A meta-analysis of the efficacy of venlafaxine extended release 75–225 mg/day for the treatment of major depressive disorder

Abstract

Objective: To evaluate the short-term efficacy of venlafaxine extended release (ER) 75–225 mg/day compared with placebo for treating major depressive disorder (MDD) and to examine associations between baseline characteristics and efficacy outcomes in MDD patients treated with venlafaxine ER 75–225 mg/day.

Research design and methods: This meta-analysis included published and unpublished short-term, double-blind, placebo-controlled, Wyeth/Pfizer sponsored studies of venlafaxine ER at doses up to 225 mg/day in adults with MDD.

Clinical trial registration: All trials were conducted before trial registration became mandatory.

Main outcome measures: Change from baseline in the 17-item Hamilton Rating Scale for Depression (HAM-D₁₇) total score was analyzed over time using a mixed-effects model for repeated measures with terms for study, treatment group, visit, interaction between treatment group and visit, and baseline score as a covariate. Associations between baseline demographic and clinical characteristics and the probability of HAM-D₁₇ response and remission at week 8 were evaluated using logistic regression models, with terms for study, treatment group, and baseline characteristics in the models. Safety and tolerability was assessed based on adverse events (AEs) and discontinuations due to AEs.

Results: The full analysis set included 1087 patients from five studies that fulfilled selection criteria. Statistically significant separation between venlafaxine ER and placebo groups for HAM-D₁₇ total score was seen at week 2 and all subsequent assessments (p-values <.0001). There was no significant interaction between treatment and baseline HAM-D₁₇ total score. Probability of HAM-D₁₇ remission at week 8 decreased with increasing baseline HAM-D₁₇ total score (p = .0012; OR: 0.94); however, baseline HAM-D₁₇ total score did not predict response. Discontinuations due to AEs were reported for 9.4% of venlafaxine-ER-treated patients compared with 3.6% of placebo-treated patients.

Key limitations: Five studies met the criteria for inclusion. Several differences in design between included studies limited the analysis: one study did not include a week 3 assessment (the week 3 time point was therefore dropped from the analysis), one study had two venlafaxine ER dose arms, which were combined into one group for the meta-analysis, and mixed- and flexible-dose studies were pooled.

Conclusions: Venlafaxine ER 75–225 mg/day effectively reduced symptoms of depression in patients with MDD overall and in patients with either lower (≤23) or higher (>23) HAM-D₁₇ total score at baseline.

Keywords:

• Major depressive disorder
• numbers needed to treat
• treatment efficacy
• venlafaxine

Transparency

Declaration of funding

This study was sponsored by Pfizer Inc.

Declaration of financial/other relationships

M.T. has disclosed that he has provided scientific consultation to Alkermes, Allergan, Astra-Zeneca, Bristol-Myers Squibb Company, Cerecor Inc., Eli Lilly & Company, Fabre-Kramer Pharmaceuticals Inc., Forest Pharmaceuticals Inc., Gerson Lehrman Group, GlaxoSmithKline, Guidepoint Global, H. Lundbeck A/S, MedAvante Inc., Merck and Co. Inc., Moksha8, Naurex Inc., Neuronetics, Inc., Novartis, Ortho-McNeil Pharmaceuticals (Johnson & Johnson; Janssen), Otsuka, Pfizer (formerly Wyeth-Ayerst Laboratories), Shire US Inc., Sunovion Pharmaceuticals Inc., Pamlab LLC (Nestle), Trius Therapeutics Inc., and Takeda; he receives grant funding from the Agency for Healthcare Research and Quality, Alkermes, AssureRx, Avanir, Forest Pharmaceuticals, Janssen, Eli Lilly & Company, National Institute of Mental Health, and Otsuka Pharmaceuticals; he has equity holdings in MedAvante Inc. and receives royalty income from American Psychiatric Foundation Inc., Guilford Publications, Herald House, Oxford University Press, and W.W. Norton & Company; his wife is employed as the Group Scientific Director for Peloton Advantage, which does business with Pfizer. Y.A. has disclosed that she is an employee of Pfizer Japan. D.W. has disclosed that she is an employee of Pfizer Inc. and holds stock and stock options from Pfizer Inc. K.D. has disclosed that she is an employee of Peloton Advantage and provided medical writing support funded by Pfizer Inc. M.B. has disclosed that he is an employee of Pfizer Canada and holds stock and stock options from Pfizer Inc. E.P. has disclosed that she is an employee of Pfizer Inc.

CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Medical writing support was provided by Peloton Advantage, LLC, (KD) and was funded by Pfizer Inc.