Fluvoxamine but not citalopram increases serum melatonin in healthy subjects-- an indication that cytochrome P450 CYP1A2 and CYP2C19 hydroxylate melatonin.
Level 2 - randomized trial
Randomized crossover trial in human subjects
PubMed 10877005 · doi:10.1007/s002280050729
What was done
Seven healthy subjects participated in three experimental sessions conducted in random order, separated by 6 to 8 days: placebo, 40 mg citalopram, and 50 mg fluvoxamine. All treatments were administered orally at 16:00. Serum melatonin concentrations were measured at regular intervals over 20 hours (16:00 to 12:00 the following day), and 20-hour melatonin area under the curve (MT-AUC(0-20)) was compared across conditions. Plasma drug levels and urinary melatonin excretion were also monitored.
What was found
Fluvoxamine increased serum MT-AUC(0-20) by a factor of 2.8 compared to placebo (P < 0.01) and increased urinary melatonin excretion, showing a clear relationship between serum melatonin and plasma fluvoxamine levels. In contrast, citalopram had no significant effect on serum melatonin AUC or urinary melatonin excretion.
Why it matters
This trial shows that fluvoxamine substantially increases circulating endogenous melatonin concentrations, likely through CYP1A2 or CYP2C19 inhibition, whereas citalopram does not share this metabolic interaction.
Limits
The study had a very small sample size of seven healthy participants, evaluated only acute single-dose administration, and did not assess clinical sleep outcomes or directly verify specific enzyme inhibition pathways.
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