A randomized, double-blind, placebo-controlled study of the efficacy and safety of vortioxetine 10 mg and 20 mg in adults with major depressive disorder

Paula L. Jacobsen, Atul R. Mahableshwarkar, Michael Serenko, Serena Chan, Madhukar H. Trivedi

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Context: Vortioxetine (Lu AA21004) is an antidepressant with a mechanism of action thought to be related to a combination of 2 pharmacologic actions: direct modulation of several receptors and inhibition of the serotonin transporter. Objective: To evaluate the efficacy of vortioxetine 10 and 20 mg once daily in outpatients with major depressive disorder. Design, Setting, and Participants: This 8-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study was conducted from July 2010 to January 2012 among adults with a primary diagnosis of recurrent major depressive disorder (DSM-IV-TR). Intervention: Eligible subjects were randomized in 1:1:1 ratio to 1 of 3 treatment arms: vortioxetine 10 mg, vortioxetine 20 mg, or placebo once daily for 8 weeks. Subjects who completed the 8-week trial entered a 2-week blinded discontinuation period to assess potential discontinuation symptoms. Main Outcome Measure: The primary endpoint was the least squares mean change in Montgomery-Asberg Depression Rating Scale (MADRS) total score from baseline. Key secondary outcomes were analyzed in the following prespecified sequential order: MADRS response (≥ 50% decrease from baseline in total score), Clinical Global Impressions-Improvement score, change from baseline in MADRS total score in subjects with baseline Hamilton Anxiety Rating Scale score ≥ 20, MADRS remission (total score ≤ 10), and change from baseline in Sheehan Disability Scale total score (all at week 8). Results: A total of 462 subjects were randomized to placebo (n = 157), vortioxetine 10 mg (n = 155), and vortioxetine 20 mg (n = 150). Mean (SE) reductions from baseline in MADRS total score (week 8) were -10.77 (± 0.807), -12.96 (± 0.832), and -14.41 (± 0.845) for the placebo, vortioxetine 10 mg (P = .058 vs placebo), and vortioxetine 20 mg (P = .002 vs placebo) groups. MADRS response/remission was achieved in 28.4%/14.2%, 33.8%/21.4%, and 39.2%/22.3% of subjects, respectively, in the 3 groups. Only MADRS response for vortioxetine 20 mg significantly separated from placebo (P = .044). Treatment was well tolerated, with the most frequently reported adverse events consisting of nausea, headache, diarrhea, and dizziness. Conclusions: Vortioxetine 20 mg significantly reduced MADRS total score at 8 weeks in this study population. Overall, vortioxetine was well tolerated in this study.

Original languageEnglish (US)
Pages (from-to)575-582
Number of pages8
JournalJournal of Clinical Psychiatry
Volume76
Issue number5
DOIs
StatePublished - May 1 2015

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Major Depressive Disorder
Placebos
Safety
Depression
vortioxetine
Rating Scales
Placebo
Efficacy
Controlled
Pharmacologic Actions
Serotonin Plasma Membrane Transport Proteins
Dizziness
Least-Squares Analysis
Diagnostic and Statistical Manual of Mental Disorders
Nausea
Antidepressive Agents
Headache
Diarrhea
Outpatients
Anxiety

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Arts and Humanities (miscellaneous)

Cite this

A randomized, double-blind, placebo-controlled study of the efficacy and safety of vortioxetine 10 mg and 20 mg in adults with major depressive disorder. / Jacobsen, Paula L.; Mahableshwarkar, Atul R.; Serenko, Michael; Chan, Serena; Trivedi, Madhukar H.

In: Journal of Clinical Psychiatry, Vol. 76, No. 5, 01.05.2015, p. 575-582.

