Low-Dose Cariprazine Is Safe, Tolerable in Bipolar Mania

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The long-term safety and tolerability of cariprazine 3 to 12 mg/day in participants with manic or mixed episodes with bipolar I disorder was assessed.

A flexible 3 to 12 mg/d dose of open-label cariprazine is tolerable for up to 16 weeks and is associated with only modest rates of sedation and weight gain in patients with bipolar mania, according to findings from a multicenter study published in the Journal of Affective Disorders.

Patients with bipolar mania between the age of 18 and 65 were administered 3 to 12 mg cariprazine (mean 6.2 mg/d) for up to 16 weeks (mean 57.7 days) to test for short-term safety outcomes (n=402). At follow-up, investigators assessed for any adverse event (AE) that occurred during treatment and also examined participants’ vital signs, laboratory values, and extrapyramidal symptom (EPS) scales. In addition, investigators assessed change in symptoms from baseline to follow-up by using the Young Mania Rating Scale (YMRS) total score.

Of the 32.8% of participants who completed the trial, withdrawal of consent (20%), AEs (16%), and protocol violation (14%) were the primary justifications for therapy discontinuation. The AEs most associated with discontinuation of therapy included akathisia (4.7%) and depression (1.5%). Serious AEs occurred in 7.5% of the participants and included mania (2.2%) and depression (1.2%).

The majority of participants (83.3%) experienced treatment-emergent AEs, which included akathisia (32.6%), headache (16.7%), constipation (10.7%), and nausea (10.4%). In addition, there was an average <1 kg increase in body weight across the cohort, with 9.3% of the participants experiencing a ≥7% weight gain. Also, approximately 3% experienced somnolence and 5.7% had sedation during treatment. At 16-week follow-up, the average change in the YMRS total score was –15.2 at week 16.

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Although this open-label study does demonstrate that cariprazine is associated with a low incidence of AEs in bipolar patients, the lack of a comparison or control group reduces the power of the findings. In addition, not including a control group limited the researchers’ ability to assess for long-term efficacy of the therapy.

The low rates of AEs, particularly somnolence, weight gain, and sedation, are clinically important “since these effects can be treatment-limiting for patients taking atypical antipsychotics.”


Ketter TA, Sachs GS, Durgam S, et al. The safety and tolerability of cariprazine in patients with manic or mixed episodes associated with bipolar I disorder: A 16-week open-label study. J Affect Disord. 2018;225:350-356.