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

Furukawa, Yuki; Oguro, Saki; Obata, Satomi; Hamza, Tasnim; Ostinelli, Edoardo G; Kasai, Kiyoto (2022). Optimal dose of brexpiprazole for augmentation therapy of antidepressant-refractory depression: a systematic review and dose-effect meta-analysis. Psychiatry and clinical neurosciences, 76(9), pp. 416-422. Wiley 10.1111/pcn.13438

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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 1,671 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 mg 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. This article is protected by copyright. All rights reserved.

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