Interaction databaseSupplement × PrescriptionReviewed May 2026

Clonazepam and Melatonin, a caution.

Both promote sleep through different mechanisms. Combined sedation may cause excessive drowsiness. However, melatonin may help facilitate benzodiazepine tapering.

One pair, every claim cited. The two substances, the type, the mechanism, the recommendation, and the primary literature.
Same shape as the other 1,729 pairs in the public database.

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At a glance

Substances
Clonazepam and Melatonin
Pair type
Caution
Evidence (highest tier)
Moderate
Source citations
4 sources
Stack Score effect
−5 to your Stack Score (per scored caution row).
Scope
Supplement × Prescription
Last verified
May 30, 2026

Caution · Moderate evidence

Caution

What is happening. Both promote sleep through different mechanisms. Combined sedation may cause excessive drowsiness. However, melatonin may help facilitate benzodiazepine tapering.

Mechanism. Clonazepam enhances GABAergic inhibition. Melatonin acts on MT1/MT2 receptors. Different sedative mechanisms are additive.

Recommendation. Low-dose melatonin (0.5-1mg) may be cautiously used. Some clinicians use melatonin to facilitate benzo tapering under supervision.

Sources (4)
  1. Baandrup L et al. Prolonged-release melatonin versus placebo for benzodiazepine discontinuation. Psychopharmacology. 2016;233(17):3251-3259. PMID 27435171
  2. Fatemeh G, Sajjad M, Niloufar R et al.. Effect of melatonin supplementation on sleep quality: a systematic review and meta-analysis of randomized controlled trials.. Journal of Neurology. 2022. PMID 33417003
  3. Tang BHY, Manalo J, Chowdhury SR et al.. Melatonin Use in the ICU: A Systematic Review and Meta-Analysis.. Critical Care Medicine. 2025. PMID 40662882
  4. Chan V, Lo K. Efficacy of dietary supplements on improving sleep quality: a systematic review and meta-analysis.. Postgraduate Medical Journal. 2022. PMID 33441476

Stack Score

How this pair moves the number.

Effect on the composite score

If both Clonazepam 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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