Melatonin and Fluvoxamine: A Drug Interaction Worth Knowing
Most people who take melatonin for sleep don't think much about what else is in their medicine cabinet. For the most part, that's a reasonable default — melatonin's interaction profile is limited. The exception worth knowing is fluvoxamine (Luvox), an SSRI used primarily for OCD and sometimes depression. The combination doesn't cause serotonin syndrome or anything acutely dangerous. What it does is push melatonin blood levels dramatically higher than the dose taken would suggest — enough that the usual reasoning about low-dose melatonin being harmless no longer applies.
The mechanism is metabolic. Melatonin is broken down primarily by cytochrome P450 1A2 (CYP1A2), a liver enzyme. Fluvoxamine is a potent inhibitor of CYP1A2 — not a mild one. A pharmacokinetic study cited in the NIH ODS melatonin fact sheet found that co-administration of fluvoxamine increased melatonin's area under the curve by approximately 17-fold. To make that concrete: 1 mg of melatonin taken while on fluvoxamine may produce systemic melatonin exposure equivalent to roughly 17 mg — well above what most researchers consider necessary or beneficial for sleep onset.
High melatonin levels from this combination are not well-characterized in terms of harm, but the dose becomes unpredictable in a way that matters. Melatonin at very high exposures is associated with next-day grogginess, prolonged sedation, and potential disruption to the circadian signaling the supplement is supposed to support. The concern is less about a specific acute risk and more that you're no longer taking the dose you think you are.
Other SSRIs don't have the same effect. Fluoxetine and sertraline primarily inhibit CYP2D6 and have little meaningful effect on CYP1A2. Fluvoxamine is unusual among antidepressants in its strong CYP1A2 inhibition — the same property also raises caffeine levels significantly (caffeine is another CYP1A2 substrate) and affects theophylline. Paroxetine and citalopram are similarly spared.
If you're on fluvoxamine and want to use melatonin, the relevant guidance is to use the lowest possible dose and to raise it with your prescriber — not because there's a dramatic risk to disclose, but because they should know the combination is in play and can advise on whether any dose adjustment makes sense. The NIH ODS melatonin fact sheet documents this interaction explicitly and is worth reading if you want the primary source.