Vortioxetine

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

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

Research output: Contribution to journalArticle

32 Citations (Scopus)

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 Results: We included 7 published and 5 unpublished shortterm (6–12 wk) RCTs in our meta-analysis.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

Original languageEnglish
Pages (from-to)174-186
Number of pages13
JournalJournal of Psychiatry and Neuroscience
Volume40
Issue number3
DOIs
Publication statusPublished - 2015 May 1

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Major Depressive Disorder
Meta-Analysis
Randomized Controlled Trials
Placebos
Confidence Intervals
Odds Ratio
Therapeutics
S 20098
vortioxetine
Outcome Assessment (Health Care)
Depression
Placebo Effect
Controlled Clinical Trials
United States Food and Drug Administration
Registries
Norepinephrine
Clinical Trials
Databases

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry
  • Pharmacology (medical)

Cite this

Vortioxetine : A meta-analysis of 12 short-term, randomized, placebo-controlled clinical trials for the treatment of major depressive disorder. / Pae, Chi Un; Wang, Sheng Min; Han, Changsu; Lee, Soo Jung; Patkar, Ashwin A.; Masand, Praksh S.; Serretti, Alessandro.

In: Journal of Psychiatry and Neuroscience, Vol. 40, No. 3, 01.05.2015, p. 174-186.

Research output: Contribution to journalArticle

Pae, Chi Un ; Wang, Sheng Min ; Han, Changsu ; Lee, Soo Jung ; Patkar, Ashwin A. ; Masand, Praksh S. ; Serretti, Alessandro. / Vortioxetine : A meta-analysis of 12 short-term, randomized, placebo-controlled clinical trials for the treatment of major depressive disorder. In: Journal of Psychiatry and Neuroscience. 2015 ; Vol. 40, No. 3. pp. 174-186.
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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– {\AA}sberg 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 shortterm (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.",
author = "Pae, {Chi Un} and Wang, {Sheng Min} and Changsu Han and Lee, {Soo Jung} and Patkar, {Ashwin A.} and Masand, {Praksh S.} and Alessandro Serretti",
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TY - JOUR

T1 - Vortioxetine

T2 - A meta-analysis of 12 short-term, randomized, placebo-controlled clinical trials for the treatment of major depressive disorder

AU - Pae, Chi Un

AU - Wang, Sheng Min

AU - Han, Changsu

AU - Lee, Soo Jung

AU - Patkar, Ashwin A.

AU - Masand, Praksh S.

AU - Serretti, Alessandro

PY - 2015/5/1

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N2 - 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 shortterm (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.

AB - 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 shortterm (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.

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