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Phase 3 study indicates brexpiprazole is safe, effective for acute schizophrenia

Results from a multicenter, randomized, double-blind, placebo-controlled study indicate that daily 2 or 4 mg doses of brexpiprazole were safe and effective among adults with acute schizophrenia.

“Preclinical models have demonstrated brexpiprazole’s efficacious functional D₂ receptor partial agonist activity and antipsychotic-like profile,” study researcher Christoph U. Correll, MD, of the Zucker Hillside Hospital in Glen Oaks, New York, and colleagues wrote. “Brexpiprazole shows partial agonism with lower intrinsic activity at the D₂ receptor and stronger antagonism at the 5-HT_2A receptor than the only currently available D₂ partial agonist, aripiprazole, suggesting a relatively lower potential to induce D₂ partial agonist-mediated adverse effects, eg, akathisia, insomnia, restlessness and nausea.”

Christoph U. Correll

Researchers assigned 623 patients diagnosed with schizophrenia who experienced acute exacerbation of the disease to receive 0.25, 2 or 4 mg of oral brexpiprazole (Lundbeck/Otsuka Pharmaceutical Co., Ltd.) or placebo once daily for 6 weeks. Study participants were from the United States, Ukraine, Romania, Serbia, Latvia, Malaysia, Japan, Poland, South Korea and Canada. Researchers conducted a 30-day follow-up.

At baseline, patients had an overall mean Positive and Negative Syndrome Scale (PANSS) score of 95.2 and a Clinical Global Impressions scale (CGI) severity score of 4.9.

At week 6, patients who received 2 or 4 mg of brexpiprazole had statistically significantly greater mean improvements in PANSS total score vs. patients who received placebo. Treatment differences were – 8.72 (Cohen’s d = 0.41; P < .0001) for 2 mg of brexpiprazole and –7.64 (Cohen’s d = 0.36; P = .0006) for 4 mg of brexpiprazole vs. placebo.

“The difference between brexpiprazole and placebo in mean change from baseline reached statistical significance at week 1 in the 2-mg group and at week 2 in the 4-mg group, and the effect was maintained throughout the remainder of the study,” according to researchers.

PANSS positive and negative subscale scores, PANSS excited component score and PANSS Marder et al factor scores regarding positive and negative symptoms, disorganized thought and uncontrolled hostility or excitement significantly improved (P < .05) among patients who received brexpiprazole vs. those who received placebo from baseline to week 6.

Regarding CGI severity scores, treatment differences were – 0.33 for patients who received 2 mg of brexpiprazole and – 0.38 for patients who received 4 mg of brexpiprazole vs. patients who received placebo.

Akathisia and increased body weight were more commonly reported among patients who received brexpiprazole than patients who received placebo.

“In this 6-week randomized, double-blind, placebo-controlled study, brexpiprazole at doses of 2 mg and 4 mg once daily demonstrated statistically significant efficacy compared with placebo and good tolerability for patients with acute exacerbation of schizophrenia,” Correll and colleagues concluded. – by Amanda Oldt

Disclosure: Correll reports financial ties with Actelion, Alexza, American Academy of Child and Adolescent Psychiatry, Bristol-Myers Squibb, Cephalon, Eli Lilly, Feinstein Institute for Medical Research, Genentech, Gerson Lehrman Group, IntraCellular Therapies, Janssen/J&J, Lundbeck, Medavante, Medscape, Merck, NARSAD, National Institute of Mental Health, Otsuka, Pfizer, ProPhase, Roche, Sunovion, Takeda, Teva and Vanda. Please see the full study for a list of all other authors’ relevant financial disclosures.