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Mental Health
Should antidepressants be used for major depressive disorder?
  1. Janus Christian Jakobsen1,2,3,
  2. Christian Gluud1,
  3. Irving Kirsch4
  1. 1 The Copenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
  2. 2 Department of Cardiology, Holbaek Hospital, Holbaek, Denmark
  3. 3 Department of Regional Health Research, The Faculty of Heath Sciences, University of Southern Denmark, Denmark
  4. 4 Program in Placebo Studies, Harvard Medical School, Boston, Massachusetts, USA
  1. Correspondence to Dr Janus Christian Jakobsen, The Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen 2100, Denmark; janusjakobsen{at}


Background Major depressive disorder is estimated by the WHO to affect more than 300 million people globally, making depression the leading cause of disability worldwide. Antidepressants are commonly used to treat depression.

Objective The study aimed to provide an update on the evidence on the effects of antidepressants compared with placebo. Should antidepressants be used for adults with major depressive disorder?

Study selection We searched the Cochrane Library, BMJ Best Practice and PubMed up to June 2019 with the search terms ‘depression’ and ‘antidepressants’ targeting reviews published in English since 1990.

Findings Several reviews have assessed the effects of antidepressants compared with placebo for depression. Generally, all the previous reviews show that antidepressants seem to have statistically significant effects on depressive symptoms, but the size of the effect has questionable importance to most patients. Antidepressants seem to have minimal beneficial effects on depressive symptoms and increase the risk of both serious and non-serious adverse events.

Conclusions The benefits of antidepressants seem to be minimal and possibly without any importance to the average patient with major depressive disorder. Antidepressants should not be used for adults with major depressive disorder before valid evidence has shown that the potential beneficial effects outweigh the harmful effects.

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  • Correction notice This article has been corrected since it was published Online First. The competing interest section now reads "Irving Kirsch is the author of “The Emperor’s New Drugs” for which he currently receives occasional royalties."

  • Contributors JCJ wrote the first draft. All authors approved the final version, and JCJ is the guarantor.

  • Funding The Copenhagen Trial Unit supported this project with part-time salary for JCJ and CG during the writing of the manuscript.

  • Competing interests Irving Kirsch is the author of “The Emperor’s New Drugs” for which he currently receives occasional royalties.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement All data relevant to the study are included in the article.