TY - JOUR
T1 - 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
AU - Mahableshwarkar, Atul R.
AU - Jacobsen, Paula L.
AU - Chen, Yinzhong
AU - Serenko, Michael
AU - Trivedi, Madhukar H.
N1 - Funding Information:
This study was supported by the Takeda Pharmaceutical Company, Ltd and H. Lundbeck A/S. The Takeda Pharmaceutical Company was involved in the design, investigator selection, conduct of the trial, collection of data, analysis and interpretation, and writing of the final study report. The authors had full control of the content of the manuscript. Atul R. Mahableshwarkar, Paula L. Jacobsen, and Yinzhong Chen are employees of Takeda Development Center Americas. Michael Serenko was an employee of Takeda Development Center Americas at the time the study was conducted. Dr. Madhukar H. Trivedi has received consulting fees from Abbott Laboratories, Inc., Abdi Ibrahim, Akzo, Alkermes, AstraZeneca, Axon Advisors, Bristol-Myers Squibb Company, Cephalon, Inc., CME Institute of Physicians, Eli Lilly & Company, Evotek, Fabre-Kramer Pharmaceuticals, Inc., Forest Pharmaceuticals, GlaxoSmithKline, Janssen Pharmaceutical Products, LP, Johnson & Johnson PRD, Libby, Lundbeck, Meade Johnson, MedAvante, Medtronic, Neuronetics, Otsuka Pharmaceuticals, Pamlab, Parke-Davis Pharmaceuticals, Inc., Pfizer, Inc., PGxHealth, Rexahn Pharmaceuticals, Sepracor, Shire Development, Sierra, Takeda, Tai Medical/Puretech Venture, Transcept, VantagePoint, Wyeth-Ayerst Laboratories and has received research support from the Agency for Healthcare Research and Quality, Corcept Therapeutics, Inc., Cyberonics, Inc., Merck, National Alliance for Research in Schizophrenia and Depression, National Institute of Mental Health, National Institute on Drug Abuse, Naurex, Novartis, Pharmacia & Upjohn, Predix Pharmaceuticals (Epix), Solvay Pharmaceuticals, Inc., Targacept, and Valiant. Assistance with writing, editing, and manuscript preparation was provided by Ann C. Sherwood, PhD and Philip Sjostedt, BPharm of The Medicine Group and was funded by the Takeda Pharmaceutical Company, Ltd and H. Lundbeck A/S. Authors had full control over the content of the manuscript and approved the final version for submission.
Publisher Copyright:
© 2015 The Author(s).
PY - 2015/6/1
Y1 - 2015/6/1
N2 - 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/.
AB - 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/.
KW - ASEX
KW - Antidepressant
KW - MDD
KW - Multimodal
KW - Treatment-emergent sexual dysfunction
UR - http://www.scopus.com/inward/record.url?scp=84929358849&partnerID=8YFLogxK
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U2 - 10.1007/s00213-014-3839-0
DO - 10.1007/s00213-014-3839-0
M3 - Article
C2 - 25575488
AN - SCOPUS:84929358849
SN - 0033-3158
VL - 232
SP - 2061
EP - 2070
JO - Psychopharmacology
JF - Psychopharmacology
IS - 12
M1 - 3839
ER -