Optimal dose of brexpiprazole for augmentation therapy of antidepressant-refractory depression: A systematic review and dose-effect meta-analysis.

Background: Brexpiprazole augmentation is an effective treatment strategy for antidepressant-refractory depression, but its optimal dosage remains unclear.

Aims: To find the optimal dosage of brexpiprazole as augmentation of other antidepressants.

Methods: We searched multiple electronic databases (from inception to September 16th, 2021) to identify double-blind, randomized placebo-controlled fixed-dose trials evaluating brexpiprazole augmentation therapy in adults (≥18 years old, both genders) with major depressive disorder not adequately responding to one or more antidepressant treatment. Our outcomes of interest at 8 weeks (range 4-12 weeks) were efficacy (treatment response defined as 50% or greater reduction in depression severity), tolerability (dropouts due to adverse effects) and acceptability (dropouts for any reason). We performed a random-effects, one-stage dose-effect meta-analysis with restricted cubic splines.

Results: Six studies met the inclusion criteria, including 1671 participants in total. The dose-efficacy curve showed an increase up to doses around 2 mg (odds ratio [OR] 1.52, 95% confidence interval [CI] 1.12-2.06) and then a decreasing trend through the higher licensed dose up to 3 mg (OR 1.40, 95% CI 0.95-2.08). The shape of the dose-tolerability curve was comparable to that of the efficacy and the dose-acceptability curve showed a monotonic increasing trend but both had wide confidence bands.

Conclusions: One to two milligrams of brexpiprazole as augmentation treatment may achieve an optimal balance between efficacy, tolerability, and acceptability in the acute treatment of antidepressant-refractory depression. However, the small number of included studies limit the reliability of the results. Further research is required to validate the findings.