunDr.eds of studies, actually, that show that THC actually worsens or even brings on psychiatric disorders. There’s a separate conversation about other compounds within the cannabis plant, like CBD, cannabidiol, where there’s maybe a signal that certain anxiety disorders might be improved by a compound like that.

Certainly, rare forms of epilepsy have been found to be improved with that compound. It really depends on what you’re looking at within the cannabis plant, but if we’re thinking about THC, the answer really is no, this is not a helpful thing. In fact, it’s probably a harmful thing to be ingesting in terms of psychiatric disorders.

Dr. Strakowski: Thank you, Leslie. Chris, what would you add to that? Do we know anything about the use of cannabis in any psychiatric condition?

Dr. Hammond: I definitely would echo what Leslie said. The popular opinion, that the media and the state legislatures have really, in many ways, put the cart before the horse — they speak about cannabis as a medication for the treatment of psychiatric conditions before we have sufficient evidence to say that it’s safe or effective for these conditions. Most of the evidence that we have, particularly in regard to the cannabinoid compound, delta 9, tetrahyDr.ocannabinol, or THC, suggests that that cannabinoid is associated with adverse mental health outcomes across different categories.

Dr. Strakowski: Our group, a long time ago, conducted a study looking at first episode of mania, and found that regular cannabis use increases the risk for subsequent manic episodes. I’m not aware of many other studies like that.

You referred, Chris, to the safety aspect. If you look at social media, the press, and the conversations where cannabis is talked about, there’s no risk, right? This is something anybody can use. There are no negative consequences. Is that true? I mean, is it really risk free?

Dr. Hammond: Research shows that that’s an inaccurate framing of the safety profile of cannabis. Again, as Leslie put it very well, cannabis is many different compounds. Using this catchall phrase of «cannabis» is not very helpful.

In regard to the main bioactive compounds of the cannabis plant, THC and cannabidiol, or CBD, what we know from studies of THC administration and from medications that have been designed to mimic THC and act on receptors that THC acts on is that those medications have clear side effects and adverse events in a percentage of patients who take them, particularly in regard to precipitating panic attacks, dysphoric episodes, and psychosis in some individuals.

Dr. Hulvershorn: I would add that it really depends on the age of the person that you’re talking about and when they’re first exposed to cannabis. If you’re talking about a person, say, under the age of 14 who uses cannabis, there’s a large amount of concern about the worsening of psychosis and mental health symptoms, but also cognitive features like memory.

There’s a very good study that was conducted in New Zealand that followed a large number of kids over time and showed significant decreases in working memory capacity for kids who used quite heavily.

Then you think about pregnant women. That’s very interesting literature, where people are finding that cannabis not only affects brain development but also a host of other systems in the body. For example, I think the risk for asthma is increased. If you look at the genes in the placenta that are affected, it has much to do with the immune system.

Women who are using cannabis during pregnancy are really exposing their fetus to a range of potential risks that we certainly don’t understand well enough, but there’s enough science that suggests this is really concerning.

If you take a step back and look at animal models, even with things like CBD products, which, again, everybody seems to be buying and they’re viewed as very safe — it’s almost hard to find things without CBD these days.

There we find, for example, in developing rats that testicular development seems to be affected with high doses of CBD. There’s just a huge array of effects, even outside of the psychiatric world, that make me very nervous about anyone using, especially a pregnant woman or a young person.

Then there’s a whole separate literature on adults. It’s hard to find studies that suggest this is a great idea. You’re going to find on the mental health side of things, and the cognitive side of things, many effects as well.

I, personally, am agnostic one way or the other. If cannabis turns out to be helpful, great. We love things that are helpful in medicine. We don’t really care where they come from. I’m not biased politically one way or the other. It’s just when you look at the totality of the literature, it’s hard to feel excited about people using cannabis at any age.

Dr. Hammond: It’s difficult to interpret the literature because of some biases there. It speaks to the importance of thoughtful research being done in this space that takes a neutral approach to assessing cannabis and looking for evidence of both potential benefit and potential harm.

The other piece that I think is of value that builds off what Leslie mentioned is the effects of cannabis and THC. The risk for harm appears to be greater in pregnant women and in young people. For adults, I think, we’re also still trying to understand what the effects are.

