Addition of Atomoxetine for Depression Incompletely Responsive to Sertraline: A Randomized, Double-Blind, Placebo-Controlled Study

David Michelson, M.D.; Lenard A. Adler, M.D.; Jay D. Amsterdam, M.D.; David L. Dunner, M.D.; Andrew A. Nierenberg, M.D.; Frederick W. Reimherr, M.D.; Alan F. Schatzberg, M.D.; Douglas K. Kelsey, M.D., Ph.D.; and David W. Williams, M.S.

Objective: Despite appropriate treatment with selective serotonin reuptake inhibitors (SSRIs), many depressed patients do not attain remission. Addition of a noradrenergic intervention in patients poorly or partially responsive to SSRIs may improve outcomes, but few well-controlled studies testing this hypothesis have been reported.

Method: Patients with major depressive disorder (confirmed by the Structured Clinical Interview for DSM-IV) were treated with sertraline at doses up to 200 mg/day in this study, conducted from June 18, 2003, to January 28, 2005. Patients who continued to experience depressive signs and symptoms after 8 weeks were randomly assigned to have atomoxetine 40 to 120 mg/day or placebo added to sertraline for a further 8 weeks.

Results: Of 276 patients starting the study, 146 with persistent depressive symptoms after 8 weeks of sertraline treatment (mean [SD] final sertraline dose: 161.1 [43.4] mg/day) were randomly assigned to addition of atomoxetine or placebo. After 8 additional weeks, there was no difference between treatment groups in mean change in symptom severity or in the proportion of patients whose symptoms remitted (sertraline/atomoxetine 29/72 [40.3%], sertraline/placebo 28/74 [37.8%], p = .865). Secondary analyses that separated the subgroups with improvements in symptoms that did not reach remission (partial responders) and those with little or no improvement (nonresponders) also showed no effect of atomoxetine. The number of patients discontinuing because of adverse events did not differ between groups.

Conclusion: In depressed patients with persistent symptoms after an initial trial of sertraline, addition of atomoxetine did not improve response more than placebo.

(J Clin Psychiatry 2007;68:582-587)

Received April 25, 2006; accepted Aug. 22, 2006. From Lilly Research Laboratories, Eli Lilly and Co., Indianapolis, Ind. (Drs. Michelson and Kelsey and Mr. Williams); the Department of Psychiatry, Indiana University, Indianapolis, Ind. (Dr. Michelson); the Department of Psychiatry, New York University, New York, N.Y. (Dr. Adler); the Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, Pa. (Dr. Amsterdam); the Center for Anxiety & Depression and the Department of Psychiatry, University of Washington, Seattle, Wash. (Dr. Dunner); the Depression Clinical & Research Program and the Department of Psychiatry, Massachusetts General Hospital/Harvard Medical School, Boston, Mass. (Dr. Nierenberg); the Mood Disorders Clinic and the Department of Psychiatry, University of Utah Health Sciences Center, Salt Lake City, Utah (Dr. Reimherr); and the Department of Psychiatry & Behavioral Sciences, Stanford University School of Medicine, Stanford, Calif. (Dr. Schatzberg).

This research was funded by Eli Lilly and Co., Indianapolis, Ind.

These data were presented as an oral presentation at the 159th annual meeting of the American Psychiatric Association, May 20-25, 2006, Toronto, Ontario, Canada.

Financial disclosure appears at the end of this article.

Corresponding author and reprints: David Michelson, M.D., Merck Research Laboratories, P.O. Box 1000, North Wales, PA 19454 (e-mail: david_michelson@merck.com).