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PSYCHIATRY

Duloxetine and Venlafaxine-XR in the Treatment of Major Depressive Disorder: A Meta-Analysis of Randomized Clinical Trials

Faculty of Pharmacy, University of Utrecht, Utrecht, Netherlands

Marc van Baardewijk, Drs

Faculty of Pharmacy, University of Utrecht

Thomas R Einarson, PhD

Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada

Reprints: Dr. Einarson, Leslie Dan Faculty of Pharmacy, University of Toronto, 19 Russell St., Toronto, ON M5S 2S2, Canada, fax 416/978-1833, t.einarson{at}utoronto.ca

BACKGROUND: Duloxetine has joined venlafaxine on the antidepressant market as a second serotonin-norepinephrine reuptake inhibitor. No previous studies have directly compared these drugs.

OBJECTIVE: To compare indirectly the efficacy and safety of extended-release (XR) venlafaxine and duloxetine, the 2 currently available serotonin-norepinephrine reuptake inhibitors (SNRIs) in treating major depressive disorder.

METHODS: Outcomes from published, randomized, placebo-controlled trials reporting on moderately to severely depressed patients (Hamilton Rating Scale for Depression [HAM-D] 15 or Montgomery-Åsberg Depression Rating Scale [MADRS] 18). A systematic literature search of Cochrane, EMBASE, and MEDLINE (1996-January 2005) was performed. Two independent reviewers judged the trials for acceptance, and last observation carried forward data were extracted. Differences in remission (8-week HAM-D score 7 or MADRS 10), response (50% decrease on either scale), and dropout rates from lack of efficacy and adverse events were meta-analyzed using a random effects model. Each rate was contrasted with placebo. Sensitivity analyses were performed to examine the robustness of the results.

RESULTS: Data were obtained from 8 trials evaluating 1754 patients for efficacy and 1791 patients for discontinuation/safety. Venlafaxine-XR rates were 17.8% (95% CI 9.0 to 26.5) and 24.4% (95% CI 15.0 to 37.7) greater than those with placebo for remission and response compared with 14.2% (95% CI 8.9 to 26.5) and 18.6% (95% CI 13.0 to 24.2) for duloxetine. Although numerically higher for venlafaxine-XR, no statistically significant differences were found between the drugs; however, both demonstrated overall remission and response rates significantly higher than the rates achieved with placebo (p < 0.001). Reported adverse events were comparable between drugs.

CONCLUSIONS: Venlafaxine-XR tends to have a favorable trend in remission and response rates compared with duloxetine. However, dropout rates and adverse events did not differ. A direct comparison is warranted to confirm this tendency.

Key Words: depression, major depressive disorder; duloxetine, venlafaxine-XR

Published Online, September 27, 2005. www.theannals.com, DOI 10.1345/aph.1G076

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