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Switching antidepressants is a common strategy for managing treatment-resistant depressed patients. However, no systematic reviews have been conducted to date.We systematically searched MEDLINE/EMBASE/Cochrane Central Register of Controlled Trials and additional sources. We included double-blind studies of patients with depressive symptomatology who were not responding to initial antidepressant monotherapy and were subsequently randomized to another antidepressant or to continue the same antidepressant. Results were pooled for meta-analysis of response + remission rates using a fixed-effects model.A total of three studies were included. Switching to another antidepressant was not superior to continuing the initial antidepressant in any of these studies. Our meta-analysis showed no significant advantages to either strategy and no significant heterogeneity of results [OR for response rates: 0.85 (95% CI: 0.55–1.30) favoring continuing].There is a discrepancy between the published evidence and the frequent decision to switch antidepressants, indicating an urgent need for more controlled studies. Pending such studies we recommend that physicians rely on more thoroughly evaluated strategies.