The safety and tolerability of cariprazine in patients with manic or mixed episodes associated with bipolar I disorder: A 16-week open-label study

Background: We evaluated the safety/tolerability of longer-term open-label treatment with cariprazine in patients who had responded to cariprazine for acute bipolar mania. Methods: In this multinational, multicenter study, open-label, flexible-dose, cariprazine 3-12 mg/d was administered for up to 16 weeks to patients (18-65 years) with bipolar mania. Safety evaluations included adverse events (AEs), laboratory values, vital signs, and extrapyramidal symptom (EPS) scales. Symptom change was evaluated by Young Mania Rating Scale (YMRS) total score change from baseline using the last observation carried forward approach. Results: Of the 402 patients taking cariprazine, 33% completed the trial; the most frequent reasons for discontinuation were withdrawal of consent (20%), AEs (16%), and protocol violation (14%). Most common AEs leading to discontinuation were akathisia (4.7%) and depression (1.5%). Mean treatment duration was 57.7 days; mean cariprazine dose was 6.2 mg/d. The incidence of serious AEs was 7.5% (most common: mania [2.2%], depression [1.2%]); 83.3% had treatment-emergent AEs, including akathisia (32.6%), headache (16.7%), constipation (10.7%), and nausea (10.4%). Mean body weight increased < 1 kg; 9.3% had >= 7% weight gain; 5.7% had sedation; 3% had somnolence. Mean changes in laboratory values, vital signs, ECGs, and ophthalmology parameters were not clinically significant. Mean YMRS total score decreased by -15.2 at week 16. Limitations: Uncontrolled, open-label design. Conclusions: Open-label cariprazine 3-12 (mean 6.2) mg/d for up to 16 weeks was generally well tolerated, with low (< 10%) rates of sedation and >= 7% weight gain. Although akathisia occurred in 33%, it yielded discontinuation in < 5%.