Comparison of SSRIs and SNRIs in major depressive disorder: a meta-analysis of head-to-head randomized clinical trials.

Background: Controversy exists whether serotonin-norepinephrine reuptake inhibitors (SNRIs) have improved efficacy compared with selective serotonin reuptake inhibitors (SSRIs).

Objective: To compare clinical outcomes of adults treated with SSRIs or SNRIs for major depressive disorder (MDD) under ideal clinical condition, research design, and outcome measure.

Methods: Electronic databases searched were Medline, Embase and Cochrane Library from inception to July 2007. Methods: Included studies were those head-to-head randomized trials comparing remission (HAMD-17

Results: Thirty-three studies were identified; 18 were rejected (patients had co-morbidities in 7, outcomes differed in 5, different follow-up in 3, and three reviews). Fifteen head-to-head trials of 3094 patients, average age was 41.9 +/- 11.9 years (for SNRIs) and 41.6 +/- 12.1 years (for SSRIs), P = 0.941. All analyses displayed non-heterogeneity (P > 0.05). The OR (under ITT) was 1.27 (1.06-1.52 95% CI) favoring SNRIs. Meta-analytic remission rates were 48.5 +/- 3.2% and 41.9 +/- 4.2% for SNRIs and SSRIs, respectively. The meta-analytic difference in remission rates between drugs was 5.7% (P = 0.007). Dropout rates due to ADRs were higher with SNRIs than SSRIs (3.2% difference, P < 0.001). Dropout rates due to LoE were non-significant between studied groups (P > 0.05).

Conclusions: Serotonin and norepinephrine reuptake inhibitors showed statistical but not clinical significance when compared with SSRIs in treating MDD.