Switching the Antidepressant After Nonresponse in Adults With Major Depression: A Systematic Literature Search and Meta-Analysis

Objective: Nonresponders to antidepressant monotherapy during acute treatment of major depression are often switched to a new antidepressant. The objective of this meta-analysis was to compare the efficacy of switching to a new antidepressant with continuation of the first antidepressant.

Data Sources: PubMed, Embase, PsycINFO, and Cochrane Central Register of Controlled Trials (CENTRAL) databases and additional sources were systematically searched independently by 2 authors up to March 2015 without language limitations. With employment of a sensitivity-enhancing search strategy, generic terms for major depression, switching, and randomized trials were combined.

Study Selection: Articles (3,234) were screened for trials of patients with major depression who had not responded to antidepressant monotherapy who were then randomized either to a new antidepressant or to continuation of the first antidepressant. Studies were subdivided into those not allowing for dose escalation in the continuation arm (strict analysis) and those allowing for dose escalation (broad analysis).

Data Extraction: Data were extracted and risk of bias was assessed independently by 2 authors, and data were pooled using random effects models.

Results: Four randomized controlled trials were included in the strict analysis and 8 in the broad analysis. In both analyses, switching was not superior to continuation: the standardized mean difference in the strict analysis was −0.17 (95% CI, −0.59 to 0.26; P = .45; I2 = 77.8%) and in the broad analysis was 0.031 (95% CI, −0.26 to 0.32; P = .836; I2 = 85.3%). All secondary outcome analyses (response and remission rates, low risk of bias studies only, leave-one-out analysis, dropouts) supported the results. There was no indication of publication bias.

Conclusions: There is a dearth of randomized controlled trials investigating switching. There is no high-level evidence that switching the antidepressant is effective when compared to simply continuing the initial antidepressant. Since there are better treatment options than switching, physicians should be cautious to switch antidepressants.