Tolerability of Novel Long-Acting Injectable Aripiprazole Tested for Bipolar Disorder
The study was designed to examine the adverse effect profile of a long-acting injectable version of the established oral treatment aripiprazole.
The findings of a study published in the Journal of Affective Disorders indicated good tolerability for the antipsychotic aripiprazole as a once-monthly injection for patients with type I bipolar disorder.
The study was designed to examine the adverse effect profile of a long-acting injectable version of the established oral treatment aripiprazole, and in particular, extrapyramidal symptoms such as akathisia and weight gain. Extrapyramidal symptoms, or involuntary movement disorders, are a common concern for patients receiving antipsychotics. Changes in weight were also monitored, as patients with bipolar disorder face higher rates of obesity than the general population.
The authors recruited 731 patients who were experiencing a manic episode at screening, determined by a Young Mania Rating Score ≥20. Participants were between the ages of 18 and 65 years and had a diagnosis of type I bipolar disorder according to the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition. Patients who had experienced rapid cycling in the previous year were excluded.
Patients were stabilized for 2 to 8 weeks with oral aripiprazole, followed by 12 to 28 weeks of a 400-mg monthly aripiprazole injection. Patients were allowed to switch to a 300-mg dose for tolerability. This was followed by a randomized, 52-week, double-blind, placebo-controlled withdrawal phase, with 133 patients in each group.
Across all phases of the study, the most notable treatment-emergent adverse effect was akathisia in 23.3% of patients, with a median onset 20 days after initiation and a median duration of 29 days. Weight gain of a median ≤1 kg occurred in 10.6% of patients. Serious treatment-emergent adverse effects, including mania and depression, occurred most frequently in the oral stabilization phase, followed by the injectable stabilization phase, and least frequently in the randomization phase. Overall, the preliminary findings suggested that adverse effects improved over time.
As was inherent to the study's withdrawal design, the authors pointed out, "each study phase was successively enriched with patients who responded to and tolerated aripiprazole." Thus, the findings' replication in real-life medical practice are currently unknown.
Disclosure: This research was supported by H. Lundbeck A/S and Otsuka Pharmaceutical Development & Commercialization, Inc.
Calabrese J, 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 [published online July 6, 2018]. J Affect Disord. doi:10.1016/j.jad.2018.06.043