The other way of parsing out effects and thinking about them is in terms of the acute effects and the acute response in the moment right after one ingests cannabis vs the long-term effects.

After acute ingestion of cannabis, it can precipitate a psychotic episode, dysphoria or severe depressive symptoms, or severe anxiety, and can cause one to be disoriented, have delayed response time, and affect the ability to Dr.ive. In that capacity, it is related to a higher risk for motor vehicle crashes.

Dr. Strakowski: That’s very interesting. In my practice, and maybe it’s atypical, but half to two thirds of my patients, particularly the younger ones, are using cannabis in some form or another. In my experience, if they’re under 21, they’re more likely to use cannabis than alcohol.

What do we tell our patients? Is there a safe level of use? Do we say to never touch it? How do we manage the social pressure and environment that our patients have to live in?

Dr. Hulvershorn: I think about what we call motivational interviewing and the substance use disorder field, which is a style of interacting with someone that’s very neutral to discuss the pros and the cons. In my practice, people are usually coming to us because of problems related to their substance use.

Not everyone is experiencing those, but for those people, it’s a pretty easy discussion. It sounds like you’re getting into trouble. Your athletic performance is suffering. Your scholastic performance is suffering.

You walk them toward understanding that, wait a minute, if I smoked less weed or no weed, I would probably be doing better in this or that domain of my life. That seems to be the most helpful thing, by allowing them to come to that conclusion.

I think it is a more difficult conversation for people who don’t identify any problems related to their use. What is the right answer? Again, I just go back to saying, “Is this good for you? It’s hard to find the literature that suggests that. Is it neutral for you? Maybe, for some people. Is it harmful for some people? Absolutely.”

I think, for me, the most impactful studies have been those that showed for certain people with certain genetic makeup, cannabis is an absolutely terrible idea. Their risk for psychosis development and things like that are so high. For other people, they could smoke weed all day and never have a problem, based on their genetics — maybe. We don’t know. It’s not like we’re doing blood tests to figure out who you are.

The safest advice, I think, is no use. That’s never going to be bad advice.

Dr. Hammond: I mostly agree with Leslie on this point but feel very, very strongly that — in this era, where in the context of popular media, celebrities and other people are stating that cannabis is good and should be put in everything — clinical providers, especially pediatric providers, need to be extremely grounded in the science, and not let popular media sway our approach and strategy for working with these young people.

There’s two decades worth of data from longitudinal studies that have followed individuals from birth or from preadolescence into their thirties and forties, that show us that, for this association between cannabis use and later adverse mental health outcomes, there is a dose effect there.

The earlier an individual starts using, the more frequent they use, and more persistent their use is over time, those individuals have poorer mental health outcomes compared with individuals who choose to abstain or individuals who use just a few times and stop.

There’s also a signal for higher-THC-potency products being associated with poorer mental health outcomes, particularly when used during adolescence.

I apply a motivational interviewing approach as well to disseminate this information to both the young people and their parents about the risks, and to communicate what the data clearly show in regard to using THC-based cannabinoid products, which is that we don’t have evidence that shows that any use is healthy to the developing brain.

There’s a large amount of evidence that suggests it’s harmful to the developing brain, so the recommendation is not to use, to delay the onset of use, if you want to use, until adulthood. Many youth choose to use. For those young people, we meet them where they’re at and try to work with them on cutting down.

Dr. Strakowski: Thank you both. There’s an interesting effort in different states, with lobbying by celebrities and legislators pushing insurance companies to fund cannabis use broadly, including in a number of psychiatric indications, with no FDA approval at this point. Do you support that? Is that a good idea?

Dr. Hammond: Absolutely not.

Dr. Strakowski: Thank you.

Dr. Hammond: I think that’s a very important statement to make. For the medical and healthcare profession to stand strong related to states requiring insurance companies to cover medical cannabis really opens the door to lawsuits that would force insurance companies to cover other undertested bioactive chemicals and health supplements.

There are insufficient safety data for medical cannabis for FDA approval for any condition right now. The FDA has approved cannabinoid-based medications. Those cannabinoid-based medications have really undergone rigorous safety and efficacy testing, and have been approved for very narrow indications, none of which are psychiatric conditions.

