Schizophrenia & Other Psychotic Disorders

Black patients presenting with psychiatric disorders to hospital emergency departments across the United States have significantly higher rates of chemical restraint than their White counterparts, new research shows.

Results of a national study showed Black patients presenting to the ED were 63% more likely to receive chemical sedation than White patients. The investigators also found White patients were more likely to receive chemical sedation at hospitals with a higher proportion of Black patients – a finding that suggests hospital demographics influence practice patterns and that structural racism may be a root cause.

“There is a large disparity in the rates at which patients who presented to EDs nationally in the United States are restrained by race. You are 63% more likely, for the same set of chief complaints, to be chemically sedated if you are Black versus if you’re White,” senior investigator Ari Friedman, MD, PhD, an assistant professor of emergency medicine, and medical ethics and health policy, University of Pennsylvania, Philadelphia, told this news organization.

University of Pennsylvania

First large-scale study

Chemical sedation, also known as chemical restraint, is used to calm and help protect patients from harming themselves or others. Previous research on racial differences in the care of ED psychiatric patients with agitation suggests that there may be treatment disparities.

“Previous research from single institutions [has] shown that Black patients are more likely than White patients to be physically restrained, and this has been shown to be true among adult patients and pediatric patients,” lead author Utsha Khatri, MD, assistant professor of emergency medicine at the Icahn School of Medicine, New York, told this news organization.

Specifically, two single-institution studies within the last year revealed similar disparities, with higher rates of physical restraint for Black and Hispanic psychiatric patients in the ED. Another recent study showed an association with race, ethnicity, and pharmacological restraint use among pediatric patients presenting to the ED for mental health concerns.

“There has been work in psychiatry on disparities in this context, although there is less work in emergency departments,” said Dr. Friedman. “We looked across all U.S. EDs as opposed to within a single health system. The major trade-offs for us were that we weren’t able to observe restraint orders, which don’t find their way into national datasets, so we had to make some inferences based on the type of medications given.”

For the study the investigators analyzed data from 2008-2018 through the National Hospital Ambulatory Medical Survey (NHAMCS) database. They examined the association of race and the administration of chemical sedation, with either an antipsychotic or ketamine, in ED visits for psychiatric disorders. These were any visit where the reason for the visit was “symptoms referable to psychological and mental disorders.”

Of the 76.2 million total ED visits evaluated, the researchers found that Black patients presenting with a psychiatric disorder were significantly more likely to receive chemical sedation with antipsychotics or ketamine than White patients presenting with the same conditions (5.3% vs. 3.0%; P < .01). This difference remained significant when accounting for admission or transfer to psychiatric facilities.
 

Combatting the forces of racism

When researchers accounted for the percent of hospital population that was Black, they found that patient race no longer affected the likelihood of chemical restraint.

“We found the key source of this racial disparity in use of chemical sedation is accounted for by the fact that hospitals that treat a higher proportion of Black patients tend to use more sedation,” said Dr. Khatri.

“Our findings suggest that patients who present to hospitals that serve a patient population that is 60% Black would have [a] roughly 1.8 times likelihood of getting chemically sedated, compared with a hospital that serves a population that is 10% Black,” she added.

“When a hospital has fewer resources, they often don’t have the staff or time to de-escalate a patient in distress and can have to resort to chemical sedation more quickly than a hospital with ample staff and resources,” said Dr. Friedman in a release.

Dr. Khatri added that the study highlights the need to combat the forces of racism by focusing not just on provider bias but by addressing the “underlying structural issues that lead to Black patients getting worse care based on where they live.”

“Hospitals have unequal distribution of resources and quality, largely patterned on the racial makeup of their patients. Dedicated training and funding for de-escalation techniques as well as sufficient staffing and availability of outpatient mental health care may help keep both patients and staff safe by reducing the use of physical restraint and chemical sedation in appropriate circumstances,” said Dr. Khatri.

Dr. Friedman noted that there will always be a need for restraint use to facilitate rapid medical evaluation and stabilization of patients, but “we want to make it as humane, thoughtful, and rare as possible, and to have a large armamentarium of alternative strategies that can be equitably applied across emergency departments.”
 

Need for widespread, systemic change

Commenting on the findings, Regina James, MD, the American Psychiatric Association’s chief of Diversity and Health Equity and deputy medical director, said the large-scale study confirms the widespread existence of racial and ethnic disparities in patients with psychiatric disorders.

Courtesy American Psychiatric Association

“This study and previous studies, not only in psychiatry but in other areas of medicine, all bring to light that there continues to be evidence of racial and ethnic disparities in health care, and this is consistent across a range of illnesses and health care services,” said Dr. James.

“It’s important that as we think about the solution, we also think about the etiology of the problem and the layers that have contributed to it – understanding, embracing, and recognizing that these differences didn’t just come up de novo. It’s policies, practices, and behaviors that got us to this point, and it’s going to be policies, practices, and behaviors that are going to move us away from this point,” noted Dr. James.

She added that future research should focus on further understanding which factors exacerbate agitation among patients and what resources directed at the hospital level, including de-escalation training, nursing staff, and waiting room crowding, may be effective at reducing the use of chemical sedation when clinically appropriate.

The authors and Dr. James report no relevant financial conflicts of interest.

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

Black patients presenting with psychiatric disorders to hospital emergency departments across the United States have significantly higher rates of chemical restraint than their White counterparts, new research shows.

Results of a national study showed Black patients presenting to the ED were 63% more likely to receive chemical sedation than White patients. The investigators also found White patients were more likely to receive chemical sedation at hospitals with a higher proportion of Black patients – a finding that suggests hospital demographics influence practice patterns and that structural racism may be a root cause.

“There is a large disparity in the rates at which patients who presented to EDs nationally in the United States are restrained by race. You are 63% more likely, for the same set of chief complaints, to be chemically sedated if you are Black versus if you’re White,” senior investigator Ari Friedman, MD, PhD, an assistant professor of emergency medicine, and medical ethics and health policy, University of Pennsylvania, Philadelphia, told this news organization.

University of Pennsylvania

First large-scale study

Chemical sedation, also known as chemical restraint, is used to calm and help protect patients from harming themselves or others. Previous research on racial differences in the care of ED psychiatric patients with agitation suggests that there may be treatment disparities.

“Previous research from single institutions [has] shown that Black patients are more likely than White patients to be physically restrained, and this has been shown to be true among adult patients and pediatric patients,” lead author Utsha Khatri, MD, assistant professor of emergency medicine at the Icahn School of Medicine, New York, told this news organization.

Specifically, two single-institution studies within the last year revealed similar disparities, with higher rates of physical restraint for Black and Hispanic psychiatric patients in the ED. Another recent study showed an association with race, ethnicity, and pharmacological restraint use among pediatric patients presenting to the ED for mental health concerns.

“There has been work in psychiatry on disparities in this context, although there is less work in emergency departments,” said Dr. Friedman. “We looked across all U.S. EDs as opposed to within a single health system. The major trade-offs for us were that we weren’t able to observe restraint orders, which don’t find their way into national datasets, so we had to make some inferences based on the type of medications given.”

For the study the investigators analyzed data from 2008-2018 through the National Hospital Ambulatory Medical Survey (NHAMCS) database. They examined the association of race and the administration of chemical sedation, with either an antipsychotic or ketamine, in ED visits for psychiatric disorders. These were any visit where the reason for the visit was “symptoms referable to psychological and mental disorders.”

Of the 76.2 million total ED visits evaluated, the researchers found that Black patients presenting with a psychiatric disorder were significantly more likely to receive chemical sedation with antipsychotics or ketamine than White patients presenting with the same conditions (5.3% vs. 3.0%; P < .01). This difference remained significant when accounting for admission or transfer to psychiatric facilities.
 

Combatting the forces of racism

When researchers accounted for the percent of hospital population that was Black, they found that patient race no longer affected the likelihood of chemical restraint.

“We found the key source of this racial disparity in use of chemical sedation is accounted for by the fact that hospitals that treat a higher proportion of Black patients tend to use more sedation,” said Dr. Khatri.

“Our findings suggest that patients who present to hospitals that serve a patient population that is 60% Black would have [a] roughly 1.8 times likelihood of getting chemically sedated, compared with a hospital that serves a population that is 10% Black,” she added.

“When a hospital has fewer resources, they often don’t have the staff or time to de-escalate a patient in distress and can have to resort to chemical sedation more quickly than a hospital with ample staff and resources,” said Dr. Friedman in a release.

Dr. Khatri added that the study highlights the need to combat the forces of racism by focusing not just on provider bias but by addressing the “underlying structural issues that lead to Black patients getting worse care based on where they live.”

“Hospitals have unequal distribution of resources and quality, largely patterned on the racial makeup of their patients. Dedicated training and funding for de-escalation techniques as well as sufficient staffing and availability of outpatient mental health care may help keep both patients and staff safe by reducing the use of physical restraint and chemical sedation in appropriate circumstances,” said Dr. Khatri.

Dr. Friedman noted that there will always be a need for restraint use to facilitate rapid medical evaluation and stabilization of patients, but “we want to make it as humane, thoughtful, and rare as possible, and to have a large armamentarium of alternative strategies that can be equitably applied across emergency departments.”
 

Need for widespread, systemic change

Commenting on the findings, Regina James, MD, the American Psychiatric Association’s chief of Diversity and Health Equity and deputy medical director, said the large-scale study confirms the widespread existence of racial and ethnic disparities in patients with psychiatric disorders.

Courtesy American Psychiatric Association

“This study and previous studies, not only in psychiatry but in other areas of medicine, all bring to light that there continues to be evidence of racial and ethnic disparities in health care, and this is consistent across a range of illnesses and health care services,” said Dr. James.

“It’s important that as we think about the solution, we also think about the etiology of the problem and the layers that have contributed to it – understanding, embracing, and recognizing that these differences didn’t just come up de novo. It’s policies, practices, and behaviors that got us to this point, and it’s going to be policies, practices, and behaviors that are going to move us away from this point,” noted Dr. James.

She added that future research should focus on further understanding which factors exacerbate agitation among patients and what resources directed at the hospital level, including de-escalation training, nursing staff, and waiting room crowding, may be effective at reducing the use of chemical sedation when clinically appropriate.

The authors and Dr. James report no relevant financial conflicts of interest.

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

Black patients presenting with psychiatric disorders to hospital emergency departments across the United States have significantly higher rates of chemical restraint than their White counterparts, new research shows.

Results of a national study showed Black patients presenting to the ED were 63% more likely to receive chemical sedation than White patients. The investigators also found White patients were more likely to receive chemical sedation at hospitals with a higher proportion of Black patients – a finding that suggests hospital demographics influence practice patterns and that structural racism may be a root cause.

“There is a large disparity in the rates at which patients who presented to EDs nationally in the United States are restrained by race. You are 63% more likely, for the same set of chief complaints, to be chemically sedated if you are Black versus if you’re White,” senior investigator Ari Friedman, MD, PhD, an assistant professor of emergency medicine, and medical ethics and health policy, University of Pennsylvania, Philadelphia, told this news organization.

University of Pennsylvania

First large-scale study

Chemical sedation, also known as chemical restraint, is used to calm and help protect patients from harming themselves or others. Previous research on racial differences in the care of ED psychiatric patients with agitation suggests that there may be treatment disparities.

“Previous research from single institutions [has] shown that Black patients are more likely than White patients to be physically restrained, and this has been shown to be true among adult patients and pediatric patients,” lead author Utsha Khatri, MD, assistant professor of emergency medicine at the Icahn School of Medicine, New York, told this news organization.

Specifically, two single-institution studies within the last year revealed similar disparities, with higher rates of physical restraint for Black and Hispanic psychiatric patients in the ED. Another recent study showed an association with race, ethnicity, and pharmacological restraint use among pediatric patients presenting to the ED for mental health concerns.

“There has been work in psychiatry on disparities in this context, although there is less work in emergency departments,” said Dr. Friedman. “We looked across all U.S. EDs as opposed to within a single health system. The major trade-offs for us were that we weren’t able to observe restraint orders, which don’t find their way into national datasets, so we had to make some inferences based on the type of medications given.”

For the study the investigators analyzed data from 2008-2018 through the National Hospital Ambulatory Medical Survey (NHAMCS) database. They examined the association of race and the administration of chemical sedation, with either an antipsychotic or ketamine, in ED visits for psychiatric disorders. These were any visit where the reason for the visit was “symptoms referable to psychological and mental disorders.”

Of the 76.2 million total ED visits evaluated, the researchers found that Black patients presenting with a psychiatric disorder were significantly more likely to receive chemical sedation with antipsychotics or ketamine than White patients presenting with the same conditions (5.3% vs. 3.0%; P < .01). This difference remained significant when accounting for admission or transfer to psychiatric facilities.
 

Combatting the forces of racism

When researchers accounted for the percent of hospital population that was Black, they found that patient race no longer affected the likelihood of chemical restraint.

“We found the key source of this racial disparity in use of chemical sedation is accounted for by the fact that hospitals that treat a higher proportion of Black patients tend to use more sedation,” said Dr. Khatri.

“Our findings suggest that patients who present to hospitals that serve a patient population that is 60% Black would have [a] roughly 1.8 times likelihood of getting chemically sedated, compared with a hospital that serves a population that is 10% Black,” she added.

“When a hospital has fewer resources, they often don’t have the staff or time to de-escalate a patient in distress and can have to resort to chemical sedation more quickly than a hospital with ample staff and resources,” said Dr. Friedman in a release.

Dr. Khatri added that the study highlights the need to combat the forces of racism by focusing not just on provider bias but by addressing the “underlying structural issues that lead to Black patients getting worse care based on where they live.”

“Hospitals have unequal distribution of resources and quality, largely patterned on the racial makeup of their patients. Dedicated training and funding for de-escalation techniques as well as sufficient staffing and availability of outpatient mental health care may help keep both patients and staff safe by reducing the use of physical restraint and chemical sedation in appropriate circumstances,” said Dr. Khatri.

Dr. Friedman noted that there will always be a need for restraint use to facilitate rapid medical evaluation and stabilization of patients, but “we want to make it as humane, thoughtful, and rare as possible, and to have a large armamentarium of alternative strategies that can be equitably applied across emergency departments.”
 

Need for widespread, systemic change

Commenting on the findings, Regina James, MD, the American Psychiatric Association’s chief of Diversity and Health Equity and deputy medical director, said the large-scale study confirms the widespread existence of racial and ethnic disparities in patients with psychiatric disorders.

Courtesy American Psychiatric Association

“This study and previous studies, not only in psychiatry but in other areas of medicine, all bring to light that there continues to be evidence of racial and ethnic disparities in health care, and this is consistent across a range of illnesses and health care services,” said Dr. James.

“It’s important that as we think about the solution, we also think about the etiology of the problem and the layers that have contributed to it – understanding, embracing, and recognizing that these differences didn’t just come up de novo. It’s policies, practices, and behaviors that got us to this point, and it’s going to be policies, practices, and behaviors that are going to move us away from this point,” noted Dr. James.

She added that future research should focus on further understanding which factors exacerbate agitation among patients and what resources directed at the hospital level, including de-escalation training, nursing staff, and waiting room crowding, may be effective at reducing the use of chemical sedation when clinically appropriate.

The authors and Dr. James report no relevant financial conflicts of interest.

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

It has been clearly established that most human infectious diseases are caused by infectious agents that have been transmitted from animals to humans.¹ Based on published estimates from the 2000s, 60% to 76% of emerging infectious disease events are transmitted from animals to humans.²

When we consider animals that cause human diseases, we usually think of rats and bats. We rarely think of the 90 million cats owned as pets in the United States, or the approximately 30 to 80 million feral cats. Many consider cats as family members, and three-fourths of cats owned in the United States are allowed to sleep on the beds of their owners.¹ These cats may be a substantial source of human disease. Researchers at the University of Liverpool have identified 273 infectious agents carried by cats, of which 151 are known to be shared with humans.¹ The most widely known of these agents are Lyssavirus, the virus that causes rabies; Bartonella henselae, the bacteria that causes cat scratch disease; and Toxoplasma gondii (T. gondii), the parasite that causes toxoplasmosis.

In my new open-access book Parasites, Pussycats and Psychosis (available at https://link.springer.com/book/10.1007/978-3-030-86811-6), I describe the relationship between cats, T. gondii, and toxoplasmosis, and detail the evidence linking T. gondii to some cases of schizophrenia, bipolar disorder, and other diseases.¹ Though human T. gondii infection is typically asymptomatic or produces minor, flu-like symptoms, there are a few important exceptions. This article outlines those exceptions, and investigates evidence that implicates a link between T. gondii and psychosis.

How T. gondii can be transmitted

T. gondii has been called “one of the most successful parasites on earth.”³ Globally, approximately one-third of the human population is infected with T. gondii, though this varies widely by country and is dependent on dietary habits and exposure to cats. A 2014 survey reported that 11% of Americans—approximately 40 million people—have been infected, as evidenced by the presence of antibodies in their blood.¹

T. gondii begins its life cycle when a cat becomes infected, usually as a kitten. Most infected cats are asymptomatic, but for approximately 8 days they excrete up to 50 million infectious oocysts in their feces daily. Depending on the temperature, these oocysts can live for 2 years or longer.It is thought that a single oocyst can cause human infection.¹ Since cats like loose soil for defecation, the infective oocysts commonly end up in gardens, uncovered sandboxes, or animal feed piles in barns. After 24 hours, the oocysts dry out and may become aerosolized. For this reason, cat owners are advised to change their cat’s litter daily.

The number of ways T. gondii can be transmitted to humans is extensive. Farm animals can become infected from contaminated feed; this causes T. gondii oocysts in animals’ muscles, which later may cause human infection if eaten as undercooked meat. Many such family outbreaks of toxoplasmosis have been described.¹

If infective oocysts get into the water supply, they may also cause outbreaks of disease. More than 200 such outbreaks have been described, including an instance in Victoria, British Columbia, in which 100 people became clinically infected.⁴

Continue to: Family outbreaks...

Family outbreaks have also been described that involve multiple children who played in an infected sandbox or dirt pile.⁵ Similarly, an outbreak has been reported in a riding stable that was home to infected cats. Infective oocysts were thought to have become aerosolized and breathed in by the patrons.⁶ Multiple other possible modes of transmission are being investigated, including sexual transmission among humans.⁷

Human infections are not always benign

In most human T. gondii cases, the infected individual experiences mild, flu-like symptoms, often with enlarged lymph nodes, or has no symptoms.¹ Thus, most people who have been infected with T. gondii are unaware because clinicians do not routinely test for it.

There are 3 exceptions to this otherwise benign clinical picture. The first is cerebral toxoplasmosis, which occurs in individuals who are immunosuppressed because they have AIDS or are receiving treatment for cancer or organ transplantation. Cerebral toxoplasmosis can be severe and was a common cause of death in patients with AIDS before the development of effective AIDS treatments.

