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An Inflammatory Biomarker as a Differential Predictor of Outcome of Depression Treatment With Escitalopram and Nortriptyline
Rudolf Uher, M.D., Ph.D.; Katherine E. Tansey, Ph.D.; Tracy Dew, B.Sc.; Wolfgang Maier, M.D.; Ole Mors, M.D., Ph.D.; Joanna Hauser, Ph.D.; Mojca Zvezdana Dernovsek, M.D.; Neven Henigsberg, M.D.; Daniel Souery, M.D., Ph.D.; Anne Farmer, M.D., F.R.C.Psych.; Peter McGuffin, Ph.D., F.R.C.P.
Am J Psychiatry 2014;:. doi:10.1176/appi.ajp.2014.14010094
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From the Department of Psychiatry, Dalhousie University, Halifax, N.S., Canada; the Social, Genetic, and Developmental Psychiatry Centre, Institute of Psychiatry, King’s College London, London; the Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, U.K.; the Department of Biochemistry, King’s College Hospital, London; the Department of Psychiatry, University of Bonn, Bonn, Germany; the Center for Psychiatric Research, Aarhus University Hospital, Risskov, Denmark; Laboratory of Psychiatric Genetics, Department of Psychiatry, Poznan University of Medical Sciences, Poznan, Poland; University Psychiatric Clinic and the Medical Faculty, University of Ljubljana, Slovenia; the Croatian Institute for Brain Research, School of Medicine, University of Zagreb, Zagreb, Croatia; Laboratoire de Psychologie Médicale, Université Libre de Bruxelles and Psy Pluriel, Centre Européen de Psychologie Médicale, Brussels.

Address correspondence to Dr. Uher (uher@dal.ca).

Copyright © 2014 by the American Psychiatric Association

Received January 26, 2014; Revised April 21, 2014; Accepted May 19, 2014.

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Abstract

Objective  Major depressive disorder has been linked with inflammatory processes, but it is unclear whether individual differences in levels of inflammatory biomarkers could help match patients to treatments that are most likely to be beneficial. The authors tested the hypothesis that C-reactive protein (CRP), a commonly available marker of systemic inflammation, predicts differential response to escitalopram (a serotonin reuptake inhibitor) and nortriptyline (a norepinephrine reuptake inhibitor).

Method  The hypothesis was tested in the Genome-Based Therapeutic Drugs for Depression (GENDEP) study, a multicenter open-label randomized clinical trial. CRP was measured with a high-sensitivity method in serum samples from 241 adult men and women with major depressive disorder randomly allocated to 12-week treatment with escitalopram (N=115) or nortriptyline (N=126). The primary outcome measure was the score on the Montgomery-Åsberg Depression Rating Scale (MADRS), administered weekly.

Results  CRP level at baseline differentially predicted treatment outcome with the two antidepressants (CRP-drug interaction: β=3.27, 95% CI=1.65, 4.89). For patients with low levels of CRP (<1 mg/L), improvement on the MADRS score was 3 points higher with escitalopram than with nortriptyline. For patients with higher CRP levels, improvement on the MADRS score was 3 points higher with nortriptyline than with escitalopram. CRP and its interaction with medication explained more than 10% of individual-level variance in treatment outcome.

Conclusions  An easily accessible peripheral blood biomarker may contribute to improvement in outcomes of major depressive disorder by personalizing treatment choice.

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