Optimal dose of aripiprazole for augmentation therapy of antidepressant-refractory depression: preliminary findings based on a systematic review and dose–effect meta-analysis

作者：Yuki Furukawa, Tasnim Hamza, Andrea Cipriani, Toshi A. Furukawa, Georgia Salanti, Edoardo G. Ostinelli · 发表于：The British Journal of Psychiatry · 年份：2021 · DOI：10.1192/bjp.2021.165 · 被引用次数：23 · 研究领域：Treatment of Major Depression、Neurotransmitter Receptor Influence on Behavior、Digital Mental Health Interventions

BACKGROUND: Aripiprazole augmentation is proven effective for antidepressant-refractory depression, but its licensed dose range is wide and optimal dosage remains unclear. AIMS: To find the optimal dosage of aripiprazole augmentation. METHOD: Multiple electronic databases were searched (from inception to 16 February 2021) to identify all assessor-masked randomised controlled trials evaluating aripiprazole augmentation therapy in adults (≥18 years old, both genders) with major depressive disorder showing inadequate response to at least one antidepressant treatment. A random-effects, one-stage dose-effect meta-analysis with restricted cubic splines was conducted. Outcomes were efficacy (treatment response: ≥50% reduction in depression severity), tolerability (drop-out due to adverse effects) and acceptability (drop-out for any reason) after 8 weeks of treatment (range 4-12 weeks). RESULTS: Ten studies met the inclusion criteria. All were individually randomised, placebo-controlled, multi-centre, parallel studies including 2625 participants in total. The maximum target dose-efficacy curve showed an increase up to doses between 2 mg (odds ratio OR = 1.46, 95% CI 1.15-1.85) and 5 mg (OR = 1.93, 95% CI 1.33-2.81), and then a non-increasing trend through the higher licensed doses up to 20 mg (OR = 1.90, 95% CI 1.52-2.37). Tolerability showed a similar trend with greater uncertainty. Acceptability showed no significant difference through the examined dose range. Certainty of evidence...