The second exception is congenital toxoplasmosis, when an infection occurs in a pregnant woman. Such infections can cause severe damage to the developing fetus, including abortion, stillbirth, and brain damage. Congenital toxoplasmosis infections occur in approximately 1 of every 10,000 births in the United States, or approximately 3,800 each year.⁸ As a result, pregnant women are advised not to change their cat’s litter and to be tested for evidence of T. gondii infection.

The third exception is eye disease. Toxoplasmosis is one of the most common causes of eye disease, especially of the retina. Each year in the United States, approximately 4,800 individuals develop systematic ocular toxoplasmosis.⁹

Continue to: Toxoplasmosis and psychosis

Until recently, cerebral infections, congenital infections, and eye disease were thought to be the main clinical problems associated with toxoplasmosis. However, accumulating evidence suggests that psychosis should be added to this list. Five lines of evidence support this.

1. T. gondii can cause psychotic symptoms. It has been known for decades that T. gondii can cause delusions, auditory hallucinations, and other psychotic symptoms.¹ In one of the earliest publications (1966), Ladee¹⁰ concluded “The literature not infrequently focuses attention on psychosis with schizophrenia or schizophreniform features that accompany chronic toxoplasmosis.” Among the cases Ladee¹⁰ described was a laboratory worker who became infected with T. gondii and developed delusions and hallucinations.¹⁰

2. Patients with schizophrenia who are infected with T. gondii have more severe psychotic symptoms. This finding has been reported in at least 7 studies.¹ Holub et al¹¹ evaluated 251 patients with schizophrenia who were treated in Prague Psychiatric Centre between 2000 and 2010. Overall, 57 participants were infected with T. gondii and 194 were not infected. Compared to those who were not infected, the infected group:

• had significantly more severe symptoms (P = .032) as measured on the Positive and Negative Symptom Scale
• were prescribed higher doses of antipsychotic medications
• had been hospitalized longer.¹¹

3. Compared with controls, patients with psychosis are significantly more likely to have antibodies against T. gondii, indicating previous infection. To date there have been approximately 100 such studies, of which at least three-fourths reported a positive association. In a 2012 meta-analysis of 38 such studies, Torrey et al¹² reported an odds ratio (OR) of 2.7—compared to persons who have not been infected, those who have been infected with T. gondii were 2.7 times more likely to have schizophrenia.¹² This study replicated the findings of a previous meta-analysis of 23 antibody studies, which also found an OR of 2.7.¹³

4. Compared with controls, individuals with schizophrenia or bipolar disorder are significantly more likely as a child to have lived in a home with a cat. Since 1995, 10 such studies have been published; 7 were positive, 2 were negative, and 1 was inconclusive.¹ Torrey et al¹⁴ reviewed 2,025 individuals with schizophrenia or bipolar disorder and 4,847 controls and found that 51% of the cases and 43% of the controls had owned a cat before age 13; this difference was highly significant (P < .001). In fact, it is surprising that any study can find a statistically significant association between cat ownership and childhood psychosis. This is because a child who did not own a cat could become infected in many locations where cats have been present, including sandboxes at school, a babysitter’s or friend’s house, or a public park. And even if a child became infected at home, they would not necessarily have owned a cat, since the neighbor’s cat could have been responsible for the oocyst contamination.

Continue to: Epidemiologically...

5. Epidemiologically, there is a close temporal correlation between the rise of cats as pets and the rise of psychosis. This can be illustrated most clearly in England, where the rise of cat ownership has been documented by writers and where there is data on the rise of psychosis, especially in the 18th and 19th centuries.¹

How many cases of psychosis might be caused by T. gondii?

In 2014, using data from the antibody studies discussed above,^12,13 Smith¹⁵ sought to discover how many cases of psychosis might be caused by T. gondii. He concluded that 21% of cases of schizophrenia might have been caused by T. gondii. Based on the annual incidence of schizophrenia in the United States, this would mean an estimated >10,000 new cases of schizophrenia each year are attributable to this parasite.

Some researchers have found links between T. gondii and several nonpsychiatric diseases and conditions, including epilepsy and brain cancer (Box^1,16-19).

Box

Clinical implications: What to tell patients about cats

What do these studies of toxoplasmosis imply for psychiatric care? As mental health professionals, part of our job is to educate our patients. Anything that appears to be a risk factor for the development of psychosis is thus of interest. Consider discussing the following with your patients.

Are cats safe? Cats that are kept exclusively indoors are safe pets because they are unlikely to become infected with T. gondii. However, cats that are allowed to go outdoors may not be safe, especially for children and young adults. What is needed is an effective vaccine that could be given to newborn kittens to prevent infection, but development of this type of vaccine has never been prioritized. At the community level, programs to decrease the number of stray and feral cats would also decrease the risk of infection.

Continue to: How to decrease risk

How to decrease risk. On a personal level, we can decrease T. gondii infections by not eating undercooked meat. Pregnant women and individuals who are immunocompromised should not change cat litter. When gardening, we should wear gloves because cats favor loose soil for depositing their feces. We should also protect children by covering sandboxes when not in use and by not allowing children to play in uncovered public sandboxes.

Treatment. Toxoplasmosis typically is treated with pyrimethamine, usually in combination with a sulfa drug. However, pyrimethamine does not cross the blood brain barrier and thus is ineffective when T. gondii infects the brain. The development of a drug that will effectively treat T. gondii in the brain should be a high priority.

For additional details on the studies discussed in this article as well as more resources on the impact T. gondii can have if proper precautions are not taken, see my open-access book at https://link.springer.com/book/10.1007/978-3-030-86811-6.

Bottom Line

Some evidence suggests that infection with Toxoplasma gondii (T. gondii) may cause psychotic symptoms, may increase an individual’s risk of developing psychosis, and may result in more severe psychotic symptoms. Cats can transmit T. gondii to humans. Educate patients that they can reduce their risk by keeping their cats inside, avoiding exposure to cat feces, particularly while pregnant or if immunocompromised, and not eating undercooked meat.

Related Resources

• Torrey EF. Parasites, Pussycats, and Psychosis: The Unknown Dangers of Human Toxoplasmosis. Springer Nature; 2022. https://link.springer.com/book/10.1007/978-3-030-86811-6

Drug Brand Names

Pyrimethamine • Daraprim

It has been clearly established that most human infectious diseases are caused by infectious agents that have been transmitted from animals to humans.¹ Based on published estimates from the 2000s, 60% to 76% of emerging infectious disease events are transmitted from animals to humans.²

When we consider animals that cause human diseases, we usually think of rats and bats. We rarely think of the 90 million cats owned as pets in the United States, or the approximately 30 to 80 million feral cats. Many consider cats as family members, and three-fourths of cats owned in the United States are allowed to sleep on the beds of their owners.¹ These cats may be a substantial source of human disease. Researchers at the University of Liverpool have identified 273 infectious agents carried by cats, of which 151 are known to be shared with humans.¹ The most widely known of these agents are Lyssavirus, the virus that causes rabies; Bartonella henselae, the bacteria that causes cat scratch disease; and Toxoplasma gondii (T. gondii), the parasite that causes toxoplasmosis.

In my new open-access book Parasites, Pussycats and Psychosis (available at https://link.springer.com/book/10.1007/978-3-030-86811-6), I describe the relationship between cats, T. gondii, and toxoplasmosis, and detail the evidence linking T. gondii to some cases of schizophrenia, bipolar disorder, and other diseases.¹ Though human T. gondii infection is typically asymptomatic or produces minor, flu-like symptoms, there are a few important exceptions. This article outlines those exceptions, and investigates evidence that implicates a link between T. gondii and psychosis.

How T. gondii can be transmitted

T. gondii has been called “one of the most successful parasites on earth.”³ Globally, approximately one-third of the human population is infected with T. gondii, though this varies widely by country and is dependent on dietary habits and exposure to cats. A 2014 survey reported that 11% of Americans—approximately 40 million people—have been infected, as evidenced by the presence of antibodies in their blood.¹

T. gondii begins its life cycle when a cat becomes infected, usually as a kitten. Most infected cats are asymptomatic, but for approximately 8 days they excrete up to 50 million infectious oocysts in their feces daily. Depending on the temperature, these oocysts can live for 2 years or longer.It is thought that a single oocyst can cause human infection.¹ Since cats like loose soil for defecation, the infective oocysts commonly end up in gardens, uncovered sandboxes, or animal feed piles in barns. After 24 hours, the oocysts dry out and may become aerosolized. For this reason, cat owners are advised to change their cat’s litter daily.

The number of ways T. gondii can be transmitted to humans is extensive. Farm animals can become infected from contaminated feed; this causes T. gondii oocysts in animals’ muscles, which later may cause human infection if eaten as undercooked meat. Many such family outbreaks of toxoplasmosis have been described.¹

If infective oocysts get into the water supply, they may also cause outbreaks of disease. More than 200 such outbreaks have been described, including an instance in Victoria, British Columbia, in which 100 people became clinically infected.⁴

Continue to: Family outbreaks...

Family outbreaks have also been described that involve multiple children who played in an infected sandbox or dirt pile.⁵ Similarly, an outbreak has been reported in a riding stable that was home to infected cats. Infective oocysts were thought to have become aerosolized and breathed in by the patrons.⁶ Multiple other possible modes of transmission are being investigated, including sexual transmission among humans.⁷

Human infections are not always benign

In most human T. gondii cases, the infected individual experiences mild, flu-like symptoms, often with enlarged lymph nodes, or has no symptoms.¹ Thus, most people who have been infected with T. gondii are unaware because clinicians do not routinely test for it.

There are 3 exceptions to this otherwise benign clinical picture. The first is cerebral toxoplasmosis, which occurs in individuals who are immunosuppressed because they have AIDS or are receiving treatment for cancer or organ transplantation. Cerebral toxoplasmosis can be severe and was a common cause of death in patients with AIDS before the development of effective AIDS treatments.

The second exception is congenital toxoplasmosis, when an infection occurs in a pregnant woman. Such infections can cause severe damage to the developing fetus, including abortion, stillbirth, and brain damage. Congenital toxoplasmosis infections occur in approximately 1 of every 10,000 births in the United States, or approximately 3,800 each year.⁸ As a result, pregnant women are advised not to change their cat’s litter and to be tested for evidence of T. gondii infection.

The third exception is eye disease. Toxoplasmosis is one of the most common causes of eye disease, especially of the retina. Each year in the United States, approximately 4,800 individuals develop systematic ocular toxoplasmosis.⁹

Continue to: Toxoplasmosis and psychosis

Until recently, cerebral infections, congenital infections, and eye disease were thought to be the main clinical problems associated with toxoplasmosis. However, accumulating evidence suggests that psychosis should be added to this list. Five lines of evidence support this.

1. T. gondii can cause psychotic symptoms. It has been known for decades that T. gondii can cause delusions, auditory hallucinations, and other psychotic symptoms.¹ In one of the earliest publications (1966), Ladee¹⁰ concluded “The literature not infrequently focuses attention on psychosis with schizophrenia or schizophreniform features that accompany chronic toxoplasmosis.” Among the cases Ladee¹⁰ described was a laboratory worker who became infected with T. gondii and developed delusions and hallucinations.¹⁰

2. Patients with schizophrenia who are infected with T. gondii have more severe psychotic symptoms. This finding has been reported in at least 7 studies.¹ Holub et al¹¹ evaluated 251 patients with schizophrenia who were treated in Prague Psychiatric Centre between 2000 and 2010. Overall, 57 participants were infected with T. gondii and 194 were not infected. Compared to those who were not infected, the infected group:

• had significantly more severe symptoms (P = .032) as measured on the Positive and Negative Symptom Scale
• were prescribed higher doses of antipsychotic medications
• had been hospitalized longer.¹¹

3. Compared with controls, patients with psychosis are significantly more likely to have antibodies against T. gondii, indicating previous infection. To date there have been approximately 100 such studies, of which at least three-fourths reported a positive association. In a 2012 meta-analysis of 38 such studies, Torrey et al¹² reported an odds ratio (OR) of 2.7—compared to persons who have not been infected, those who have been infected with T. gondii were 2.7 times more likely to have schizophrenia.¹² This study replicated the findings of a previous meta-analysis of 23 antibody studies, which also found an OR of 2.7.¹³

4. Compared with controls, individuals with schizophrenia or bipolar disorder are significantly more likely as a child to have lived in a home with a cat. Since 1995, 10 such studies have been published; 7 were positive, 2 were negative, and 1 was inconclusive.¹ Torrey et al¹⁴ reviewed 2,025 individuals with schizophrenia or bipolar disorder and 4,847 controls and found that 51% of the cases and 43% of the controls had owned a cat before age 13; this difference was highly significant (P < .001). In fact, it is surprising that any study can find a statistically significant association between cat ownership and childhood psychosis. This is because a child who did not own a cat could become infected in many locations where cats have been present, including sandboxes at school, a babysitter’s or friend’s house, or a public park. And even if a child became infected at home, they would not necessarily have owned a cat, since the neighbor’s cat could have been responsible for the oocyst contamination.

Continue to: Epidemiologically...

5. Epidemiologically, there is a close temporal correlation between the rise of cats as pets and the rise of psychosis. This can be illustrated most clearly in England, where the rise of cat ownership has been documented by writers and where there is data on the rise of psychosis, especially in the 18th and 19th centuries.¹

How many cases of psychosis might be caused by T. gondii?

In 2014, using data from the antibody studies discussed above,^12,13 Smith¹⁵ sought to discover how many cases of psychosis might be caused by T. gondii. He concluded that 21% of cases of schizophrenia might have been caused by T. gondii. Based on the annual incidence of schizophrenia in the United States, this would mean an estimated >10,000 new cases of schizophrenia each year are attributable to this parasite.

Some researchers have found links between T. gondii and several nonpsychiatric diseases and conditions, including epilepsy and brain cancer (Box^1,16-19).

Box

Clinical implications: What to tell patients about cats

What do these studies of toxoplasmosis imply for psychiatric care? As mental health professionals, part of our job is to educate our patients. Anything that appears to be a risk factor for the development of psychosis is thus of interest. Consider discussing the following with your patients.

Are cats safe? Cats that are kept exclusively indoors are safe pets because they are unlikely to become infected with T. gondii. However, cats that are allowed to go outdoors may not be safe, especially for children and young adults. What is needed is an effective vaccine that could be given to newborn kittens to prevent infection, but development of this type of vaccine has never been prioritized. At the community level, programs to decrease the number of stray and feral cats would also decrease the risk of infection.

Continue to: How to decrease risk

How to decrease risk. On a personal level, we can decrease T. gondii infections by not eating undercooked meat. Pregnant women and individuals who are immunocompromised should not change cat litter. When gardening, we should wear gloves because cats favor loose soil for depositing their feces. We should also protect children by covering sandboxes when not in use and by not allowing children to play in uncovered public sandboxes.

Treatment. Toxoplasmosis typically is treated with pyrimethamine, usually in combination with a sulfa drug. However, pyrimethamine does not cross the blood brain barrier and thus is ineffective when T. gondii infects the brain. The development of a drug that will effectively treat T. gondii in the brain should be a high priority.

For additional details on the studies discussed in this article as well as more resources on the impact T. gondii can have if proper precautions are not taken, see my open-access book at https://link.springer.com/book/10.1007/978-3-030-86811-6.

Bottom Line

Some evidence suggests that infection with Toxoplasma gondii (T. gondii) may cause psychotic symptoms, may increase an individual’s risk of developing psychosis, and may result in more severe psychotic symptoms. Cats can transmit T. gondii to humans. Educate patients that they can reduce their risk by keeping their cats inside, avoiding exposure to cat feces, particularly while pregnant or if immunocompromised, and not eating undercooked meat.

Related Resources

• Torrey EF. Parasites, Pussycats, and Psychosis: The Unknown Dangers of Human Toxoplasmosis. Springer Nature; 2022. https://link.springer.com/book/10.1007/978-3-030-86811-6

Drug Brand Names

Pyrimethamine • Daraprim

It has been clearly established that most human infectious diseases are caused by infectious agents that have been transmitted from animals to humans.¹ Based on published estimates from the 2000s, 60% to 76% of emerging infectious disease events are transmitted from animals to humans.²

When we consider animals that cause human diseases, we usually think of rats and bats. We rarely think of the 90 million cats owned as pets in the United States, or the approximately 30 to 80 million feral cats. Many consider cats as family members, and three-fourths of cats owned in the United States are allowed to sleep on the beds of their owners.¹ These cats may be a substantial source of human disease. Researchers at the University of Liverpool have identified 273 infectious agents carried by cats, of which 151 are known to be shared with humans.¹ The most widely known of these agents are Lyssavirus, the virus that causes rabies; Bartonella henselae, the bacteria that causes cat scratch disease; and Toxoplasma gondii (T. gondii), the parasite that causes toxoplasmosis.

In my new open-access book Parasites, Pussycats and Psychosis (available at https://link.springer.com/book/10.1007/978-3-030-86811-6), I describe the relationship between cats, T. gondii, and toxoplasmosis, and detail the evidence linking T. gondii to some cases of schizophrenia, bipolar disorder, and other diseases.¹ Though human T. gondii infection is typically asymptomatic or produces minor, flu-like symptoms, there are a few important exceptions. This article outlines those exceptions, and investigates evidence that implicates a link between T. gondii and psychosis.

How T. gondii can be transmitted

T. gondii has been called “one of the most successful parasites on earth.”³ Globally, approximately one-third of the human population is infected with T. gondii, though this varies widely by country and is dependent on dietary habits and exposure to cats. A 2014 survey reported that 11% of Americans—approximately 40 million people—have been infected, as evidenced by the presence of antibodies in their blood.¹

T. gondii begins its life cycle when a cat becomes infected, usually as a kitten. Most infected cats are asymptomatic, but for approximately 8 days they excrete up to 50 million infectious oocysts in their feces daily. Depending on the temperature, these oocysts can live for 2 years or longer.It is thought that a single oocyst can cause human infection.¹ Since cats like loose soil for defecation, the infective oocysts commonly end up in gardens, uncovered sandboxes, or animal feed piles in barns. After 24 hours, the oocysts dry out and may become aerosolized. For this reason, cat owners are advised to change their cat’s litter daily.

The number of ways T. gondii can be transmitted to humans is extensive. Farm animals can become infected from contaminated feed; this causes T. gondii oocysts in animals’ muscles, which later may cause human infection if eaten as undercooked meat. Many such family outbreaks of toxoplasmosis have been described.¹

If infective oocysts get into the water supply, they may also cause outbreaks of disease. More than 200 such outbreaks have been described, including an instance in Victoria, British Columbia, in which 100 people became clinically infected.⁴

Continue to: Family outbreaks...

