Duloxetine, 60 mg Once Daily, for Major Depressive Disorder: A Randomized Double-Blind Placebo-Controlled Trial

Michael J. Detke, M.D., Ph.D.; Yili Lu, Ph.D.; David J. Goldstein, M.D., Ph.D.; John R. Hayes, M.D.; and Mark A. Demitrack, M.D.

Background: Despite treatment advances, major depressive disorder (MDD) is still a significant cause of morbidity and mortality. Current therapies frequently fall short of providing full remission. In addition, physical symptoms are commonly seen in MDD patients, increasing overall morbidity and health care utilization. Duloxetine hydrochloride, a dual reuptake inhibitor of serotonin and norepinephrine, was evaluated for efficacy and tolerability/safety in the treatment of MDD and associated physical symptoms.

Method: In this multicenter, double-blind, parallel-group study, adult patients with DSM-IV MDD were randomly assigned to receive placebo (N=122) or duloxetine (60 mg/day, N=123) for 9 weeks. The primary efficacy measure was the 17-item Hamilton Rating Scale for Depression (HAM-D-17) total score. Painful physical symptoms were assessed using visual analog scales, and global illness and quality of life were evaluated using the Clinical Global Impressions-Severity scale, the Patient Global Impressions-Improvement scale, and the Quality of Life in Depression Scale. Safety and tolerability were determined by monitoring discontinuation rates, adverse events, vital signs, and laboratory results.

Results: Duloxetine was significantly superior to placebo (p<.001) in reducing HAM-D-17 total scores, starting at week 2. The estimated probability of remission for duloxetine-treated patients (44%) was almost 3 times that of placebo patients (16%). Duloxetine significantly reduced painful physical symptoms in comparison with placebo. Discontinuation due to adverse events for duloxetine-treated patients (13.8%) compared favorably with the rates reported for SSRIs in other studies. Nausea, dry mouth, and somnolence were the most common adverse events; no significant incidence of hypertension was seen.

Conclusion: Duloxetine, 60 mg/day, is a well-tolerated and effective treatment for MDD that reduces painful physical symptoms. These findings suggest that duloxetine may be a first-line treatment for patients with MDD and associated painful physical symptoms.

Received Dec. 17, 2001; accepted Feb. 1, 2002. From the Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Ind. (Drs. Detke, Lu, Goldstein, Hayes, and Demitrack); the Department of Psychiatry, Indiana University Medical School, Indianapolis (Drs. Detke, Hayes, and Demitrack); the Departments of Psychiatry, McLean Hospital, Belmont, and Harvard Medical School, Boston, Mass. (Dr. Detke); and the Department of Pharmacology and Toxicology, Indiana University Medical School, Indianapolis (Dr. Goldstein). Dr. Demitrack is currently employed by Wyeth, Radnor, Pa.

All of the authors are employed by Eli Lilly and Co. and accept full responsibility for the conduct of this trial. The authors had full access to all data from the trial and participated in the decision to publish the data.

The authors thank the Clinical Operations staff and Statistical Analysts of the Duloxetine Antidepressant Team for their excellent implementation of this trial, the clinical investigators and staff, and the many patients who generously agreed to participate in this clinical trial. We also thank Dr. Robert K. McNamara and Karen Burkey for their editorial assistance.

Corresponding author and reprints: Michael J. Detke, M.D., Ph.D., Lilly Corporate Center, Indianapolis, IN 46285 (e-mail:detke_michael@lilly.com).