Efficacy, acceptability, and safety of adjunctive aripiprazole in treatment-resistant depression: a meta-analysis of randomized controlled trials

Background Treatment-resistant depression (TRD) is common and potentially life-threatening in adults, and the benefits and risks of adjunctive aripiprazole in these patients remain controversial. Therefore, we conducted a meta-analysis of randomized controlled trials (RCTs) to assess the efficacy, acceptability, safety, and quality of life of adjunctive aripiprazole in patients with TRD. Methods RCTs published in PubMed, Web of Science, and Embase were systematically reviewed to evaluate the efficacy and safety profiles of TRD patients who were treated with adjunctive aripiprazole. The main outcome measures included response rate, remission rate, changes from baseline in Montgomery-Asberg Depression Rating Scale (MADRS), Clinical Global Impression-severity (CGI-S), Clinical Global Impression-improvement (CGI-I), 17-Item Hamilton Rating Scale for Depression (HAM-D17), Sheehan Disability scale (SDS), and Inventory of Depressive Symptomatology Self-Report Scale (IDS-SR), discontinuation due to adverse events, and adverse events. Risk ratio (RR) or weight mean difference with 95% confidence intervals (CIs) were pooled using a fixed-effects or random-effects model according to the heterogeneity among studies. Results A total of 8 RCTs involving 2,260 patients were included in this meta-analysis. Adjunctive aripiprazole was associated with a significantly higher remission rate (RR =1.64, 95% CI: 1.42 to 1.89; P<0.001) and response rate (RR =1.45, 95% CI: 1.13 to 1.87; P=0.004) than other treatments. Moreover, adjunctive aripiprazole had greater changes in MADRS score, CGI-S score, CGI-I score, HAM-D17 score, SDS score, and IDS-SR score. There were more patients treated with adjunctive aripiprazole who discontinued their treatments due to adverse events. The incidence of adverse events was significantly higher in the adjunctive aripiprazole group than in other treatment groups. Conclusion The adjunctive aripiprazole showed benefits in improving the response rate, remission rate, and the quality of life in patients with TRD. However, clinicians should interpret these findings with caution due to the evidence of potential treatment-related side effects.