Research output: Contribution to journalArticle

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abstract = "Context: Vortioxetine (Lu AA21004) is an antidepressant with a mechanism of action thought to be related to a combination of 2 pharmacologic actions: direct modulation of several receptors and inhibition of the serotonin transporter. Objective: To evaluate the efficacy of vortioxetine 10 and 20 mg once daily in outpatients with major depressive disorder. Design, Setting, and Participants: This 8-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study was conducted from July 2010 to January 2012 among adults with a primary diagnosis of recurrent major depressive disorder (DSM-IV-TR). Intervention: Eligible subjects were randomized in 1:1:1 ratio to 1 of 3 treatment arms: vortioxetine 10 mg, vortioxetine 20 mg, or placebo once daily for 8 weeks. Subjects who completed the 8-week trial entered a 2-week blinded discontinuation period to assess potential discontinuation symptoms. Main Outcome Measure: The primary endpoint was the least squares mean change in Montgomery-Asberg Depression Rating Scale (MADRS) total score from baseline. Key secondary outcomes were analyzed in the following prespecified sequential order: MADRS response (≥ 50{\%} decrease from baseline in total score), Clinical Global Impressions-Improvement score, change from baseline in MADRS total score in subjects with baseline Hamilton Anxiety Rating Scale score ≥ 20, MADRS remission (total score ≤ 10), and change from baseline in Sheehan Disability Scale total score (all at week 8). Results: A total of 462 subjects were randomized to placebo (n = 157), vortioxetine 10 mg (n = 155), and vortioxetine 20 mg (n = 150). Mean (SE) reductions from baseline in MADRS total score (week 8) were -10.77 (± 0.807), -12.96 (± 0.832), and -14.41 (± 0.845) for the placebo, vortioxetine 10 mg (P = .058 vs placebo), and vortioxetine 20 mg (P = .002 vs placebo) groups. MADRS response/remission was achieved in 28.4{\%}/14.2{\%}, 33.8{\%}/21.4{\%}, and 39.2{\%}/22.3{\%} of subjects, respectively, in the 3 groups. Only MADRS response for vortioxetine 20 mg significantly separated from placebo (P = .044). Treatment was well tolerated, with the most frequently reported adverse events consisting of nausea, headache, diarrhea, and dizziness. Conclusions: Vortioxetine 20 mg significantly reduced MADRS total score at 8 weeks in this study population. Overall, vortioxetine was well tolerated in this study.",
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AU - Chan, Serena

AU - Trivedi, Madhukar H.

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N2 - Context: Vortioxetine (Lu AA21004) is an antidepressant with a mechanism of action thought to be related to a combination of 2 pharmacologic actions: direct modulation of several receptors and inhibition of the serotonin transporter. Objective: To evaluate the efficacy of vortioxetine 10 and 20 mg once daily in outpatients with major depressive disorder. Design, Setting, and Participants: This 8-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study was conducted from July 2010 to January 2012 among adults with a primary diagnosis of recurrent major depressive disorder (DSM-IV-TR). Intervention: Eligible subjects were randomized in 1:1:1 ratio to 1 of 3 treatment arms: vortioxetine 10 mg, vortioxetine 20 mg, or placebo once daily for 8 weeks. Subjects who completed the 8-week trial entered a 2-week blinded discontinuation period to assess potential discontinuation symptoms. Main Outcome Measure: The primary endpoint was the least squares mean change in Montgomery-Asberg Depression Rating Scale (MADRS) total score from baseline. Key secondary outcomes were analyzed in the following prespecified sequential order: MADRS response (≥ 50% decrease from baseline in total score), Clinical Global Impressions-Improvement score, change from baseline in MADRS total score in subjects with baseline Hamilton Anxiety Rating Scale score ≥ 20, MADRS remission (total score ≤ 10), and change from baseline in Sheehan Disability Scale total score (all at week 8). Results: A total of 462 subjects were randomized to placebo (n = 157), vortioxetine 10 mg (n = 155), and vortioxetine 20 mg (n = 150). Mean (SE) reductions from baseline in MADRS total score (week 8) were -10.77 (± 0.807), -12.96 (± 0.832), and -14.41 (± 0.845) for the placebo, vortioxetine 10 mg (P = .058 vs placebo), and vortioxetine 20 mg (P = .002 vs placebo) groups. MADRS response/remission was achieved in 28.4%/14.2%, 33.8%/21.4%, and 39.2%/22.3% of subjects, respectively, in the 3 groups. Only MADRS response for vortioxetine 20 mg significantly separated from placebo (P = .044). Treatment was well tolerated, with the most frequently reported adverse events consisting of nausea, headache, diarrhea, and dizziness. Conclusions: Vortioxetine 20 mg significantly reduced MADRS total score at 8 weeks in this study population. Overall, vortioxetine was well tolerated in this study.

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