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

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.

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 Creators:
Hennings, Johannes M.1, 2, Author           
Heel, Sarah3, Author
Lechner, Katharina3, Author
Uhr, Manfred2, 3, 4, 5, Author           
Dose, Tatjana3, Author           
Schaaf, Ludwig3, 6, Author           
Holsboer, Florian3, 5, 7, Author           
Lucae, Susanne1, Author           
Fulda, Stephany3, Author           
Kloiber, Stefan1, 5, Author           
Affiliations:
1RG Susanne Lucae, Psychiatric Pharmacogenetics, Dept. Clinical Research, Max Planck Institute of Psychiatry, Max Planck Society, ou_2040299              
2Dept. Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Max Planck Society, ou_2035295              
3Max Planck Institute of Psychiatry, Max Planck Society, ou_1607137              
4Dept. Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Max Planck Society, ou_2035294              
5Clinical Research, Max Planck Institute of Psychiatry, Max Planck Society, ou_2035296              
6RG Günter Stalla, Clinical Neuroendocrinology, Dept. Clinical Research, Max Planck Institute of Psychiatry, Max Planck Society, ou_2040301              
7Emeritiertes wissenschaftliches Mitglied, Max Planck Institute of Psychiatry, Max Planck Society, ou_2074301              

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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.

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Language(s): eng - English
 Dates: 2019-01-10
 Publication Status: Published online
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Title: JCI Insight
Source Genre: Journal
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Publ. Info: Ann Arbor : American Society for Clinical Investigation (ASCI)
Pages: - Volume / Issue: 4 (1) Sequence Number: e123786 Start / End Page: - Identifier: ISSN: 2379-3708
CoNE: https://pure.mpg.de/cone/journals/resource/2379-3708