NutriStack
Hydroxyzine and Melatonin, a caution.
Melatonin can add to hydroxyzine's sedating effects, especially when hydroxyzine is used at night for itching, anxiety, or sleep. Hydroxyzine can impair cognition after morning dosing and can leave residual impairment after evening dosing, while melatonin can increase sleepiness and affect performance in some settings. The combined effect can matter for older adults and people who need to drive early the next day.
One pair, every claim cited. The two substances, the type, the mechanism, the recommendation, and the primary literature.
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At a glance
- Substances
- Hydroxyzine and Melatonin
- Pair type
- Caution
- Evidence (highest tier)
- Emerging
- Source citations
- 2 sources
- Stack Score effect
- −5 to your Stack Score (per scored caution row).
- Scope
- Supplement × Prescription
- Last verified
- May 30, 2026
Caution · Emerging evidence
Caution
What is happening. Melatonin can add to hydroxyzine's sedating effects, especially when hydroxyzine is used at night for itching, anxiety, or sleep. Hydroxyzine can impair cognition after morning dosing and can leave residual impairment after evening dosing, while melatonin can increase sleepiness and affect performance in some settings. The combined effect can matter for older adults and people who need to drive early the next day.
Mechanism. Hydroxyzine reduces wakefulness through central H1 receptor blockade. Melatonin promotes sleepiness through MT1/MT2 receptor signaling and circadian phase effects, so the combination can deepen sedation without a predictable timing workaround.
Recommendation. Avoid routine use of melatonin on top of hydroxyzine unless your prescriber agrees. If combined, use the lowest effective melatonin dose and avoid alcohol or other sedatives. Do not drive the next morning if you feel groggy, slowed, or unsteady.
Sources (2)
- Nave R, Iani C, Herer P, Gopher D, Lavie P. Residual effects of daytime administration of melatonin on performance relevant to flight. Behav Brain Res. 2002;131(1-2):87-95. PMID 11844575
- Conen S, Theunissen EL, Vermeeren A, Ramaekers JG. Short-term effects of morning versus evening dose of hydroxyzine 50 mg on cognition in healthy volunteers. J Clin Psychopharmacol. 2011;31(3):294-301. PMID 21508863
Stack Score
How this pair moves the number.
Effect on the composite score
If both Hydroxyzine and Melatonin are in the same stack, this pair applies −5 to your Stack Score (per scored caution row).
The full algorithm, the clamping rules, and four worked stacks are documented at /methodology/stack-score.
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