A randomized, double-blind, duloxetine-referenced study comparing efficacy and tolerability of 2 fixed doses of vortioxetine in the acute treatment of adults with MDD.

Abstract

RATIONALE:

Vortioxetine has reduced depressive symptoms in adults with major depressive disorder (MDD) in multiple clinical trials.

OBJECTIVES:

The aim of this study is to evaluate the efficacy, safety, and tolerability of vortioxetine 15 and 20 mg vs placebo in adults with MDD.

METHODS:

Patients were randomized 1:1:1:1 to vortioxetine 15 mg, vortioxetine 20 mg, duloxetine 60 mg (active reference), or placebo. The primary efficacy endpoint was mean change in Montgomery-Åsberg Depression Rating Scale (MADRS) total score at week 8 (MMRM). Safety/tolerability assessments included physical examinations, vital signs, laboratory evaluations, electrocardiograms, adverse events (AEs), Columbia-Suicide Severity Rating Scale, Arizona Sexual Experiences Scale, and Discontinuation-Emergent Signs and Symptoms checklist.

RESULTS:

Six hundred and fourteen patients were randomized. Mean changes in MADRS scores were -12.83 (±0.834), -14.30 (±0.890), -15.57 (±0.880), and -16.90 (±0.884) for placebo, vortioxetine 15 mg (P = .224), vortioxetine 20 mg (P = .023), and duloxetine 60 mg (P < .001) (P vs placebo), respectively. AEs reported by ≥5 % of vortioxetine patients included nausea, headache, diarrhea, dizziness, dry mouth, constipation, vomiting, insomnia, fatigue, and upper respiratory infection. Treatment-emergent sexual dysfunction, suicidal ideation or behavior, and discontinuation symptoms were not significantly different between vortioxetine and placebo.

CONCLUSIONS:

Vortioxetine 20 mg significantly reduced MADRS total scores after 8 weeks of treatment. Both vortioxetine doses were well tolerated.

CLINICAL TRIAL REGISTRATION:

ClinicalTrials.gov identifier NCT01153009; www.clinicaltrials.gov/ .

• Authors: Atul R Mahableshwarkar, Paula L Jacobsen, Yinzhong Chen, Michael Serenko, Madhukar H Trivedi
• Journal: Psychopharmacology (Psychopharmacology (Berl)) Vol. 232 Issue 12 Pg. 2061-70 (Jun 2015) ISSN: 1432-2072 [Electronic] Germany
• PMID: 25575488 (Publication Type: Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antidepressive Agents
• Piperazines
• Serotonin Uptake Inhibitors
• Sulfides
• Vortioxetine
• Duloxetine Hydrochloride

Topics

• Adolescent
• Adult
• Aged
• Antidepressive Agents (adverse effects, therapeutic use)
• Depressive Disorder, Major (drug therapy, psychology)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Duloxetine Hydrochloride (adverse effects, therapeutic use)
• Electrocardiography (drug effects)
• Fatigue (complications, psychology)
• Female
• Humans
• Male
• Middle Aged
• Piperazines (adverse effects, therapeutic use)
• Psychiatric Status Rating Scales
• Selective Serotonin Reuptake Inhibitors (adverse effects, therapeutic use)
• Sleep Initiation and Maintenance Disorders (complications, psychology)
• Suicidal Ideation
• Sulfides (adverse effects, therapeutic use)
• Vortioxetine
• Young Adult