Efficacy of adjunctive low-dose cariprazine in major depressive disorder: a randomized, double-blind, placebo-controlled trial

This 19-week, double-blind, placebo-controlled, randomized phase 2 study evaluated the efficacy, safety, and tolerability of adjunctive cariprazine (0.1–0.3 and 1.0–2.0 mg/day) as an antidepressant treatment for adults with treatment-resistant major depressive disorder (MDD) (NCT00854100). The primary endpoint was change in the Montgomery–Åsberg Depression Rating Scale (MADRS) total score and the secondary was change in the Clinical Global Impression-Intensity score. Additional efficacy parameters were also assessed. A total of 231 patients were randomized. None of the predefined parameters reached significance for either cariprazine doses, but higher doses yielded numerically greater mean changes in MADRS and Clinical Global Impression-Intensity scores, and MADRS response and remission rates, compared with placebo. No differences were seen on any measures between cariprazine 0.1–0.3 mg/day and placebo. Cariprazine was relatively well tolerated, and common treatment-emergent adverse events (incidence ≥5% and twice the placebo group rate) in both dosage groups included headache, arthralgia, restlessness, fatigue, increased appetite, insomnia, dry mouth, and constipation. In conclusion, both cariprazine doses were relatively well tolerated; although differences were not statistically significant, patients treated with cariprazine 1.0–2.0 mg/day had greater mean decreases in measures of depression symptoms compared with placebo, which is consistent with another adjunctive cariprazine MDD study, and thus warrants further investigation.