title: Antidepressant efficacy of agomelatine: meta-analysis of published and unpublished studies.
abstract: OBJECTIVE
  To systematically review published and unpublished efficacy studies of agomelatine in people with depression.
  
  
  METHODS
  Systematic review and meta-analysis.
  
  
  METHODS
  Literature search (Pubmed, Embase, Medline), Cochrane Central Register of Controlled Trials, European Medicines Agency (EMA) regulatory file for agomelatine, manufacturers of agomelatine (Servier).
  
  
  METHODS
  Double blind randomised placebo and comparator controlled trials of agomelatine in depression with standard depression rating scales.
  
  
  RESULTS
  Studies were pooled by using a random effects model with DerSimonian and Laird weights for comparisons with placebo and comparator antidepressant. The primary efficacy measure (change in rating scale score) was summarised with standardised mean difference (SMD; a measure of effect size) and secondary outcome measures with relative risks. All results were presented with 95% confidence intervals. Statistical heterogeneity was explored by visual inspection of funnel plots and by the I(2) statistic. Moderators of effect were explored by meta-regression.
  
  
  RESULTS
  We identified 20 trials with 7460 participants meeting inclusion criteria (11 in the published literature, four from the European Medicines Agency file, and five from the manufacturer). Almost all studies used the 17 item Hamilton depression rating scale (score 0-50). Agomelatine was significantly more effective than placebo with an effect size (SMD) of 0.24 (95% confidence interval 0.12 to 0.35) and relative risk of response 1.25 (1.11 to 1.4). Compared with other antidepressants, agomelatine showed equal efficacy (SMD 0.00, -0.09 to 0.10). Significant heterogeneity was uncovered in most analyses, though risk of bias was low. Published studies were more likely than unpublished studies to have results that suggested advantages for agomelatine.
  
  
  CONCLUSIONS
  Agomelatine is an effective antidepressant with similar efficacy to standard antidepressants. Published trials generally had more favourable results than unpublished studies.
authors.affiliation: King's College London, Institute of Pharmaceutical Science, London SE1 9NH, UK.
authors.forename: David
authors.initials: D
authors.lastname: Taylor
authors.forename: Anna
authors.initials: A
authors.lastname: Sparshatt
authors.forename: Seema
authors.initials: S
authors.lastname: Varma
authors.forename: Olubanke
authors.initials: O
authors.lastname: Olofinjana
mesh_terms: D000081:Acetamides / Q000009:adverse effects / Q000627:therapeutic use*; D000928:Antidepressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D003863:Depression / Q000188:drug therapy*; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome; D009281:Naphthalenes
chemical_list: D000081:Acetamides; D000928:Antidepressive Agents; C084711:agomelatine; D009281:Naphthalenes