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Early Switch Strategy in Patients With Major Depressive Disorder: A Double-Blind, Randomized Study

Romera, Irene MD*†; Pérez, Victor MD, PhD; Menchón, Jose Manuel MD, PhD§; Schacht, Alexander PhD; Papen, Rita FH; Neuhauser, Doris MSc; Abbar, Mocrane MD#; Svanborg, Pär MD, PhD**††; Gilaberte, Inmaculada MD, PhD‡‡

Journal of Clinical Psychopharmacology: August 2012 - Volume 32 - Issue 4 - p 479–486
doi: 10.1097/JCP.0b013e31825d9958
Original Contributions

Objective Antidepressant switch is a commonly used strategy in the absence of an adequate response, but optimum timing is not well established. We compared the efficacy of an early and a conventional antidepressant switch strategy in patients with major depressive disorder.

Methods Patients with no or minimal improvement (<30% reduction in baseline 17-item Hamilton Depression Rating Scale [HAMD17] score) after 4 weeks on escitalopram 10 mg/d were randomized to either early switch strategy with duloxetine 60 to 120 mg/d for 12 weeks (arm A) or conventional switch strategy (arm B): 4 further weeks on escitalopram 10 to 20 mg/d; then, in case of nonresponse (response, ≥50% reduction in HAMD17), switch to duloxetine 60 to 120 mg/d for 8 weeks, or continued escitalopram in responders. Co-primary end points were time to confirmed response and remission (HAMD17, ≤7). Strategies were compared using Kaplan-Meier, logistic regression, and repeated-measures analyses.

Results Sixty-seven percent (566 of 840) of patients showed no or minimal improvement and were randomized to arm A (282 patients) or arm B (284 patients). No between-strategy differences in time to confirmed response (25% Kaplan-Meier estimates, 3.9 vs 4.0 weeks, P = 0.213) or remission (6.0 vs 7.9 weeks, P = 0.075) were found. Rates of confirmed responders were similar (64.9% vs 64.1%); however, more patients randomized to early switch achieved confirmed remission (43.3% vs 35.6%; P = 0.048).

Conclusions Although no differences in the primary end points were found, a higher remission rate was seen with the early switch strategy. Our findings suggest that further investigations to reevaluate the conventional approach to antidepressant switch strategy would be worthwhile.

Supplemental digital content is available in the text.

From *Eli Lilly and Company, Madrid; †Universidad Autónoma de Barcelona, Departamento de Psiquiatría; ‡Hospital de Sant Pau i de la Santa Creu. UAB, CIBERSAM; §Hospital Universitari de Bellvitge-IDIBELL, University of Barcelona. CIBERSAM, Hospitalet de Llobregat, Barcelona, Spain; ∥Eli Lilly and Company, Bad Homburg, Germany; ¶Eli Lilly and Company, Vienna, Austria; #Hôspital Carémeau, Nîmes, France; **Eli Lilly and Company, Solna; ††Department of Clinical Neuroscience, Psychiatry Section, Karolinska Institutet, Stockholm, Sweden; and ‡‡Eli Lilly and Company, Madrid, Spain.

Received May 3, 2011; accepted after revision January 24, 2012.

Reprints: Irene Romera, MD, Clinical Research Physician Neuroscience, Medical Department, Eli Lilly and Company, Avenida de la Industria, 30, 28108-Alcobendas, Madrid, Spain (e-mail:

This study was funded by Eli Lilly and Company.

The data described in this article were partially presented at the International Forum on Mood and Anxiety Disorders in Vienna, Austria, on November 17–19, 2010.

This trial was registered on on December 16, 2008 (Identifier: NCT00810069;

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© 2012 Lippincott Williams & Wilkins, Inc.