Drug & supplement interaction

Melatonin + Doxylamine Succinate

Doxylamine Succinate brand name: Unisom.

Moderate Interaction
Medically reviewed by · Updated October 2026
The bottom line Moderate

Melatonin has a moderate interaction with Doxylamine Succinate. Theoretically, taking melatonin with drugs that lower the seizure threshold might increase the risk of seizure activity.

Read the full interaction report
SeverityModerate
LikelihoodPossible
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Melatonin and Doxylamine Succinate

Here is the interaction we found between these two, with the evidence behind it.

Moderate

SEIZURE THRESHOLD LOWERING DRUGS

Why this applies to Doxylamine Succinate

Doxylamine Succinate falls under SEIZURE THRESHOLD LOWERING DRUGS — the group Melatonin interacts with.

Theoretically, taking melatonin with drugs that lower the seizure threshold might increase the risk of seizure activity.
Some clinical evidence suggests that melatonin may increase the frequency of seizures in certain patients, particularly children with neurological disabilities.
Severity Moderate Likelihood Possible Evidence D

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Both melatonin and doxylamine (the sleep aid in Unisom) can, in theory, nudge your brain's seizure threshold a little lower. That just means it could become slightly easier for a seizure to happen. Honestly, for most healthy adults who use these occasionally for sleep, this is a very mild, mostly theoretical concern. The clearest signal comes from a specific group: children with neurological conditions, where melatonin has sometimes been linked to more frequent seizures.

So if you or a family member has epilepsy or any seizure history, it is worth a quick chat with your pharmacist or doctor before combining them. Also keep in mind that stacking two sedating products can leave you extra drowsy, groggy, or foggy the next morning. Don't start or stop anything on your own, just ask first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Sheldon SH. Pro-convulsant effects of oral melatonin in neurologically disabled children. Lancet 1998;351:1254. PubMed
  2. Stewart LS. Endogenous melatonin and epileptogenesis: facts and hypothesis. Int J Neurosci 2001;107:77-85.. PubMed

What These Ratings Mean

Every interaction above is graded three ways — here’s the key to each label.

Severity how clinically significant the interaction is
Major

Clinically significant. Avoid the combination, or use only under close professional supervision.

Moderate

Usually worth avoiding or managing — may need monitoring, a dose change, or timing apart.

Minor

Generally not serious. Be aware of it and mention it to your pharmacist.

Likelihood how strong the evidence is that the interaction actually happens in people
  • LikelyWell-controlled human studies have demonstrated the likely existence of this interaction.
  • ProbableInteraction has not been documented in well-controlled studies, however, the interaction has been demonstrated in some small human studies or in controlled animal studies in conjunction with multiple case reports.
  • PossibleInteraction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.
  • UnlikelyInteraction has been demonstrated in animal or in lab research but has been shown not to occur in humans.
Evidence the quality of the studies behind the rating (graded A–D)
  • AHigh-quality meta-analysis (quantitative systematic review).
  • BCase-control study.
  • CConsensus.
  • DAnecdotal evidence.

These ratings are for information only. Never start, stop, or otherwise change your therapy before speaking with your provider.

Keep it in perspective

Melatonin Also Interacts With Other Medications

Melatonin has 1,116 moderate, 346 minor known drug interactions in our database — the Doxylamine Succinate one above is one of them. If you take anything else, check it against the full list below.

Moderate 1,116 Minor 346 No known interaction 1,368 (incl. Doxylamine Succinate)
Taking anything else?

Check Another of Your Medications Against Melatonin

Covers the 2,830 medications we’ve checked against Melatonin. Pick one to open its full report.

From our Q&A

Questions About Melatonin or Doxylamine Succinate

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Melatonin or Doxylamine Succinate, not necessarily both, but if one is close to what you were about to ask it will usually go further than a database entry can:

Not quite your question? Ask our pharmacists directly — it is free, there is no account required, and answers usually come back within 24 hours.

Everything else you take

See Every Supplement That Interacts With Doxylamine Succinate

This page covers Melatonin only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Doxylamine Succinate page lists 52 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Henbane (major), Scopolia (major), Angel's Trumpet (moderate) and Bacopa (moderate).

By severity: 3 major · 38 moderate · 11 minor.

From our pharmacist’s overview on the Doxylamine Succinate page

“Someone reaching for doxylamine succinate (Unisom) to fall asleep is often the same person browsing the supplement aisle, and that pairing deserves genuine care here. Doxylamine is a strongly anticholinergic antihistamine, meaning it dries you out, fogs thinking, and slows digestion, and 30 of the 52 flagged ingredients pile more of th…”

Reviewed by 2 · Jul 18, 2026

Open the Doxylamine Succinate interaction page

One more smart check

Taking Melatonin as Part of a Dietary Supplement Product? Check It for Interactions

We hold 2,885 real supplement products containing Melatonin, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Melatonin. Your product may carry other ingredients that interact with Doxylamine Succinate too, on top of Melatonin — and those would not show on this page. Find your product and we’ll check every ingredient on its label:

How much people look this up

Where Melatonin and Doxylamine Succinate Sit Against Everything Else

Out of every supplement and medication people look up on HelloPharmacist, here is where these two land this week — and which way each has been moving.

