title: Duloxetine compared with fluoxetine and venlafaxine: use of meta-regression analysis for indirect comparisons.
abstract: BACKGROUND
  Data comparing duloxetine with existing antidepressant treatments is limited. A comparison of duloxetine with fluoxetine has been performed but no comparison with venlafaxine, the other antidepressant in the same therapeutic class with a significant market share, has been undertaken. In the absence of relevant data to assess the place that duloxetine should occupy in the therapeutic arsenal, indirect comparisons are the most rigorous way to go. We conducted a systematic review of the efficacy of duloxetine, fluoxetine and venlafaxine versus placebo in the treatment of Major Depressive Disorder (MDD), and performed indirect comparisons through meta-regressions.
  
  
  METHODS
  The bibliography of the Agency for Health Care Policy and Research and the CENTRAL, Medline, and Embase databases were interrogated using advanced search strategies based on a combination of text and index terms. The search focused on randomized placebo-controlled clinical trials involving adult patients treated for acute phase Major Depressive Disorder. All outcomes were derived to take account for varying placebo responses throughout studies. Primary outcome was treatment efficacy as measured by Hedge's g effect size. Secondary outcomes were response and dropout rates as measured by log odds ratios. Meta-regressions were run to indirectly compare the drugs. Sensitivity analysis, assessing the influence of individual studies over the results, and the influence of patients' characteristics were run.
  
  
  RESULTS
  22 studies involving fluoxetine, 9 involving duloxetine and 8 involving venlafaxine were selected. Using indirect comparison methodology, estimated effect sizes for efficacy compared with duloxetine were 0.11 [-0.14;0.36] for fluoxetine and 0.22 [0.06;0.38] for venlafaxine. Response log odds ratios were -0.21 [-0.44;0.03], 0.70 [0.26;1.14]. Dropout log odds ratios were -0.02 [-0.33;0.29], 0.21 [-0.13;0.55]. Sensitivity analyses showed that results were consistent.
  
  
  CONCLUSIONS
  Fluoxetine was not statistically different in either tolerability or efficacy when compared with duloxetine. Venlafaxine was significantly superior to duloxetine in all analyses except dropout rate. In the absence of relevant data from head-to-head comparison trials, results suggest that venlafaxine is superior compared with duloxetine and that duloxetine does not differentiate from fluoxetine.
authors.affiliation: Unit 669, Institut Nationale de la Santé et de la Recherche Médicale (INSERM), F-75014, Paris, France. laurent.eckert@gmail.com
authors.forename: Laurent
authors.initials: L
authors.lastname: Eckert
authors.forename: Christophe
authors.initials: C
authors.lastname: Lançon
mesh_terms: D000928:Antidepressive Agents / Q000627:therapeutic use*; D018687:Antidepressive Agents, Second-Generation / Q000627:therapeutic use*; D003511:Cyclohexanols / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy*; D000068736:Duloxetine Hydrochloride; D005473:Fluoxetine / Q000627:therapeutic use*; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D012044:Regression Analysis; D013876:Thiophenes / Q000627:therapeutic use*; D016896:Treatment Outcome; D000069470:Venlafaxine Hydrochloride
chemical_list: D000928:Antidepressive Agents; D018687:Antidepressive Agents, Second-Generation; D003511:Cyclohexanols; D013876:Thiophenes; D005473:Fluoxetine; D000069470:Venlafaxine Hydrochloride; D000068736:Duloxetine Hydrochloride