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

To assess the long-term efficacy and safety of aripiprazole as an augmentation strategy for major depressive disorder (MDD). Ovid MEDLINE, PsycInfo, and Embase databases were systematically searched for clinical studies of adult patients with MDD on long-term aripiprazole augmentation. Long-term follow-up was defined as ≥ 6 months. Primary outcome was remission from depression. Secondary outcome was incidence of adverse effects. 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. 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).