Which placebo to cure depression? A thought-provoking network meta-analysis

BMC Medicine

Bruno Falissard²  Anne Solène Maria⁵  Jean Michel Reymann¹  Philippe Charlier³  Bruno Millet⁴  Florian Naudet⁴ 

[1] Laboratoire de Pharmacologie Expérimentale et Clinique, Faculté de Médecine, CS34317, 2 Avenue du Pr Léon Bernard, 35043 Rennes, France;AP-HP, Hôpital Paul Brousse, Département de santé publique, Villejuif, France;Laboratory of Medical Ethics, University of Paris 5, 45 St Pères Street, 75006 Paris, France;Centre Hospitalier Guillaume Régnier, Service Hospitalo-Universitaire de Psychiatrie, Rennes, France;Université Paris-Sud and Université Paris Descartes, UMR-S0669, Paris, France

关键词: Publication bias;    Meta-analysis;    Major depressive disorder;    Placebo;    Antidepressants;   

Others  :  855618
DOI  :  10.1186/1741-7015-11-230

 received in 2013-02-07, accepted in 2013-10-04,  发布年份 2013

【 摘 要 】

Background

Antidepressants are often considered to be mere placebos despite the fact that meta-analyses are able to rank them. It follows that it should also be possible to rank different placebos, which are all made of sucrose. To explore this issue, which is rather more epistemological than clinical, we designed an unusual meta-analysis to investigate whether the effects of placebo in one situation are different from the effects of placebo in another situation.

Methods

Published and unpublished studies were searched for by three reviewers on Medline, the Cochrane Library, Embase, clinicaltrials.gov, Current Controlled Trial, in bibliographies, and by mailing key organizations. The following studies in first-line treatment for major depressive disorder were considered to construct an “evidence network”: 1) randomized controlled trials (RCTs) versus placebo on fluoxetine, venlafaxine and 2) fluoxetine versus venlafaxine head-to-head RCTs.

Two network meta-analyses were run to indirectly compare response and remission rates among three different placebos: 1) fluoxetine placebo, 2) venlafaxine placebo, and 3) venlafaxine/fluoxetine placebo (that is, placebo compared to both venlafaxine and fluoxetine). Publication biases were assessed using funnel plots and statistically tested.

Results

The three placebos were not significantly different in terms of response or remission. The antidepressant agents were significantly more efficacious than the placebos, and venlafaxine was more efficacious than fluoxetine. The funnel plots, however, showed a major publication bias.

Conclusion

The presence of significant levels of publication bias indicates that we cannot even be certain of the conclusion that sucrose equals sucrose in trials of major depressive disorder. This result should remind clinicians to step back to take a more objective view when interpreting a scientific result. It is of crucial importance for their practice, far more so than ranking antidepressant efficacy.

【 授权许可】

   
2013 Naudet et al.; licensee BioMed Central Ltd.

【 图 表 】

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