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Cariprazine reduces depressive symptoms in bipolar depression

In a phase 3 study, cariprazine, both taken at 1.5 mg per day and 3 mg per day, was more effective than placebo in improving depressive symptoms in adults with bipolar I depression.

Prior research has shown cariprazine’s efficacy over placebo in reducing depressive symptoms in this patient population, but the difference remained significant for only the 1.5 mg per day dosage after adjustment, Willie Earley, MD, of Allergan Inc., and colleagues wrote.

In this double-blind placebo-controlled study, adult outpatients with bipolar I disorder and a current depressive episode were randomly assigned to receive placebo (n = 158) or cariprazine at 1.5 mg per day (n = 157) or 3 mg per day (n = 165) to further examine its efficacy, safety and tolerability.

Earley and colleagues reported changes from baseline to week 6 as measured by the Montgomery-Åsberg Depression Rating Scale (MADRS) score and the Clinical Global Impressions severity (CGI-S) score. They also examined change from baseline in the Hamilton Anxiety Rating Scale (HAM-A) and Hamilton Depression Rating Scale (HAM-D) remission rates as well as rates of MADRS response and remission.

Analysis revealed that both doses of cariprazine were more effective than placebo in reducing depressive symptoms among patients with bipolar I depression. After adjustment, the mean differences in MADRS total score were –2.5 (95% CI, –4.6 to –0.4) for cariprazine at 1.5 mg per day and –3 (95% CI, –5.1 to –0.9) for cariprazine at 3 mg per day.

In addition, the investigators found that both cariprazine doses were linked to lower CGI-S scores compared with placebo; however, the differences were not statistically significant after adjustment.

HAM-A scores improved significantly in the cariprazine 1.5-mg group compared with the placebo group, but not in the 3-mg group. MADRS response rates were significantly greater in the cariprazine 3-mg group (51.8%), but not in the 1.5-mg group (48.1%), compared with the placebo group (39.7%); however, remission rates were significantly higher in both the cariprazine groups (33.1% for 1.5 mg, and 32.3% for 3 mg) at week 6. HAM-D remission rates were significantly greater in the cariprazine 1.5-mg group, but not in the 3-mg group.

Cariprazine was generally well-tolerated, according to Earley and colleagues. Common treatment-emergent adverse events — most of which were mild or moderate in intensity — were nausea, akathisia, dizziness and sedation. The results also showed that average changes in weight and metabolic parameters were small and comparable across treatment groups.

The researchers also noted that the study had greater rates of completion (81% to 85%) than many other atypical antipsychotic bipolar I depression studies.

“The high completion rates are particularly compelling given the outpatient status of the participants,” they wrote in the American Journal of Psychiatry. “The greater rates of completion may be attributable to the more gradual titration method used in this study, in which participants in the 3.0 mg/day group reached that dosage on day 15, compared with on day 1 in a cariprazine bipolar I mania phase 3 pivotal trial, which may have led to increased tolerability.” – by Savannah Demko

Disclosure: Earley is an employee of Allergan and former employee of Forest Laboratories. He reports owning stock in Allergan, AstraZeneca and Eli Lilly. Please see the study for all other authors’ relevant financial disclosures.