Hennings Johannes M, Heel Sarah, Lechner Katharina, Uhr Manfred, Dose Tatjana, Schaaf Ludwig, Holsboer Florian, Lucae Susanne, Fulda Stephany, Kloiber Stefan
Max Planck Institute of Psychiatry, Munich, Germany.
Clinic for Neuroendocrinology and Andrology, Max Planck Institute of Psychiatry, Munich, Germany.
JCI Insight. 2019 Jan 10;4(1):e123786. doi: 10.1172/jci.insight.123786.
Weight gain and metabolic changes during treatment with antidepressant drugs have emerged as an important concern, particularly in long-term treatment. It is still a matter of ongoing debate whether weight gain and metabolic perturbations with antidepressant use are the consequence of increased appetite and weight gain, respectively, or represents direct pharmacological effects of the drug on metabolism.
We therefore conducted a proof-of-concept, open-label clinical trial, hypothesizing that in exceptionally healthy men no change of metabolic parameters would occur under mirtazapine, when environmental factors such as nutrition, sleep, and physical exercise were controlled and kept constant. Over a 3-week preparation phase, 10 healthy, young men were attuned to a standardized diet adjusted to their individual caloric need, to a regular sleep/wake cycle and moderate exercise. Continuing this protocol, we administered 30 mg mirtazapine daily for 7 days.
While no significant weight gain or changes in resting energy expenditure were observed under these conditions, hunger and appetite for sweets increased with mirtazapine, accompanied by a shift in energy substrate partitioning towards carbohydrate substrate preference as assessed by indirect calorimetry. Furthermore, with mirtazapine, insulin and C-peptide release increased in response to a standardized meal.
Our findings provide important insights into weight-independent metabolic changes associated with mirtazapine and allow a better understanding of the long-term metabolic effects observed in patients treated with antidepressant drugs.
gov NCT00878540.
Nothing to declare.
抗抑郁药物治疗期间的体重增加和代谢变化已成为一个重要问题，尤其是在长期治疗中。抗抑郁药物使用导致的体重增加和代谢紊乱究竟是食欲增加和体重增加的结果，还是药物对代谢的直接药理作用，仍是一个持续争论的问题。
因此，我们进行了一项概念验证性开放标签临床试验，假设在营养、睡眠和体育锻炼等环境因素得到控制并保持不变的情况下，米氮平对极其健康的男性的代谢参数不会产生变化。在为期3周的准备阶段，10名健康的年轻男性调整到适应其个体热量需求的标准化饮食、规律的睡眠/清醒周期和适度运动。继续该方案，我们每天给予30毫克米氮平，持续7天。
在这些条件下，未观察到显著的体重增加或静息能量消耗变化，但米氮平使饥饿感和对甜食的食欲增加，通过间接量热法评估，能量底物分配向碳水化合物底物偏好发生转变。此外，服用米氮平后，对标准化餐的胰岛素和C肽释放增加。
我们的研究结果为与米氮平相关的非体重依赖性代谢变化提供了重要见解，并有助于更好地理解抗抑郁药物治疗患者中观察到的长期代谢效应。
美国国立医学图书馆临床试验注册中心编号NCT00878540。
无。
