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

A meta-analysis

  • ORIGINAL PAPER
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European Archives of Psychiatry and Clinical Neuroscience Aims and scope Submit manuscript

Abstract

Objective

Meta-analysis of all available trials of Venlafaxine in the treatment of major depressive disorders, including treatment resistant depression and long-term relapse prevention.

Methods

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 Trials were identified through searches of Medline, Embase, Cochrane Library and through accessing unpublished trials held by the manufacturer.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.

Results

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).

Conclusion

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.

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Acknowledgement

Potential financial competing interests: This work was funded by Wyeth Pharma GmbH. Some of the authors have received funding for research and or consulting from a number of organizations: Hans-Jurgen Moller has received research grants/support from, serves as a consultant or is on the advisory board for, or is a member of the speaker bureau for the following companies: AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Eisai, GlaxoSmithKline, Janssen Cilag, Lundbeck, Merck, Novartis, Organon, Pfizer, Sanofi Aventis, Sepracor, Servier, Wyeth. Michael Bauer has received grant/research support from The Stanley Medical Research Institute, NARSAD, GlaxoSmithKline, Eli Lilly & Company, and AstraZeneca. Michael Bauer is a consultant for Eli Lilly& Company, GlaxoSmithKline, Novartis, Servier Deutschland, Wyeth and Novartis Pharmaceuticals. He has received speaker honoraria from AstraZeneca, Eli Lilly & Company, Lundbeck GmbH, GlaxoSmithKline, Pfizer, Sanofi-Aventis and Wyeth Pharmaceuticals. Hans-Peter Volz has received fees, funding or salary from Wyeth Pharma GmbH, Lundbeck GmbH, Pfizer Pharma GmbH, Lilly Deutschland GmbH, Glaxo SmithKline GmbH & CO. KG. Puvan Tharmanathan has received consultancy fees from Wyeth Inc. Nick Freemantle has received fees for consulting, grants for research and travel and speaker fees from Wyeth, the manufacturer of venlafaxine.

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This work was funded by Wyeth Pharma GmbH.

Appendix

Appendix

Table 2 Data from trials comparing venlafaxine and SSRIs
Table 3 Data from trials comparing tricyclics and venlafaxine
Table 4 Treatment resistant trials
Table 5 Long term relapse prevention trials

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Bauer, M., Tharmanathan, P., Volz, HP. et al. The effect of venlafaxine compared with other antidepressants and placebo in the treatment of major depression. Eur Arch Psychiatry Clin Neurosci 259, 172–185 (2009). https://doi.org/10.1007/s00406-008-0849-0

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