Drug & supplement interaction

Tianeptine + Phenelzine Sulfate

Phenelzine Sulfate brand name: Nardil.

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

Phenelzine Sulfate falls into 2 drug categories that Tianeptine can interact with; the most serious is rated major. Tianeptine may increase the toxicity of MAOIs.

Read the full interaction report
SeverityMajor
LikelihoodProbable
Interactions2
EvidenceC
What do Severity, Likelihood & Evidence mean?
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Interaction report

Tianeptine and Phenelzine Sulfate

These two interact in 2 distinct ways. Each one is explained separately below.

Why Are There 2 Interactions?

Tianeptine interacts with whole categories of medication. Phenelzine Sulfate falls into 2 of those categories, so it can interact with Tianeptine in 2 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Major).

Major

MONOAMINE OXIDASE INHIBITORS (MAOIs)

1 of 2

Why this applies to Phenelzine Sulfate

Phenelzine Sulfate falls under MONOAMINE OXIDASE INHIBITORS (MAOIs) — the group Tianeptine interacts with.

Tianeptine may increase the toxicity of MAOIs.
Concomitant use of tianeptine and non-selective MAOIs might increase the risk of cardiovascular collapse, hypertension, fever, convulsions, and death.
Severity Major Likelihood Probable Evidence C

Interaction 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..

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

This is one combination I really want you to steer clear of. Phenelzine (Nardil) is an MAOI, meaning it slows down the breakdown of brain chemicals like serotonin and norepinephrine so more of them stick around. Tianeptine acts on some of those same systems, and at higher doses it also behaves like an opioid. Putting the two together can push things into dangerous territory.

When MAOIs are mixed with a substance like this, people can run into a sudden spike in blood pressure, high fever, racing or unstable heart function, seizures, and in the worst cases collapse or death. That is not a scare tactic, it is a recognized and serious risk. Please do not combine these, and talk with your doctor or pharmacist before using any tianeptine product.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Summary of Product Characteristics Stablo: Tianeptine. 2008. Available at: https://www.servier.com.ve/sites/default/files/spc-pil/spc-stablon.pdf
Moderate

CNS DEPRESSANTS

2 of 2

Phenelzine Sulfate also falls under CNS DEPRESSANTS.

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 short version: mixing tianeptine with phenelzine (Nardil) is a combination I'd really want you to avoid. The interaction we have on file is about added sedation. At higher doses tianeptine behaves like an opioid, so stacking it with another nervous system depressant can deepen drowsiness, slow your breathing, and in a documented case led to dangerous respiratory depression. That alone is reason for caution.

But there's a second, bigger worry that's specific to phenelzine. It's an MAOI, and MAOIs are notorious for serious reactions when combined with drugs that touch serotonin or opioid pathways. This evidence is theoretical, not proven, yet the stakes are high. Please don't combine these. Talk with 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 8 major, 268 moderate known drug interactions in our database — the Phenelzine Sulfate one above is among them. If you take anything else, check it against the full list below.

Major 8 Moderate 268 No known interaction 2,554 (incl. Phenelzine Sulfate)
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.

Everything else you take

See Every Supplement That Interacts With Phenelzine Sulfate

This page covers Tianeptine only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Phenelzine Sulfate page lists 144 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), Bitter Orange (major) and Brewer's Yeast (major).

By severity: 18 major · 111 moderate · 15 minor.

From our pharmacist’s overview on the Phenelzine Sulfate page

“Few medications demand as much dietary and supplement care as phenelzine sulfate (Nardil), an older MAOI antidepressant, and this list backs that up, with 18 of its 144 recorded interactions rated major. The two dominant themes are sedation and blood pressure.”

Reviewed by 2 · Jul 18, 2026

Open the Phenelzine Sulfate interaction page

How much people look this up

Where Tianeptine and Phenelzine Sulfate 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

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

29 days ago today
Medication Phenelzine Sulfate
Top half

#1,065 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 Phenelzine

What Is Phenelzine Used For?

Brand name: Nardil

Phenelzine is used to treat depression — specifically the types described as atypical, nonendogenous, or neurotic depression. This often includes people who have a mix of anxiety and depression, or who have phobic or hypochondriacal features (strong fears about illness or physical symptoms).

It is generally not the first antidepressant a doctor will try. It is best suited for patients who have already tried other antidepressants without enough relief. There is less evidence supporting its use in severe depression with classic biological features (called endogenous depression).

See full Phenelzine 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.

8Major
268Moderate
0Minor
2,553No known interaction
8 Major 268 Moderate 2,553 No interaction
Major

8 interactions

Moderate

268 interactions

Showing 60 of 268 moderate interactions — see all 268 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 Phenelzine Sulfate, 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 Phenelzine Sulfate supplement interactions › Every supplement checked against Phenelzine Sulfate, ranked by severity Phenelzine 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 Phenelzine Sulfate Together: Common Questions

Can you take Tianeptine with Phenelzine Sulfate?
This is rated a major interaction, so the combination is best avoided unless your doctor or pharmacist has specifically told you otherwise. Read the full details on this page and confirm with your pharmacist before combining them.
Why are there 2 interactions listed for Tianeptine and Phenelzine Sulfate?
Phenelzine Sulfate belongs to more than one drug category, and Tianeptine 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 Tianeptine and Phenelzine Sulfate interaction?
We rate it Major. This is a clinically significant combination that is generally best avoided, or used only under the direct supervision of your physician or pharmacist.

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

Still Have a Question About Phenelzine Sulfate 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.