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Review: no substantial differences in efficacy or effectiveness between second-generation antidepressants for major depressive disorder

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Question: Are there any differences in efficacy between second-generation antidepressants used to treat major depressive disorder (MDD)?

Outcomes: Efficacy, effectiveness, quality of life, onset of action, adverse events.


Design: Systematic review and meta-analysis.

Data sources: PubMed, Embase, PsycINFO, the Cochrane Library and International Pharmaceutical Abstracts (from 1980 to August 2011) were searched for published articles, using combined search terms for ‘MDD’ with a list of 13 second-generation antidepressants and their trade names. In addition, reference lists of reviews and letters to the editor were searched using Scopus. Sources searched for unpublished literature included the FDA, clinical trial registries and conference proceedings. Manufacturers were contacted to ask for any completed research on the drugs.

Study selection and analysis: For assessment of efficacy or effectiveness, head-to-head randomised controlled trials (RCTs) of at least 6-weeks' duration which compared two or more second-generation antidepressant drugs in adults were included. Studies were divided into those addressing efficacy and those addressing effectiveness using a tool based on aspects of study design. For assessment of harms, observational studies with 1000 participants or more and a follow-up of 12 weeks or more were included …

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  • Sources of funding Agency for Healthcare Research and Quality.

  • ▸ Notes are available online only at


  • Competing interests J B is on the speaker's bureau of Sunovion and has received research funding from Pfizer.