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Michael E. Thase, MD; A. John Rush, MD; Robert H. Howland, MD; Susan G. Kornstein, MD; James H. Kocsis, MD; Alan J. Gelenberg, MD; Alan F. Schatzberg, MD; Lorrin M. Koran, MD; Martin B. Keller, MD; James M. Russell, MD; Robert M. A. Hirschfeld, MD; Lisa M. LaVange, PhD; Daniel N. Klein, PhD; Jan Fawcett, MD; Wilma Harrison, MD

Arch Gen Psychiatry. 2002;59:233-239.

Background  Although various strategies have been proposed to treat antidepressant nonresponders, little controlled research has been published that examines prospectively the use of switching to an alternate antidepressant.

Methods  This was a multisite study in which outpatients with chronic major depression (with or without concurrent dysthymia), who failed to respond to 12 weeks of double-blind treatment with either sertraline hydrochloride (n = 117) or imipramine hydrochloride (n = 51), were crossed over or switched to 12 additional weeks of double-blind treatment with the alternate medication. Outcome measures included the 24-item Hamilton Rating Scale for Depression and the Clinical Global Impressions–Severity and Improvement scales.

Results  The switch from sertraline to imipramine (mean dosage, 221 mg/d) and from imipramine to sertraline (mean dosage, 163 mg/d) resulted in clinically and statistically significant improvements. The switch to sertraline treatment was associated with fewer adverse effect complaints and significantly less attrition owing to adverse effects. Although sertraline treatment also resulted in significantly higher response rates in the intent-to-treat samples (60% in the sertraline group and 44% in the imipramine group), neither the intent-to-treat remission rates nor the response and remission rates among study completers differed significantly. Moreover, after considering the effect of attrition, there were no significant treatment effects on the more comprehensive generalized estimating equation analyses of the continuous dependent measures.

Conclusions  More than 50% of chronically depressed antidepressant nonresponders benefited from a switch from imipramine to sertraline, or vice versa, despite a high degree of chronicity. As in the initial trial, sertraline was generally better tolerated than imipramine. Switching to a standard antidepressant of a different class is a useful treatment strategy for antidepressant nonresponders and could be considered a standard of comparison for future studies of novel alternate strategies.

From the Departments of Psychiatry, University of Pittsburgh School of Medicine, and Western Psychiatric Institute and Clinic, Pittsburgh, Pa (Drs Thase and Howland), The University of Texas Southwestern Medical Center at Dallas (Dr Rush), Medical College of Virginia, Virginia Commonwealth University, Richmond (Dr Kornstein), Cornell University School of Medicine, New York, NY (Dr Kocsis), University of Arizona, Tucson (Dr Gelenberg), Stanford University School of Medicine, Stanford, Calif (Drs Schatzberg and Koran), Butler Hospital, Brown University, Providence, RI (Dr Keller), and The University of Texas Medical Branch at Galveston (Drs Russell and Hirschfeld); Quintiles, Inc, Research Triangle Park, North Carolina (Dr LaVange); Departments of Psychiatry, State University of New York at Stony Brook (Dr Klein), and Rush-Presbyterian-St Luke's Medical Center, Chicago, Ill (Dr Fawcett); Pfizer Inc and Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York (Dr Harrison). The following authors have served as paid consultants to these companies: Pfizer Inc (Drs Thase, Rush, Kornstein, Kocsis, Gelenberg, Schatzberg, Koran, Keller, Russell, Hirschfeld, LaVange, and Fawcett) and Abbott Laboratories, North Chicago, Ill (Drs Hirschfeld and Fawcett). Drs Kocsis, Gelenberg, and Harrison own stock in Pfizer Inc.

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