The effect of venlafaxine compared with other antidepressants and placebo in the treatment of major depression

Meta-analysis of all available trials of Venlafaxine in the treatment of major depressive disorders, including treatment resistant depression and long-term relapse prevention. We conducted a meta-analysis comparing venlafaxine and tricyclics, or selective serotonin reuptake inhibitors (SSRIs), in major depression. We also included trials comparing venlafaxine and alternative antidepressants in subjects with treatment resistant depression, or compared with placebo in long-term relapse prevention. Trials were identified through searches of Medline, Embase, Cochrane Library and through accessing unpublished trials held by the manufacturer. Results based on intention to treat analyses where available, were pooled using theoretically exact conditional maximum likelihood methods for fixed effects (primary analyses), and numerical simulation using a Gibbs sampler for full random effects. Compared to all SSRIs for the treatment of major depression (fluoxetine, paroxetine, sertraline, citalopram, escitalopram and fluvoxamine), venlafaxine was associated with a greater response [odds ratio 1.15 (95% CI 1.02-1.29)] and remission [odds ratio 1.19 (95% CI 1.06-1.34)]. Overall drop out rates appeared similar for SSRIs and venlafaxine. Compared to tricyclics, response to venlafaxine was estimated to be greater by exact method, odds ratio 1.21 (95% CI 1.03-1.43), but not statistically significantly different, using a full random effects method odds ratio 1.22 (95% CI 0.96-1.54). We observed no difference in remission rates (odds ratio 1.06 (95% CI 0.74-1.63)). Tricyclics were less well tolerated with higher overall drop out rates. Compared to alternative antidepressants in treatment resistant depression (trials included comparison with sertraline, bupropion, fluoxetine, citalopram, and one with a range of agents-mostly SSRIs), the odds ratio for response was 1.35 (95% CI 1.19-1.54). The odds ratio for remission was 1.35 (95% CI 1.20-1.52). Compared to placebo the odds ratio for relapse prevention with venlafaxine was 0.37 (95% CI 0.27-0.51). This meta analysis provides evidence of the clinical efficacy of venlafaxine in achieving therapeutic response and remission in patients with major depression. Venlafaxine appears more effective than SSRIs, and at least as effective as tricyclic antidepressants, in the treatment of major depressive episode. Venlafaxine appeared more effective than comparators in treatment resistant depression. In addition, venlafaxine effective in reducing relapse when given long term after major depressive episode.