Family outbreaks have also been described that involve multiple children who played in an infected sandbox or dirt pile.⁵ Similarly, an outbreak has been reported in a riding stable that was home to infected cats. Infective oocysts were thought to have become aerosolized and breathed in by the patrons.⁶ Multiple other possible modes of transmission are being investigated, including sexual transmission among humans.⁷

Human infections are not always benign

In most human T. gondii cases, the infected individual experiences mild, flu-like symptoms, often with enlarged lymph nodes, or has no symptoms.¹ Thus, most people who have been infected with T. gondii are unaware because clinicians do not routinely test for it.

There are 3 exceptions to this otherwise benign clinical picture. The first is cerebral toxoplasmosis, which occurs in individuals who are immunosuppressed because they have AIDS or are receiving treatment for cancer or organ transplantation. Cerebral toxoplasmosis can be severe and was a common cause of death in patients with AIDS before the development of effective AIDS treatments.

The second exception is congenital toxoplasmosis, when an infection occurs in a pregnant woman. Such infections can cause severe damage to the developing fetus, including abortion, stillbirth, and brain damage. Congenital toxoplasmosis infections occur in approximately 1 of every 10,000 births in the United States, or approximately 3,800 each year.⁸ As a result, pregnant women are advised not to change their cat’s litter and to be tested for evidence of T. gondii infection.

The third exception is eye disease. Toxoplasmosis is one of the most common causes of eye disease, especially of the retina. Each year in the United States, approximately 4,800 individuals develop systematic ocular toxoplasmosis.⁹

Continue to: Toxoplasmosis and psychosis

Until recently, cerebral infections, congenital infections, and eye disease were thought to be the main clinical problems associated with toxoplasmosis. However, accumulating evidence suggests that psychosis should be added to this list. Five lines of evidence support this.

1. T. gondii can cause psychotic symptoms. It has been known for decades that T. gondii can cause delusions, auditory hallucinations, and other psychotic symptoms.¹ In one of the earliest publications (1966), Ladee¹⁰ concluded “The literature not infrequently focuses attention on psychosis with schizophrenia or schizophreniform features that accompany chronic toxoplasmosis.” Among the cases Ladee¹⁰ described was a laboratory worker who became infected with T. gondii and developed delusions and hallucinations.¹⁰

2. Patients with schizophrenia who are infected with T. gondii have more severe psychotic symptoms. This finding has been reported in at least 7 studies.¹ Holub et al¹¹ evaluated 251 patients with schizophrenia who were treated in Prague Psychiatric Centre between 2000 and 2010. Overall, 57 participants were infected with T. gondii and 194 were not infected. Compared to those who were not infected, the infected group:

• had significantly more severe symptoms (P = .032) as measured on the Positive and Negative Symptom Scale
• were prescribed higher doses of antipsychotic medications
• had been hospitalized longer.¹¹

3. Compared with controls, patients with psychosis are significantly more likely to have antibodies against T. gondii, indicating previous infection. To date there have been approximately 100 such studies, of which at least three-fourths reported a positive association. In a 2012 meta-analysis of 38 such studies, Torrey et al¹² reported an odds ratio (OR) of 2.7—compared to persons who have not been infected, those who have been infected with T. gondii were 2.7 times more likely to have schizophrenia.¹² This study replicated the findings of a previous meta-analysis of 23 antibody studies, which also found an OR of 2.7.¹³

4. Compared with controls, individuals with schizophrenia or bipolar disorder are significantly more likely as a child to have lived in a home with a cat. Since 1995, 10 such studies have been published; 7 were positive, 2 were negative, and 1 was inconclusive.¹ Torrey et al¹⁴ reviewed 2,025 individuals with schizophrenia or bipolar disorder and 4,847 controls and found that 51% of the cases and 43% of the controls had owned a cat before age 13; this difference was highly significant (P < .001). In fact, it is surprising that any study can find a statistically significant association between cat ownership and childhood psychosis. This is because a child who did not own a cat could become infected in many locations where cats have been present, including sandboxes at school, a babysitter’s or friend’s house, or a public park. And even if a child became infected at home, they would not necessarily have owned a cat, since the neighbor’s cat could have been responsible for the oocyst contamination.

Continue to: Epidemiologically...

5. Epidemiologically, there is a close temporal correlation between the rise of cats as pets and the rise of psychosis. This can be illustrated most clearly in England, where the rise of cat ownership has been documented by writers and where there is data on the rise of psychosis, especially in the 18th and 19th centuries.¹

How many cases of psychosis might be caused by T. gondii?

In 2014, using data from the antibody studies discussed above,^12,13 Smith¹⁵ sought to discover how many cases of psychosis might be caused by T. gondii. He concluded that 21% of cases of schizophrenia might have been caused by T. gondii. Based on the annual incidence of schizophrenia in the United States, this would mean an estimated >10,000 new cases of schizophrenia each year are attributable to this parasite.

Some researchers have found links between T. gondii and several nonpsychiatric diseases and conditions, including epilepsy and brain cancer (Box^1,16-19).

Box

Clinical implications: What to tell patients about cats

What do these studies of toxoplasmosis imply for psychiatric care? As mental health professionals, part of our job is to educate our patients. Anything that appears to be a risk factor for the development of psychosis is thus of interest. Consider discussing the following with your patients.

Are cats safe? Cats that are kept exclusively indoors are safe pets because they are unlikely to become infected with T. gondii. However, cats that are allowed to go outdoors may not be safe, especially for children and young adults. What is needed is an effective vaccine that could be given to newborn kittens to prevent infection, but development of this type of vaccine has never been prioritized. At the community level, programs to decrease the number of stray and feral cats would also decrease the risk of infection.

Continue to: How to decrease risk

How to decrease risk. On a personal level, we can decrease T. gondii infections by not eating undercooked meat. Pregnant women and individuals who are immunocompromised should not change cat litter. When gardening, we should wear gloves because cats favor loose soil for depositing their feces. We should also protect children by covering sandboxes when not in use and by not allowing children to play in uncovered public sandboxes.

Treatment. Toxoplasmosis typically is treated with pyrimethamine, usually in combination with a sulfa drug. However, pyrimethamine does not cross the blood brain barrier and thus is ineffective when T. gondii infects the brain. The development of a drug that will effectively treat T. gondii in the brain should be a high priority.

For additional details on the studies discussed in this article as well as more resources on the impact T. gondii can have if proper precautions are not taken, see my open-access book at https://link.springer.com/book/10.1007/978-3-030-86811-6.

Bottom Line

Some evidence suggests that infection with Toxoplasma gondii (T. gondii) may cause psychotic symptoms, may increase an individual’s risk of developing psychosis, and may result in more severe psychotic symptoms. Cats can transmit T. gondii to humans. Educate patients that they can reduce their risk by keeping their cats inside, avoiding exposure to cat feces, particularly while pregnant or if immunocompromised, and not eating undercooked meat.

Related Resources

• Torrey EF. Parasites, Pussycats, and Psychosis: The Unknown Dangers of Human Toxoplasmosis. Springer Nature; 2022. https://link.springer.com/book/10.1007/978-3-030-86811-6

Drug Brand Names

Pyrimethamine • Daraprim

A novel virtual reality (VR) intervention significantly reduces agoraphobia in patients with psychosis, new research suggests.

The cognitive-behavioral therapy–based treatment was particularly effective for patients with the highest level of avoidance of everyday situations.

Courtesy University of Oxford

“Virtual reality is an inherently therapeutic medium which could be extremely useful in mental health services,” study investigator Daniel Freeman, PhD, DClinPsy, professor of clinical psychology, University of Oxford (England), told this news organization.  “This intervention is coming; the question really is when.”

The study was published online  in The Lancet Psychiatry.
 

Real-world feel

Immersive VR involves interactive three-dimensional computer-generated environments that produce the sensation of being in the real world.

For patients with psychosis, dealing with the real world can be an anxious experience, particularly if they have verbal or auditory hallucinations.

Some may develop agoraphobia and start to avoid places or situations. A virtual environment allows patients to practice dealing with situations that make them anxious or uncomfortable and to learn to reengage in everyday situations.

The study included 346 patients diagnosed with schizophrenia or a related disorder. The mean age of the patients was 37.2 years (67% were men, 85% were White). Most were single and unemployed. All were receiving treatment for psychosis and had difficulty going out because of anxiety.

The researchers randomly assigned 174 participants to an automated VR cognitive therapy intervention (gameChange) plus usual care and 172 to usual care alone. Trial assessors were blinded to group allocation.

The gameChange intervention was delivered in six sessions that were conducted over a 6-week period. Each session involved 30 minutes of VR.

A session begins when participants enter the virtual therapist’s office. They are met by a coach who guides them through the therapy. They can choose from among six VR social situations. These include a cafe, a general practice waiting room, a pub, a bus, opening the front door of their home onto the street, or entering a small local shop.

Each scenario has five levels of difficulty that are based on the number and proximity of people in the social situation and the degree of social interaction. Users can work their way through these various levels.

The virtual sessions took place in patients’ homes in about 50% of cases; the remainder were conducted in the clinic. A mental health worker was in the room during the therapy.

Between virtual sessions, participants were encouraged to apply what they learned in the real world, for example, by spending time in a pub.

Usual care typically included regular visits from a community mental health worker and occasional outpatient appointments with a psychiatrist.
 

Widely applicable?

The primary outcome was the eight-item Oxford Agoraphobic Avoidance Scale (O-AS) questionnaire. This scale assesses distress and avoidance related to performing increasingly difficult everyday tasks.

The researchers assessed patients at baseline, at the conclusion of the 6-week treatment, and at 26 weeks.

Compared with the group that received usual care alone, the VR therapy group demonstrated a significant reduction in both agoraphobic avoidance (O-AS adjusted mean difference, -0.47; 95% confidence interval [CI], –0.88 to –0.06; Cohen’s d, –0.18; P = .026) and distress (–4.33; 95% CI, –7.78 to –0.87; Cohen’s d, –0.26; P = .014) at 6 weeks.

This translates to being able to do about 1.5 more activities on the O-AS, such as going to a shopping center alone, said Dr. Freeman.

Further analyses showed that VR therapy was especially effective for patients with severe agoraphobia. On average, these patients could complete two more O-AS activities at 26 weeks, said Dr. Freeman.

The authors believe the intervention worked by reducing defense behaviors, such as avoiding eye contact and fearful thoughts.

There was no significant difference in occurrence of adverse events between the study groups. These events, which were mild, transient, and did not affect the outcome, included side effects such as claustrophobia when using headsets.

The intervention would likely work for patients with agoraphobia who do not have psychosis, said Dr. Freeman. “Agoraphobia is often the final common pathway in lots of mental health conditions.”

Automated VR not only addresses the problem of patients being too afraid to leave home for in-person treatment but may also help address the shortage of trained mental health care providers.

The intervention is available at pilot implementation sites in the United Kingdom and a few sites in the United States, he said.
 

‘Cool, interesting’

Commenting on the research, Arash Javanbakht, MD, associate professor (clinical scholar), Wayne State University, Detroit, described the study as “cool and interesting.”

However, he said, the findings were not surprising, because exposure therapy has proved effective in treating phobias. Because of the significant lack of access to exposure therapy providers, “the more mechanized, the more automated therapies that can be easily used, the better,” he said.

He noted the VR therapy did not require a high level of training; the study used peer support staff who sat next to those using the technology.

He also liked the fact that the intervention “focused on things that in reality impair a person’s life,” for example, not being able to go to the grocery store.

However, he wondered why the investigators studied VR for patients with psychosis and agoraphobia and not for those with just agoraphobia.

In addition, he noted that the treatment’s efficacy was partly due to having someone next to the participants offering support, which the control group didn’t have.

Dr. Javanbakht has researched augmented therapy (AR) for delivering exposure therapy. This technology, which mixes virtually created objects with reality and allows users to move around their real environment, is newer and more advanced than VR but is more complicated, he said.

He explained that AR is more appropriate for delivering exposure therapy in certain situations.

“The basis of exposure therapy is ‘extinction learning’ – exposing a person to a fear cue over and over again until the fear response is extinguished,” and extinction learning is “context dependent,” said Dr. Javanbakht.

“VR is good when you need to create the whole context and environment, and AR is good when you need to focus on specific objects or cues in the environment,” for example, spiders or snakes, he said.

The study was funded by the National Institute of Health Research. Dr. Freeman is a founder and a non-executive director of Oxford VR, which will commercialize the therapy. He holds equity in and receives personal payments from Oxford VR; holds a contract for his university team to advise Oxford VR on treatment development; and reports grants from the National Institute for Health Research, the Medical Research Council, and the International Foundation. Dr. Javanbakht has a patent for an AR exposure therapy.

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

A novel virtual reality (VR) intervention significantly reduces agoraphobia in patients with psychosis, new research suggests.

The cognitive-behavioral therapy–based treatment was particularly effective for patients with the highest level of avoidance of everyday situations.

Courtesy University of Oxford

“Virtual reality is an inherently therapeutic medium which could be extremely useful in mental health services,” study investigator Daniel Freeman, PhD, DClinPsy, professor of clinical psychology, University of Oxford (England), told this news organization.  “This intervention is coming; the question really is when.”

The study was published online  in The Lancet Psychiatry.
 

Real-world feel

Immersive VR involves interactive three-dimensional computer-generated environments that produce the sensation of being in the real world.

For patients with psychosis, dealing with the real world can be an anxious experience, particularly if they have verbal or auditory hallucinations.

Some may develop agoraphobia and start to avoid places or situations. A virtual environment allows patients to practice dealing with situations that make them anxious or uncomfortable and to learn to reengage in everyday situations.

The study included 346 patients diagnosed with schizophrenia or a related disorder. The mean age of the patients was 37.2 years (67% were men, 85% were White). Most were single and unemployed. All were receiving treatment for psychosis and had difficulty going out because of anxiety.

The researchers randomly assigned 174 participants to an automated VR cognitive therapy intervention (gameChange) plus usual care and 172 to usual care alone. Trial assessors were blinded to group allocation.

The gameChange intervention was delivered in six sessions that were conducted over a 6-week period. Each session involved 30 minutes of VR.

A session begins when participants enter the virtual therapist’s office. They are met by a coach who guides them through the therapy. They can choose from among six VR social situations. These include a cafe, a general practice waiting room, a pub, a bus, opening the front door of their home onto the street, or entering a small local shop.

Each scenario has five levels of difficulty that are based on the number and proximity of people in the social situation and the degree of social interaction. Users can work their way through these various levels.

The virtual sessions took place in patients’ homes in about 50% of cases; the remainder were conducted in the clinic. A mental health worker was in the room during the therapy.

Between virtual sessions, participants were encouraged to apply what they learned in the real world, for example, by spending time in a pub.

Usual care typically included regular visits from a community mental health worker and occasional outpatient appointments with a psychiatrist.
 

Widely applicable?

The primary outcome was the eight-item Oxford Agoraphobic Avoidance Scale (O-AS) questionnaire. This scale assesses distress and avoidance related to performing increasingly difficult everyday tasks.

The researchers assessed patients at baseline, at the conclusion of the 6-week treatment, and at 26 weeks.

Compared with the group that received usual care alone, the VR therapy group demonstrated a significant reduction in both agoraphobic avoidance (O-AS adjusted mean difference, -0.47; 95% confidence interval [CI], –0.88 to –0.06; Cohen’s d, –0.18; P = .026) and distress (–4.33; 95% CI, –7.78 to –0.87; Cohen’s d, –0.26; P = .014) at 6 weeks.

This translates to being able to do about 1.5 more activities on the O-AS, such as going to a shopping center alone, said Dr. Freeman.

Further analyses showed that VR therapy was especially effective for patients with severe agoraphobia. On average, these patients could complete two more O-AS activities at 26 weeks, said Dr. Freeman.

The authors believe the intervention worked by reducing defense behaviors, such as avoiding eye contact and fearful thoughts.

There was no significant difference in occurrence of adverse events between the study groups. These events, which were mild, transient, and did not affect the outcome, included side effects such as claustrophobia when using headsets.

The intervention would likely work for patients with agoraphobia who do not have psychosis, said Dr. Freeman. “Agoraphobia is often the final common pathway in lots of mental health conditions.”

Automated VR not only addresses the problem of patients being too afraid to leave home for in-person treatment but may also help address the shortage of trained mental health care providers.

The intervention is available at pilot implementation sites in the United Kingdom and a few sites in the United States, he said.
 

‘Cool, interesting’

Commenting on the research, Arash Javanbakht, MD, associate professor (clinical scholar), Wayne State University, Detroit, described the study as “cool and interesting.”

However, he said, the findings were not surprising, because exposure therapy has proved effective in treating phobias. Because of the significant lack of access to exposure therapy providers, “the more mechanized, the more automated therapies that can be easily used, the better,” he said.

He noted the VR therapy did not require a high level of training; the study used peer support staff who sat next to those using the technology.

He also liked the fact that the intervention “focused on things that in reality impair a person’s life,” for example, not being able to go to the grocery store.

However, he wondered why the investigators studied VR for patients with psychosis and agoraphobia and not for those with just agoraphobia.

In addition, he noted that the treatment’s efficacy was partly due to having someone next to the participants offering support, which the control group didn’t have.

Dr. Javanbakht has researched augmented therapy (AR) for delivering exposure therapy. This technology, which mixes virtually created objects with reality and allows users to move around their real environment, is newer and more advanced than VR but is more complicated, he said.

He explained that AR is more appropriate for delivering exposure therapy in certain situations.

“The basis of exposure therapy is ‘extinction learning’ – exposing a person to a fear cue over and over again until the fear response is extinguished,” and extinction learning is “context dependent,” said Dr. Javanbakht.

“VR is good when you need to create the whole context and environment, and AR is good when you need to focus on specific objects or cues in the environment,” for example, spiders or snakes, he said.

The study was funded by the National Institute of Health Research. Dr. Freeman is a founder and a non-executive director of Oxford VR, which will commercialize the therapy. He holds equity in and receives personal payments from Oxford VR; holds a contract for his university team to advise Oxford VR on treatment development; and reports grants from the National Institute for Health Research, the Medical Research Council, and the International Foundation. Dr. Javanbakht has a patent for an AR exposure therapy.

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

A novel virtual reality (VR) intervention significantly reduces agoraphobia in patients with psychosis, new research suggests.

The cognitive-behavioral therapy–based treatment was particularly effective for patients with the highest level of avoidance of everyday situations.

Courtesy University of Oxford

“Virtual reality is an inherently therapeutic medium which could be extremely useful in mental health services,” study investigator Daniel Freeman, PhD, DClinPsy, professor of clinical psychology, University of Oxford (England), told this news organization.  “This intervention is coming; the question really is when.”

