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Review: benefits of antidepressants over placebo limited except in very severe depression

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What are the effects of antidepressant medications across a range of initial symptoms severities in people with depression?


Depression severity measured using the Hamilton Depression Rating Scale (HDRS).



Systematic review and individual patient data meta analysis.

Data sources:

PubMed, PsycINFO and the Cochrane Library were searched from January 1980 to March 2009. References from meta analyses and reviews were hand searched.

Study selection and analysis

Placebo-controlled RCTs of US Food and Drug Association-approved antidepressants in adult outpatients with major or minor depressive disorders were included. Studies were excluded if they examined only patients with a specific subtype or severity of depression, compared medication versus placebo for less than 6 weeks, excluded patients on the basis of a placebo washout period, did not use the Hamilton Depression Rating Scale (HDRS), were not published in English, or study authors could not provide individual patient data. Study authors were contacted for individual patient data. Analyses of covariance were used to look at the effect of baseline symptom severity on symptom-change scores with the antidepressant medication versus placebo. The analyses …

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  • Source of funding The National Institute of Mental Health, Bethesda, Maryland, USA.


  • Competing interests None.

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