APA 2021 Roundup: New Antipsychotic Class, Anxious America

Some of the latest research advancements in the field of psychiatry presented at the American Psychiatric Association (APA) virtual meeting included MDMA-assisted psychotherapy for PTSD remission, an amphetamine patch for kids with ADHD, and a rapid-acting dissolving film to calm agitation in schizophrenia and bipolar disorder. Below are a few more research highlights.

Fewer Adverse Events With Novel TAAR1 Agonist

Treatment with the investigational agent SEP-363856, a trace amine-associated receptor 1 (TAAR1) agonist with serotonin 5-HT1A agonist activity, yielded far fewer adverse events compared with atypical antipsychotics on the market today, Seth Hopkins, PhD, of Sunovion Pharmaceuticals in Marlborough, Massachusetts, reported here.

After demonstrating efficacy for treatment of schizophrenia in a study published in the New England Journal of Medicine in April 2020, new data suggest that SEP-363856 has a lower cumulative risk for adverse events and a distinctly different adverse event profile compared with atypical antipsychotics, and is the “first of a new class of CND-active compounds.”

While atypical antipsychotics block the dopamine D2 receptor directly, this oral agent doesn’t bind to this receptor, nor 5-HT2A receptors or other neuroreceptors.

Researchers found no metabolic safety signal, as changes in weight parameters like glycated hemoglobin were similar between the treatment and placebo groups. However, participants on treatment did see slightly higher rates of somnolence, agitation, and nausea.

Drawing on the FDA real-world adverse event reporting database to compare adverse events with the 11 most recently approved atypical antipsychotics, SEP-363856 had a cumulative rate of adverse events below 20% for antipsychotic class-specific risks.

“These results support characterization of SEP-363856 as a novel class for the treatment of schizophrenia,” the group wrote in their poster.

The FDA granted breakthrough therapy designation to this agent in May 2019.

COVID Fears Still Run High

Results from a new public opinion poll reflected high levels of COVID-related anxiety among Americans.

The online survey sponsored by the APA drew upon a sample of 1,000 U.S. adults from March 26 through April 5, 2021. Even a year after the start of the COVID-19 pandemic, 64% of respondents said they fear a family member or loved one catching the virus. About 50% still fear contracting COVID-19 themselves.

Of note, 41% of participants said they’re more anxious now than they were in 2020; young people ages 18 to 29 were more likely to report this. Additionally, parents expressed ongoing concern about their children’s mental well-being.

Interestingly, COVID-related anxiety was stratified among races, with white adults reporting the lowest rates of anxiety (59%) versus Hispanics/Latinos (73%) and Black adults (76%).

Not surprisingly, 43% said the pandemic had a significant impact on their mental health, marked by a small uptick in alcohol consumption and drug use versus last year.

“This poll shows that even as vaccines become more widespread, Americans are still worried about the mental state of their children,” said APA president Jeffrey Geller, MD, MPH, in a statement. “This is a call to action for policymakers, who need to remember that in our COVID-19 recovery, there’s no health without mental health.”

“While most people, including most children, will likely adapt and recover well as we emerge from the pandemic, we know from previous research that for some, the mental health impacts of this trauma and distress will continue to have repercussions into the future,” added APA CEO and medical director Saul Levin, MD, MPA. “We need to be prepared to help those who need it in the coming months and years.”

Cariprazine Improves Functioning in Bipolar Depression

A post-hoc analysis of a phase IIb trial found a significant improvement in functioning with the atypical antipsychotic cariprazine (Vraylar), reported Mauricio Tohen, MD, DrPH, MBA, of the University of New Mexico Health Sciences Center in Albuquerque.

Among 388 patients with bipolar I depression, 1.5 mg/day of cariprazine yielded a significant difference in Functional Assessment Short Test (FAST) scale total score — a -5.3-point change from baseline versus placebo after 8 weeks of treatment.

In a breakdown of FAST subscales, the least squares mean difference of scores favored 1.5-mg cariprazine versus placebo:

• Autonomy: -0.8-point change from baseline vs placebo (P<0.05)
• Occupational functioning: -1.2 point change (P<0.05)
• Cognitive functioning: -1.2 point change (P<0.01)
• Leisure time: -0.5 point change (P<0.05)
• Interpersonal relationships: -1.4 point change (P<0.01)

Issue with finances was the only FAST subscale score that wasn’t significantly different from placebo.

“Although no firm conclusions can be made from a post hoc analysis, our results suggest that in addition to improving depression symptoms, cariprazine may also have beneficial effects across domains of functional impairment that have been reported to influence a return to well-being in patients with bipolar depression,” the group wrote in their poster.

Acting as a dopamine D3-preferring D3/D2 receptor partial agonist and serotonin 5-HT1A receptor partial agonist, cariprazine was first approved in September 2015 for the treatment of adults with bipolar I disorder, including for manic, mixed, and depressive episodes, as well as for schizophrenia.