Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
J Clin Psychopharmacol. 2013 Feb;33(1):99-103. doi: 10.1097/JCP.0b013e31827cb179.
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.
治疗多种精神药理学药物与增加瘦素血浆浓度有关。我们在 76 名成年抑郁症患者经过 6 天的洗脱期后，再次在 35 天的阿米替林或帕罗西汀治疗后，以及在 73 名抑郁症患者经过 28 天的米氮平或文拉法辛治疗后，测量了瘦素血浆浓度。在接受阿米替林和米氮平治疗期间，瘦素血浆浓度增加，即使在控制体重指数增加的情况下，也与治疗反应无关[2 个队列分别为 14.5（13.8）与 20.3（18.7）ng/mL，以及 12.2（15.8）与 14.4（16.5）ng/mL]。相比之下，帕罗西汀和文拉法辛治疗与瘦素血浆浓度的变化无关[14.8（12.0）与 13.6（10.6）；15.9（17.3）与 13.5（14.6）ng/mL]，也与体重增加无关。我们的结论是，与体重变化相比，接受阿米替林或米氮平治疗与瘦素分泌增加有关。因此，高瘦素水平显然不能有效控制体重增加，表明存在瘦素抵抗。瘦素抵抗可能是通过抗组胺作用于整合与能量平衡相关信号的下丘脑核来介导的。
