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Leptin Plasma Concentrations Increase During Antidepressant Treatment With Amitriptyline and Mirtazapine, But Not Paroxetine and Venlafaxine: Leptin Resistance Mediated by Antihistaminergic Activity?

Schilling, Claudia MD*; Gilles, Maria MD*; Blum, Werner F. MD; Daseking, Emmerich MD*; Colla, Michael MD*‡; Weber-Hamann, Bettina MD; Lederbogen, Florian MD*; Krumm, Bertram PhD*; Heuser, Isabella MD, PhD*‡; Wudy, Stefan A. MD; Kopf, Daniel MD; Deuschle, Michael MD*

Journal of Clinical Psychopharmacology: February 2013 - Volume 33 - Issue 1 - p 99–103
doi: 10.1097/JCP.0b013e31827cb179
Brief Reports

Treatment with several psychopharmacological agents has been associated with increased leptin plasma concentrations. We measured leptin plasma concentrations in 76 adult depressed patients after a 6-day washout phase and again after 35 days of treatment with amitriptyline or paroxetine, as well as in 73 depressed patients after 28 days of treatment with either mirtazapine or venlafaxine. Leptin plasma concentrations increased during treatment with amitriptyline and mirtazapine, even after controlling for increased body mass index and irrespective of response to treatment [14.5 (13.8) vs 20.3 (18.7) ng/mL, and 12.2 (15.8) vs 14.4 (16.5) ng/mL in the 2 cohorts, respectively]. In contrast, paroxetine and venlafaxine treatment was not associated with changes in leptin plasma concentrations [14.8 (12.0) vs 13.6 (10.6); 15.9 (17.3) vs 13.5 (14.6) ng/mL] nor with weight gain. We conclude that treatment with amitriptyline or mirtazapine is associated with an increase in leptin secretion beyond change in weight. Thus, high leptin levels apparently are ineffective in the control of weight gain, indicating leptin resistance. Leptin resistance may be mediated by an antihistaminergic effect on hypothalamic nuclei integrating signals relevant for energy balance.

From the *Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim; †Lilly Research Laboratories, Eli Lilly & Co, Bad Homburg; ‡Department of Psychiatry, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin; §Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg; ∥Peptide Hormone Research Laboratory, Center of Child and Adolescent Medicine, Justus Liebig University, Giessen; and ¶Marienkrankenhaus, Department of Geriatric Medicine, Hamburg, Germany.

Received October 31, 2011; accepted after revision May 14, 2012.

Reprints: Maria Gilles, MD, Central Institute of Mental Health, J5, 68159 Mannheim, Germany (e-mail:

This study was supported by German Research Council grants DFG De 660/1-1 (Dr Deuschle and Dr Heuser) and DFG De 660/7-1 (Dr Deuschle and Dr Weber-Hamann).

Dr Schilling and Dr Gilles contributed equally to this work.

Clinical Trials Registration: The studies were registered in (NCT 01049347) and (DRKS00000008).

© 2013 Lippincott Williams & Wilkins, Inc.