They’ve been approved for chemotherapy-associated nausea and vomiting, treatment-resistant seizures related to two rare seizure disorders that emerge during childhood, and related to tuberous sclerosis, and one related to treating multiple sclerosis–associated spasticity and central neuropathic pain.

Dr. Hulvershorn: Steve, I think it’s important for listeners to be aware that there is a process in place for any therapeutic to become tested and reviewed. We see an industry that stands to make an enormous amount of money, and that is really the motivation for this industry.

These are not folks who are, out of the kindness of their heart, just hoping for better treatments for people. There are many ways you could channel that desire that does not include cannabis making money.

It’s really a profit-motivated industry. They’re very effective at lobbying. The public, unfortunately, has been sort of manipulated by this industry to believe that these are healthy, safe, and natural just because they grow in the ground.

Unfortunately, that’s really the issue. I think people just need to keep that in mind. Someone stands to make a large amount of money off of this. This is a very calculated, strategic approach that goes state by state but is nationally organized, and is potentially, like Chris says, for many reasons, really harmful.

I see it as sort of a bullying approach. Like if your Dr.ug works, Medicaid will pay for it. Medicaid in each state will review the studies. The FDA obviously leads the way. To cut the line without the research is really not helpful — circumventing the process that’s been in place for a long time and works well.

Dr. Hammond: Yes, it sets a dangerous precedent.

Dr. Strakowski: I was going to add the same, that it’s potentially dangerous. Thank you both, Dr.s Hulvershorn and Hammond, for a really good, lively discussion. I know we could talk for a very long time about this situation.

I do think it’s clear for listeners, most of whom are practitioners, that at this point in time, there just really does not seem to be strong evidence for the use of cannabis-based products for any psychiatric condition.

I do think we have to approach the people we’re working with around their psychiatric conditions to manage use and abuse wisely, like we would with any other substance. I appreciate everyone who’s tuned in today to watch us. I hope this is useful for your practice. Thank you.

Stephen M. Strakowski, MD, has disclosed the following relevant financial relationships:

• Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Roche; Procter & Gamble; Novartis; Sunovion
• Received income in an amount equal to or greater than $250 from: Roche; Procter & Gamble; Novartis; Sunovion; Oxford University Press

Leslie A. Hulvershorn, MD, MSc, has disclosed the following relevant financial relationships:

• Received income in an amount equal to or greater than $250 from: Greenwich Biosciences, educational grant for Summit

Christopher J. Hammond, MD, PhD, has disclosed the following relevant financial relationships:

• Received research grant from National Institutes of Health Grants; Bench to Bench Award; Substance Abuse and Mental Health Services Administration; Doris Duke.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Stephen M. Strakowski, MD: Hello. Thank you all for joining us today. I’m very excited to have some great guests to talk about what I consider an active controversy. I’m Stephen M. Strakowski. I’m a professor and vice chair of psychiatry at Indiana University, and professor and associate vice president at University of Texas in Austin.

Today we’re going to talk about cannabis. As all of you are aware, everyone’s talking about cannabis. We hear constantly on social media and in interviews, particularly with relevance to psychiatric disorders, that everyone should be thinking about using cannabis. That seems to be the common conversation.

Last week, I had a patient who said, “All my friends tell me I need to be on cannabis.” That was their solution to her problems. With that in mind, let me introduce our guests, who are both experts on this, to talk about the role of cannabis in psychiatric disorders today.

First, I want to welcome Dr. Leslie Hulvershorn. Dr. Hulvershorn is an associate professor and chair at Indiana University in Indianapolis. Dr. Christopher Hammond is an assistant professor and the director of the co-occurring disorders program at Johns Hopkins. Welcome!

Leslie A. Hulvershorn, MD, MSc: Thank you.

Christopher J. Hammond, MD, PhD: Thank you.

Dr. Strakowski: Leslie, as I mentioned, many people are talking about how cannabis could be a good treatment for psychiatric disorders. Is that true?

Dr. Hulvershorn: If you look at what defines a good treatment, what you’re looking for is clinical trials, ideally randomized, placebo-controlled clinical trials.

When we look at research related to cannabis, we see very few of those trials, and we see that the cannabis plant is actually quite complicated and there are many different compounds that come from it. So we need to look at all the different compounds.

