Both cause sedation - enhanced drowsiness
Benadryl (diphenhydramine) is an anticholinergic sedative. Combined with melatonin, may cause excessive drowsiness, next-day grogginess, cognitive impairment.
Choose one or the other. If combining, use minimal doses.
Be aware of enhanced sedation; don't drive
Both cause sedation - enhanced drowsiness. Choose one or the other. If combining, use minimal doses.
Be aware of enhanced sedation; don't drive
This interaction is rated “Caution” by Formulate. Benadryl (diphenhydramine) is an anticholinergic sedative. Combined with melatonin, may cause excessive drowsiness, next-day grogginess, cognitive impairment.
Studies from our registry that mention diphenhydramine or melatonin. Each links to the primary source and the other Formulate pages citing it.
Mentions melatonin · 2013
Meta-analysis: melatonin for the treatment of primary sleep disorders
Ferracioli-Oda E, Qawasmi A, Bloch MH · PLOS ONE
Meta-analysis of 19 RCTs (n=1,683) found melatonin reduced sleep-onset latency by ~7 minutes, increased total sleep time by ~8 minutes, and improved overall sleep quality — small but consistent effect across populations.
Mentions melatonin · 2012
The effect of magnesium supplementation on primary insomnia in elderly: a double-blind placebo-controlled clinical trial
Abbasi B, Kimiagar M, Sadeghniiat K, et al. · Journal of Research in Medical Sciences
8-week RCT in elderly with insomnia: 500mg/day magnesium significantly improved subjective insomnia score, sleep efficiency, sleep onset latency, and serum melatonin concentration.
Mentions melatonin · 2007
Efficacy of prolonged release melatonin in insomnia patients aged 55–80 years: quality of sleep and next-day alertness outcomes
Wade AG, Ford I, Crawford G, et al. · Current Medical Research and Opinion
3-week RCT in older insomnia patients (n=354) found prolonged-release melatonin 2mg improved sleep quality and morning alertness, supporting lower doses (1–3mg) over the often-oversold 5–10mg.
Other interactions to know
Melatonin may affect blood clotting
Melatonin may enhance SSRI side effects
Complementary sleep support
Check your full stack in the free interaction checker.
The free checker lets you add any combination of supplements and medications at once. The free web app goes further — every stack change surfaces interaction alerts automatically.
Medical disclaimer. This page is for educational purposes only and does not replace advice from a qualified healthcare provider.
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