The study was published online  in The Lancet Psychiatry.
 

Real-world feel

Immersive VR involves interactive three-dimensional computer-generated environments that produce the sensation of being in the real world.

For patients with psychosis, dealing with the real world can be an anxious experience, particularly if they have verbal or auditory hallucinations.

Some may develop agoraphobia and start to avoid places or situations. A virtual environment allows patients to practice dealing with situations that make them anxious or uncomfortable and to learn to reengage in everyday situations.

The study included 346 patients diagnosed with schizophrenia or a related disorder. The mean age of the patients was 37.2 years (67% were men, 85% were White). Most were single and unemployed. All were receiving treatment for psychosis and had difficulty going out because of anxiety.

The researchers randomly assigned 174 participants to an automated VR cognitive therapy intervention (gameChange) plus usual care and 172 to usual care alone. Trial assessors were blinded to group allocation.

The gameChange intervention was delivered in six sessions that were conducted over a 6-week period. Each session involved 30 minutes of VR.

A session begins when participants enter the virtual therapist’s office. They are met by a coach who guides them through the therapy. They can choose from among six VR social situations. These include a cafe, a general practice waiting room, a pub, a bus, opening the front door of their home onto the street, or entering a small local shop.

Each scenario has five levels of difficulty that are based on the number and proximity of people in the social situation and the degree of social interaction. Users can work their way through these various levels.

The virtual sessions took place in patients’ homes in about 50% of cases; the remainder were conducted in the clinic. A mental health worker was in the room during the therapy.

Between virtual sessions, participants were encouraged to apply what they learned in the real world, for example, by spending time in a pub.

Usual care typically included regular visits from a community mental health worker and occasional outpatient appointments with a psychiatrist.
 

Widely applicable?

The primary outcome was the eight-item Oxford Agoraphobic Avoidance Scale (O-AS) questionnaire. This scale assesses distress and avoidance related to performing increasingly difficult everyday tasks.

The researchers assessed patients at baseline, at the conclusion of the 6-week treatment, and at 26 weeks.

Compared with the group that received usual care alone, the VR therapy group demonstrated a significant reduction in both agoraphobic avoidance (O-AS adjusted mean difference, -0.47; 95% confidence interval [CI], –0.88 to –0.06; Cohen’s d, –0.18; P = .026) and distress (–4.33; 95% CI, –7.78 to –0.87; Cohen’s d, –0.26; P = .014) at 6 weeks.

This translates to being able to do about 1.5 more activities on the O-AS, such as going to a shopping center alone, said Dr. Freeman.

Further analyses showed that VR therapy was especially effective for patients with severe agoraphobia. On average, these patients could complete two more O-AS activities at 26 weeks, said Dr. Freeman.

The authors believe the intervention worked by reducing defense behaviors, such as avoiding eye contact and fearful thoughts.

There was no significant difference in occurrence of adverse events between the study groups. These events, which were mild, transient, and did not affect the outcome, included side effects such as claustrophobia when using headsets.

The intervention would likely work for patients with agoraphobia who do not have psychosis, said Dr. Freeman. “Agoraphobia is often the final common pathway in lots of mental health conditions.”

Automated VR not only addresses the problem of patients being too afraid to leave home for in-person treatment but may also help address the shortage of trained mental health care providers.

The intervention is available at pilot implementation sites in the United Kingdom and a few sites in the United States, he said.
 

‘Cool, interesting’

Commenting on the research, Arash Javanbakht, MD, associate professor (clinical scholar), Wayne State University, Detroit, described the study as “cool and interesting.”

However, he said, the findings were not surprising, because exposure therapy has proved effective in treating phobias. Because of the significant lack of access to exposure therapy providers, “the more mechanized, the more automated therapies that can be easily used, the better,” he said.

He noted the VR therapy did not require a high level of training; the study used peer support staff who sat next to those using the technology.

He also liked the fact that the intervention “focused on things that in reality impair a person’s life,” for example, not being able to go to the grocery store.

However, he wondered why the investigators studied VR for patients with psychosis and agoraphobia and not for those with just agoraphobia.

In addition, he noted that the treatment’s efficacy was partly due to having someone next to the participants offering support, which the control group didn’t have.

Dr. Javanbakht has researched augmented therapy (AR) for delivering exposure therapy. This technology, which mixes virtually created objects with reality and allows users to move around their real environment, is newer and more advanced than VR but is more complicated, he said.

He explained that AR is more appropriate for delivering exposure therapy in certain situations.

“The basis of exposure therapy is ‘extinction learning’ – exposing a person to a fear cue over and over again until the fear response is extinguished,” and extinction learning is “context dependent,” said Dr. Javanbakht.

“VR is good when you need to create the whole context and environment, and AR is good when you need to focus on specific objects or cues in the environment,” for example, spiders or snakes, he said.

The study was funded by the National Institute of Health Research. Dr. Freeman is a founder and a non-executive director of Oxford VR, which will commercialize the therapy. He holds equity in and receives personal payments from Oxford VR; holds a contract for his university team to advise Oxford VR on treatment development; and reports grants from the National Institute for Health Research, the Medical Research Council, and the International Foundation. Dr. Javanbakht has a patent for an AR exposure therapy.

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

High rates of antipsychotic switching in first episode psychosis (FEP) suggests first-line prescribing is less than optimal and does not follow recent clinical guidance.

In a large-scale, real-world analysis of U.K. prescribing patterns, researchers found more than two-thirds of patients who received antipsychotics for FEP switched medication, and almost half switched drugs three times.

VladimirSorokin/Getty Images

Although this is “one of the largest real-world studies examining antipsychotic treatment strategies,” it reflects findings from previous, smaller studies showing “antipsychotic switching in first episode psychosis is high,” said study investigator Aimee Brinn, Institute of Psychiatry, Psychology & Neuroscience at King’s College London.

This may reflect reports of poor efficacy and suggests that first-line prescribing is “suboptimal,” Ms. Brinn noted. In addition, olanzapine remains the most popular antipsychotic for prescribing despite recent guidelines indicating it is “not ideal ... due to its dangerous metabolic side effects,” she added.

The findings were presented at the Congress of the Schizophrenia International Research Society (SIRS) 2022.
 

Real-world data

The response to, and tolerability of, antipsychotics differs between patients with FEP; and prescribing patterns “reflect clinician and patient-led decisionmaking,” Ms. Brinn told meeting attendees.

Since randomized controlled trials “do not necessarily reflect prescribing practice in real-world clinical settings,” the researchers gathered data from a large mental health care electronic health record dataset.

The investigators examined records from the South London and Maudsley NHS Foundation Trust (SLaM), which has a catchment area of 1.2 million individuals across four boroughs of London. The group sees approximately 37,500 active patients per week.

The team used the Clinical Interactive Record Search tool to extract data on 2,309 adults with FEP who received care from a SLaM early intervention in psychosis service between April 1, 2008, and March 31, 2019.

They found that 12 different antipsychotics were prescribed as first-line treatment. The most common were olanzapine (43.9%), risperidone (24.7%), and aripiprazole (19.9%).

Results showed that over 81,969.5 person-years of follow-up, at a minimum of 24 months per patient, 68.8% had an antipsychotic switch. The most common first treatment switch, in 17.9% of patients, was from olanzapine to aripiprazole.

Of patients who switched to aripiprazole, 48.4% stayed on the drug, 26% switched back to olanzapine, and 25.6% received other treatment. Overall, 44.7% of patients switched medication at least three times.

Among patients with FEP who did not switch, 42.2% were prescribed olanzapine, 26.2% risperidone, 23.3% aripiprazole, 5.6% quetiapine, and 2.7% amisulpride.

During the post-presentation discussion, Ms. Brinn was asked whether the high rate of first-line olanzapine prescribing could be because patients started treatment as inpatients and were then switched once they were moved to community care.

“We found that a lot of patients would be prescribed olanzapine for around 7 days at the start of their prescription and then switch,” Ms. Brinn said, adding it is “likely” they started as inpatients. The investigators are currently examining the differences between inpatient and outpatient prescriptions to verify whether this is indeed the case, she added.
 

‘Pulling out the big guns too fast?’

Commenting on the findings, Thomas W. Sedlak, MD, PhD, Johns Hopkins University School of Medicine, Baltimore, said the study raises a “number of questions.”

Both olanzapine and risperidone “tend to have higher treatment effect improvements than aripiprazole, so it’s curious that a switch to aripiprazole was common,” said Dr. Sedlak, who was not involved with the research.

“Are we pulling out the ‘big guns’ too fast, or inappropriately, especially as olanzapine and risperidone carry greater risk of weight gain?” he asked. In addition, “now that olanzapine is available with samidorphan to mitigate weight gain, will that shape future patterns, if it can be paid for?”

Dr. Sedlak noted it was unclear why olanzapine was chosen so often as first-line treatment in the study and agreed it is “possible that hospitalized patients had been prescribed a ‘stronger’ medication like olanzapine compared to never-hospitalized patients.”

He also underlined that it is “not clear if patients in this FEP program are representative of all FEP patients.”

“For instance, if the program is well known to inpatient hospital social workers, then the program might be disproportionately filled with patients who have had more severe symptoms,” Dr. Sedlak said.

The study was supported by Janssen-Cilag. The investigators and Dr. Sedlak have disclosed no relevant financial relationships.

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

High rates of antipsychotic switching in first episode psychosis (FEP) suggests first-line prescribing is less than optimal and does not follow recent clinical guidance.

In a large-scale, real-world analysis of U.K. prescribing patterns, researchers found more than two-thirds of patients who received antipsychotics for FEP switched medication, and almost half switched drugs three times.

VladimirSorokin/Getty Images

Although this is “one of the largest real-world studies examining antipsychotic treatment strategies,” it reflects findings from previous, smaller studies showing “antipsychotic switching in first episode psychosis is high,” said study investigator Aimee Brinn, Institute of Psychiatry, Psychology & Neuroscience at King’s College London.

This may reflect reports of poor efficacy and suggests that first-line prescribing is “suboptimal,” Ms. Brinn noted. In addition, olanzapine remains the most popular antipsychotic for prescribing despite recent guidelines indicating it is “not ideal ... due to its dangerous metabolic side effects,” she added.

The findings were presented at the Congress of the Schizophrenia International Research Society (SIRS) 2022.
 

Real-world data

The response to, and tolerability of, antipsychotics differs between patients with FEP; and prescribing patterns “reflect clinician and patient-led decisionmaking,” Ms. Brinn told meeting attendees.

Since randomized controlled trials “do not necessarily reflect prescribing practice in real-world clinical settings,” the researchers gathered data from a large mental health care electronic health record dataset.

The investigators examined records from the South London and Maudsley NHS Foundation Trust (SLaM), which has a catchment area of 1.2 million individuals across four boroughs of London. The group sees approximately 37,500 active patients per week.

The team used the Clinical Interactive Record Search tool to extract data on 2,309 adults with FEP who received care from a SLaM early intervention in psychosis service between April 1, 2008, and March 31, 2019.

They found that 12 different antipsychotics were prescribed as first-line treatment. The most common were olanzapine (43.9%), risperidone (24.7%), and aripiprazole (19.9%).

Results showed that over 81,969.5 person-years of follow-up, at a minimum of 24 months per patient, 68.8% had an antipsychotic switch. The most common first treatment switch, in 17.9% of patients, was from olanzapine to aripiprazole.

Of patients who switched to aripiprazole, 48.4% stayed on the drug, 26% switched back to olanzapine, and 25.6% received other treatment. Overall, 44.7% of patients switched medication at least three times.

Among patients with FEP who did not switch, 42.2% were prescribed olanzapine, 26.2% risperidone, 23.3% aripiprazole, 5.6% quetiapine, and 2.7% amisulpride.

During the post-presentation discussion, Ms. Brinn was asked whether the high rate of first-line olanzapine prescribing could be because patients started treatment as inpatients and were then switched once they were moved to community care.

“We found that a lot of patients would be prescribed olanzapine for around 7 days at the start of their prescription and then switch,” Ms. Brinn said, adding it is “likely” they started as inpatients. The investigators are currently examining the differences between inpatient and outpatient prescriptions to verify whether this is indeed the case, she added.
 

‘Pulling out the big guns too fast?’

Commenting on the findings, Thomas W. Sedlak, MD, PhD, Johns Hopkins University School of Medicine, Baltimore, said the study raises a “number of questions.”

Both olanzapine and risperidone “tend to have higher treatment effect improvements than aripiprazole, so it’s curious that a switch to aripiprazole was common,” said Dr. Sedlak, who was not involved with the research.

“Are we pulling out the ‘big guns’ too fast, or inappropriately, especially as olanzapine and risperidone carry greater risk of weight gain?” he asked. In addition, “now that olanzapine is available with samidorphan to mitigate weight gain, will that shape future patterns, if it can be paid for?”

Dr. Sedlak noted it was unclear why olanzapine was chosen so often as first-line treatment in the study and agreed it is “possible that hospitalized patients had been prescribed a ‘stronger’ medication like olanzapine compared to never-hospitalized patients.”

He also underlined that it is “not clear if patients in this FEP program are representative of all FEP patients.”

“For instance, if the program is well known to inpatient hospital social workers, then the program might be disproportionately filled with patients who have had more severe symptoms,” Dr. Sedlak said.

The study was supported by Janssen-Cilag. The investigators and Dr. Sedlak have disclosed no relevant financial relationships.

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

High rates of antipsychotic switching in first episode psychosis (FEP) suggests first-line prescribing is less than optimal and does not follow recent clinical guidance.

In a large-scale, real-world analysis of U.K. prescribing patterns, researchers found more than two-thirds of patients who received antipsychotics for FEP switched medication, and almost half switched drugs three times.

VladimirSorokin/Getty Images

Although this is “one of the largest real-world studies examining antipsychotic treatment strategies,” it reflects findings from previous, smaller studies showing “antipsychotic switching in first episode psychosis is high,” said study investigator Aimee Brinn, Institute of Psychiatry, Psychology & Neuroscience at King’s College London.

This may reflect reports of poor efficacy and suggests that first-line prescribing is “suboptimal,” Ms. Brinn noted. In addition, olanzapine remains the most popular antipsychotic for prescribing despite recent guidelines indicating it is “not ideal ... due to its dangerous metabolic side effects,” she added.

The findings were presented at the Congress of the Schizophrenia International Research Society (SIRS) 2022.
 

Real-world data

The response to, and tolerability of, antipsychotics differs between patients with FEP; and prescribing patterns “reflect clinician and patient-led decisionmaking,” Ms. Brinn told meeting attendees.

Since randomized controlled trials “do not necessarily reflect prescribing practice in real-world clinical settings,” the researchers gathered data from a large mental health care electronic health record dataset.

The investigators examined records from the South London and Maudsley NHS Foundation Trust (SLaM), which has a catchment area of 1.2 million individuals across four boroughs of London. The group sees approximately 37,500 active patients per week.

The team used the Clinical Interactive Record Search tool to extract data on 2,309 adults with FEP who received care from a SLaM early intervention in psychosis service between April 1, 2008, and March 31, 2019.

They found that 12 different antipsychotics were prescribed as first-line treatment. The most common were olanzapine (43.9%), risperidone (24.7%), and aripiprazole (19.9%).

Results showed that over 81,969.5 person-years of follow-up, at a minimum of 24 months per patient, 68.8% had an antipsychotic switch. The most common first treatment switch, in 17.9% of patients, was from olanzapine to aripiprazole.

Of patients who switched to aripiprazole, 48.4% stayed on the drug, 26% switched back to olanzapine, and 25.6% received other treatment. Overall, 44.7% of patients switched medication at least three times.

Among patients with FEP who did not switch, 42.2% were prescribed olanzapine, 26.2% risperidone, 23.3% aripiprazole, 5.6% quetiapine, and 2.7% amisulpride.

During the post-presentation discussion, Ms. Brinn was asked whether the high rate of first-line olanzapine prescribing could be because patients started treatment as inpatients and were then switched once they were moved to community care.

“We found that a lot of patients would be prescribed olanzapine for around 7 days at the start of their prescription and then switch,” Ms. Brinn said, adding it is “likely” they started as inpatients. The investigators are currently examining the differences between inpatient and outpatient prescriptions to verify whether this is indeed the case, she added.
 

‘Pulling out the big guns too fast?’

Commenting on the findings, Thomas W. Sedlak, MD, PhD, Johns Hopkins University School of Medicine, Baltimore, said the study raises a “number of questions.”

Both olanzapine and risperidone “tend to have higher treatment effect improvements than aripiprazole, so it’s curious that a switch to aripiprazole was common,” said Dr. Sedlak, who was not involved with the research.

“Are we pulling out the ‘big guns’ too fast, or inappropriately, especially as olanzapine and risperidone carry greater risk of weight gain?” he asked. In addition, “now that olanzapine is available with samidorphan to mitigate weight gain, will that shape future patterns, if it can be paid for?”

Dr. Sedlak noted it was unclear why olanzapine was chosen so often as first-line treatment in the study and agreed it is “possible that hospitalized patients had been prescribed a ‘stronger’ medication like olanzapine compared to never-hospitalized patients.”

He also underlined that it is “not clear if patients in this FEP program are representative of all FEP patients.”

“For instance, if the program is well known to inpatient hospital social workers, then the program might be disproportionately filled with patients who have had more severe symptoms,” Dr. Sedlak said.

The study was supported by Janssen-Cilag. The investigators and Dr. Sedlak have disclosed no relevant financial relationships.

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

Olanzapine plus samidorphan (Lybalvi) vs. olanzapine alone is associated with less weight gain while achieving similar clinical outcomes in patients with recent-onset severe mental illness, new research suggests. However, at least one expert says the weight difference between the two drugs is of “questionable clinical benefit.”

Last year, the Food and Drug Administration approved the drug for the treatment of adults with schizophrenia or bipolar I disorder, as a maintenance monotherapy or as either monotherapy or an adjunct to lithium or valproate for acute manic or mixed episodes.

In the ENLIGHTEN-Early trial, researchers examined weight-gain profiles of more than 400 patients with early schizophrenia, schizophreniform disorder, or bipolar I disorder.

Results showed those given combination treatment gained just over half the amount of weight as those given monotherapy. They were also 36% less likely to gain at least 10% of their body weight during the 12-week treatment period.

Courtesy Mount Sinai Health System

Potential benefit

“Early intervention with antipsychotic treatment is critical in shaping the course of treatment and the disease trajectory,” coinvestigator Christine Graham, PhD, with Alkermes, which manufactures the drug, told this news organization.

Olanzapine is a “highly effective antipsychotic, but it’s really avoided a lot in this population,” Dr. Graham said. Therefore, patients “could really stand to benefit” from a combination that delivers the same amount of antipsychotic effect, but “reduces the propensity” for clinically significant weight gain, she added.

