Second-Generation Antipsychotics Becoming Primary Bipolar Disorder Therapy

Taeho Greg Rhee, PhD

The 2020 American Psychiatric Association (APA) Annual Meeting was cancelled this year, with plans made to convert the world-leading psychiatry conference into a two-part virtual session and educational platform for attendees.

In lieu of regular on-site coverage, HCPLive® will be running a series of interviews, insights, and reporting on topics that frequently headline the APA meeting—featuring familiar experts.

Bipolar disease treatment strategies have changed significantly over the last 2 decades, according to a new assessment considering the influence of second-generation antipsychotics in outpatient care.

A team of investigators, led by Taeho Greg Rhee, PhD, of the Yale School of Medicine, conducted a trends analysis of pharmacological agents in the outpatient therapeutic management of bipolar disorder.

As Rhee and colleagues noted, the prescription variety for bipolar disorder have been on the rise in the last 20 years, when second-generation antipsychotics—including aripiprazole, brexpiprazole, cariprazine, and pimavanserin—began to reach US Food and Drug Administration (FDA) marketing approval.

The team used nationally representative data from the 1997-2016 National Ambulatory Medical Care Surveys to assess trends across differing drug classes: mood stabilizers, first- and second-generation antipsychotics, and antidepressants among psychiatrist visits for patients with a primary diagnosis of bipolar disorder.

They used a logistic regression model to identify statistically significant trends, with covariates including age, gender, race/ethnicity, and primary insurance.

Rhee and colleagues observed a more prevalent prescription of antipsychotics—from 12.4% of all outpatient visits for bipolar disorder in 1997-2000, to a more than four-fold increase to 51.4% in 2013-2016 (adjusted OR, 5.05; 95% CI, 3.65-7.01). As the drug class became the majority prescription, mood stabilizer prescriptions dropped from 62.3% to 26.4% in the same time period (adjusted OR, 0.18; 95% CI, 0.13-0.27).

Investigators also reported notable increased prescriptions for antidepressants—from 47.0% to 57.5%—and antidepressants without a mood stabilizer (17.9% to 40.9%; adjusted OR, 2.88; 95% CI, 2.06-4.03).

In an HCPLive® Peer Exchange panel discussion on the disparity between first-generation and second-generation antipsychotics, Richard Jackson, MD, noted the feasibility of long-acting injection therapies for patients with regular outpatient visits—and the fact that second-generation antipsychotics are not completely safe, but more manageable than their predecessors.

“I think they’re much better tolerated,” he noted. “I’ve seen patients with potentially more metabolic side effects as far as weight gain and things of that nature, but the more severe movement disorders and acute side effects are certainly diminished.”

Rhee and colleagues concluded the changes in bipolar disorder treatment have been substantial in the last 20 years, with second-generation antipsychotics largely supplanting mood stabilizers as the primary therapy.

“Antidepressant prescriptions persisted despite a lack of evidence for their efficacy in bipolar disorder and concerns about increasing the risk of mania,” they wrote. “Research is needed to compare the real-world effectiveness and tolerability of newer antipsychotics with those of traditional mood stabilizers.”

The study, “20-Year Trends in the Pharmacologic Treatment of Bipolar Disorder by Psychiatrists in Outpatient Care Settings,” was published online in The American Journal of Psychiatry.