A meta-analysis of clinical trials comparing the serotonin (5HT)-2 receptor antagonists trazodone and nefazodone with selective serotonin reuptake inhibitors for the treatment of major depressive disorder

ObjectiveTo compare response rates among patients with major depressive disorder (MDD) treated with either a serotonin-2 (5HT2-) receptor antagonist or a selective serotonin reuptake inhibitor (SSRI).MethodsMedline and PubMed were searched for double-blind, randomized clinical trials comparing either trazodone or nefazodone with an SSRI for the treatment of MDD. Data from 9 reports involving a total 988 patients were identified and combined using a random-effects model.ResultsPatients randomized to treatment with a 5HT2 antagonist were as likely to experience clinical response as patients randomized to treatment with an SSRI (RR = 1.002, 95% CI: 0.85–1.17, P = 0.978). Pooled response rates for trazodone/nefazodone and the SSRIs were 61.1% and 61.7%, respectively. There was also no difference in overall discontinuation rates (P = 0.334), discontinuation due to adverse events (P = 0.676), or discontinuation due to inefficacy (P = 0.289) between the two groups.ConclusionsThese results suggest that the 5HT2-receptor antagonists trazodone and nefazodone and the SSRIs do not differ with respect to their overall efficacy and tolerability in the treatment of MDD. Although the sample size was relatively large and conveyed sufficient statistical power to test for differences in the overall sample, depression is a heterogeneous condition and differences may exist between treatments in particular subgroups of patients.