title: Leptin plasma concentrations increase during antidepressant treatment with amitriptyline and mirtazapine, but not paroxetine and venlafaxine: leptin resistance mediated by antihistaminergic activity?
abstract: 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.
authors.affiliation: Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Schilling
authors.forename: Maria
authors.initials: M
authors.lastname: Gilles
authors.forename: Werner F
authors.initials: WF
authors.lastname: Blum
authors.forename: Emmerich
authors.initials: E
authors.lastname: Daseking
authors.forename: Michael
authors.initials: M
authors.lastname: Colla
authors.forename: Bettina
authors.initials: B
authors.lastname: Weber-Hamann
authors.forename: Florian
authors.initials: F
authors.lastname: Lederbogen
authors.forename: Bertram
authors.initials: B
authors.lastname: Krumm
authors.forename: Isabella
authors.initials: I
authors.lastname: Heuser
authors.forename: Stefan A
authors.initials: SA
authors.lastname: Wudy
authors.forename: Daniel
authors.initials: D
authors.lastname: Kopf
authors.forename: Michael
authors.initials: M
authors.lastname: Deuschle
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000639:Amitriptyline / Q000009:adverse effects / Q000627:therapeutic use*; D000704:Analysis of Variance; D000928:Antidepressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D003511:Cyclohexanols / Q000009:adverse effects / Q000627:therapeutic use*; D003863:Depression / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D005260:Female; D006801:Humans; D020738:Leptin / Q000097:blood*; D008297:Male; D008803:Mianserin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008875:Middle Aged; D000078785:Mirtazapine; D017374:Paroxetine / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D015854:Up-Regulation; D000069470:Venlafaxine Hydrochloride; D015430:Weight Gain / Q000187:drug effects; D055815:Young Adult
chemical_list: D000928:Antidepressive Agents; D015415:Biomarkers; D003511:Cyclohexanols; D020738:Leptin; D000639:Amitriptyline; D008803:Mianserin; D017374:Paroxetine; D000069470:Venlafaxine Hydrochloride; D000078785:Mirtazapine