Dr. Kahn noted in his meeting presentation that antipsychotics are the “cornerstone” of the treatment of serious mental illness, but that “many are associated with concerning weight gain and cardiometabolic effects.”

While olanzapine is an effective medication, it has “one of the highest weight gain” profiles of the available antipsychotics and patients early on in their illness are “especially vulnerable,” Dr. Kahn said.

Previous studies have shown the combination of olanzapine plus samidorphan is similarly effective as olanzapine, but is associated with less weight gain.

To determine its impact in recent-onset illness, the current researchers screened patients with schizophrenia, schizophreniform disorder, or bipolar I disorder. The patients were aged 16-39 years and had an initial onset of active phase symptoms less than 4 years previously. They had less than 24 weeks’ cumulative lifetime exposure to antipsychotics.

Participants were randomly assigned to receive olanzapine plus samidorphan or olanzapine alone for 12 weeks, and then followed up for safety assessment for a further 4 weeks.

A total of 426 patients were recruited and 76.5% completed the study. The mean age was 25.8 years, 66.2% were men, 66.4% were White, and 28.2% were Black.

The mean body mass index at baseline was 23.69 kg/m². The most common diagnosis among the participants was schizophrenia (62.9%) followed by bipolar I disorder (21.6%).
 

Less weight gain

Results of the 12-week study showed a significant difference in percent change in body weight from baseline between the two treatment groups, with a gain of 4.91% for the olanzapine plus samidorphan group vs. 6.77% for the olanzapine-alone group (between-group difference, 1.87%; P = .012).

Dr. Kahn noted this equates to an average weight gain of 2.8 kg (6.2 pounds) with olanzapine plus samidorphan and a gain of about 5 kg (11pounds) with olanzapine.

“It’s not a huge difference, but it’s certainly a significant one,” he said. “I also think it’s clinically important and significant.”

The reduction in weight gain compared with olanzapine was even maintained in patients assigned to olanzapine plus samidorphan who dropped out and did not complete the study, Dr. Kahn reported. “No one really had a weight gain,” he said.

In contrast, patients in the olanzapine groups who dropped out of the study had weight gain larger than their counterparts who stayed in it.

Further analysis showed the proportion of patients who gained 10% or more of their body weight by week 12 was 21.9% for those receiving olanzapine plus samidorphan vs. 30.4% for those receiving just olanzapine (odds ratio, 0.64; P = .075).

As expected, the improvement in Clinical Global Impression–Severity scale scores was almost identical between the olanzapine + samidorphan and olanzapine-only groups.

For safety, Dr. Kahn said the adverse event rates were “very, very similar” between the two treatment arms, which was a pattern that was repeated for serious AEs. This led him to note that “nothing out of the ordinary” was observed.
 

Clinical impact 'questionable'

Commenting on the study, Laura LaChance, MD, a psychiatrist at St. Mary’s Hospital Centre, McGill University, Montreal, said the actual amount of weight loss shown in the study “is of questionable clinical significance.”

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

Olanzapine plus samidorphan (Lybalvi) vs. olanzapine alone is associated with less weight gain while achieving similar clinical outcomes in patients with recent-onset severe mental illness, new research suggests. However, at least one expert says the weight difference between the two drugs is of “questionable clinical benefit.”

Last year, the Food and Drug Administration approved the drug for the treatment of adults with schizophrenia or bipolar I disorder, as a maintenance monotherapy or as either monotherapy or an adjunct to lithium or valproate for acute manic or mixed episodes.

In the ENLIGHTEN-Early trial, researchers examined weight-gain profiles of more than 400 patients with early schizophrenia, schizophreniform disorder, or bipolar I disorder.

Results showed those given combination treatment gained just over half the amount of weight as those given monotherapy. They were also 36% less likely to gain at least 10% of their body weight during the 12-week treatment period.

Courtesy Mount Sinai Health System

Potential benefit

“Early intervention with antipsychotic treatment is critical in shaping the course of treatment and the disease trajectory,” coinvestigator Christine Graham, PhD, with Alkermes, which manufactures the drug, told this news organization.

Olanzapine is a “highly effective antipsychotic, but it’s really avoided a lot in this population,” Dr. Graham said. Therefore, patients “could really stand to benefit” from a combination that delivers the same amount of antipsychotic effect, but “reduces the propensity” for clinically significant weight gain, she added.

Dr. Kahn noted in his meeting presentation that antipsychotics are the “cornerstone” of the treatment of serious mental illness, but that “many are associated with concerning weight gain and cardiometabolic effects.”

While olanzapine is an effective medication, it has “one of the highest weight gain” profiles of the available antipsychotics and patients early on in their illness are “especially vulnerable,” Dr. Kahn said.

Previous studies have shown the combination of olanzapine plus samidorphan is similarly effective as olanzapine, but is associated with less weight gain.

To determine its impact in recent-onset illness, the current researchers screened patients with schizophrenia, schizophreniform disorder, or bipolar I disorder. The patients were aged 16-39 years and had an initial onset of active phase symptoms less than 4 years previously. They had less than 24 weeks’ cumulative lifetime exposure to antipsychotics.

Participants were randomly assigned to receive olanzapine plus samidorphan or olanzapine alone for 12 weeks, and then followed up for safety assessment for a further 4 weeks.

A total of 426 patients were recruited and 76.5% completed the study. The mean age was 25.8 years, 66.2% were men, 66.4% were White, and 28.2% were Black.

The mean body mass index at baseline was 23.69 kg/m². The most common diagnosis among the participants was schizophrenia (62.9%) followed by bipolar I disorder (21.6%).
 

Less weight gain

Results of the 12-week study showed a significant difference in percent change in body weight from baseline between the two treatment groups, with a gain of 4.91% for the olanzapine plus samidorphan group vs. 6.77% for the olanzapine-alone group (between-group difference, 1.87%; P = .012).

Dr. Kahn noted this equates to an average weight gain of 2.8 kg (6.2 pounds) with olanzapine plus samidorphan and a gain of about 5 kg (11pounds) with olanzapine.

“It’s not a huge difference, but it’s certainly a significant one,” he said. “I also think it’s clinically important and significant.”

The reduction in weight gain compared with olanzapine was even maintained in patients assigned to olanzapine plus samidorphan who dropped out and did not complete the study, Dr. Kahn reported. “No one really had a weight gain,” he said.

In contrast, patients in the olanzapine groups who dropped out of the study had weight gain larger than their counterparts who stayed in it.

Further analysis showed the proportion of patients who gained 10% or more of their body weight by week 12 was 21.9% for those receiving olanzapine plus samidorphan vs. 30.4% for those receiving just olanzapine (odds ratio, 0.64; P = .075).

As expected, the improvement in Clinical Global Impression–Severity scale scores was almost identical between the olanzapine + samidorphan and olanzapine-only groups.

For safety, Dr. Kahn said the adverse event rates were “very, very similar” between the two treatment arms, which was a pattern that was repeated for serious AEs. This led him to note that “nothing out of the ordinary” was observed.
 

Clinical impact 'questionable'

Commenting on the study, Laura LaChance, MD, a psychiatrist at St. Mary’s Hospital Centre, McGill University, Montreal, said the actual amount of weight loss shown in the study “is of questionable clinical significance.”

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

Olanzapine plus samidorphan (Lybalvi) vs. olanzapine alone is associated with less weight gain while achieving similar clinical outcomes in patients with recent-onset severe mental illness, new research suggests. However, at least one expert says the weight difference between the two drugs is of “questionable clinical benefit.”

Last year, the Food and Drug Administration approved the drug for the treatment of adults with schizophrenia or bipolar I disorder, as a maintenance monotherapy or as either monotherapy or an adjunct to lithium or valproate for acute manic or mixed episodes.

In the ENLIGHTEN-Early trial, researchers examined weight-gain profiles of more than 400 patients with early schizophrenia, schizophreniform disorder, or bipolar I disorder.

Results showed those given combination treatment gained just over half the amount of weight as those given monotherapy. They were also 36% less likely to gain at least 10% of their body weight during the 12-week treatment period.

Courtesy Mount Sinai Health System

Potential benefit

“Early intervention with antipsychotic treatment is critical in shaping the course of treatment and the disease trajectory,” coinvestigator Christine Graham, PhD, with Alkermes, which manufactures the drug, told this news organization.

Olanzapine is a “highly effective antipsychotic, but it’s really avoided a lot in this population,” Dr. Graham said. Therefore, patients “could really stand to benefit” from a combination that delivers the same amount of antipsychotic effect, but “reduces the propensity” for clinically significant weight gain, she added.

Dr. Kahn noted in his meeting presentation that antipsychotics are the “cornerstone” of the treatment of serious mental illness, but that “many are associated with concerning weight gain and cardiometabolic effects.”

While olanzapine is an effective medication, it has “one of the highest weight gain” profiles of the available antipsychotics and patients early on in their illness are “especially vulnerable,” Dr. Kahn said.

Previous studies have shown the combination of olanzapine plus samidorphan is similarly effective as olanzapine, but is associated with less weight gain.

To determine its impact in recent-onset illness, the current researchers screened patients with schizophrenia, schizophreniform disorder, or bipolar I disorder. The patients were aged 16-39 years and had an initial onset of active phase symptoms less than 4 years previously. They had less than 24 weeks’ cumulative lifetime exposure to antipsychotics.

Participants were randomly assigned to receive olanzapine plus samidorphan or olanzapine alone for 12 weeks, and then followed up for safety assessment for a further 4 weeks.

A total of 426 patients were recruited and 76.5% completed the study. The mean age was 25.8 years, 66.2% were men, 66.4% were White, and 28.2% were Black.

The mean body mass index at baseline was 23.69 kg/m². The most common diagnosis among the participants was schizophrenia (62.9%) followed by bipolar I disorder (21.6%).
 

Less weight gain

Results of the 12-week study showed a significant difference in percent change in body weight from baseline between the two treatment groups, with a gain of 4.91% for the olanzapine plus samidorphan group vs. 6.77% for the olanzapine-alone group (between-group difference, 1.87%; P = .012).

Dr. Kahn noted this equates to an average weight gain of 2.8 kg (6.2 pounds) with olanzapine plus samidorphan and a gain of about 5 kg (11pounds) with olanzapine.

“It’s not a huge difference, but it’s certainly a significant one,” he said. “I also think it’s clinically important and significant.”

The reduction in weight gain compared with olanzapine was even maintained in patients assigned to olanzapine plus samidorphan who dropped out and did not complete the study, Dr. Kahn reported. “No one really had a weight gain,” he said.

In contrast, patients in the olanzapine groups who dropped out of the study had weight gain larger than their counterparts who stayed in it.

Further analysis showed the proportion of patients who gained 10% or more of their body weight by week 12 was 21.9% for those receiving olanzapine plus samidorphan vs. 30.4% for those receiving just olanzapine (odds ratio, 0.64; P = .075).

As expected, the improvement in Clinical Global Impression–Severity scale scores was almost identical between the olanzapine + samidorphan and olanzapine-only groups.

For safety, Dr. Kahn said the adverse event rates were “very, very similar” between the two treatment arms, which was a pattern that was repeated for serious AEs. This led him to note that “nothing out of the ordinary” was observed.
 

Clinical impact 'questionable'

Commenting on the study, Laura LaChance, MD, a psychiatrist at St. Mary’s Hospital Centre, McGill University, Montreal, said the actual amount of weight loss shown in the study “is of questionable clinical significance.”

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

Psychiatric disorders are tied to an increased risk of COVID-19 breakthrough infection, particularly among older adults, new research shows.

“Psychiatric disorders remained significantly associated with incident breakthrough infections above and beyond sociodemographic and medical factors, suggesting that mental health is important to consider in conjunction with other risk factors,” wrote the investigators, led by Aoife O’Donovan, PhD, University of California, San Francisco.

Individuals with psychiatric disorders “should be prioritized for booster vaccinations and other critical preventive efforts, including increased SARS-CoV-2 screening, public health campaigns, or COVID-19 discussions during clinical care,” they added.

The study was published online in JAMA Network Open.
 

Elderly most vulnerable

The researchers reviewed the records of 263,697 veterans who were fully vaccinated against COVID-19.

Just over a half (51.4%) had one or more psychiatric diagnoses within the last 5 years and 14.8% developed breakthrough COVID-19 infections, confirmed by a positive SARS-CoV-2 test.

Psychiatric diagnoses among the veterans included depression, posttraumatic stress, anxiety, adjustment disorder, substance use disorder, bipolar disorder, psychosis, ADHD, dissociation, and eating disorders.

In the overall sample, a history of any psychiatric disorder was associated with a 7% higher incidence of breakthrough COVID-19 infection in models adjusted for potential confounders (adjusted relative risk, 1.07; 95% confidence interval, 1.05-1.09) and a 3% higher incidence in models additionally adjusted for underlying medical comorbidities and smoking (aRR, 1.03; 95% CI, 1.01-1.05).

Most psychiatric disorders were associated with a higher incidence of breakthrough infection, with the highest relative risk observed for substance use disorders (aRR, 1.16; 95% CI, 1.12 -1.21) and adjustment disorder (aRR, 1.13; 95% CI, 1.10-1.16) in fully adjusted models.

Older vaccinated veterans with psychiatric illnesses appear to be most vulnerable to COVID-19 reinfection.

In veterans aged 65 and older, all psychiatric disorders were associated with an increased incidence of breakthrough infection, with increases in the incidence rate ranging from 3% to 24% in fully adjusted models.

In the younger veterans, in contrast, only anxiety, adjustment, and substance use disorders were associated with an increased incidence of breakthrough infection in fully adjusted models.

Psychotic disorders were associated with a 10% lower incidence of breakthrough infection among younger veterans, perhaps because of greater social isolation, the researchers said.
 

Risky behavior or impaired immunity?

“Although some of the larger observed effect sizes are compelling at an individual level, even the relatively modest effect sizes may have a large effect at the population level when considering the high prevalence of psychiatric disorders and the global reach and scale of the pandemic,” Dr. O’Donovan and colleagues wrote.

They noted that psychiatric disorders, including depression, schizophrenia, and bipolar disorders, have been associated with impaired cellular immunity and blunted response to vaccines. Therefore, it’s possible that those with psychiatric disorders have poorer responses to COVID-19 vaccination.

It’s also possible that immunity following vaccination wanes more quickly or more strongly in people with psychiatric disorders and they could have less protection against new variants, they added.

Patients with psychiatric disorders could be more apt to engage in risky behaviors for contracting COVID-19, which could also increase the risk for breakthrough infection, they said.

The study was supported by a UCSF Department of Psychiatry Rapid Award and UCSF Faculty Resource Fund Award. Dr. O’Donovan reported no relevant disclosures.

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

Psychiatric disorders are tied to an increased risk of COVID-19 breakthrough infection, particularly among older adults, new research shows.

“Psychiatric disorders remained significantly associated with incident breakthrough infections above and beyond sociodemographic and medical factors, suggesting that mental health is important to consider in conjunction with other risk factors,” wrote the investigators, led by Aoife O’Donovan, PhD, University of California, San Francisco.

Individuals with psychiatric disorders “should be prioritized for booster vaccinations and other critical preventive efforts, including increased SARS-CoV-2 screening, public health campaigns, or COVID-19 discussions during clinical care,” they added.

The study was published online in JAMA Network Open.
 

Elderly most vulnerable

The researchers reviewed the records of 263,697 veterans who were fully vaccinated against COVID-19.

Just over a half (51.4%) had one or more psychiatric diagnoses within the last 5 years and 14.8% developed breakthrough COVID-19 infections, confirmed by a positive SARS-CoV-2 test.

Psychiatric diagnoses among the veterans included depression, posttraumatic stress, anxiety, adjustment disorder, substance use disorder, bipolar disorder, psychosis, ADHD, dissociation, and eating disorders.

In the overall sample, a history of any psychiatric disorder was associated with a 7% higher incidence of breakthrough COVID-19 infection in models adjusted for potential confounders (adjusted relative risk, 1.07; 95% confidence interval, 1.05-1.09) and a 3% higher incidence in models additionally adjusted for underlying medical comorbidities and smoking (aRR, 1.03; 95% CI, 1.01-1.05).

Most psychiatric disorders were associated with a higher incidence of breakthrough infection, with the highest relative risk observed for substance use disorders (aRR, 1.16; 95% CI, 1.12 -1.21) and adjustment disorder (aRR, 1.13; 95% CI, 1.10-1.16) in fully adjusted models.

Older vaccinated veterans with psychiatric illnesses appear to be most vulnerable to COVID-19 reinfection.

In veterans aged 65 and older, all psychiatric disorders were associated with an increased incidence of breakthrough infection, with increases in the incidence rate ranging from 3% to 24% in fully adjusted models.

In the younger veterans, in contrast, only anxiety, adjustment, and substance use disorders were associated with an increased incidence of breakthrough infection in fully adjusted models.

Psychotic disorders were associated with a 10% lower incidence of breakthrough infection among younger veterans, perhaps because of greater social isolation, the researchers said.
 

Risky behavior or impaired immunity?

“Although some of the larger observed effect sizes are compelling at an individual level, even the relatively modest effect sizes may have a large effect at the population level when considering the high prevalence of psychiatric disorders and the global reach and scale of the pandemic,” Dr. O’Donovan and colleagues wrote.

They noted that psychiatric disorders, including depression, schizophrenia, and bipolar disorders, have been associated with impaired cellular immunity and blunted response to vaccines. Therefore, it’s possible that those with psychiatric disorders have poorer responses to COVID-19 vaccination.

It’s also possible that immunity following vaccination wanes more quickly or more strongly in people with psychiatric disorders and they could have less protection against new variants, they added.

Patients with psychiatric disorders could be more apt to engage in risky behaviors for contracting COVID-19, which could also increase the risk for breakthrough infection, they said.

The study was supported by a UCSF Department of Psychiatry Rapid Award and UCSF Faculty Resource Fund Award. Dr. O’Donovan reported no relevant disclosures.

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

Psychiatric disorders are tied to an increased risk of COVID-19 breakthrough infection, particularly among older adults, new research shows.

“Psychiatric disorders remained significantly associated with incident breakthrough infections above and beyond sociodemographic and medical factors, suggesting that mental health is important to consider in conjunction with other risk factors,” wrote the investigators, led by Aoife O’Donovan, PhD, University of California, San Francisco.

Individuals with psychiatric disorders “should be prioritized for booster vaccinations and other critical preventive efforts, including increased SARS-CoV-2 screening, public health campaigns, or COVID-19 discussions during clinical care,” they added.

The study was published online in JAMA Network Open.
 

Elderly most vulnerable

The researchers reviewed the records of 263,697 veterans who were fully vaccinated against COVID-19.

