Drug & supplement interaction

Melatonin + Tiagabine

Tiagabine brand name: Gabitril.

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

Tiagabine falls into 4 drug categories that Melatonin can interact with; the most serious is rated moderate. Theoretically, taking melatonin might increase the sedative effects of CNS depressants.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions4
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Melatonin and Tiagabine

These two interact in 4 distinct ways. Each one is explained separately below.

Why Are There 4 Interactions?

Melatonin interacts with whole categories of medication. Tiagabine falls into 4 of those categories, so it can interact with Melatonin in 4 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

CNS DEPRESSANTS

1 of 4

Why this applies to Tiagabine

Tiagabine falls under CNS DEPRESSANTS — the group Melatonin interacts with.

Theoretically, taking melatonin might increase the sedative effects of CNS depressants.
Melatonin has sedative effects. Theoretically, concomitant use of melatonin with alcohol, benzodiazepines, or other sedative drugs might cause additive sedation.
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

Here's the gist with melatonin and tiagabine (Gabitril): this isn't a chemical clash where one changes how the other is broken down. Instead, it's an overlap in effect. Tiagabine already works by calming overactive brain signals, and it commonly causes drowsiness, dizziness, trouble concentrating, and that foggy or slowed-down feeling. Melatonin sends its own "time to wind down" signal, so stacking the two could leave you more sedated than you'd expect.

I want to be honest about the strength here: this concern is theoretical, based on how each works, not on strong studies showing harm. For many people it's a non-issue, but it's worth a quick chat with your pharmacist or doctor, especially before driving or if you already feel sleepy on tiagabine. Don't change either one on your own.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Foster BC, Cvijovic K, Boon HS, et al. Melatonin Interaction Resulting in Severe Sedation. J Pharm Pharm Sci 2015;18(2):124-31. PubMed
Moderate

SEIZURE THRESHOLD LOWERING DRUGS

2 of 4

Tiagabine also falls under SEIZURE THRESHOLD LOWERING DRUGS.

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

Here's the situation with these two. You take tiagabine (Gabitril) to help prevent partial seizures, and the concern is that melatonin might work against that goal. This isn't about melatonin changing how your body breaks down tiagabine. Instead, some evidence suggests melatonin itself may lower the seizure threshold in certain people, meaning seizures could become a little easier to trigger.

I'll be honest that this is mostly theoretical, based on how melatonin behaves, with some reports of more frequent seizures, especially in children with neurological conditions. For many adults it may be fine, but since your medication's whole job is seizure control, please run it by your pharmacist or doctor first rather than starting it on your own.

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
Moderate

ANTICONVULSANTS

3 of 4

Tiagabine also falls under ANTICONVULSANTS.

Theoretically, melatonin may reduce the effects of anticonvulsants. Some clinical research suggests that melatonin may increase the frequency of seizures in certain patients, particularly children with neurological impairment.
Severity Moderate Likelihood Possible Evidence B

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

Here's the practical concern with pairing melatonin and tiagabine (Gabitril). Tiagabine isn't a prodrug, so it doesn't need to be switched on by your body to work. The worry here isn't about melatonin changing how tiagabine is broken down. Instead, some clinical research suggests melatonin itself may slightly lower the seizure threshold in certain people, meaning it could make seizures a little easier to trigger. That could work against what tiagabine is doing for you.

This signal showed up mostly in children with neurological conditions, and part of the concern is theoretical, so it doesn't mean melatonin will cause problems for everyone. Still, because tiagabine is a seizure medicine, I'd want you to loop in your pharmacist or neurologist before adding melatonin, rather than starting it on your own.

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
Minor

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

4 of 4

Tiagabine also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.

Theoretically, melatonin might increase levels of drugs metabolized by CYP3A4.
Laboratory research shows that certain lots of melatonin inhibit CYP3A4. Theoretically, combined administration of melatonin with certain drugs metabolized by CYP3A4 may reduce the metabolism of these drugs, resulting in increased serum levels. Until more is known, use melatonin cautiously in patients taking drugs metabolized by these enzymes.
Severity Minor 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

Here's the short version: your liver uses an enzyme called CYP3A4 to break down tiagabine (Gabitril). Some lab studies hint that certain batches of melatonin can slow that same enzyme down. If that happened in the body, tiagabine could clear a little more slowly and its levels might creep up, which could mean more of its usual side effects, things like drowsiness, dizziness, trouble concentrating, or feeling shaky.

The reassuring part is that this connection is only theoretical, drawn from test-tube and animal work, not from real patients. It's rated minor. Still, since tiagabine already affects alertness, the two together could leave you extra sleepy. Before adding melatonin, just run it by your pharmacist or doctor so they can keep an eye on how you feel.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Foster BC, Cvijovic K, Boon HS, et al. Melatonin Interaction Resulting in Severe Sedation. J Pharm Pharm Sci 2015;18(2):124-31. 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 1,115 moderate, 345 minor known drug interactions in our database — the Tiagabine one above is among them. If you take anything else, check it against the full list below.

Moderate 1,115 Minor 345 No known interaction 1,370 (incl. Tiagabine)
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 Tiagabine

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 Tiagabine, 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 Tiagabine

This page covers Melatonin only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Tiagabine page lists 214 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: 1,4-butanediol (major), Activated Charcoal (major), Beer (major), Gamma-hydroxybutyrate (ghb) (major) and Grapefruit (major).

By severity: 9 major · 157 moderate · 48 minor.

From our pharmacist’s overview on the Tiagabine page

“Anyone taking tiagabine (Gabitril) for seizures should treat its supplement interactions with real vigilance. The drug is cleared by the liver enzyme CYP3A4, so grapefruit can push its blood level up while St.”

Reviewed by 2 · Jul 18, 2026

Open the Tiagabine 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 Tiagabine 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 Tiagabine 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%

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

29 days ago today
Medication Tiagabine
Steady interest

#1,753 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 Tiagabine

What Is Tiagabine Used For?

Brand name: Gabitril

Tiagabine hydrochloride tablets are approved as add-on (adjunctive) therapy for partial seizures in adults and adolescents aged 12 and older. It is not used alone — it is always added to an existing seizure medication regimen.

Both the film-coated and standard tablet forms of tiagabine hydrochloride carry this same indication. The safety and effectiveness of tiagabine have not been established for any other condition.

See full Tiagabine 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
1,115Moderate
345Minor
1,369No known interaction
1,115 Moderate 345 Minor 1,369 No interaction
Moderate

1,115 interactions

Showing 60 of 1,115 moderate interactions — see all 1,115 on the Melatonin page.

Minor

345 interactions

Showing 60 of 345 minor interactions — see all 345 on the Melatonin page.

No interaction 1,369 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 1,369 medications checked with no known interaction — see the full Melatonin list.

See the full Melatonin interactions page
See every supplement checked against Tiagabine, 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 Tiagabine supplement interactions › Every supplement checked against Tiagabine, ranked by severity Tiagabine 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 Tiagabine Together: Common Questions

Can you take Melatonin with Tiagabine?
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.
Why are there 4 interactions listed for Melatonin and Tiagabine?
Tiagabine belongs to more than one drug category, and Melatonin interacts with each of those categories a little differently. We list every one so nothing is missed — your overall risk is driven by the most serious of them.
How serious is the Melatonin and Tiagabine 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 Tiagabine 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.