Extended-release Trazodone in Major Depressive Disorder: A Randomized, Double-blind, Placebo-controlled Study

David V Sheehan; Harry A Croft; E Roderich Gossen; Randy J Levitt; Claire Brullé; Sylvie Bouchard; Anna Rozova

Extended-release Trazodone in Major Depressive Disorder: A Randomized, Double-blind, Placebo-controlled Study

Psychiatry (Edgmont). 2009 May;6(5):20-33.

Authors

David V Sheehan¹, Harry A Croft, E Roderich Gossen, Randy J Levitt, Claire Brullé, Sylvie Bouchard, Anna Rozova

Affiliation

¹ Dr. Sheehan is Distinguished University Health Professor, Professor of Psychiatry, Director, Depression and Anxiety Disorders Research Institute, University of South Florida College of Medicine, Tampa, Florida; Dr. Croft is Medical Director, San Antonio Psychiatric Research Center, San Antonio, Texas; Drs. Gossen, Levitt, Brullé, and Rozova are from Labopharm Inc., Laval, Québec, Canada; and Dr. Bouchard is from Lakeshore General Hospital, Montréal, Québec, Canada.

PMID: 19724732
PMCID: PMC2719441

Abstract

Objective: To investigate the efficacy, safety, and clinical benefit of a once-daily formulation of trazodone (Trazodone Contramid((c)) OAD) in the treatment of major depressive disorder.

Design/participants: In this double-blind study, 412 patients with major depressive disorder (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria) were randomized 1:1 to receive either Trazodone Contramid OAD (150 to 375mg) or placebo. Treatment was titrated over two weeks to each individual optimal dose. Patients then continued six weeks of treatment; further dose adjustments were allowed based on efficacy and tolerability.

Measurements: The primary end point was change in the 17-item Hamilton Depression Rating Scale total score from baseline to last study visit. Secondary end points included Hamilton Depression Rating Scale responders/remitters, change in Montgomery-Asberg Depression Rating Scale, Clinician and Patient Global Improvement Scales, and quality of sleep.

Results: From the end of titration to the end of the six-week treatment period, the mean maximum daily dose of the intent-to-treat population was 310mg for the active group and 355mg for the placebo group. There was a statistically significant difference between trazodone and placebo on the mean HAMD-17 score (-11.4 vs. -9.3, P=0.012). A significant difference was present as early as Week 1 and was maintained at all subsequent study visits. Many secondary end points supported these findings, including improvements in quality of sleep. The most frequent adverse events were the same for both the treatment and placebo groups: headache and somnolence. There were no serious adverse events that were considered related to treatment. There were no clinically significant electrocardiogram or laboratory abnormalities.

Conclusions: The trazodone Contramid formulation was more effective than placebo in major depressive disorder and was well tolerated.

Keywords: Hamilton Depression Rating Scale; Major depressive disorder; antidepressant; extended release; placebo-controlled trial; serotonin-2 antagonist/reuptake inhibitor (SARI); trazodone.