Vortioxetine: a meta-analysis of 12 short-term, randomized, placebo-controlled clinical trials for the treatment of major depressive disorder

Vortioxetine: a meta-analysis of 12 short-term, randomized, placebo-controlled clinical trials for the treatment of major depressive disorder

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J Psychiatry Neurosci 2015;40(3):174-186

Chi-Un Pae, MD, PhD; Sheng-Min Wang, MD, PhD; Changsu Han, MD, PhD; Soo-Jung Lee, MD, PhD; Ashwin A. Patkar, MD; Praksh S. Masand, MD; Alessandro Serretti, MD, PhD

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Results: We included 7 published and 5 unpublished short-term (6–12 wk) RCTs in our meta-analysis.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).

Limitations: Studies examining the role of vortioxetine in the treatment of MDD are limited.

Conclusion: 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.


Submitted May 7, 2014; Revised July 5, Aug. 11, 2014; Accepted Aug. 12, 2014; Early-released Oct. 28, 2014

Acknowledgements: This study was supported by a grant of the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (HI12C0003).

Affiliations: From the Department of Psychiatry, The Catholic University of Korea College of Medicine, Seoul, Republic of Korea (Pae, Wang, Lee); Department of Psychiatry and Behavioural Sciences, Duke University Medical Center, Durham, NC, USA (Pae, Patkar); Department of Psychiatry, Korea University, College of Medicine, Seoul, Republic of Korea (Han); Global Medical Education, New York, NY, USA (Masand); and Institute of Psychiatry, Department of Biomedical and NeuroMotor Sciences, University of Bologna, Bologna, Italy (Serretti).

Competing interests: None declared.

Contributors: All authors designed the study. C. Pae, S.-M. Wang, C. Han and S.-J. Lee acquired and analyzed the data, which P. Masand and A. Serretti also analyzed. C. Pae, S.-M. Wang, C. Han, S.-J. Lee and A. Patkar wrote the article, which all authors reviewed and approved for publication.

DOI: 10.1503/jpn.140120

Correspondence to: C.-U. Pae, Department of Psychiatry, Bucheon St. Mary’s Hospital, The Catholic University of Korea College of Medicine, 2 Sosa-Dong, Wonmi-Gu, Bucheon 420717, Kyeonggi-Do, Republic of Korea; pae@catholic.ac.kr