title: Vortioxetine: a meta-analysis of 12 short-term, randomized, placebo-controlled clinical trials for the treatment of major depressive disorder.
abstract: BACKGROUND
  Vortioxetine was approved by the U.S. Food and Drug Administration (FDA) in September 2013 for treating major depressive disorder (MDD). Thus far, a number of randomized, double-blind, placebo-controlled clinical trials (RCTs) of vortioxetine have been conducted in patients with MDD. We performed a meta-analysis to increase the statistical power of these studies and enhance our current understanding of the role of vortioxetine in the treatment of MDD.
  
  
  METHODS
  We performed an extensive search of databases and the clinical trial registry. The mean change in total scores on the 24-item Hamilton Rating Scale for Depression (HAM-D) and the Montgomery- Åsberg Depression Rating Scale (MADRS) from the baseline were the primary outcome measures. The secondary efficacy measures were the response and remission rates, as defined by a 50% or greater reduction in HAM-D/MADRS total scores and as a score of 10 or less in the MADRS and 7 or less in the HAM-D total scores at the end of treatment.
  
  
  RESULTS
  We included 7 published and 5 unpublished short-term (6-12 wk) RCTs in our meta-analysis. Vortioxetine was significantly more effective than placebo, with an effect size (standardized mean difference [SMD]) of -0.217 (95% confidence interval [CI] -0.313 to -0.122) and with odds ratios (ORs) for response and remission of 1.652 (95% CI 1.321 to 2.067) and 1.399 (95% CI 1.104 to 1.773), respectively. Those treated with vortioxetine did not differ significantly from those treated with selective norepinephrine reuptake inhibitors/agomelatine with regard to the SMD of the primary outcome measure (0.081, -0.062 to 0.223) or for response (OR 0.815, 95% CI 0.585 to 1.135) and remission (OR 0.843, 95% CI 0.575 to 1.238) rates. Discontinuation owing to lack of efficacy (OR 0.541, 95% CI 0.308 to 0.950) was significantly less common among those treated with vortioxetine than among those who received placebo, whereas discontinuation owing to adverse events (AEs; OR 1.530, 95% CI 1.144 to 2.047) was significantly more common among those treated with vortioxetine than among those receiving placebo. There was no significant difference in discontinuation rates between vortioxetine and comparators owing to inefficacy (OR 0.983, 95% CI 0.585 to 1.650), whereas discontinuation owing to AEs was significantly less common in the vortioxetine than in the comparator group (OR 0.728, 95% CI 0.554 to 0.957).
  
  
  CONCLUSIONS
  Studies examining the role of vortioxetine in the treatment of MDD are limited.
  
  
  CONCLUSIONS
  Although our results suggest that vortioxetine may be an effective treatment option for MDD, they should be interpreted and translated into clinical practice with caution, as the meta-analysis was based on a limited number of heterogeneous RCTs.
authors.affiliation: Department of Psychiatry, The Catholic University of Korea College of Medicine, Seoul, Republic of Korea, and Department of Psychiatry and Behavioural Sciences, Duke University Medical Center, Durham, NC, USA.
authors.forename: Chi-Un
authors.initials: CU
authors.lastname: Pae
authors.affiliation: Department of Psychiatry, The Catholic University of Korea College of Medicine, Seoul, Republic of Korea.
authors.forename: Sheng-Min
authors.initials: SM
authors.lastname: Wang
authors.affiliation: Department of Psychiatry, Korea University, College of Medicine, Seoul, Republic of Korea.
authors.forename: Changsu
authors.initials: C
authors.lastname: Han
authors.affiliation: Department of Psychiatry, The Catholic University of Korea College of Medicine, Seoul, Republic of Korea.
authors.forename: Soo-Jung
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Department of Psychiatry and Behavioural Sciences, Duke University Medical Center, Durham, NC, USA.
authors.forename: Ashwin A
authors.initials: AA
authors.lastname: Patkar
authors.affiliation: Global Medical Education, New York, NY, USA.
authors.forename: Praksh S
authors.initials: PS
authors.lastname: Masand
authors.affiliation: Institute of Psychiatry, Department of Biomedical and NeuroMotor Sciences, University of Bologna, Bologna, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Serretti
mesh_terms: D000928:Antidepressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy*; D006801:Humans; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D013440:Sulfides / Q000009:adverse effects / Q000627:therapeutic use*; D000078784:Vortioxetine
chemical_list: D000928:Antidepressive Agents; D010879:Piperazines; D013440:Sulfides; D000078784:Vortioxetine