title: Relative efficacy and tolerability of vortioxetine versus selected antidepressants by indirect comparisons of similar clinical studies.
abstract: BACKGROUND
  Vortioxetine is an antidepressant with multimodal activity which has shown efficacy in major depressive disorder (MDD) patients in six of ten short-term, randomized, placebo-controlled trials (completed end 2012).
  
  
  METHODS
  We performed meta-regression analyses to indirectly compare vortioxetine to seven marketed antidepressants with different mechanisms of action. To ensure study comparability, only experimental drug and placebo arms from placebo-controlled registration studies were included in primary analyses. The main outcomes were efficacy (standardized mean difference in change from baseline to 2 months on primary endpoint [MADRS/HAM-D]), and tolerability (withdrawal rate due to adverse events).
  
  
  RESULTS
  For efficacy, estimates of treatment effect (negative estimates favor vortioxetine) for vortioxetine versus comparators were: agomelatine, -0.16 (p = 0.11); desvenlafaxine, 0.03 (p = 0.80); duloxetine, 0.09 (p = 0.42); escitalopram, -0.05 (p = 0.70); sertraline, -0.04 (p = 0.83); venlafaxine IR/XR, 0.12 (p = 0.33); and vilazodone, -0.25 (p = 0.11). For tolerability, all but one combination was numerically in favor of vortioxetine (odds ratio < 1), although not all differences were statistically significant: agomelatine, 1.77 (p = 0.03); desvenlafaxine, 0.58 (p = 0.04); duloxetine, 0.75 (p = 0.26); escitalopram, 0.67 (p = 0.28); sertraline, 0.30 (p = 0.01); venlafaxine, 0.47 (p = 0.01); and vilazodone, 0.64 (p = 0.18). Sensitivity analyses did not significantly alter antidepressant effect estimates or relative ranking.
  
  
  CONCLUSIONS
  These meta-regression data show that vortioxetine offers a comparable or favorable combination of efficacy (measured by MADRS/HAM-D) and tolerability (measured by withdrawal rate due to adverse events) versus other antidepressants in registration studies in MDD. Alternative methods like mixed-treatment comparison and inclusion of all randomized studies and active reference arms may provide complementary information to this analysis (more evidence but also more heterogeneity). Key messages: Indirect comparisons based on registration studies allow a useful comparison between a recently approved antidepressant and an approved drug. Vortioxetine offers a comparable or favorable combination of efficacy (measured by MADRS/HAM-D assessments) and tolerability (measured by withdrawal rate due to adverse events) versus other antidepressants in registration studies in MDD.
authors.affiliation: Centre Hospitalier Universitaire , Clermont-Ferrand , France.
authors.forename: Pierre-Michel
authors.initials: PM
authors.lastname: Llorca
authors.forename: Christophe
authors.initials: C
authors.lastname: Lançon
authors.forename: Mélanie
authors.initials: M
authors.lastname: Brignone
authors.forename: Benoît
authors.initials: B
authors.lastname: Rive
authors.forename: Samir
authors.initials: S
authors.lastname: Salah
authors.forename: Larry
authors.initials: L
authors.lastname: Ereshefsky
authors.forename: Clément
authors.initials: C
authors.lastname: Francois
mesh_terms: D000081:Acetamides / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000627:therapeutic use*; D001572:Benzofurans / Q000627:therapeutic use; D015283:Citalopram / Q000627:therapeutic use; D003511:Cyclohexanols / Q000627:therapeutic use; D003865:Major Depressive Disorder / Q000188:drug therapy*; D000069468:Desvenlafaxine Succinate; D000068736:Duloxetine Hydrochloride; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000627:therapeutic use; D007211:Indoles / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000627:therapeutic use*; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D020280:Sertraline / Q000627:therapeutic use; D013440:Sulfides / Q000627:therapeutic use*; D013876:Thiophenes / Q000627:therapeutic use; D000069470:Venlafaxine Hydrochloride; D000069503:Vilazodone Hydrochloride; D000078784:Vortioxetine; D009281:Naphthalenes
chemical_list: D000081:Acetamides; D000928:Antidepressive Agents; D001572:Benzofurans; D015283:Citalopram; D003511:Cyclohexanols; D000069468:Desvenlafaxine Succinate; D000068736:Duloxetine Hydrochloride; D006993:Hypnotics and Sedatives; D007211:Indoles; D010879:Piperazines; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline; D013440:Sulfides; D013876:Thiophenes; D000069470:Venlafaxine Hydrochloride; D000069503:Vilazodone Hydrochloride; D000078784:Vortioxetine; C084711:agomelatine; D009281:Naphthalenes
keywords: Antidepressants; Comparative evidence; Major depressive disorder; Vortioxetine