Drug & supplement interaction

Tianeptine + Primidone

Primidone brand name: Mysoline.

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

Tianeptine has a moderate interaction with Primidone. Tianeptine has sedative effects; high doses may have additive effects with other CNS depressants.

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

Tianeptine and Primidone

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

Moderate

CNS DEPRESSANTS

Why this applies to Primidone

Primidone falls under CNS DEPRESSANTS — the group Tianeptine interacts with.

Tianeptine has sedative effects; high doses may have additive effects with other CNS depressants.
Higher doses of tianeptine have opioid like effects and may have additive effects with other sedative drugs. In one case report, a 42-year-old male presented with respiratory depression and aspiration pneumonia due to concomitant use of high-dose tianeptine and alprazolam.
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 simple version: both of these can slow down your central nervous system. Primidone itself is a sedating seizure medicine (and your body even converts part of it into phenobarbital, a barbiturate), so it already makes many people drowsy. Tianeptine, especially at the high doses found in those over-the-counter or 'gas station' products, can act like an opioid. Stack the two together and the sleepiness, slowed breathing, confusion, and dizziness can pile up.

This concern is based mostly on how these drugs work, not on lots of hard data, so I won't overstate it. But a real case showed dangerous breathing problems when high-dose tianeptine was mixed with another sedative. Please don't combine these without talking to your doctor or pharmacist first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Lauhan R, Hsu A, Alam A, Beizai K. Tianeptine Abuse and Dependence: Case Report and Literature Review. Psychosomatics. 2018;59(6):547-553. PubMed
  2. Lucaj S, Leo RJ. Tianeptine Sodium: A Nootropic With Potentially Lethal Consequences. Prim Care Companion CNS Disord. 2018;20(4).
  3. Samuels BA, Nautiyal KM, Kruegel AC, et al. The Behavioral Effects of the Antidepressant Tianeptine Require the Mu-Opioid Receptor. Neuropsychopharmacology. 2017;42(10):2052-2063. 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

Tianeptine Also Interacts With Other Medications

Tianeptine has 9 major, 267 moderate known drug interactions in our database — the Primidone one above is one of them. If you take anything else, check it against the full list below.

Major 9 Moderate 267 No known interaction 2,554 (incl. Primidone)
Taking anything else?

Check Another of Your Medications Against Tianeptine

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

From our Q&A

Questions About Tianeptine or Primidone

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Tianeptine or Primidone, 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 Primidone

This page covers Tianeptine only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Primidone page lists 124 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 Kava (major).

By severity: 7 major · 101 moderate · 16 minor.

Open the Primidone interaction page

How much people look this up

Where Tianeptine and Primidone 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 Tianeptine
Top half

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

29 days ago today
Medication Primidone
Steady interest

#1,993 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 Tianeptine

What is Tianeptine?

  • Depression (prescription use in some countries)
  • Anxiety
  • Mood enhancement
  • Pain relief
  • Self-treatment of opioid withdrawal
  • Recreational euphoria

Tianeptine is a prescription antidepressant in some countries, but it is NOT approved by the FDA in the United States and is illegally sold in dietary supplements and 'gas station' products. At high doses it acts like an opioid and carries serious risks of addiction, overdose, and dangerous withdrawal. We strongly advise against using over-the-counter tianeptine products and urge anyone considering it to talk with a doctor or pharmacist first.

Read the full Tianeptine monograph & all interactions
Medication

About Primidone

What Is Primidone Used For?

Brand name: Mysoline

Primidone — available as Mysoline and as generic primidone tablets — is used to control several types of epileptic seizures, including grand mal (major convulsive), psychomotor, and focal (partial) seizures. It can be used alone or alongside other seizure medicines.

Both Mysoline and primidone tablets may be particularly helpful for grand mal seizures that haven't responded to other anticonvulsant treatments.

See full Primidone drug information
Keep checking

Other Drugs & Tianeptine

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

9Major
267Moderate
0Minor
2,553No known interaction
9 Major 267 Moderate 2,553 No interaction
Major

9 interactions

Moderate

267 interactions

Showing 60 of 267 moderate interactions — see all 267 on the Tianeptine page.

No interaction 2,553 drugs checked — show the list

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

Showing the 60 most looked-up of 2,553 medications checked with no known interaction — see the full Tianeptine list.

See the full Tianeptine interactions page
See every supplement checked against Primidone, 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
Tianeptine monograph › Uses, safety, and every drug interaction in one place Primidone supplement interactions › Every supplement checked against Primidone, ranked by severity Primidone 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 Tianeptine and Primidone Together: Common Questions

Can you take Tianeptine with Primidone?
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 Tianeptine and Primidone 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 Primidone and Tianeptine?

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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.