Section 10 · Monograph

Melatonin

Reviewed Nov 2026FDA label

OTC, generic onlyHormone supplement

Indications

REGULATORY NOTE: Melatonin is regulated in the United States as a dietary supplement under DSHEA (1994), NOT as an FDA-approved drug. There is no official FDA prescribing information; potency, purity, and labeling accuracy are not verified by the FDA prior to marketing.FDA-labeled
Commonly used (per NIH/NCCIH consumer guidance) for short-term management of jet lag.FDA-labeled
Used for delayed sleep-wake phase disorder, one of the better-evidenced uses.FDA-labeled
Used for non-24-hour sleep-wake disorder in blind individuals without light perception.FDA-labeled
Commonly self-administered for general sleep-onset difficulty/insomnia, though evidence for chronic insomnia is limited.FDA-labeled

General/chronic adult insomnia — widely used OTC, but major clinical practice guidelines recommend against routine use for chronic insomnia, citing insufficient evidence.Off-label
Pediatric insomnia associated with neurodevelopmental disorders (ADHD, autism spectrum disorder) — common pediatric off-label/complementary use.Off-label
Shift-work-related sleep disturbance.Off-label
Perioperative anxiolysis (adjunctive, investigational).Off-label

Melatonin (N-acetyl-5-methoxytryptamine) is an endogenous hormone synthesized in the pineal gland from tryptophan via serotonin, with secretion driven by the suprachiasmatic nucleus (SCN) in response to darkness and suppressed by light.
Exerts sleep-promoting and chronobiotic effects primarily via agonism at MT1 and MT2 receptors in the SCN, reducing SCN-mediated wake-promoting signals and helping entrain/shift the circadian clock.
Timing relative to endogenous circadian phase determines whether exogenous melatonin produces a phase advance (evening dosing) or phase delay (morning dosing) — the basis for its distinct uses in jet lag vs. delayed sleep phase disorder.

No FDA-established or standardized dosing exists. Studies have used doses ranging from about 0.1 mg to 10 mg, most commonly 0.5-5 mg, taken up to 1-2 hours before desired bedtime.
Jet lag: commonly 0.5-5 mg near target bedtime at destination, started day of travel or shortly before, for several days after arrival.
Delayed sleep-wake phase disorder: low doses (~0.5-3 mg) timed several hours before habitual sleep onset (earlier than bedtime) to shift circadian phase.
Non-24-hour sleep-wake disorder (blind adults without light perception): typically dosed about 1 hour before preferred bedtime or at a fixed clock time.
Extended/prolonged-release formulations more closely mimic endogenous overnight secretion pattern.
Because it is an unregulated supplement, actual content of OTC products (including gummies) frequently does not match the labeled dose — counsel patients toward USP-verified or third-party-tested products.

Pediatric use: substantially lower doses typically used (e.g., 0.5-3 mg), individualized; long-term safety data in children are limited.

No formal FDA-recognized contraindications exist because melatonin is not an FDA-regulated drug.
NIH/NCCIH advise against use in pregnancy and breastfeeding due to insufficient safety data.
Caution in autoimmune disease given melatonin's immunomodulatory activity.
Caution in patients with seizure disorders and in hepatic or renal impairment (reduced clearance, prolonged effect).

CYP1A2 inhibitors (e.g., fluvoxamine) — can markedly increase melatonin exposure.
Sedative-hypnotics, benzodiazepines, alcohol — additive CNS depression.
Anticoagulants/antiplatelets — theoretical additive bleeding risk.
Immunosuppressants — theoretical antagonism of therapeutic effect; caution in transplant recipients and autoimmune disease.
Antidiabetic agents — may affect glucose tolerance; monitor glucose in diabetic patients.
Hormonal contraceptives — may inhibit melatonin metabolism (CYP1A2), increasing levels.
Caffeine — may reduce melatonin's sleep-promoting effect.

Generally well tolerated short-term. Most common: next-day drowsiness/grogginess, headache, dizziness, nausea.
Children: daytime sleepiness, enuresis/bedwetting, headache, dizziness, agitation.
Uncommon: mood changes/irritability, vivid dreams, mild hypothermia, transient impaired glucose tolerance.
Rare allergic reactions including angioedema.
Long-term safety (especially chronic pediatric use) has not been well established.
Product-quality concern: studies have found substantial mislabeling of OTC melatonin products (actual content 74%-347% of labeled amount in one analysis; some products contained unlisted serotonin). Unsupervised pediatric ingestion (often flavored gummies) is a growing cause of ED visits.

No routine laboratory monitoring required.
Assess for next-day sedation/grogginess and effect on daytime function, especially in older adults and before driving.
Monitor blood glucose trends in diabetic patients.
Counsel on product variability/quality given lack of FDA regulation.
Reassess ongoing need/benefit periodically.

NIH/NCCIH advise pregnant and breastfeeding women to avoid melatonin supplementation due to insufficient evidence of safety in these populations.