Just over a half (51.4%) had one or more psychiatric diagnoses within the last 5 years and 14.8% developed breakthrough COVID-19 infections, confirmed by a positive SARS-CoV-2 test.

Psychiatric diagnoses among the veterans included depression, posttraumatic stress, anxiety, adjustment disorder, substance use disorder, bipolar disorder, psychosis, ADHD, dissociation, and eating disorders.

In the overall sample, a history of any psychiatric disorder was associated with a 7% higher incidence of breakthrough COVID-19 infection in models adjusted for potential confounders (adjusted relative risk, 1.07; 95% confidence interval, 1.05-1.09) and a 3% higher incidence in models additionally adjusted for underlying medical comorbidities and smoking (aRR, 1.03; 95% CI, 1.01-1.05).

Most psychiatric disorders were associated with a higher incidence of breakthrough infection, with the highest relative risk observed for substance use disorders (aRR, 1.16; 95% CI, 1.12 -1.21) and adjustment disorder (aRR, 1.13; 95% CI, 1.10-1.16) in fully adjusted models.

Older vaccinated veterans with psychiatric illnesses appear to be most vulnerable to COVID-19 reinfection.

In veterans aged 65 and older, all psychiatric disorders were associated with an increased incidence of breakthrough infection, with increases in the incidence rate ranging from 3% to 24% in fully adjusted models.

In the younger veterans, in contrast, only anxiety, adjustment, and substance use disorders were associated with an increased incidence of breakthrough infection in fully adjusted models.

Psychotic disorders were associated with a 10% lower incidence of breakthrough infection among younger veterans, perhaps because of greater social isolation, the researchers said.
 

Risky behavior or impaired immunity?

“Although some of the larger observed effect sizes are compelling at an individual level, even the relatively modest effect sizes may have a large effect at the population level when considering the high prevalence of psychiatric disorders and the global reach and scale of the pandemic,” Dr. O’Donovan and colleagues wrote.

They noted that psychiatric disorders, including depression, schizophrenia, and bipolar disorders, have been associated with impaired cellular immunity and blunted response to vaccines. Therefore, it’s possible that those with psychiatric disorders have poorer responses to COVID-19 vaccination.

It’s also possible that immunity following vaccination wanes more quickly or more strongly in people with psychiatric disorders and they could have less protection against new variants, they added.

Patients with psychiatric disorders could be more apt to engage in risky behaviors for contracting COVID-19, which could also increase the risk for breakthrough infection, they said.

The study was supported by a UCSF Department of Psychiatry Rapid Award and UCSF Faculty Resource Fund Award. Dr. O’Donovan reported no relevant disclosures.

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

Patients with first-episode psychosis (FEP) show altered speech patterns and content that could pinpoint symptom severity – and help predict future relapse, two new studies suggest.

In the first study, an algorithm was created to analyze speech patterns and semantic content to create novel “speech networks.” Compared with their healthy peers, patients with FEP had smaller and more fragmented networks. At-risk individuals had fragmented values that were in between those of the FEP and healthy control groups.

“This suggests that semantic speech networks can enable deeper phenotyping of formal thought disorder and psychosis,” said lead author Caroline Nettekoven, PhD, department of psychiatry, University of Cambridge, England.

In the second study, Janna N. de Boer, MD, University of Groningen, the Netherlands, and colleagues examined patients with FEP who did and did not experience relapse after 24 months of follow-up.

An algorithm based on natural language processing (NLP) of speech recordings predicted the relapses with an accuracy of more than 80%.

NLP “is a powerful tool with high potential for clinical application and diagnosis and differentiation, given its ease in acquirement, low cost, and naturally low patient burden,” said de Boer.

The findings for both studies were presented at the annual congress of the Schizophrenia International Research Society.
 

Fragmented networks

Dr. Nettekoven noted that previous research has shown “mapping the speech of a psychosis patient as a network and analyzing the network using graph theory is useful for understanding formal thought disorder.”

However, these tools ignore the semantic content of speech, which is a “key feature” that is altered in psychotic language, she added.

The researchers therefore proposed a “novel type of network to map the content of speech.”

For example, if someone said, “I see a man,” a semantic speech network developed from this sentence would have the first and last words connected by “the edge” to the word “see,” Dr. Nettekoven explained.

To explore further, the investigators developed an algorithm known as “netts” that automatically creates semantic speech networks from transcribed speech.

They first applied the algorithm to transcribed speech from a general population sample of 436 individuals and then to a clinical sample (n = 53) comprising patients with FEP, those at clinical high risk for psychosis, and a healthy control group.

Comparing the general population sample with randomly generated semantic speech networks, the investigators found that networks from the general population had fewer but larger connected components, which “reflects the nonrandom nature of speech,” said Dr. Nettekoven.

In the clinical sample, networks from the FEP group had a significantly higher number of connected components compared with the healthy control group (P = .05) and a significantly smaller median connected-component size (P < .01).

“So patients’ mental speech networks are more fragmented than those from controls,” said Dr. Nettekoven. She added that the networks from clinically high-risk individuals “showed fragmentation values in between [those of] patients and controls.”

A further clustering analysis suggested the semantic speech networks “capture a novel signal that is not already described” by other NLP measures, Dr. Nettekoven said. In addition, the network features were related to negative symptom scores and scores on the Thought and Language Index.

However, Dr. Nettekoven noted that these relationships “did not survive correcting for multiple comparisons.”
 

Relapse predictor

During her presentation of the second study, Dr. de Boer said that “predicting relapse remains challenging” in FEP.

However, she noted that recent developments in NLP have proved to be effective in a “range of applications,” including early symptom recognition and differential diagnosis in psychosis.

To determine whether NLP could help predict relapse, the study included 104 patients aged 16-55 years with FEP whose conditions had been in remission for 3-6 months. Speech recordings were made at baseline and after 3 and 6 months and were analyzed via OpenSMILE software.

After a follow-up of 24 months, 24 of the patients remaining in the study had not experienced relapse, while 21 patients had experienced relapse. There were no significant age, education, or gender differences between those who did and those who did not experience relapse.

On the basis of speech analysis, the investigators identified a machine learning classifier, which showed an accuracy of 80.8% in predicting relapse 3 months in advance of the occurrence.
 

‘Valid and informative’

Commenting on the studies, Eric J. Tan, PhD, Centre for Mental Health, Swinburne University of Technology, Melbourne, said they are “but two of a variety of ways in which speech can be analyzed and are both equally valid and informative.”

The key takeaway “is that both studies are examples of the ways in which speech can be used clinically, such as for predicting relapse and for the potential proxy measure for the assessment of symptom severity,” said Dr. Tan, who was not involved with the research.

The studies also show that “speech is sensitive to different stages of the disorder, as well as its individual symptoms,” he added.

However, Dr. Tan noted that although “speech may be more of a sign of an underlying pathology or dysfunction, given that it waxes and wanes with illness severity, more analyses are needed before drawing definitive conclusions.” This is especially needed “given the relative infancy of quantitative speech analysis,” he said.

“It would also be useful to conduct these analyses across a variety of different languages to look for commonalities and differences that will help shed light on the variables most closely linked to the disorder,” Dr. Tan concluded.

The investigators have reported no relevant financial relationships. Dr. Tan has received an Early Career Research Fellowship from the National Health and Medical Research Council of Australia.

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

Patients with first-episode psychosis (FEP) show altered speech patterns and content that could pinpoint symptom severity – and help predict future relapse, two new studies suggest.

In the first study, an algorithm was created to analyze speech patterns and semantic content to create novel “speech networks.” Compared with their healthy peers, patients with FEP had smaller and more fragmented networks. At-risk individuals had fragmented values that were in between those of the FEP and healthy control groups.

“This suggests that semantic speech networks can enable deeper phenotyping of formal thought disorder and psychosis,” said lead author Caroline Nettekoven, PhD, department of psychiatry, University of Cambridge, England.

In the second study, Janna N. de Boer, MD, University of Groningen, the Netherlands, and colleagues examined patients with FEP who did and did not experience relapse after 24 months of follow-up.

An algorithm based on natural language processing (NLP) of speech recordings predicted the relapses with an accuracy of more than 80%.

NLP “is a powerful tool with high potential for clinical application and diagnosis and differentiation, given its ease in acquirement, low cost, and naturally low patient burden,” said de Boer.

The findings for both studies were presented at the annual congress of the Schizophrenia International Research Society.
 

Fragmented networks

Dr. Nettekoven noted that previous research has shown “mapping the speech of a psychosis patient as a network and analyzing the network using graph theory is useful for understanding formal thought disorder.”

However, these tools ignore the semantic content of speech, which is a “key feature” that is altered in psychotic language, she added.

The researchers therefore proposed a “novel type of network to map the content of speech.”

For example, if someone said, “I see a man,” a semantic speech network developed from this sentence would have the first and last words connected by “the edge” to the word “see,” Dr. Nettekoven explained.

To explore further, the investigators developed an algorithm known as “netts” that automatically creates semantic speech networks from transcribed speech.

They first applied the algorithm to transcribed speech from a general population sample of 436 individuals and then to a clinical sample (n = 53) comprising patients with FEP, those at clinical high risk for psychosis, and a healthy control group.

Comparing the general population sample with randomly generated semantic speech networks, the investigators found that networks from the general population had fewer but larger connected components, which “reflects the nonrandom nature of speech,” said Dr. Nettekoven.

In the clinical sample, networks from the FEP group had a significantly higher number of connected components compared with the healthy control group (P = .05) and a significantly smaller median connected-component size (P < .01).

“So patients’ mental speech networks are more fragmented than those from controls,” said Dr. Nettekoven. She added that the networks from clinically high-risk individuals “showed fragmentation values in between [those of] patients and controls.”

A further clustering analysis suggested the semantic speech networks “capture a novel signal that is not already described” by other NLP measures, Dr. Nettekoven said. In addition, the network features were related to negative symptom scores and scores on the Thought and Language Index.

However, Dr. Nettekoven noted that these relationships “did not survive correcting for multiple comparisons.”
 

Relapse predictor

During her presentation of the second study, Dr. de Boer said that “predicting relapse remains challenging” in FEP.

However, she noted that recent developments in NLP have proved to be effective in a “range of applications,” including early symptom recognition and differential diagnosis in psychosis.

To determine whether NLP could help predict relapse, the study included 104 patients aged 16-55 years with FEP whose conditions had been in remission for 3-6 months. Speech recordings were made at baseline and after 3 and 6 months and were analyzed via OpenSMILE software.

After a follow-up of 24 months, 24 of the patients remaining in the study had not experienced relapse, while 21 patients had experienced relapse. There were no significant age, education, or gender differences between those who did and those who did not experience relapse.

On the basis of speech analysis, the investigators identified a machine learning classifier, which showed an accuracy of 80.8% in predicting relapse 3 months in advance of the occurrence.
 

‘Valid and informative’

Commenting on the studies, Eric J. Tan, PhD, Centre for Mental Health, Swinburne University of Technology, Melbourne, said they are “but two of a variety of ways in which speech can be analyzed and are both equally valid and informative.”

The key takeaway “is that both studies are examples of the ways in which speech can be used clinically, such as for predicting relapse and for the potential proxy measure for the assessment of symptom severity,” said Dr. Tan, who was not involved with the research.

The studies also show that “speech is sensitive to different stages of the disorder, as well as its individual symptoms,” he added.

However, Dr. Tan noted that although “speech may be more of a sign of an underlying pathology or dysfunction, given that it waxes and wanes with illness severity, more analyses are needed before drawing definitive conclusions.” This is especially needed “given the relative infancy of quantitative speech analysis,” he said.

“It would also be useful to conduct these analyses across a variety of different languages to look for commonalities and differences that will help shed light on the variables most closely linked to the disorder,” Dr. Tan concluded.

The investigators have reported no relevant financial relationships. Dr. Tan has received an Early Career Research Fellowship from the National Health and Medical Research Council of Australia.

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

Patients with first-episode psychosis (FEP) show altered speech patterns and content that could pinpoint symptom severity – and help predict future relapse, two new studies suggest.

In the first study, an algorithm was created to analyze speech patterns and semantic content to create novel “speech networks.” Compared with their healthy peers, patients with FEP had smaller and more fragmented networks. At-risk individuals had fragmented values that were in between those of the FEP and healthy control groups.

“This suggests that semantic speech networks can enable deeper phenotyping of formal thought disorder and psychosis,” said lead author Caroline Nettekoven, PhD, department of psychiatry, University of Cambridge, England.

In the second study, Janna N. de Boer, MD, University of Groningen, the Netherlands, and colleagues examined patients with FEP who did and did not experience relapse after 24 months of follow-up.

An algorithm based on natural language processing (NLP) of speech recordings predicted the relapses with an accuracy of more than 80%.

NLP “is a powerful tool with high potential for clinical application and diagnosis and differentiation, given its ease in acquirement, low cost, and naturally low patient burden,” said de Boer.

The findings for both studies were presented at the annual congress of the Schizophrenia International Research Society.
 

Fragmented networks

Dr. Nettekoven noted that previous research has shown “mapping the speech of a psychosis patient as a network and analyzing the network using graph theory is useful for understanding formal thought disorder.”

However, these tools ignore the semantic content of speech, which is a “key feature” that is altered in psychotic language, she added.

The researchers therefore proposed a “novel type of network to map the content of speech.”

For example, if someone said, “I see a man,” a semantic speech network developed from this sentence would have the first and last words connected by “the edge” to the word “see,” Dr. Nettekoven explained.

To explore further, the investigators developed an algorithm known as “netts” that automatically creates semantic speech networks from transcribed speech.

They first applied the algorithm to transcribed speech from a general population sample of 436 individuals and then to a clinical sample (n = 53) comprising patients with FEP, those at clinical high risk for psychosis, and a healthy control group.

Comparing the general population sample with randomly generated semantic speech networks, the investigators found that networks from the general population had fewer but larger connected components, which “reflects the nonrandom nature of speech,” said Dr. Nettekoven.

In the clinical sample, networks from the FEP group had a significantly higher number of connected components compared with the healthy control group (P = .05) and a significantly smaller median connected-component size (P < .01).

“So patients’ mental speech networks are more fragmented than those from controls,” said Dr. Nettekoven. She added that the networks from clinically high-risk individuals “showed fragmentation values in between [those of] patients and controls.”

A further clustering analysis suggested the semantic speech networks “capture a novel signal that is not already described” by other NLP measures, Dr. Nettekoven said. In addition, the network features were related to negative symptom scores and scores on the Thought and Language Index.

However, Dr. Nettekoven noted that these relationships “did not survive correcting for multiple comparisons.”
 

Relapse predictor

During her presentation of the second study, Dr. de Boer said that “predicting relapse remains challenging” in FEP.

However, she noted that recent developments in NLP have proved to be effective in a “range of applications,” including early symptom recognition and differential diagnosis in psychosis.

To determine whether NLP could help predict relapse, the study included 104 patients aged 16-55 years with FEP whose conditions had been in remission for 3-6 months. Speech recordings were made at baseline and after 3 and 6 months and were analyzed via OpenSMILE software.

After a follow-up of 24 months, 24 of the patients remaining in the study had not experienced relapse, while 21 patients had experienced relapse. There were no significant age, education, or gender differences between those who did and those who did not experience relapse.

On the basis of speech analysis, the investigators identified a machine learning classifier, which showed an accuracy of 80.8% in predicting relapse 3 months in advance of the occurrence.
 

‘Valid and informative’

Commenting on the studies, Eric J. Tan, PhD, Centre for Mental Health, Swinburne University of Technology, Melbourne, said they are “but two of a variety of ways in which speech can be analyzed and are both equally valid and informative.”

The key takeaway “is that both studies are examples of the ways in which speech can be used clinically, such as for predicting relapse and for the potential proxy measure for the assessment of symptom severity,” said Dr. Tan, who was not involved with the research.

The studies also show that “speech is sensitive to different stages of the disorder, as well as its individual symptoms,” he added.

However, Dr. Tan noted that although “speech may be more of a sign of an underlying pathology or dysfunction, given that it waxes and wanes with illness severity, more analyses are needed before drawing definitive conclusions.” This is especially needed “given the relative infancy of quantitative speech analysis,” he said.

“It would also be useful to conduct these analyses across a variety of different languages to look for commonalities and differences that will help shed light on the variables most closely linked to the disorder,” Dr. Tan concluded.

The investigators have reported no relevant financial relationships. Dr. Tan has received an Early Career Research Fellowship from the National Health and Medical Research Council of Australia.

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

A long-acting subcutaneous antipsychotic (LASCA) suspension that combines risperidone with a novel copolymer substantially reduces risk for relapse and prolongs time to impending relapse for patients with schizophrenia, new research suggests.

In the phase 3 Risperidone Subcutaneous Extended-Release (RISE) trial, which included more than 500 patients with schizophrenia, those who received the novel combination treatment, known as TV-46000, had relapse reduced by 80% with monthly administration and by 63.5% with the bimonthly dose.

“Long-acting injectable medications are grossly underutilized,” study investigator John M. Kane, MD, Hofstra University, Hempstead, N.Y., told this news organization.

The attributes of TV-46000, which include its subcutaneous delivery rather than intramuscular injections, its being active within 24 hours of first treatment, and its being administered monthly or bimonthly, “might be advantageous for some patients,” Dr. Kane noted.

Because it is also effective in reducing risk for relapse, TV-46000 is “another alternative when people are looking at the possibility of using a long-acting injectable formulation,” he added.

The findings were presented at the annual congress of the Schizophrenia International Research Society.
 

Time to relapse

To examine the efficacy and safety of monthly and bimonthly doses of the drug, the researchers recruited patients aged 13-65 years who were diagnosed with schizophrenia more than a year previously and who had experienced at least one relapse in the previous 24 months.

After a screening period of up to 4 weeks, participants entered a 12-week pretreatment phase, during which their condition was stabilized on oral risperidone. During this period, the patients’ conditions had to remain stable for at least 4 consecutive weeks.

Patients were then randomly assigned in a 1:1:1 ratio to receive TV-46000 monthly, TV-46000 every 2 months, or matching placebo. All doses were given as subcutaneous injections.

Treatment was continued until participants experienced a relapse event, met at least one criteria for study withdrawal, or the study recorded a total of 90 or more relapse events.

Of 1,267 patients screened, 863 were enrolled in the study, and 544 underwent randomization. The median age of the patients who underwent randomization was 52 years; 61% were male; and the majority (59%) were Black.

In addition, the average length of time with the disease was 20.8 years, and the average time since the most recent relapse was 10.2 months.

The primary endpoint was time to impending relapse, the criteria for which included the following:

• Increases in Positive and Negative Syndrome Scale (PANSS) scores from randomization.
• Hospitalization because of worsening psychotic symptoms.
• Violent behavior resulting in clinically significant injury or damage.