If you think about THC, delta 9 or delta 8, depending on the version, that’s the active ingredient that we most often think about when we say “cannabis.” If you look at THC studies, there really is no evidence that I could find that it helps psychiatric disorders.

What we do find is an enormous literature, many hunDr.eds of studies, actually, that show that THC actually worsens or even brings on psychiatric disorders. There’s a separate conversation about other compounds within the cannabis plant, like CBD, cannabidiol, where there’s maybe a signal that certain anxiety disorders might be improved by a compound like that.

Certainly, rare forms of epilepsy have been found to be improved with that compound. It really depends on what you’re looking at within the cannabis plant, but if we’re thinking about THC, the answer really is no, this is not a helpful thing. In fact, it’s probably a harmful thing to be ingesting in terms of psychiatric disorders.

Dr. Strakowski: Thank you, Leslie. Chris, what would you add to that? Do we know anything about the use of cannabis in any psychiatric condition?

Dr. Hammond: I definitely would echo what Leslie said. The popular opinion, that the media and the state legislatures have really, in many ways, put the cart before the horse — they speak about cannabis as a medication for the treatment of psychiatric conditions before we have sufficient evidence to say that it’s safe or effective for these conditions. Most of the evidence that we have, particularly in regard to the cannabinoid compound, delta 9, tetrahyDr.ocannabinol, or THC, suggests that that cannabinoid is associated with adverse mental health outcomes across different categories.

Dr. Strakowski: Our group, a long time ago, conducted a study looking at first episode of mania, and found that regular cannabis use increases the risk for subsequent manic episodes. I’m not aware of many other studies like that.

You referred, Chris, to the safety aspect. If you look at social media, the press, and the conversations where cannabis is talked about, there’s no risk, right? This is something anybody can use. There are no negative consequences. Is that true? I mean, is it really risk free?

Dr. Hammond: Research shows that that’s an inaccurate framing of the safety profile of cannabis. Again, as Leslie put it very well, cannabis is many different compounds. Using this catchall phrase of «cannabis» is not very helpful.

In regard to the main bioactive compounds of the cannabis plant, THC and cannabidiol, or CBD, what we know from studies of THC administration and from medications that have been designed to mimic THC and act on receptors that THC acts on is that those medications have clear side effects and adverse events in a percentage of patients who take them, particularly in regard to precipitating panic attacks, dysphoric episodes, and psychosis in some individuals.

Dr. Hulvershorn: I would add that it really depends on the age of the person that you’re talking about and when they’re first exposed to cannabis. If you’re talking about a person, say, under the age of 14 who uses cannabis, there’s a large amount of concern about the worsening of psychosis and mental health symptoms, but also cognitive features like memory.

There’s a very good study that was conducted in New Zealand that followed a large number of kids over time and showed significant decreases in working memory capacity for kids who used quite heavily.

Then you think about pregnant women. That’s very interesting literature, where people are finding that cannabis not only affects brain development but also a host of other systems in the body. For example, I think the risk for asthma is increased. If you look at the genes in the placenta that are affected, it has much to do with the immune system.

Women who are using cannabis during pregnancy are really exposing their fetus to a range of potential risks that we certainly don’t understand well enough, but there’s enough science that suggests this is really concerning.

If you take a step back and look at animal models, even with things like CBD products, which, again, everybody seems to be buying and they’re viewed as very safe — it’s almost hard to find things without CBD these days.

There we find, for example, in developing rats that testicular development seems to be affected with high doses of CBD. There’s just a huge array of effects, even outside of the psychiatric world, that make me very nervous about anyone using, especially a pregnant woman or a young person.

Then there’s a whole separate literature on adults. It’s hard to find studies that suggest this is a great idea. You’re going to find on the mental health side of things, and the cognitive side of things, many effects as well.

I, personally, am agnostic one way or the other. If cannabis turns out to be helpful, great. We love things that are helpful in medicine. We don’t really care where they come from. I’m not biased politically one way or the other. It’s just when you look at the totality of the literature, it’s hard to feel excited about people using cannabis at any age.

Dr. Hammond: It’s difficult to interpret the literature because of some biases there. It speaks to the importance of thoughtful research being done in this space that takes a neutral approach to assessing cannabis and looking for evidence of both potential benefit and potential harm.

