REVIEW OF: Furukawa Y et al, Psychiatry Clin Neurosci 2022;76(9):416–422

STUDY TYPE: Meta-analysis of placebo-controlled trials

In 2015, brexpiprazole (Rexulti) was approved as adjunctive therapy for major depression, with a wide dosing range from 0.5 to 3 mg. This meta-analysis synthesized existing studies to find the sweet spot within that range.

The authors included six double-blind randomized placebo-controlled studies that compared brexpiprazole augmentation of antidepressants with placebo augmentation. Included patients (n=1671) had treatment-resistant depression, defined as inadequate response to one to three antidepressants, without other serious psychiatric comorbidities. The duration of each trial was six weeks. The primary outcome was response (≥50% reduction in depression severity). Secondary outcomes were acceptability (dropouts for any reason) and tolerability (dropouts due to adverse effects). All the included studies were funded by the manufacturer of brexpiprazole, Otsuka.

The benefits of brexpiprazole augmentation increased as the dose increased, but the response rates began to plateau around 2 mg/day (OR 1.52, 95% CI 1.12–2.06). After that, the dose-efficacy curve showed a slightly decreasing trend through the licensed dose of 3 mg (OR 1.40, 95% CI 0.95–2.08). The mean dose of brexpiprazole required to produce 50% of the maximum effect (ED50) was 0.88 mg, and the mean dose to produce 95% of the maximum effect (ED95) was 1.79 mg. Dropouts for adverse effects peaked around 2 mg, and dropouts for any reason increased as the dose increased.

CARLAT TAKE

When using brexpiprazole to augment antidepressants, aim for a daily dose of 1–2 mg. Higher doses may benefit the rare patient, but on average they lead to diminishing returns.