title: Which placebo to cure depression? A thought-provoking network meta-analysis.
abstract: 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  Published and unpublished studies were searched for by three reviewers on Medline, the Cochrane Library, Embase, clinicaltrials.gov, Current Controlled Trial, in bibliographies, and by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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: INSERM U669, Maison de Solenn, 97 Boulevard de Port Royal, 75679 Paris Cedex 14, France. floriannaudet@gmail.com.
authors.forename: Florian
authors.initials: F
authors.lastname: Naudet
authors.forename: Bruno
authors.initials: B
authors.lastname: Millet
authors.forename: Philippe
authors.initials: P
authors.lastname: Charlier
authors.forename: Jean Michel
authors.initials: JM
authors.lastname: Reymann
authors.forename: Anne Solène
authors.initials: AS
authors.lastname: Maria
authors.forename: Bruno
authors.initials: B
authors.lastname: Falissard
mesh_terms: D000928:Antidepressive Agents / Q000008:administration & dosage*; D035843:Biomedical Research / Q000379:methods; D002986:Clinical Trials as Topic; D003511:Cyclohexanols / Q000008:administration & dosage; D003863:Depression / Q000188:drug therapy*; D005473:Fluoxetine / Q000008:administration & dosage; D006801:Humans; D010919:Placebos / Q000008:administration & dosage*; D016896:Treatment Outcome; D000069470:Venlafaxine Hydrochloride
chemical_list: D000928:Antidepressive Agents; D003511:Cyclohexanols; D010919:Placebos; D005473:Fluoxetine; D000069470:Venlafaxine Hydrochloride