title: Agomelatine efficacy and acceptability revisited: systematic review and meta-analysis of published and unpublished randomised trials.
abstract: BACKGROUND
  Agomelatine is a novel antidepressant drug with narrative, non-systematic reviews making claims of efficacy.
  
  
  OBJECTIVE
  The present study systematically reviewed published and unpublished evidence of the acute and long-term efficacy and acceptability of agomelatine compared with placebo in the treatment of major depression.
  
  
  METHODS
  Randomised controlled trials comparing agomelatine with placebo in the treatment of unipolar major depression were systematically reviewed. Primary outcomes were (a) Hamilton Rating Scale for Depression (HRSD) score at the end of treatment (short-term studies) and (b) number of relapses (long-term studies).
  
  
  RESULTS
  Meta-analyses included 10 acute-phase and 3 relapse prevention studies. Seven of the included studies were unpublished. Acute treatment with agomelatine was associated with a statistically significant superiority over placebo of -1.51 HRSD points (99% CI -2.29 to -0.73, nine studies). Data extracted from three relapse prevention studies failed to show significant effects of agomelatine over placebo (relative risk 0.78, 99% CI 0.41-1.48). Secondary efficacy analyses showed a significant advantage of agomelatine over placebo in terms of response (with no effect for remission). None of the negative trials were published and conflicting results between published and unpublished studies were observed.
  
  
  CONCLUSIONS
  We found evidence suggesting that a clinically important difference between agomelatine and placebo in patients with unipolar major depression is unlikely. There was evidence of substantial publication bias.
authors.affiliation: Department of Psychiatry II, Ulm University, Ulm, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Koesters
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Guaiana
authors.forename: Andrea
authors.initials: A
authors.lastname: Cipriani
authors.forename: Thomas
authors.initials: T
authors.lastname: Becker
authors.forename: Corrado
authors.initials: C
authors.lastname: Barbui
mesh_terms: D000081:Acetamides / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy*; D006801:Humans; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D055502:Secondary Prevention; D016896:Treatment Outcome; D055815:Young Adult; D009281:Naphthalenes
chemical_list: D000081:Acetamides; D000928:Antidepressive Agents; C084711:agomelatine; D009281:Naphthalenes