title: A randomised, double-blind, placebo-controlled, duloxetine-referenced study of the efficacy and tolerability of vortioxetine in the acute treatment of adults with generalised anxiety disorder.
abstract: OBJECTIVE
  This study aims to evaluate the efficacy and tolerability of vortioxetine 2.5-, 5- and 10-mg once-daily doses vs. placebo in the treatment of generalised anxiety disorder (GAD).
  
  
  METHODS
  In this 8-week, multicentre, double-blind, placebo-controlled, parallel-group, phase 3 study, patients with a primary GAD diagnosis were randomised to receive placebo (n = 157), vortioxetine 2.5 mg, vortioxetine 5 mg, vortioxetine 10 mg or duloxetine 60 mg once daily (n = 156 each). The primary end-point, mean change from baseline in Hamilton Anxiety Scale (HAM-A) total score and key secondary end-points for the 5- and 10-mg vortioxetine doses were analysed in a prespecified sequential testing procedure (all at week 8). Sexual dysfunction was evaluated using the Arizona Sexual Experiences Scale.
  
  
  RESULTS
  Differences from placebo in the primary efficacy end-point were not statistically significant for the vortioxetine groups. The mean difference from placebo was significant in the duloxetine arm. For all secondary efficacy end-points, results were similar among the vortioxetine groups and did not reach statistical significance. The vortioxetine 10-mg group showed separation from placebo on the Hospital Anxiety and Depression anxiety subscore (nominal p = 0.036). Duloxetine 60 mg significantly improved the primary end-point (p < 0.05 vs. placebo), validating the study. Nausea, dry mouth, diarrhoea, nasopharyngitis, headache, dizziness, somnolence, vomiting, dyspepsia, constipation and fatigue were reported in ≥ 5% of patients receiving vortioxetine. Rates of treatment-emergent sexual dysfunction (TESD) in the vortioxetine dosing groups were similar to placebo.
  
  
  CONCLUSIONS
  In this study, vortioxetine 2.5-, 5- and 10-mg once-daily doses showed no significant improvement in HAM-A total scores vs. placebo. Vortioxetine was well tolerated at all doses and was not associated with TESD.
authors.affiliation: Takeda Development Center Americas, Deerfield, IL, USA.
authors.forename: A R
authors.initials: AR
authors.lastname: Mahableshwarkar
authors.forename: P L
authors.initials: PL
authors.lastname: Jacobsen
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
authors.forename: J S
authors.initials: JS
authors.lastname: Simon
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014151:Anti-Anxiety Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001008:Anxiety Disorders / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D000068736:Duloxetine Hydrochloride; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage* / Q000009:adverse effects; D013440:Sulfides / Q000008:administration & dosage* / Q000009:adverse effects; D013876:Thiophenes / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D000078784:Vortioxetine; D055815:Young Adult
chemical_list: D014151:Anti-Anxiety Agents; D010879:Piperazines; D013440:Sulfides; D013876:Thiophenes; D000078784:Vortioxetine; D000068736:Duloxetine Hydrochloride