Well tolerated?

In the intent-to-treat population, which comprised all adults who underwent randomization, monthly TV-46000 was associated with a fivefold prolongation of time to impending relapse in comparison with placebo; TV-46000 given every 2 months prolonged the time 2.7-fold.

This translated into a significant benefit vs. placebo for both TV-46000 monthly (hazard ratio for impending relapse, 0.2) and TV-46000 every 2 months (HR, 0.375; P < .0001 for both comparisons).

At the trial’s endpoint, impending relapse rates were 29% in the placebo group vs. 7% in the TV-46000 monthly group and 13% in the group that received TV-46000 every 2 months (P < .0001 for both).

While more patients in the two active-treatment groups met the strict criteria for remission, which included no relapse during the study and PANSS scores of 3 or less for at least 6 months prior to the study endpoint, the differences were not significant.

Treatment-related adverse events (AEs) were experienced by 39%-42% of the TV-46000 groups and by 26% of the placebo group. Serious AEs were experienced by 4%-6% of the TV-46000 groups and by 8% of the placebo group.

The investigators note that TV-46000 was “well tolerated” and that there were no new safety signals in comparison with what is already known about risperidone and “other long-acting risperidone formulations.”

Expanding on the reasons why long-acting antipsychotics are underprescribed, Dr. Kane said that “doctors often overestimate how adherent their patients are.”

He added that doctors may worry they are “insulting” their patient by suggesting they receive injections in order to increase adherence and that doctors are “not very good” at having these types of conversation with their patients.

“We did a study where we trained the clinical staff on how to have those conversations, and the result was the uptake [in patients switching to long-acting antipsychotics] was very high,” Dr. Kane said.

The personnel who received training included all of the medical team, therapists, who spend “much more time” with the patient than does the prescriber, and also social workers, case managers, and rehabilitation counselors, who are typically “not very familiar” with the idea of long-acting medications, he added.
 

‘Highly desirable’ option

Commenting on the study, Stephen R. Saklad, PharmD, director of the psychiatric pharmacy program, University of Texas Health Science Center at San Antonio, said that to call TV-46000 a LASCA rather than a depot injection is merely a “change in nomenclature.”

However, compared with a once-monthly subcutaneous injection of risperidone (Perseris), which was approved by the U.S. Food and Drug Administration in 2018 for the treatment of schizophrenia, the new drug has fewer injection site reactions, said Dr. Saklad, who was not involved with the current research.

That benefit plus having efficacy similar to that of oral risperidone and having the “more patient- and clinician-desirable administration location” of the upper arm as well as the abdomen means the option to switch a risperidone-stabilized patient directly to TV-46000 monthly or bimonthly is “highly desirable,” he added.

Dr. Saklad also noted the reduction in the likelihood of impending relapse with TV-46000 over placebo is a relatively large effect size “and shows the value toward improving the care of these patients.”

In addition, he agreed with Dr. Kane that the uptake of long-acting antipsychotics is “deplorably low.”

“This is due to a number of factors that include patient reluctance to get a ‘shot’ or ‘jab,’ clinician inexperience with LAIs during training, and the incorrect presentation of LAIs as a punishment paradigm for ‘bad’ patients,” Dr. Saklad said.

He added that “everyone tires of taking their medication or just forgets to take a dose,” and most patients with other disorders will resume their medication the next day.

However, patients with schizophrenia have a “specific cognitive difficulty” in making the connection between stopping their medication and a later relapse. If they miss a dose, they will “incorrectly conclude that they are now ‘well’ and don’t need the medication any longer,” he said.

Dr. Saklad stressed that for a patient with schizophrenia a relapse can mean substantial loss of function and of assets such as housing or support networks, and many “will complete suicide.”

The study was supported by Teva Branded Pharmaceutical Products R&D. Dr. Kane reported relationships with Alkermes, Allergan, Dainioppon Sumitomo, H. Lundbeck, Indivior, Intracellular Therapies, Janssen, Janssen Pharmaceuticals, Johnson & Johnson, LB Pharmaceuticals, Merck, Neurocine, North Shore Therapeutics, Novartis Pharmaceutical, Otsuka, Reviva, Roche, Saladex, Sunovion, Takeda, Teva, Otsuka, Lundbeck, Sunovion, UptoDate, and Vanguard Research Group.

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

A long-acting subcutaneous antipsychotic (LASCA) suspension that combines risperidone with a novel copolymer substantially reduces risk for relapse and prolongs time to impending relapse for patients with schizophrenia, new research suggests.

In the phase 3 Risperidone Subcutaneous Extended-Release (RISE) trial, which included more than 500 patients with schizophrenia, those who received the novel combination treatment, known as TV-46000, had relapse reduced by 80% with monthly administration and by 63.5% with the bimonthly dose.

“Long-acting injectable medications are grossly underutilized,” study investigator John M. Kane, MD, Hofstra University, Hempstead, N.Y., told this news organization.

The attributes of TV-46000, which include its subcutaneous delivery rather than intramuscular injections, its being active within 24 hours of first treatment, and its being administered monthly or bimonthly, “might be advantageous for some patients,” Dr. Kane noted.

Because it is also effective in reducing risk for relapse, TV-46000 is “another alternative when people are looking at the possibility of using a long-acting injectable formulation,” he added.

The findings were presented at the annual congress of the Schizophrenia International Research Society.
 

Time to relapse

To examine the efficacy and safety of monthly and bimonthly doses of the drug, the researchers recruited patients aged 13-65 years who were diagnosed with schizophrenia more than a year previously and who had experienced at least one relapse in the previous 24 months.

After a screening period of up to 4 weeks, participants entered a 12-week pretreatment phase, during which their condition was stabilized on oral risperidone. During this period, the patients’ conditions had to remain stable for at least 4 consecutive weeks.

Patients were then randomly assigned in a 1:1:1 ratio to receive TV-46000 monthly, TV-46000 every 2 months, or matching placebo. All doses were given as subcutaneous injections.

Treatment was continued until participants experienced a relapse event, met at least one criteria for study withdrawal, or the study recorded a total of 90 or more relapse events.

Of 1,267 patients screened, 863 were enrolled in the study, and 544 underwent randomization. The median age of the patients who underwent randomization was 52 years; 61% were male; and the majority (59%) were Black.

In addition, the average length of time with the disease was 20.8 years, and the average time since the most recent relapse was 10.2 months.

The primary endpoint was time to impending relapse, the criteria for which included the following:

• Increases in Positive and Negative Syndrome Scale (PANSS) scores from randomization.
• Hospitalization because of worsening psychotic symptoms.
• Violent behavior resulting in clinically significant injury or damage.

Well tolerated?

In the intent-to-treat population, which comprised all adults who underwent randomization, monthly TV-46000 was associated with a fivefold prolongation of time to impending relapse in comparison with placebo; TV-46000 given every 2 months prolonged the time 2.7-fold.

This translated into a significant benefit vs. placebo for both TV-46000 monthly (hazard ratio for impending relapse, 0.2) and TV-46000 every 2 months (HR, 0.375; P < .0001 for both comparisons).

At the trial’s endpoint, impending relapse rates were 29% in the placebo group vs. 7% in the TV-46000 monthly group and 13% in the group that received TV-46000 every 2 months (P < .0001 for both).

While more patients in the two active-treatment groups met the strict criteria for remission, which included no relapse during the study and PANSS scores of 3 or less for at least 6 months prior to the study endpoint, the differences were not significant.

Treatment-related adverse events (AEs) were experienced by 39%-42% of the TV-46000 groups and by 26% of the placebo group. Serious AEs were experienced by 4%-6% of the TV-46000 groups and by 8% of the placebo group.

The investigators note that TV-46000 was “well tolerated” and that there were no new safety signals in comparison with what is already known about risperidone and “other long-acting risperidone formulations.”

Expanding on the reasons why long-acting antipsychotics are underprescribed, Dr. Kane said that “doctors often overestimate how adherent their patients are.”

He added that doctors may worry they are “insulting” their patient by suggesting they receive injections in order to increase adherence and that doctors are “not very good” at having these types of conversation with their patients.

“We did a study where we trained the clinical staff on how to have those conversations, and the result was the uptake [in patients switching to long-acting antipsychotics] was very high,” Dr. Kane said.

The personnel who received training included all of the medical team, therapists, who spend “much more time” with the patient than does the prescriber, and also social workers, case managers, and rehabilitation counselors, who are typically “not very familiar” with the idea of long-acting medications, he added.
 

‘Highly desirable’ option

Commenting on the study, Stephen R. Saklad, PharmD, director of the psychiatric pharmacy program, University of Texas Health Science Center at San Antonio, said that to call TV-46000 a LASCA rather than a depot injection is merely a “change in nomenclature.”

However, compared with a once-monthly subcutaneous injection of risperidone (Perseris), which was approved by the U.S. Food and Drug Administration in 2018 for the treatment of schizophrenia, the new drug has fewer injection site reactions, said Dr. Saklad, who was not involved with the current research.

That benefit plus having efficacy similar to that of oral risperidone and having the “more patient- and clinician-desirable administration location” of the upper arm as well as the abdomen means the option to switch a risperidone-stabilized patient directly to TV-46000 monthly or bimonthly is “highly desirable,” he added.

Dr. Saklad also noted the reduction in the likelihood of impending relapse with TV-46000 over placebo is a relatively large effect size “and shows the value toward improving the care of these patients.”

In addition, he agreed with Dr. Kane that the uptake of long-acting antipsychotics is “deplorably low.”

“This is due to a number of factors that include patient reluctance to get a ‘shot’ or ‘jab,’ clinician inexperience with LAIs during training, and the incorrect presentation of LAIs as a punishment paradigm for ‘bad’ patients,” Dr. Saklad said.

He added that “everyone tires of taking their medication or just forgets to take a dose,” and most patients with other disorders will resume their medication the next day.

However, patients with schizophrenia have a “specific cognitive difficulty” in making the connection between stopping their medication and a later relapse. If they miss a dose, they will “incorrectly conclude that they are now ‘well’ and don’t need the medication any longer,” he said.

Dr. Saklad stressed that for a patient with schizophrenia a relapse can mean substantial loss of function and of assets such as housing or support networks, and many “will complete suicide.”

The study was supported by Teva Branded Pharmaceutical Products R&D. Dr. Kane reported relationships with Alkermes, Allergan, Dainioppon Sumitomo, H. Lundbeck, Indivior, Intracellular Therapies, Janssen, Janssen Pharmaceuticals, Johnson & Johnson, LB Pharmaceuticals, Merck, Neurocine, North Shore Therapeutics, Novartis Pharmaceutical, Otsuka, Reviva, Roche, Saladex, Sunovion, Takeda, Teva, Otsuka, Lundbeck, Sunovion, UptoDate, and Vanguard Research Group.

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

A long-acting subcutaneous antipsychotic (LASCA) suspension that combines risperidone with a novel copolymer substantially reduces risk for relapse and prolongs time to impending relapse for patients with schizophrenia, new research suggests.

In the phase 3 Risperidone Subcutaneous Extended-Release (RISE) trial, which included more than 500 patients with schizophrenia, those who received the novel combination treatment, known as TV-46000, had relapse reduced by 80% with monthly administration and by 63.5% with the bimonthly dose.

“Long-acting injectable medications are grossly underutilized,” study investigator John M. Kane, MD, Hofstra University, Hempstead, N.Y., told this news organization.

The attributes of TV-46000, which include its subcutaneous delivery rather than intramuscular injections, its being active within 24 hours of first treatment, and its being administered monthly or bimonthly, “might be advantageous for some patients,” Dr. Kane noted.

Because it is also effective in reducing risk for relapse, TV-46000 is “another alternative when people are looking at the possibility of using a long-acting injectable formulation,” he added.

The findings were presented at the annual congress of the Schizophrenia International Research Society.
 

Time to relapse

To examine the efficacy and safety of monthly and bimonthly doses of the drug, the researchers recruited patients aged 13-65 years who were diagnosed with schizophrenia more than a year previously and who had experienced at least one relapse in the previous 24 months.

After a screening period of up to 4 weeks, participants entered a 12-week pretreatment phase, during which their condition was stabilized on oral risperidone. During this period, the patients’ conditions had to remain stable for at least 4 consecutive weeks.

Patients were then randomly assigned in a 1:1:1 ratio to receive TV-46000 monthly, TV-46000 every 2 months, or matching placebo. All doses were given as subcutaneous injections.

Treatment was continued until participants experienced a relapse event, met at least one criteria for study withdrawal, or the study recorded a total of 90 or more relapse events.

Of 1,267 patients screened, 863 were enrolled in the study, and 544 underwent randomization. The median age of the patients who underwent randomization was 52 years; 61% were male; and the majority (59%) were Black.

In addition, the average length of time with the disease was 20.8 years, and the average time since the most recent relapse was 10.2 months.

The primary endpoint was time to impending relapse, the criteria for which included the following:

• Increases in Positive and Negative Syndrome Scale (PANSS) scores from randomization.
• Hospitalization because of worsening psychotic symptoms.
• Violent behavior resulting in clinically significant injury or damage.

Well tolerated?

In the intent-to-treat population, which comprised all adults who underwent randomization, monthly TV-46000 was associated with a fivefold prolongation of time to impending relapse in comparison with placebo; TV-46000 given every 2 months prolonged the time 2.7-fold.

This translated into a significant benefit vs. placebo for both TV-46000 monthly (hazard ratio for impending relapse, 0.2) and TV-46000 every 2 months (HR, 0.375; P < .0001 for both comparisons).

At the trial’s endpoint, impending relapse rates were 29% in the placebo group vs. 7% in the TV-46000 monthly group and 13% in the group that received TV-46000 every 2 months (P < .0001 for both).

While more patients in the two active-treatment groups met the strict criteria for remission, which included no relapse during the study and PANSS scores of 3 or less for at least 6 months prior to the study endpoint, the differences were not significant.

Treatment-related adverse events (AEs) were experienced by 39%-42% of the TV-46000 groups and by 26% of the placebo group. Serious AEs were experienced by 4%-6% of the TV-46000 groups and by 8% of the placebo group.

The investigators note that TV-46000 was “well tolerated” and that there were no new safety signals in comparison with what is already known about risperidone and “other long-acting risperidone formulations.”

Expanding on the reasons why long-acting antipsychotics are underprescribed, Dr. Kane said that “doctors often overestimate how adherent their patients are.”

He added that doctors may worry they are “insulting” their patient by suggesting they receive injections in order to increase adherence and that doctors are “not very good” at having these types of conversation with their patients.

“We did a study where we trained the clinical staff on how to have those conversations, and the result was the uptake [in patients switching to long-acting antipsychotics] was very high,” Dr. Kane said.

The personnel who received training included all of the medical team, therapists, who spend “much more time” with the patient than does the prescriber, and also social workers, case managers, and rehabilitation counselors, who are typically “not very familiar” with the idea of long-acting medications, he added.
 

‘Highly desirable’ option

Commenting on the study, Stephen R. Saklad, PharmD, director of the psychiatric pharmacy program, University of Texas Health Science Center at San Antonio, said that to call TV-46000 a LASCA rather than a depot injection is merely a “change in nomenclature.”

However, compared with a once-monthly subcutaneous injection of risperidone (Perseris), which was approved by the U.S. Food and Drug Administration in 2018 for the treatment of schizophrenia, the new drug has fewer injection site reactions, said Dr. Saklad, who was not involved with the current research.

That benefit plus having efficacy similar to that of oral risperidone and having the “more patient- and clinician-desirable administration location” of the upper arm as well as the abdomen means the option to switch a risperidone-stabilized patient directly to TV-46000 monthly or bimonthly is “highly desirable,” he added.

Dr. Saklad also noted the reduction in the likelihood of impending relapse with TV-46000 over placebo is a relatively large effect size “and shows the value toward improving the care of these patients.”

In addition, he agreed with Dr. Kane that the uptake of long-acting antipsychotics is “deplorably low.”

“This is due to a number of factors that include patient reluctance to get a ‘shot’ or ‘jab,’ clinician inexperience with LAIs during training, and the incorrect presentation of LAIs as a punishment paradigm for ‘bad’ patients,” Dr. Saklad said.

He added that “everyone tires of taking their medication or just forgets to take a dose,” and most patients with other disorders will resume their medication the next day.

However, patients with schizophrenia have a “specific cognitive difficulty” in making the connection between stopping their medication and a later relapse. If they miss a dose, they will “incorrectly conclude that they are now ‘well’ and don’t need the medication any longer,” he said.

Dr. Saklad stressed that for a patient with schizophrenia a relapse can mean substantial loss of function and of assets such as housing or support networks, and many “will complete suicide.”

The study was supported by Teva Branded Pharmaceutical Products R&D. Dr. Kane reported relationships with Alkermes, Allergan, Dainioppon Sumitomo, H. Lundbeck, Indivior, Intracellular Therapies, Janssen, Janssen Pharmaceuticals, Johnson & Johnson, LB Pharmaceuticals, Merck, Neurocine, North Shore Therapeutics, Novartis Pharmaceutical, Otsuka, Reviva, Roche, Saladex, Sunovion, Takeda, Teva, Otsuka, Lundbeck, Sunovion, UptoDate, and Vanguard Research Group.

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

AUT00206, a novel compound that targets potassium channels in brain interneurons, not only improves gamma oscillations in patients with schizophrenia, it also improves their symptoms, new randomized trial data suggest.

In a randomized, double-blind study that included two dozen men with schizophrenia, AUT00206, compared with placebo, increased the power of gamma oscillations, which were in turn associated with positive symptom scores.

The investigators note that targeting a potassium channel linked to brain gamma oscillations may offer a novel way to treat schizophrenia.

In addition, lead author Charles Large, PhD, chief executive officer, Autifony Therapeutics, Stevenage, United Kingdom, told this news organization that it may be “important” to study patients relatively early in their disease course. Participants in the current study were diagnosed less than 5 years previously.

Many previous trials in this area have failed, “and some of the questions were maybe the patients were sort of beyond the point in which you can actually make a difference,” Dr. Large said.

The findings were presented at the Congress of the Schizophrenia International Research Society (SIRS) 2022.
 

‘Opportunity to intervene’

Dr. Large noted that patients with chronic, long-term symptoms of schizophrenia have been treated with antipsychotics for decades, “and the pathology of that stage is then different.”

For the current study, the investigators hypothesized that the brain may be more “plastic” earlier on in the disease course, and so “maybe there’s an opportunity to intervene and make a change,” said Dr. Large.

In addition, patients with schizophrenia have abnormalities in both their resting state and induced and evolved gamma oscillations, which can include increased resting state power – and reduced power and “phase locking” to cyclical stimuli – the researchers note.