The other piece that I think is of value that builds off what Leslie mentioned is the effects of cannabis and THC. The risk for harm appears to be greater in pregnant women and in young people. For adults, I think, we’re also still trying to understand what the effects are.

The other way of parsing out effects and thinking about them is in terms of the acute effects and the acute response in the moment right after one ingests cannabis vs the long-term effects.

After acute ingestion of cannabis, it can precipitate a psychotic episode, dysphoria or severe depressive symptoms, or severe anxiety, and can cause one to be disoriented, have delayed response time, and affect the ability to Dr.ive. In that capacity, it is related to a higher risk for motor vehicle crashes.

Dr. Strakowski: That’s very interesting. In my practice, and maybe it’s atypical, but half to two thirds of my patients, particularly the younger ones, are using cannabis in some form or another. In my experience, if they’re under 21, they’re more likely to use cannabis than alcohol.

What do we tell our patients? Is there a safe level of use? Do we say to never touch it? How do we manage the social pressure and environment that our patients have to live in?

Dr. Hulvershorn: I think about what we call motivational interviewing and the substance use disorder field, which is a style of interacting with someone that’s very neutral to discuss the pros and the cons. In my practice, people are usually coming to us because of problems related to their substance use.

Not everyone is experiencing those, but for those people, it’s a pretty easy discussion. It sounds like you’re getting into trouble. Your athletic performance is suffering. Your scholastic performance is suffering.

You walk them toward understanding that, wait a minute, if I smoked less weed or no weed, I would probably be doing better in this or that domain of my life. That seems to be the most helpful thing, by allowing them to come to that conclusion.

I think it is a more difficult conversation for people who don’t identify any problems related to their use. What is the right answer? Again, I just go back to saying, “Is this good for you? It’s hard to find the literature that suggests that. Is it neutral for you? Maybe, for some people. Is it harmful for some people? Absolutely.”

I think, for me, the most impactful studies have been those that showed for certain people with certain genetic makeup, cannabis is an absolutely terrible idea. Their risk for psychosis development and things like that are so high. For other people, they could smoke weed all day and never have a problem, based on their genetics — maybe. We don’t know. It’s not like we’re doing blood tests to figure out who you are.

The safest advice, I think, is no use. That’s never going to be bad advice.

Dr. Hammond: I mostly agree with Leslie on this point but feel very, very strongly that — in this era, where in the context of popular media, celebrities and other people are stating that cannabis is good and should be put in everything — clinical providers, especially pediatric providers, need to be extremely grounded in the science, and not let popular media sway our approach and strategy for working with these young people.

There’s two decades worth of data from longitudinal studies that have followed individuals from birth or from preadolescence into their thirties and forties, that show us that, for this association between cannabis use and later adverse mental health outcomes, there is a dose effect there.

The earlier an individual starts using, the more frequent they use, and more persistent their use is over time, those individuals have poorer mental health outcomes compared with individuals who choose to abstain or individuals who use just a few times and stop.

There’s also a signal for higher-THC-potency products being associated with poorer mental health outcomes, particularly when used during adolescence.

I apply a motivational interviewing approach as well to disseminate this information to both the young people and their parents about the risks, and to communicate what the data clearly show in regard to using THC-based cannabinoid products, which is that we don’t have evidence that shows that any use is healthy to the developing brain.

There’s a large amount of evidence that suggests it’s harmful to the developing brain, so the recommendation is not to use, to delay the onset of use, if you want to use, until adulthood. Many youth choose to use. For those young people, we meet them where they’re at and try to work with them on cutting down.

Dr. Strakowski: Thank you both. There’s an interesting effort in different states, with lobbying by celebrities and legislators pushing insurance companies to fund cannabis use broadly, including in a number of psychiatric indications, with no FDA approval at this point. Do you support that? Is that a good idea?

Dr. Hammond: Absolutely not.

Dr. Strakowski: Thank you.

Dr. Hammond: I think that’s a very important statement to make. For the medical and healthcare profession to stand strong related to states requiring insurance companies to cover medical cannabis really opens the door to lawsuits that would force insurance companies to cover other undertested bioactive chemicals and health supplements.

