Diphenhydramine Interactions

Both diphenhydramine and melatonin cause sedation through different mechanisms (H1 antagonism and MT1/MT2 agonism). Combined use produces additive CNS depression, next-day drowsiness, impaired cognition, and increased fall risk, especially in older adults.

Diphenhydramine (a sedating antihistamine) and valerian root both produce CNS depression through GABAergic and histaminergic pathways. Used together, sedation, psychomotor impairment, and respiratory depression risks are additive.