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Melatonin

Class

Endogenous neurohormone, melatonin receptor agonist

Mechanism

Activation of MT1 and MT2 melatonin receptors in the suprachiasmatic nucleus of the hypothalamus, which regulates circadian rhythms and promotes sleep onset and maintenance.

FDA-Approved Use

None

Off-Label Use

Insomnia

Formulation

Various formulations: immediate-release oral tablets, controlled-release oral tablets, sublingual, and topical

Titration

2–10 mg taken nightly, typically 1–2 hours before bedtime.

Dose Range

2–10 mg/day

Kinetics

Hepatic metabolism (CYP1A2); reached peak plasma concentrations ~ 30-60 minutes (dependent on formulation)

Common AEs

Daytime sleepiness, headache, dizziness, fatigue

Serious/Rare AEs

None reported

Monitoring

None

Black Box Warning

None

Considerations

Melatonin is most effective for sleep disturbances related to circadian rhythm disruptions rather than general insomnia. Its benefits can vary in conditions like dementia, Parkinson’s disease (PD), traumatic brain injury (TBI), and neurodevelopmental conditions, where sleep problems often have complex causes. Because melatonin is sold as a supplement, product quality and dosing can be inconsistent, so using trusted brands is important. Monitor older adults closely for increased daytime drowsiness or interactions with other medications.