title: A randomized, double-blind, duloxetine-referenced study comparing efficacy and tolerability of 2 fixed doses of vortioxetine in the acute treatment of adults with MDD.
abstract: BACKGROUND
  Vortioxetine has reduced depressive symptoms in adults with major depressive disorder (MDD) in multiple clinical trials.
  
  
  OBJECTIVE
  The aim of this study is to evaluate the efficacy, safety, and tolerability of vortioxetine 15 and 20 mg vs placebo in adults with MDD.
  
  
  METHODS
  Patients were randomized 1:1:1:1 to vortioxetine 15 mg, vortioxetine 20 mg, duloxetine 60 mg (active reference), or placebo. The primary efficacy endpoint was mean change in Montgomery-Åsberg Depression Rating Scale (MADRS) total score at week 8 (MMRM). Safety/tolerability assessments included physical examinations, vital signs, laboratory evaluations, electrocardiograms, adverse events (AEs), Columbia-Suicide Severity Rating Scale, Arizona Sexual Experiences Scale, and Discontinuation-Emergent Signs and Symptoms checklist.
  
  
  RESULTS
  Six hundred and fourteen patients were randomized. Mean changes in MADRS scores were -12.83 (±0.834), -14.30 (±0.890), -15.57 (±0.880), and -16.90 (±0.884) for placebo, vortioxetine 15 mg (P = .224), vortioxetine 20 mg (P = .023), and duloxetine 60 mg (P < .001) (P vs placebo), respectively. AEs reported by ≥5 % of vortioxetine patients included nausea, headache, diarrhea, dizziness, dry mouth, constipation, vomiting, insomnia, fatigue, and upper respiratory infection. Treatment-emergent sexual dysfunction, suicidal ideation or behavior, and discontinuation symptoms were not significantly different between vortioxetine and placebo.
  
  
  CONCLUSIONS
  Vortioxetine 20 mg significantly reduced MADRS total scores after 8 weeks of treatment. Both vortioxetine doses were well tolerated.
  
  
  BACKGROUND
  ClinicalTrials.gov identifier NCT01153009; www.clinicaltrials.gov/ .
authors.affiliation: CNS Medicine, Clinical Science, CNS Statistics, Pharmacovigilance, Takeda Development Center Americas, 1 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
authors.forename: Michael
authors.initials: M
authors.lastname: Serenko
authors.forename: Madhukar H
authors.initials: MH
authors.lastname: Trivedi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000523:psychology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D000068736:Duloxetine Hydrochloride / Q000009:adverse effects / Q000627:therapeutic use*; D004562:Electrocardiography / Q000187:drug effects; D005221:Fatigue / Q000150:complications / Q000523:psychology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D011569:Psychiatric Status Rating Scales; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D007319:Sleep Initiation and Maintenance Disorders / Q000150:complications / Q000523:psychology; D059020:Suicidal Ideation; D013440:Sulfides / Q000009:adverse effects / Q000627:therapeutic use*; D000078784:Vortioxetine; D055815:Young Adult
chemical_list: D000928:Antidepressive Agents; D000068736:Duloxetine Hydrochloride; D010879:Piperazines; D017367:Selective Serotonin Reuptake Inhibitors; D013440:Sulfides; D000078784:Vortioxetine