Supplement Melatonin
Top 5%

#58 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Doxylamine Succinate
Steady interest

#1,742 of 2,830 medications looked up here in the last 7 days

29 days ago today

Position among everything looked up on this site, not a measure of how commonly either one is used or how important it is. A supplement can climb this list because of a news story. It counts every request to the page, automated ones included, and nothing here identifies anyone.

Supplement

About Melatonin

What is Melatonin?

Melatonin
  • Trouble falling asleep (insomnia)
  • Jet lag
  • Delayed sleep phase syndrome
  • Non-24-hour sleep-wake disorder
  • Shift-work sleep problems
  • Sleep problems in some children with conditions like autism or ADHD

Melatonin is a hormone your body makes naturally to help control your sleep-wake cycle, and the supplement form is widely used to help with sleep timing problems and jet lag. The evidence is strongest for certain circadian (body-clock) disorders and is more mixed for everyday insomnia. It is generally well tolerated for short-term use, but talk with your pharmacist or doctor before starting, especially for children or during pregnancy.

Read the full Melatonin monograph & all interactions
Medication

About Diphenhydramine

What Is Diphenhydramine Used For?

Brand name: Unisom

Most oral diphenhydramine products temporarily relieve symptoms of hay fever and other upper respiratory allergies: runny nose, sneezing, itchy and watery eyes, and an itchy nose or throat. They also temporarily relieve runny nose and sneezing from the common cold.

After Bite Xtra is a topical gel. It is used for temporary relief of pain and itching from minor burns, minor cuts or scrapes, insect bites, minor skin irritations, and rashes from poison ivy, poison oak and poison sumac.

See full Diphenhydramine drug information
Keep checking

Other Drugs & Melatonin

Browse every other medication we’ve checked against Melatonin — both the ones with a known interaction and the ones without. Select any drug for the full detail.

0Major
1,116Moderate
346Minor
1,367No known interaction
1,116 Moderate 346 Minor 1,367 No interaction
Moderate

1,116 interactions

Showing 60 of 1,116 moderate interactions — see all 1,116 on the Melatonin page.

Minor

346 interactions

Showing 60 of 346 minor interactions — see all 346 on the Melatonin page.

No interaction 1,367 drugs checked — show the list

We also checked Melatonin against these medications and found no known interaction in our sources. Open any page to confirm.

Showing the 60 most looked-up of 1,367 medications checked with no known interaction — see the full Melatonin list.

See the full Melatonin interactions page
See every supplement checked against Doxylamine Succinate, ranked by severity
Sources

Sources & How We Checked

Interaction details are evidence-graded and sourced from the Natural Medicines database. The medication overview comes from MedlinePlus.

Content is written and reviewed by licensed HelloPharmacist pharmacists. See our data sources and editorial standards for how this information is built and checked.

Parts of this content are provided by the Therapeutic Research Center, LLC.

DISCLAIMER: Currently this does not check for drug-drug interactions. This is not an all-inclusive comprehensive list of potential interactions and is for informational purposes only. Not all interactions are known or well-reported in the scientific literature, and new interactions are continually being reported. Input is needed from a qualified healthcare provider including a pharmacist before starting any therapy. Application of clinical judgment is necessary.

© 2021 Therapeutic Research Center, LLC

Keep exploring
Melatonin monograph › Uses, safety, and every drug interaction in one place Doxylamine Succinate supplement interactions › Every supplement checked against Doxylamine Succinate, ranked by severity Diphenhydramine drug information › The full plain-English guide to this medication Supplement interaction checker › Check any supplement or product against your medications Browse medications A–Z › Every drug we've checked against herbs & supplements Ask a pharmacist › Free, personal answer from our licensed team
Pharmacist Counseling Corner

Taking Melatonin and Doxylamine Succinate Together: Common Questions

Can you take Melatonin with Doxylamine Succinate?
There is a moderate interaction, so it may be acceptable with monitoring or timing changes — but check with your pharmacist first. Read the full details on this page and confirm with your pharmacist before combining them.
How serious is the Melatonin and Doxylamine Succinate interaction?
We rate it Moderate. This combination may require monitoring, a dose adjustment, or separating the times you take each one. Consult your pharmacist before using them together.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

Still Have a Question About Doxylamine Succinate and Melatonin?

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This information is for education only and is not a substitute for professional medical advice. Always check with your pharmacist or doctor before starting, stopping, or combining supplements and medications.