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Fluvoxamine Strongly Inhibits Melatonin Metabolism in a Patient With Low-Amplitude Melatonin Profile

Michael Grözinger, MD; Sebastian Härtter, PhD; Ximing Wang, MD; Joachim Röschke, MD, PhD; Christoph Hiemke, PhD; Dirk-Matthias Rose, MD
Arch Gen Psychiatry. 2000;57(8):812-813. doi:10.1001/archpsyc.57.8.812.
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Fluvoxamine maleate increases early morning concentrations of melatonin in humans.1,2 The serotonin reuptake inhibitor was therefore assumed to enhance the melatonin production by providing a precursor surplus of serotonin. Alternatively, fluvoxamine might inhibit the melatonin metabolism. The following case report strongly supports the second hypothesis.

A 51-year-old female patient with a family history of sleeplessness suffered from chronic primary insomnia, which had proved resistant to various therapies. Nocturnal serum profiles of melatonin were studied in the condition without drugs, under separate administration of fluvoxamine and melatonin, and under the combined treatment. For the measurements, the patient remained in darkness all night and did not use any substances interfering with the secretion or metabolism of melatonin. Cortisol (Becton Dickinson, Heidelberg, Germany) and melatonin concentrations (anti–rabbit antibodies; Stockgrand Ltd, Guildford, England, and melatonin tracer labeled with iodine 125; Nen Life Sciences Products, Brussels, Belgium) (sensitivity, 2 pg/mL; maximal interassay coefficient of variation, 16.3% in low controls) were determined by radioimmunoassay. No cross-reactivity with fluvoxamine was revealed. Fluvoxamine was measured by automated high-performance liquid chromatography.3

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The nocturnal serum concentrations of melatonin when the patients was unmedicated (A), and when she was given fluvoxamine only (B), melatonin only (C), and both melatonin and fluvoxamine (D).

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