Brexpiprazole versus placebo or other antidepressive agents for treating depression

Background Brexpiprazole is the newest antipsychotic drug approved as an adjunctive for treatment‐resistant depression. This systematic review provides comprehensive, high‐quality evidence effects of brexpiprazole in major depressive disorder (MDD) based on existing and emerging randomised controlled trials (RCTs). Objectives To evaluate benefits harms monotherapy or adjunct treatment acute longer‐term MDD compared to placebo other antidepressive agents. Search methods We used standard, extensive Cochrane search methods. The latest date was November 2021. Selection criteria included RCTs people with a history non‐response one more antidepressant monotherapies comparing Data collection analysis standard Primary outcomes were 1. response treatment, measured number participants who achieved 50% reduction score validated scale depression, 2. dropouts due any reason, 3. adverse effects, all at eight weeks (acute treatment). Our secondary 4. responded after two 18 weeks, remission 5. total events, 6. social functioning adjustment, 7. health‐related quality life. GRADE assess certainty each outcome. Main results retrieved nine studies 3424 defined lack least monotherapy. age 65 years seven studies, 75 study, older than study. Inclusion required diagnosis current episode per Diagnostic Statistical Manual Mental Disorders Text Revision Fourth Edition additional minimal scores Montgomery–Åsberg Depression Rating Scale (MADRS) Hamilton which varied across studies. Eight versus antidepressant. One study added combination ketamine. Four fixed dosages five flexible brexpiprazole. manufacturer sponsored independently funded. superior achieving (odds ratio (OR) 1.47, 95% confidence interval (CI) 1.23 1.75; 8 3409 participants; high‐certainty evidence). More dropped out cause (OR 1.37, CI 1.02 1.83; 7 2523 evidence) 2.88, 1.37 6.05; 6 2472 when 1.46, 1.19 1.79; 3358 When change MADRS, also demonstrated better efficacy (mean difference (MD) –1.39, –1.96 –0.82; 3263 Compared placebo, add‐on probably likely result akathisia 2.95, 2.06 4.21; moderate‐certainty weight gain 3.14, 2.19 4.49; 9 risk bias between low unclear most Only high selective reporting bias; however, this had small sample size its impact overall not considered significant. main (response symptoms, remission, cause, effects) high. downgraded level moderate indirectness. Authors' conclusions supports comparison adults depression short‐term findings limited by common (akathisia gain). There insufficient children. In addition, we found no that antidepressants where only lacked sufficient data establish long‐term treatment. Active comparators, different groups cost‐effect analyses are needed precisely clinical role MDD.