Long-term Efficacy and Tolerability of Adjunctive Aripiprazole for Major Depressive Disorder: Systematic Review and Meta-analysis.

Objective: To assess the long-term efficacy and safety of aripiprazole as an augmentation strategy for major depressive disorder (MDD). Data Sources: Ovid MEDLINE, PsycInfo, and Embase databases were systematically searched for clinical studies of adult patients with MDD on long-term aripiprazole augmentation. Study Selection and Data Extraction: Long-term follow-up was defined as ≥ 6 months. Primary outcome was remission from depression. Secondary outcome was incidence of adverse effects. Results: Four open-label studies were included in this review. Random effects meta-analysis of 3 studies (n = 2,117) revealed a weighted average remission proportion of 0.33 (0.16-0.51), showing trend of improved response with duration of treatment. Three studies (n = 2,231) provided adverse effects data. Medically significant weight gain (25%-28% participants) was higher in studies with patients receiving doses ≥ 5 mg and lower (3.5%) in a study using doses < 5 mg. Akathisia (15%-16%), insomnia (12%-17%), somnolence (14%), and fatigue (18%) were common adverse effects. Tardive dyskinesia risk was low (< 1%) at 1-year follow-up. All included studies were open-label, noncontrolled studies, with longest follow-up of 52 weeks, limiting efficacy and safety conclusions. Conclusions: Aripiprazole augmentation may be an effective long-term strategy for treatment of refractory MDD. Lower maintenance doses (2-5 mg) of aripiprazole may be effective and have fewer side effects compared to larger doses (> 5 mg-10 mg).