New atypical antipsychotic FDA approved for use in bipolar I and schizophrenia

The Food and Drug Administration on Sept. 17 approved cariprazine, an atypical antipsychotic, for the acute treatment of manic or mixed episodes in bipolar I disorder and schizophrenia in adults.

Results from three separate controlled trials in adults with manic or mixed episodes of bipolar I disorder showed cariprazine (Vraylar) was associated with improved total scores on the Young Mania Rating Scale (YMRS), compared with placebo. In three separate placebo-controlled trials in adults with schizophrenia, the study drug was associated with improvements in Positive and Negative Syndrome Scale (PANSS) total scores in patients with schizophrenia, compared with placebo. Cariprazine also demonstrated efficacy in the Clinical Global Impressions–Severity (CGI-S) rating scale, which was the secondary efficacy endpoint in the respective trials for each condition. In all, 2,700 persons were enrolled in the trials.

The recommended dose of cariprazine in adults with bipolar I is once daily at 3-6 mg per day. For schizophrenia in adults, 1.5-6 mg/day is the recommended dose.

Adverse reactions occurring in at least 5% of the study population and at a rate of twice that in the placebo groups were extrapyramidal symptoms, akathisia, dyspepsia, vomiting, somnolence, and restlessness in the bipolar group. In the group with schizophrenia, the most commonly reported adverse events were extrapyramidal symptoms and akathisia.

Cariprazine is a dopamine-2 and dopamine-3 receptor partial agonist, tending toward the D3 receptor. Although its mechanism of action in schizophrenia and bipolar I disorder is unknown, the drug’s codeveloper, Gedeon Richter said in a statement that cariprazine’s efficacy “could be mediated through a combination of partial agonist activity at central D2 and serotonin 5-HT1A receptors and antagonist activity at serotonin 5-HT2A receptors.” In the United States and Canada, the drug is licensed to Actavis, now Allergan. Vraylar is manufactured by Forest Laboratories.

Data indicating the drug’s ability to improve flat affect in schizophrenia were presented at this year’s annual congress of the European College of Neuropsychopharmacology in Amsterdam. According to Gedeon Richter and Allergan, cariprazine also is being investigated for the treatment of bipolar depression and as adjunctive treatment for major depressive disorder in adults.

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