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Effect of mirtazapine on metabolism and energy substrate partitioning in healthy men
Johannes M. Hennings, … , Stephany Fulda, Stefan Kloiber
Johannes M. Hennings, … , Stephany Fulda, Stefan Kloiber
Published January 10, 2019
Citation Information: JCI Insight. 2019;4(1):e123786. https://doi.org/10.1172/jci.insight.123786.
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Clinical Medicine Metabolism Neuroscience

Effect of mirtazapine on metabolism and energy substrate partitioning in healthy men

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Abstract

BACKGROUND. 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. METHODS. 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. RESULTS. 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. CONCLUSION. 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. TRIAL REGISTRATION. ClinicalTrials.gov NCT00878540. FUNDING. Nothing to declare.

Authors

Johannes M. Hennings, Sarah Heel, Katharina Lechner, Manfred Uhr, Tatjana Dose, Ludwig Schaaf, Florian Holsboer, Susanne Lucae, Stephany Fulda, Stefan Kloiber

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Figure 1

Overview of the study.

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Overview of the study.
(A) Study flow diagram. (B) Study protocol. Note ...
(A) Study flow diagram. (B) Study protocol. Note that the narrowing bars in the upper part of B are intended to symbolize the extent of standardization means, i.e., instructions for regular sleep, exercise, and nutrition at the screening visit, control of hunger/satiety, adaptation of caloric need, sleep diaries, and activity protocols at control visits during the preparatory phase, and, finally, the continuation of standardized diet, sleep/wake cycle, and physical activity during the laboratory phase under continuous 24 hours/day visual control.

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