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

• Published in: Psychopharmacology Vol. 232; no. 12; pp. 2061 - 2070
• Main Authors: Mahableshwarkar, Atul R., Jacobsen, Paula L., Chen, Yinzhong, Serenko, Michael, Trivedi, Madhukar H.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.06.2015; Springer; Springer Nature B.V
• Subjects: Adolescent; Adult; Aged; Antidepressants; Antidepressive Agents - adverse effects; Antidepressive Agents - therapeutic use; Biomedical and Life Sciences; Biomedicine; Depressive Disorder, Major - drug therapy; Depressive Disorder, Major - psychology; Dosage and administration; Dose-Response Relationship, Drug; Double-Blind Method; Drug therapy; Duloxetine Hydrochloride - adverse effects; Duloxetine Hydrochloride - therapeutic use; Electrocardiography - drug effects; Fatigue - complications; Fatigue - psychology; Female; Humans; Major depressive disorder; Male; Mental depression; Middle Aged; Neurosciences; Original Investigation; Patient outcomes; Pharmacology/Toxicology; Piperazines - adverse effects; Piperazines - therapeutic use; Psychiatric Status Rating Scales; Psychiatry; Psychopharmacology; Serotonin Uptake Inhibitors - adverse effects; Serotonin Uptake Inhibitors - therapeutic use; Sleep Initiation and Maintenance Disorders - complications; Sleep Initiation and Maintenance Disorders - psychology; Suicidal Ideation; Sulfides - adverse effects; Sulfides - therapeutic use; Vortioxetine; Young Adult; Antidepressant; ASEX; Multimodal; MDD; Treatment-emergent sexual dysfunction
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-014-3839-0

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/ .