title: A randomized, double-blind trial of 2.5 mg and 5 mg vortioxetine (Lu AA21004) versus placebo for 8 weeks in adults with major depressive disorder.
abstract: OBJECTIVE
  Vortioxetine (Lu AA21004) is an investigational antidepressant. In vitro studies indicate that vortioxetine is a 5-HT(3), 5-HT(7), and 5-HT(1D) receptor antagonist, 5-HT(1B) receptor partial agonist, 5-HT(1A) receptor agonist and inhibitor of the 5-HT transporter. This trial assessed the efficacy and tolerability of 2.5 and 5 mg vortioxetine for the treatment of MDD.
  
  
  METHODS
  Adults (N = 611) with MDD were randomized to 8 weeks of double-blind treatment with placebo, vortioxetine (2.5 or 5 mg) or active reference (duloxetine 60 mg). The primary measure was change from baseline in the 24-item Hamilton Depression Scale (HAM-D24). Secondary endpoints included responder rate, Clinical Global Impression Scale-Global Improvement scale (CGI-I), and remission rate. Participants were monitored for adverse events (AEs), and treatment-emergent sexual dysfunction using the Arizona Sexual Experiences (ASEX) scale.
  
  
  RESULTS
  Both doses of vortioxetine were associated with declines in HAM-D24 total scores compared to placebo but were not statistically significant. At 8 weeks, changes from baseline were [mean (SE)]: -10.50 (0.76) placebo, -12.04 (0.74) 2.5 mg vortioxetine, and -11.08 (0.74) 5 mg vortioxetine. Secondary outcome measures in the vortioxetine groups, including responder rate, CGI-I, and remission rate, were also not significantly different from placebo. Duloxetine treatment was associated with declines in HAM-D24 total score [-13.47(0.75); p = 0.005] as well as significant improvements in secondary outcome measures versus placebo (p ≤ 0.05). The most common AEs for vortioxetine were nausea, dry mouth, and headache. Rates of sexual dysfunction (ASEX) were 51.0%, 37.5%, 46.9%, and 33.3% in the vortioxetine 2.5 mg, vortioxetine 5 mg, duloxetine, and placebo groups, respectively.
  
  
  CONCLUSIONS
  In this study of adults with MDD treated for 8 weeks with vortioxetine 2.5 mg or 5 mg per day, reductions in depression symptoms were not statistically significant compared with placebo. Study limitations are discussed, including patient characteristics, MDD severity, drug dosing, and aspects of trial design. Both doses of vortioxetine were well tolerated. This trial has been registered at clinicaltrials.gov #NCT00672620.
authors.affiliation: Takeda Global Research and Development Center, One Takeda Parkway, Deerfield, IL 60015, USA. atul.mahableshwarkar@takeda.com
authors.forename: Atul R
authors.initials: AR
authors.lastname: Mahableshwarkar
authors.forename: Paula L
authors.initials: PL
authors.lastname: Jacobsen
authors.forename: Yinzhong
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D003865:Major Depressive Disorder / Q000188:drug therapy*; D004311:Double-Blind Method; D000068736:Duloxetine Hydrochloride; D005260:Female; D006801:Humans; D008297:Male; D010879:Piperazines / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D010919:Placebos; D012735:Sexual Dysfunction, Physiological / Q000139:chemically induced; D059020:Suicidal Ideation; D013440:Sulfides / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D013876:Thiophenes / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome; D000078784:Vortioxetine
chemical_list: D000928:Antidepressive Agents; D010879:Piperazines; D010919:Placebos; D013440:Sulfides; D013876:Thiophenes; D000078784:Vortioxetine; D000068736:Duloxetine Hydrochloride