Re-evaluation of the efficacy and tolerability of venlafaxine vs SSRI: meta-analysis

Rationale A number of reviews have claimed that the selective serotonin and noradrenalin re-uptake inhibitor venlafaxine is more effective than selective serotonin re-uptake inhibitors (SSRIs) in achieving remission and symptom reduction in major depression. Objectives The aim of this study was to systematically review studies on the efficacy of venlafaxine vs SSRI and to evaluate the influence of methodological issues on the effect sizes. Materials and methods Following a systematic literature search, we pooled data on depression scores, response, remission and dropout rates. We also performed sub-group analyses. Results Seventeen studies were included. We found no significant superiority in remission rates (risk ratio [RR]=1.07, 95% confidence intervals [95%CI]=0.99 to 1.15, numbers needed to treat [NNT]=34) and a small superiority in response rates (RR=1.06, 95%CI=1.01 to 1.12, NNT=27) over SSRIs. There was a small advantage to venlafaxine in change scores (effect size=-0.09, 95%CI=-0.16 to -0.02, p=0.013), which did not reach significance when post-treatment scores were used (effect size=-0.06, 95%CI=-0.13 to 0.00). Discontinuation rates due to adverse events were 45% higher in the venlafaxine group. The main reasons for the differences between this analysis and previous reviews were the exclusion of studies with methodological limitations, avoiding to pool selectively reported study results and exclusion of studies available as abstracts only. Conclusions Our analysis does not support a clinically significant superiority of venlafaxine over SSRIs. Differences between our study and previous reviews were not accounted for by technical aspects of data synthesis, but rather by study selection and choice of outcome parameters.