Adverse Events Caused by Once-Monthly Aripiprazole Are Time Limited

Vial and injection
Vial and injection
Investigators assessed the safety and tolerability of once-monthly aripiprazole 400 mg in patients with bipolar disorder I who were already stabilized on oral aripiprazole.

Patients taking aripiprazole 400 mg once monthly for maintenance treatment of bipolar I disorder experienced only time-limited adverse events, supporting the idea that once-monthly aripiprazole 400 mg is a well-tolerated treatment, according to results published in the Journal of Affective Disorders.

Prior studies of aripiprazole once-monthly 400 mg have demonstrated its efficacy and safety for the maintenance treatment of bipolar disorder I.

The study included participants with bipolar disorder I who were stabilized on oral aripiprazole for 2 to 8 weeks and then switched to aripiprazole once-monthly 400 mg (12-28 weeks). Participants who met stability criteria were then randomly assigned to continued aripiprazole once-monthly 400 mg (n=133) or placebo (n=133) up to week 52. The researchers collected data on treatment-emergent adverse events. They also performed a separate analysis on new-onset akathisia.

The most prevalent treatment-emergent adverse events were akathisia, which occurred in 23.3% of participants, and weight gain, which occurred in 10.6% of participants.

The median time to onset of akathisia was 20 days after starting aripiprazole, and the median duration was 29 days for the first occurrence. Of participants who reported akathisia, 12.5% (21/168) experienced >1 episode. The prevalence of new-onset akathisia decreased over time.

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Most participants who experienced weight gain reported that it started within 3 months after their first aripiprazole once-monthly 400-mg injection, rather than with oral aripiprazole. Weight gain tended to plateau at 36 weeks, with a mean weight gain of ≤1.0 kg.

“Knowing the temporal patterns of [adverse events] can help the clinicians and patients in setting expectations for the treatment, thus informing clinical decision-making,” the researchers wrote.


This research was supported by H. Lundbeck A/S and Otsuka Pharmaceutical Development & Commercialization, Inc.


Calabrese JR, Sanchez R, Jin N, et al. The safety and tolerability of aripiprazole once-monthly as maintenance treatment for bipolar I disorder. a double-blind, placebo-controlled randomized withdrawal study. J Affect Disord. 2018;241:425-432.