Previous studies have suggested such abnormalities are associated with dysfunction in parvalbumin-expressing interneurons (PVINs) found in cortical and subcortical circuits.

Moreover, Kv3.1 potassium channels expressed on PVINs are integral to establishing and maintaining fast-firing activity and to network synchronization across the brain. They may, therefore, offer a “potential therapeutic approach” for countering PVIN dysfunction, the investigators write.

To examine the impact of AUT00206, a novel Kv3.1/Kv3.2 positive neuromodulator, on resting state and induced gamma oscillations, they conducted a randomized, double-blind study in 24 men with schizophrenia who were aged 18-50 years.

Participants had been diagnosed less than 5 years previously and were stable on a maximum of two antipsychotic medications. They were randomly assigned 2:1 to a loading 2,000-mg dose of AUT00206 on day 1 and then 800 mg twice daily for 27 days or to placebo.

At baseline/day 1, and on a further 3 days over the treatment period, the men underwent resting-state electroencephalography, 40-Hz auditory steady-state response stimulation, and deviant and standard stimulation in an auditory oddball paradigm to assess resting state, induced, and evoked oscillations, respectively.
 

Positive associations

Results showed that early auditory gamma responses were increased at day 28 in patients who received AUT00206 but not in those who received placebo. The active drug was also associated with increases in the power of gamma oscillations from Day 5 in response to stimuli but not in phase locking.

There was also a significant positive association between frontal resting gamma power and baseline Positive and Negative Syndrome Scale (PANSS) positive symptom severity scores (r = 0.675; P < .001).

Moreover, changes in PANSS positive scores were significantly correlated with a decrease in frontal resting gamma power in patients treated with AUT00206 (r = 0.532; P = .05).

While a similar correlation was not found with placebo, the investigators note this “may be in part due to the low number” of individuals in the group.

They add that a larger study is now needed to confirm their findings and to “explore efficacy versus clinical symptoms.”

However, Dr. Large noted that participants in their next study will have fragile X syndrome.

He added the reason for this is “not because we’ve given up on schizophrenia – we feel that schizophrenia is a massive opportunity.”

Patients with schizophrenia are heterogeneous, both in terms of their clinical course and prior treatment. So it is “impossible” for a company of their size to take all of that into account in a single study, Dr. Large said.

In contrast, fragile X is “genetically homogenous,” and so it is possible to focus on the deficit and then translate the findings out into a “broader population.”
 

Preliminary but worth pursuing?

Commenting on the study, James M. McNally, PhD, assistant professor of psychiatry, Harvard Medical School, Boston, said the findings are “quite preliminary” and that the investigators provided “limited information as to how their findings were derived.”

Nevertheless, it is “nice to see that they observed a significant correlation between resting gamma and positive symptom severity at baseline [and] that the observed change in gamma correlates with change in PANSS scores,” said Dr. McNally, who was not involved with the research.

He added that the “idea of targeting Kv3.1 function to restore PV neuron/gamma activity is very interesting and worth pursuing.”

The study was funded by Autifony Therapeutics, of which Dr. Large is an employee.

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

AUT00206, a novel compound that targets potassium channels in brain interneurons, not only improves gamma oscillations in patients with schizophrenia, it also improves their symptoms, new randomized trial data suggest.

In a randomized, double-blind study that included two dozen men with schizophrenia, AUT00206, compared with placebo, increased the power of gamma oscillations, which were in turn associated with positive symptom scores.

The investigators note that targeting a potassium channel linked to brain gamma oscillations may offer a novel way to treat schizophrenia.

In addition, lead author Charles Large, PhD, chief executive officer, Autifony Therapeutics, Stevenage, United Kingdom, told this news organization that it may be “important” to study patients relatively early in their disease course. Participants in the current study were diagnosed less than 5 years previously.

Many previous trials in this area have failed, “and some of the questions were maybe the patients were sort of beyond the point in which you can actually make a difference,” Dr. Large said.

The findings were presented at the Congress of the Schizophrenia International Research Society (SIRS) 2022.
 

‘Opportunity to intervene’

Dr. Large noted that patients with chronic, long-term symptoms of schizophrenia have been treated with antipsychotics for decades, “and the pathology of that stage is then different.”

For the current study, the investigators hypothesized that the brain may be more “plastic” earlier on in the disease course, and so “maybe there’s an opportunity to intervene and make a change,” said Dr. Large.

In addition, patients with schizophrenia have abnormalities in both their resting state and induced and evolved gamma oscillations, which can include increased resting state power – and reduced power and “phase locking” to cyclical stimuli – the researchers note.

Previous studies have suggested such abnormalities are associated with dysfunction in parvalbumin-expressing interneurons (PVINs) found in cortical and subcortical circuits.

Moreover, Kv3.1 potassium channels expressed on PVINs are integral to establishing and maintaining fast-firing activity and to network synchronization across the brain. They may, therefore, offer a “potential therapeutic approach” for countering PVIN dysfunction, the investigators write.

To examine the impact of AUT00206, a novel Kv3.1/Kv3.2 positive neuromodulator, on resting state and induced gamma oscillations, they conducted a randomized, double-blind study in 24 men with schizophrenia who were aged 18-50 years.

Participants had been diagnosed less than 5 years previously and were stable on a maximum of two antipsychotic medications. They were randomly assigned 2:1 to a loading 2,000-mg dose of AUT00206 on day 1 and then 800 mg twice daily for 27 days or to placebo.

At baseline/day 1, and on a further 3 days over the treatment period, the men underwent resting-state electroencephalography, 40-Hz auditory steady-state response stimulation, and deviant and standard stimulation in an auditory oddball paradigm to assess resting state, induced, and evoked oscillations, respectively.
 

Positive associations

Results showed that early auditory gamma responses were increased at day 28 in patients who received AUT00206 but not in those who received placebo. The active drug was also associated with increases in the power of gamma oscillations from Day 5 in response to stimuli but not in phase locking.

There was also a significant positive association between frontal resting gamma power and baseline Positive and Negative Syndrome Scale (PANSS) positive symptom severity scores (r = 0.675; P < .001).

Moreover, changes in PANSS positive scores were significantly correlated with a decrease in frontal resting gamma power in patients treated with AUT00206 (r = 0.532; P = .05).

While a similar correlation was not found with placebo, the investigators note this “may be in part due to the low number” of individuals in the group.

They add that a larger study is now needed to confirm their findings and to “explore efficacy versus clinical symptoms.”

However, Dr. Large noted that participants in their next study will have fragile X syndrome.

He added the reason for this is “not because we’ve given up on schizophrenia – we feel that schizophrenia is a massive opportunity.”

Patients with schizophrenia are heterogeneous, both in terms of their clinical course and prior treatment. So it is “impossible” for a company of their size to take all of that into account in a single study, Dr. Large said.

In contrast, fragile X is “genetically homogenous,” and so it is possible to focus on the deficit and then translate the findings out into a “broader population.”
 

Preliminary but worth pursuing?

Commenting on the study, James M. McNally, PhD, assistant professor of psychiatry, Harvard Medical School, Boston, said the findings are “quite preliminary” and that the investigators provided “limited information as to how their findings were derived.”

Nevertheless, it is “nice to see that they observed a significant correlation between resting gamma and positive symptom severity at baseline [and] that the observed change in gamma correlates with change in PANSS scores,” said Dr. McNally, who was not involved with the research.

He added that the “idea of targeting Kv3.1 function to restore PV neuron/gamma activity is very interesting and worth pursuing.”

The study was funded by Autifony Therapeutics, of which Dr. Large is an employee.

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

AUT00206, a novel compound that targets potassium channels in brain interneurons, not only improves gamma oscillations in patients with schizophrenia, it also improves their symptoms, new randomized trial data suggest.

In a randomized, double-blind study that included two dozen men with schizophrenia, AUT00206, compared with placebo, increased the power of gamma oscillations, which were in turn associated with positive symptom scores.

The investigators note that targeting a potassium channel linked to brain gamma oscillations may offer a novel way to treat schizophrenia.

In addition, lead author Charles Large, PhD, chief executive officer, Autifony Therapeutics, Stevenage, United Kingdom, told this news organization that it may be “important” to study patients relatively early in their disease course. Participants in the current study were diagnosed less than 5 years previously.

Many previous trials in this area have failed, “and some of the questions were maybe the patients were sort of beyond the point in which you can actually make a difference,” Dr. Large said.

The findings were presented at the Congress of the Schizophrenia International Research Society (SIRS) 2022.
 

‘Opportunity to intervene’

Dr. Large noted that patients with chronic, long-term symptoms of schizophrenia have been treated with antipsychotics for decades, “and the pathology of that stage is then different.”

For the current study, the investigators hypothesized that the brain may be more “plastic” earlier on in the disease course, and so “maybe there’s an opportunity to intervene and make a change,” said Dr. Large.

In addition, patients with schizophrenia have abnormalities in both their resting state and induced and evolved gamma oscillations, which can include increased resting state power – and reduced power and “phase locking” to cyclical stimuli – the researchers note.

Previous studies have suggested such abnormalities are associated with dysfunction in parvalbumin-expressing interneurons (PVINs) found in cortical and subcortical circuits.

Moreover, Kv3.1 potassium channels expressed on PVINs are integral to establishing and maintaining fast-firing activity and to network synchronization across the brain. They may, therefore, offer a “potential therapeutic approach” for countering PVIN dysfunction, the investigators write.

To examine the impact of AUT00206, a novel Kv3.1/Kv3.2 positive neuromodulator, on resting state and induced gamma oscillations, they conducted a randomized, double-blind study in 24 men with schizophrenia who were aged 18-50 years.

Participants had been diagnosed less than 5 years previously and were stable on a maximum of two antipsychotic medications. They were randomly assigned 2:1 to a loading 2,000-mg dose of AUT00206 on day 1 and then 800 mg twice daily for 27 days or to placebo.

At baseline/day 1, and on a further 3 days over the treatment period, the men underwent resting-state electroencephalography, 40-Hz auditory steady-state response stimulation, and deviant and standard stimulation in an auditory oddball paradigm to assess resting state, induced, and evoked oscillations, respectively.
 

Positive associations

Results showed that early auditory gamma responses were increased at day 28 in patients who received AUT00206 but not in those who received placebo. The active drug was also associated with increases in the power of gamma oscillations from Day 5 in response to stimuli but not in phase locking.

There was also a significant positive association between frontal resting gamma power and baseline Positive and Negative Syndrome Scale (PANSS) positive symptom severity scores (r = 0.675; P < .001).

Moreover, changes in PANSS positive scores were significantly correlated with a decrease in frontal resting gamma power in patients treated with AUT00206 (r = 0.532; P = .05).

While a similar correlation was not found with placebo, the investigators note this “may be in part due to the low number” of individuals in the group.

They add that a larger study is now needed to confirm their findings and to “explore efficacy versus clinical symptoms.”

However, Dr. Large noted that participants in their next study will have fragile X syndrome.

He added the reason for this is “not because we’ve given up on schizophrenia – we feel that schizophrenia is a massive opportunity.”

Patients with schizophrenia are heterogeneous, both in terms of their clinical course and prior treatment. So it is “impossible” for a company of their size to take all of that into account in a single study, Dr. Large said.

In contrast, fragile X is “genetically homogenous,” and so it is possible to focus on the deficit and then translate the findings out into a “broader population.”
 

Preliminary but worth pursuing?

Commenting on the study, James M. McNally, PhD, assistant professor of psychiatry, Harvard Medical School, Boston, said the findings are “quite preliminary” and that the investigators provided “limited information as to how their findings were derived.”

Nevertheless, it is “nice to see that they observed a significant correlation between resting gamma and positive symptom severity at baseline [and] that the observed change in gamma correlates with change in PANSS scores,” said Dr. McNally, who was not involved with the research.

He added that the “idea of targeting Kv3.1 function to restore PV neuron/gamma activity is very interesting and worth pursuing.”

The study was funded by Autifony Therapeutics, of which Dr. Large is an employee.

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

The Food and Drug Administration has approved dexmedetomidine (Igalmi, BioXcel Therapeutics) sublingual film for the acute treatment of agitation associated with schizophrenia or bipolar I or II disorder in adults.

This is the first FDA-approved, orally dissolving, self-administered sublingual treatment for this indication. With a demonstrated onset of action as early as 20 minutes, it shows a high response rate in patients at both 120-mcg and 180-mcg doses.

Olivier Le Moal/Getty Images

An estimated 7.3 million individuals in the United States are diagnosed with schizophrenia or bipolar disorders, and up to one-quarter of them experience episodes of agitation that can occur 10-17 times annually. These episodes represent a significant burden for patients, caregivers, and the health care system.

“There are large numbers of patients who experience agitation associated with schizophrenia and bipolar disorders, and this condition has been a long-standing challenge for health care professionals to treat,” said John Krystal, MD, the Robert L. McNeil Jr. Professor of Translational Research and chair of the department of psychiatry at Yale University, New Haven, Conn.

“The approval of Igalmi, a self-administered film with a desirable onset of action, represents a milestone moment. It provides health care teams with an innovative tool to help control agitation. As clinicians, we welcome this much-needed new oral treatment option,” he added.

“Igalmi is the first new acute treatment for schizophrenia or bipolar disorder–associated agitation in nearly a decade and represents a differentiated approach to helping patients manage this difficult and debilitating symptom,” said Vimal Mehta, PhD, CEO of BioXcel Therapeutics.

The FDA approval of Igalmi is based on data from two pivotal randomized, double-blinded, placebo-controlled, parallel-group, phase 3 trials that evaluated Igalmi for the acute treatment of agitation associated with schizophrenia (SERENITY I) or bipolar I or II disorder (SERENITY II).

The most common adverse reactions (incidence ≥5% and at least twice the rate of placebo) were somnolence, paresthesia or oral hypoesthesia, dizziness, dry mouth, hypotension, and orthostatic hypotension. All adverse drug reactions were mild to moderate in severity. While Igalmi was not associated with any treatment-related serious adverse effects in phase 3 studies, it may cause notable side effects, including hypotension, orthostatic hypotension, bradycardia, QT interval prolongation, and somnolence.

As previously reported by this news organization, data from the phase 3 SERENITY II trial that evaluated Igalmi in bipolar disorders were published in JAMA.

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

The Food and Drug Administration has approved dexmedetomidine (Igalmi, BioXcel Therapeutics) sublingual film for the acute treatment of agitation associated with schizophrenia or bipolar I or II disorder in adults.

This is the first FDA-approved, orally dissolving, self-administered sublingual treatment for this indication. With a demonstrated onset of action as early as 20 minutes, it shows a high response rate in patients at both 120-mcg and 180-mcg doses.

Olivier Le Moal/Getty Images

An estimated 7.3 million individuals in the United States are diagnosed with schizophrenia or bipolar disorders, and up to one-quarter of them experience episodes of agitation that can occur 10-17 times annually. These episodes represent a significant burden for patients, caregivers, and the health care system.

“There are large numbers of patients who experience agitation associated with schizophrenia and bipolar disorders, and this condition has been a long-standing challenge for health care professionals to treat,” said John Krystal, MD, the Robert L. McNeil Jr. Professor of Translational Research and chair of the department of psychiatry at Yale University, New Haven, Conn.

“The approval of Igalmi, a self-administered film with a desirable onset of action, represents a milestone moment. It provides health care teams with an innovative tool to help control agitation. As clinicians, we welcome this much-needed new oral treatment option,” he added.

“Igalmi is the first new acute treatment for schizophrenia or bipolar disorder–associated agitation in nearly a decade and represents a differentiated approach to helping patients manage this difficult and debilitating symptom,” said Vimal Mehta, PhD, CEO of BioXcel Therapeutics.

The FDA approval of Igalmi is based on data from two pivotal randomized, double-blinded, placebo-controlled, parallel-group, phase 3 trials that evaluated Igalmi for the acute treatment of agitation associated with schizophrenia (SERENITY I) or bipolar I or II disorder (SERENITY II).

The most common adverse reactions (incidence ≥5% and at least twice the rate of placebo) were somnolence, paresthesia or oral hypoesthesia, dizziness, dry mouth, hypotension, and orthostatic hypotension. All adverse drug reactions were mild to moderate in severity. While Igalmi was not associated with any treatment-related serious adverse effects in phase 3 studies, it may cause notable side effects, including hypotension, orthostatic hypotension, bradycardia, QT interval prolongation, and somnolence.

As previously reported by this news organization, data from the phase 3 SERENITY II trial that evaluated Igalmi in bipolar disorders were published in JAMA.

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

The Food and Drug Administration has approved dexmedetomidine (Igalmi, BioXcel Therapeutics) sublingual film for the acute treatment of agitation associated with schizophrenia or bipolar I or II disorder in adults.

This is the first FDA-approved, orally dissolving, self-administered sublingual treatment for this indication. With a demonstrated onset of action as early as 20 minutes, it shows a high response rate in patients at both 120-mcg and 180-mcg doses.

Olivier Le Moal/Getty Images

An estimated 7.3 million individuals in the United States are diagnosed with schizophrenia or bipolar disorders, and up to one-quarter of them experience episodes of agitation that can occur 10-17 times annually. These episodes represent a significant burden for patients, caregivers, and the health care system.

“There are large numbers of patients who experience agitation associated with schizophrenia and bipolar disorders, and this condition has been a long-standing challenge for health care professionals to treat,” said John Krystal, MD, the Robert L. McNeil Jr. Professor of Translational Research and chair of the department of psychiatry at Yale University, New Haven, Conn.

“The approval of Igalmi, a self-administered film with a desirable onset of action, represents a milestone moment. It provides health care teams with an innovative tool to help control agitation. As clinicians, we welcome this much-needed new oral treatment option,” he added.

“Igalmi is the first new acute treatment for schizophrenia or bipolar disorder–associated agitation in nearly a decade and represents a differentiated approach to helping patients manage this difficult and debilitating symptom,” said Vimal Mehta, PhD, CEO of BioXcel Therapeutics.

The FDA approval of Igalmi is based on data from two pivotal randomized, double-blinded, placebo-controlled, parallel-group, phase 3 trials that evaluated Igalmi for the acute treatment of agitation associated with schizophrenia (SERENITY I) or bipolar I or II disorder (SERENITY II).

The most common adverse reactions (incidence ≥5% and at least twice the rate of placebo) were somnolence, paresthesia or oral hypoesthesia, dizziness, dry mouth, hypotension, and orthostatic hypotension. All adverse drug reactions were mild to moderate in severity. While Igalmi was not associated with any treatment-related serious adverse effects in phase 3 studies, it may cause notable side effects, including hypotension, orthostatic hypotension, bradycardia, QT interval prolongation, and somnolence.

As previously reported by this news organization, data from the phase 3 SERENITY II trial that evaluated Igalmi in bipolar disorders were published in JAMA.

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