There are insufficient safety data for medical cannabis for FDA approval for any condition right now. The FDA has approved cannabinoid-based medications. Those cannabinoid-based medications have really undergone rigorous safety and efficacy testing, and have been approved for very narrow indications, none of which are psychiatric conditions.

They’ve been approved for chemotherapy-associated nausea and vomiting, treatment-resistant seizures related to two rare seizure disorders that emerge during childhood, and related to tuberous sclerosis, and one related to treating multiple sclerosis–associated spasticity and central neuropathic pain.

Dr. Hulvershorn: Steve, I think it’s important for listeners to be aware that there is a process in place for any therapeutic to become tested and reviewed. We see an industry that stands to make an enormous amount of money, and that is really the motivation for this industry.

These are not folks who are, out of the kindness of their heart, just hoping for better treatments for people. There are many ways you could channel that desire that does not include cannabis making money.

It’s really a profit-motivated industry. They’re very effective at lobbying. The public, unfortunately, has been sort of manipulated by this industry to believe that these are healthy, safe, and natural just because they grow in the ground.

Unfortunately, that’s really the issue. I think people just need to keep that in mind. Someone stands to make a large amount of money off of this. This is a very calculated, strategic approach that goes state by state but is nationally organized, and is potentially, like Chris says, for many reasons, really harmful.

I see it as sort of a bullying approach. Like if your Dr.ug works, Medicaid will pay for it. Medicaid in each state will review the studies. The FDA obviously leads the way. To cut the line without the research is really not helpful — circumventing the process that’s been in place for a long time and works well.

Dr. Hammond: Yes, it sets a dangerous precedent.

Dr. Strakowski: I was going to add the same, that it’s potentially dangerous. Thank you both, Dr.s Hulvershorn and Hammond, for a really good, lively discussion. I know we could talk for a very long time about this situation.

I do think it’s clear for listeners, most of whom are practitioners, that at this point in time, there just really does not seem to be strong evidence for the use of cannabis-based products for any psychiatric condition.

I do think we have to approach the people we’re working with around their psychiatric conditions to manage use and abuse wisely, like we would with any other substance. I appreciate everyone who’s tuned in today to watch us. I hope this is useful for your practice. Thank you.

Stephen M. Strakowski, MD, has disclosed the following relevant financial relationships:

• Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Roche; Procter & Gamble; Novartis; Sunovion
• Received income in an amount equal to or greater than $250 from: Roche; Procter & Gamble; Novartis; Sunovion; Oxford University Press

Leslie A. Hulvershorn, MD, MSc, has disclosed the following relevant financial relationships:

• Received income in an amount equal to or greater than $250 from: Greenwich Biosciences, educational grant for Summit

Christopher J. Hammond, MD, PhD, has disclosed the following relevant financial relationships:

• Received research grant from National Institutes of Health Grants; Bench to Bench Award; Substance Abuse and Mental Health Services Administration; Doris Duke.

A version of this article appeared on Medscape.com.

TOPLINE:

Attention-deficit/hyperactivity disorder (ADHD) and comorbid psychiatric disorders are associated with a twofold increased risk for schizophrenia, new research shows.

METHODOLOGY:

• Investigators analyzed the data of 211,705 people aged 5-19 years (74% male; 54% aged 5-9 years) diagnosed with ADHD during 2010-2018 from the Health Insurance Review and Assessment Service database of South Korea.
• Participants with a diagnosis of schizophrenia or psychosis anytime in the 3 years prior to ADHD diagnosis were excluded.
• Investigators split participants into two groups — a group of those diagnosed with at least one psychiatric comorbidity within a year of ADHD diagnosis and another group comprising those with ADHD and no psychiatric comorbidities.

