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

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Hennings,  Johannes M.
RG Susanne Lucae, Psychiatric Pharmacogenetics, Dept. Clinical Research, Max Planck Institute of Psychiatry, Max Planck Society;
Dept. Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Max Planck Society;

Heel,  Sarah
Max Planck Institute of Psychiatry, Max Planck Society;

Lechner,  Katharina
Max Planck Institute of Psychiatry, Max Planck Society;

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Uhr,  Manfred
Max Planck Institute of Psychiatry, Max Planck Society;
Dept. Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Max Planck Society;
Dept. Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Max Planck Society;
Clinical Research, Max Planck Institute of Psychiatry, Max Planck Society;

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Dose,  Tatjana
Max Planck Institute of Psychiatry, Max Planck Society;

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Schaaf,  Ludwig
RG Günter Stalla, Clinical Neuroendocrinology, Dept. Clinical Research, Max Planck Institute of Psychiatry, Max Planck Society;
Max Planck Institute of Psychiatry, Max Planck Society;

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Holsboer,  Florian
Clinical Research, Max Planck Institute of Psychiatry, Max Planck Society;
Max Planck Institute of Psychiatry, Max Planck Society;
Emeritiertes wissenschaftliches Mitglied, Max Planck Institute of Psychiatry, Max Planck Society;

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Lucae,  Susanne
RG Susanne Lucae, Psychiatric Pharmacogenetics, Dept. Clinical Research, Max Planck Institute of Psychiatry, Max Planck Society;

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Fulda,  Stephany
Max Planck Institute of Psychiatry, Max Planck Society;

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Kloiber,  Stefan
RG Susanne Lucae, Psychiatric Pharmacogenetics, Dept. Clinical Research, Max Planck Institute of Psychiatry, Max Planck Society;
Clinical Research, Max Planck Institute of Psychiatry, Max Planck Society;

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Citation

Hennings, J. M., Heel, S., Lechner, K., Uhr, M., Dose, T., Schaaf, L., et al. (2019). Effect of mirtazapine on metabolism and energy substrate partitioning in healthy men. JCI Insight, 4(1): e123786. doi:10.1172/jci.insight.123786.


Cite as: https://hdl.handle.net/21.11116/0000-0006-084A-F
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.