Brexpiprazole as Adjunctive Treatment for Major Depressive Disorder Following Treatment Failure With at Least One Antidepressant in the Current Episode: a Systematic Review and Meta-Analysis

摘要

Background This systematic review and meta-analysis included double-blind, randomized, placebo-controlled trials of brexpiprazole adjunctive treatment (0.5–3 mg/d) for major depressive disorder where antidepressant treatment had failed. Methods The outcomes were the response rate (primary), remission rate (secondary), Montgomery ?sberg Depression Rating Scale score (secondary), Sheehan Disability Scale scores (secondary), Clinical Global Impression–Improvement/Severity scores, discontinuation rate, and individual adverse events. A subgroup meta-analysis of the data at week 6 compared outcomes by dose 2 mg/d or ≤2 mg/d (2 mg/d is the recommended dose). Results We identified 9 studies (n?=?3391). Compared with placebo, brexpiprazole (any dose) was superior for response rate (risk ratio [RR]?=?0.93, 95% confidence interval [95% CI]?=?0.89?0.97, number needed to treat?=?17), remission rate (RR?=?0.95, 95% CI?=?0.93?0.98, number needed to treat?=?25), Montgomery ?sberg Depression Rating Scale score (standardized mean difference =??0.20, 95% CI?=??0.29, ?0.11), Sheehan Disability Scale score (standardized mean difference?=??0.12, 95% CI?=??0.21, ?0.04), and Clinical Global Impression–Improvement/Severity scores but was associated with a higher discontinuation rate, akathisia, insomnia, restlessness, somnolence, and weight increase. Doses 2 mg/d had a significantly higher RR for response rate than ≤2 mg/d (0.96 vs 0.89); moreover, compared with placebo, doses 2 mg/d were associated with higher incidences of akathisia (RR?=?4.58) and somnolence (RR?=?7.56) as well as were marginally associated with a higher incidence of weight increase (RR?=?3.14, P =?.06). Compared with placebo, doses ≤2 mg/d were associated with higher incidences of akathisia (RR?=?2.28) and weight increase (RR?=?4.50). Conclusions Brexpiprazole adjunctive treatment is effective for major depressive disorder when antidepressant treatment fails. At 6 weeks, doses ≤2 mg/d presented a better risk/benefit balance than 2 mg/d.