TAKEAWAY:

• 37% (77,890) of those with ADHD had at least one comorbid psychiatric disorder.
• Participants with one psychiatric comorbidity had a 2.1-fold increased risk for a schizophrenia diagnosis than participants with no comorbidity (adjusted hazard ratio [aHR], 2.14; 95% CI, 2.05-2.23).
• Schizophrenia risk increased with each additional comorbidity. There was a fourfold increased risk for schizophrenia in study participants with three or more psychiatric comorbidities (aHR, 4.26; 95% CI, 3.90-4.65) than those with no comorbidity.
• Psychiatric comorbidities included autism spectrum disorder, which had the strongest link to increased schizophrenia risk (aHR, 2.43; 95% CI, 2.26-2.62). Other comorbidities that showed strong associations were intellectual disability (aHR, 1.83; 95% CI, 1.72-1.95), tic disorder (aHR, 1.77; 95% CI, 1.66-1.88), depression (aHR,1.68; 95% CI, 1.60-1.77), and bipolar disorder (aHR, 1.67; 95% CI, 1.53-1.83).

IN PRACTICE:

“To our knowledge, this is the first study to investigate schizophrenia risk among children and adolescents with ADHD, with a particular focus on psychiatric comorbidities,” the researchers wrote. They also noted that although patients had no psychiatric comorbidities at the time of ADHD diagnosis, the occurrence of psychiatric comorbidities was frequently observed prior to schizophrenia diagnosis. 

“These findings highlighted the significance of carefully monitoring psychiatric comorbidities in patients with ADHD to effectively mitigate the burden of schizophrenia,” they noted.

SOURCE:

Soo Min Jeon, PharmD, PhD, of Jeju National University in Jeju, South Korea, led the study, which was published online on November 30, 2023 in JAMA Network Open. 

LIMITATIONS:

Since the diagnosis of ADHD, schizophrenia, and other psychiatric comorbidities were based on diagnostic codes, the possibility of underdiagnosis or overdiagnosis cannot be ruled out. Also, some patients with ADHD chose the general health consultation (International Classification of Diseases - Z code) due to the social stigma surrounding mental health problems.

DISCLOSURES:

The study was funded by the Basic Science Research Program through the Ministry of Education and the Health Insurance Review and Assessment Service. Author disclosures can be found in the original paper.

A version of this article appeared on Medscape.com.

TOPLINE:

Attention-deficit/hyperactivity disorder (ADHD) and comorbid psychiatric disorders are associated with a twofold increased risk for schizophrenia, new research shows.

METHODOLOGY:

• Investigators analyzed the data of 211,705 people aged 5-19 years (74% male; 54% aged 5-9 years) diagnosed with ADHD during 2010-2018 from the Health Insurance Review and Assessment Service database of South Korea.
• Participants with a diagnosis of schizophrenia or psychosis anytime in the 3 years prior to ADHD diagnosis were excluded.
• Investigators split participants into two groups — a group of those diagnosed with at least one psychiatric comorbidity within a year of ADHD diagnosis and another group comprising those with ADHD and no psychiatric comorbidities.

TAKEAWAY:

• 37% (77,890) of those with ADHD had at least one comorbid psychiatric disorder.
• Participants with one psychiatric comorbidity had a 2.1-fold increased risk for a schizophrenia diagnosis than participants with no comorbidity (adjusted hazard ratio [aHR], 2.14; 95% CI, 2.05-2.23).
• Schizophrenia risk increased with each additional comorbidity. There was a fourfold increased risk for schizophrenia in study participants with three or more psychiatric comorbidities (aHR, 4.26; 95% CI, 3.90-4.65) than those with no comorbidity.
• Psychiatric comorbidities included autism spectrum disorder, which had the strongest link to increased schizophrenia risk (aHR, 2.43; 95% CI, 2.26-2.62). Other comorbidities that showed strong associations were intellectual disability (aHR, 1.83; 95% CI, 1.72-1.95), tic disorder (aHR, 1.77; 95% CI, 1.66-1.88), depression (aHR,1.68; 95% CI, 1.60-1.77), and bipolar disorder (aHR, 1.67; 95% CI, 1.53-1.83).

IN PRACTICE:

“To our knowledge, this is the first study to investigate schizophrenia risk among children and adolescents with ADHD, with a particular focus on psychiatric comorbidities,” the researchers wrote. They also noted that although patients had no psychiatric comorbidities at the time of ADHD diagnosis, the occurrence of psychiatric comorbidities was frequently observed prior to schizophrenia diagnosis. 

“These findings highlighted the significance of carefully monitoring psychiatric comorbidities in patients with ADHD to effectively mitigate the burden of schizophrenia,” they noted.

