Safety, tolerability, and efficacy of vortioxetine (Lu AA21004) in major depressive disorder: results of an open-label, flexible-dose, 52-week extension study

Int Clin Psychopharmacol. 2014 Jan;29(1):36-44. doi: 10.1097/YIC.0000000000000010.


Patients with major depressive disorder often experience relapse after responding to treatment; therefore, maintenance therapy with antidepressants is recommended for maintaining response or remission. This multicenter, open-label, flexible-dose, 52-week extension study evaluated the long-term safety, tolerability, and maintenance of efficacy in study participants who had completed one of two randomized, double-blind, placebo-controlled, 8-week dose-ranging vortioxetine trials in study participants with major depressive disorder. At the open-label baseline, all study participants were switched to vortioxetine 5 mg/day for the first week, with subsequent dose adjustments from 2.5 to 10 mg/day on the basis of response and tolerability. Treatment with vortioxetine for 52 weeks was well tolerated, with no new safety signals identified. Among the 834 evaluable study participants, treatment-emergent adverse events were reported in 70.6%, with the most common in the combined (all doses) population of nausea (15.2%), headache (12.4%), nasopharyngitis (9.8%), diarrhea (7.2%), and dizziness (6.8%). The rate of adverse events related to sexual dysfunction was low and weight gain was minimal. Laboratory values, vital signs, ECGs, physical examinations, and Columbia-Suicide Severity Rating Scale results showed no trends of clinical concern. The change in the severity of depressive and anxiety symptoms was maintained throughout the study as reflected by a 24-item Hamilton Depression Scale total score of 8.2 at week 52 (from 17.6 at open-label baseline) in the observed case data set.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antidepressive Agents, Second-Generation / adverse effects
  • Antidepressive Agents, Second-Generation / therapeutic use*
  • Anxiety / psychology
  • Depression / psychology
  • Depressive Disorder, Major / drug therapy*
  • Double-Blind Method
  • Duloxetine Hydrochloride
  • Female
  • Humans
  • Male
  • Middle Aged
  • Piperazines / adverse effects
  • Piperazines / therapeutic use*
  • Psychiatric Status Rating Scales
  • Sexual Dysfunction, Physiological / chemically induced
  • Suicidal Ideation
  • Sulfides / adverse effects
  • Sulfides / therapeutic use*
  • Thiophenes / therapeutic use
  • Treatment Outcome
  • Vortioxetine
  • Weight Gain / drug effects
  • Young Adult


  • Antidepressive Agents, Second-Generation
  • Piperazines
  • Sulfides
  • Thiophenes
  • Vortioxetine
  • Duloxetine Hydrochloride