SOURCE:

Soo Min Jeon, PharmD, PhD, of Jeju National University in Jeju, South Korea, led the study, which was published online on November 30, 2023 in JAMA Network Open. 

LIMITATIONS:

Since the diagnosis of ADHD, schizophrenia, and other psychiatric comorbidities were based on diagnostic codes, the possibility of underdiagnosis or overdiagnosis cannot be ruled out. Also, some patients with ADHD chose the general health consultation (International Classification of Diseases - Z code) due to the social stigma surrounding mental health problems.

DISCLOSURES:

The study was funded by the Basic Science Research Program through the Ministry of Education and the Health Insurance Review and Assessment Service. Author disclosures can be found in the original paper.

A version of this article appeared on Medscape.com.

TOPLINE:

Attention-deficit/hyperactivity disorder (ADHD) and comorbid psychiatric disorders are associated with a twofold increased risk for schizophrenia, new research shows.

METHODOLOGY:

• Investigators analyzed the data of 211,705 people aged 5-19 years (74% male; 54% aged 5-9 years) diagnosed with ADHD during 2010-2018 from the Health Insurance Review and Assessment Service database of South Korea.
• Participants with a diagnosis of schizophrenia or psychosis anytime in the 3 years prior to ADHD diagnosis were excluded.
• Investigators split participants into two groups — a group of those diagnosed with at least one psychiatric comorbidity within a year of ADHD diagnosis and another group comprising those with ADHD and no psychiatric comorbidities.

TAKEAWAY:

• 37% (77,890) of those with ADHD had at least one comorbid psychiatric disorder.
• Participants with one psychiatric comorbidity had a 2.1-fold increased risk for a schizophrenia diagnosis than participants with no comorbidity (adjusted hazard ratio [aHR], 2.14; 95% CI, 2.05-2.23).
• Schizophrenia risk increased with each additional comorbidity. There was a fourfold increased risk for schizophrenia in study participants with three or more psychiatric comorbidities (aHR, 4.26; 95% CI, 3.90-4.65) than those with no comorbidity.
• Psychiatric comorbidities included autism spectrum disorder, which had the strongest link to increased schizophrenia risk (aHR, 2.43; 95% CI, 2.26-2.62). Other comorbidities that showed strong associations were intellectual disability (aHR, 1.83; 95% CI, 1.72-1.95), tic disorder (aHR, 1.77; 95% CI, 1.66-1.88), depression (aHR,1.68; 95% CI, 1.60-1.77), and bipolar disorder (aHR, 1.67; 95% CI, 1.53-1.83).

IN PRACTICE:

“To our knowledge, this is the first study to investigate schizophrenia risk among children and adolescents with ADHD, with a particular focus on psychiatric comorbidities,” the researchers wrote. They also noted that although patients had no psychiatric comorbidities at the time of ADHD diagnosis, the occurrence of psychiatric comorbidities was frequently observed prior to schizophrenia diagnosis. 

“These findings highlighted the significance of carefully monitoring psychiatric comorbidities in patients with ADHD to effectively mitigate the burden of schizophrenia,” they noted.

SOURCE:

Soo Min Jeon, PharmD, PhD, of Jeju National University in Jeju, South Korea, led the study, which was published online on November 30, 2023 in JAMA Network Open. 

LIMITATIONS:

Since the diagnosis of ADHD, schizophrenia, and other psychiatric comorbidities were based on diagnostic codes, the possibility of underdiagnosis or overdiagnosis cannot be ruled out. Also, some patients with ADHD chose the general health consultation (International Classification of Diseases - Z code) due to the social stigma surrounding mental health problems.

DISCLOSURES:

The study was funded by the Basic Science Research Program through the Ministry of Education and the Health Insurance Review and Assessment Service. Author disclosures can be found in the original paper.

A version of this article appeared on Medscape.com.

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

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

Cohen_Lee_S_BOSTON_web.jpg

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

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

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

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

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

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

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

Looking ahead

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

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

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

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

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

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

Cohen_Lee_S_BOSTON_web.jpg

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

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

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

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

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

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

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

Looking ahead

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

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

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

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

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

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

Cohen_Lee_S_BOSTON_web.jpg

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

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

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

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

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

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

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

Looking ahead

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

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

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

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