Drug & supplement interaction

1,4-butanediol + Amitriptyline, Perphenazine

Amitriptyline, Perphenazine brand names: Triavil, Etrafon, Etrafon-A, Etrafon-Forte.

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

1,4-butanediol has a major interaction with Amitriptyline, Perphenazine. Theoretically, concomitant use of 1,4-butanediol with CNS depressants may potentiate respiratory and CNS depression.

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

1,4-butanediol and Amitriptyline, Perphenazine

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

Major

CNS DEPRESSANTS

Why this applies to Amitriptyline, Perphenazine

Amitriptyline, Perphenazine falls under CNS DEPRESSANTS — the group 1,4-butanediol interacts with.

Theoretically, concomitant use of 1,4-butanediol with CNS depressants may potentiate respiratory and CNS depression.
1,4-Butanediol is metabolized to gamma-hydroxybutyrate (GHB). Concomitant use of CNS depressants with GHB may cause serious CNS and respiratory depression.
Severity Major Likelihood Probable Evidence D

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

Let me start with the most important point: 1,4-butanediol is not a real supplement. It's a toxic industrial chemical that your body turns into GHB, a strong sedative that can stop your breathing. It shouldn't be swallowed at all, no matter what medicines you take.

Triavil combines amitriptyline (a sedating tricyclic antidepressant) with perphenazine (an antipsychotic). Both already make you drowsy and slow down the brain. Stacking GHB on top of them can pile on the sedation, leading to deep sleepiness, confusion, very slow or stopped breathing, and a dangerous drop in blood pressure. This warning is based on anecdotal reports, but the risk here is serious. Please talk with your pharmacist or doctor, and never use 1,4-butanediol.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Anon. Multistate outbreak of poisonings associated with illicit use of gamma hydroxy butyrate. JAMA 1991;265:447-8. DOI
  2. Product information for Xyrem. Jazz Pharmaceuticals, Inc. Palo Alto, CA. March 2022.

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

1,4-butanediol Also Interacts With Other Medications

1,4-butanediol has 249 major, 21 moderate known drug interactions in our database — the Amitriptyline, Perphenazine one above is one of them. If you take anything else, check it against the full list below.

Major 249 Moderate 21 No known interaction 2,560 (incl. Amitriptyline, Perphenazine)
Taking anything else?

Check Another of Your Medications Against 1,4-butanediol

Covers the 2,830 medications we’ve checked against 1,4-butanediol. Pick one to open its full report.

Everything else you take

See Every Supplement That Interacts With Amitriptyline, Perphenazine

This page covers 1,4-butanediol only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Amitriptyline, Perphenazine page lists 311 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), American Hellebore (major), Arsenic (major), Beer (major) and Cesium (major).

By severity: 19 major · 235 moderate · 57 minor.

From our pharmacist’s overview on the Amitriptyline, Perphenazine page

“Alcohol is the risk I'd flag first for anyone taking amitriptyline with perphenazine (Triavil, Etrafon). Beer and wine both carry major ratings here, and 78 of the 311 ingredients on file deepen the drowsiness this antidepressant and antipsychotic combination already causes, sometimes to the point of slowed breathing.”

Reviewed by 2 · Jul 18, 2026

Open the Amitriptyline, Perphenazine interaction page

How much people look this up

Where 1,4-butanediol and Amitriptyline, Perphenazine 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 1,4-butanediol
Top half

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

29 days ago today
Medication Amitriptyline, Perphenazine
Top half

#1,245 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 1,4-butanediol

What is 1,4-butanediol?

  • Marketed illegally as a 'recreational' or party substance
  • Falsely sold as a sleep aid
  • Falsely promoted for bodybuilding or muscle growth
  • Industrial solvent and chemical manufacturing

1,4-butanediol is a toxic industrial chemical, not a safe dietary supplement. Once swallowed, the body converts it into GHB, a powerful central nervous system depressant that can cause coma, dangerous breathing problems, addiction, and death. It should never be taken as a supplement or recreational substance.

Read the full 1,4-butanediol monograph & all interactions
Keep checking

Other Drugs & 1,4-butanediol

Browse every other medication we’ve checked against 1,4-butanediol — both the ones with a known interaction and the ones without. Select any drug for the full detail.

249Major
21Moderate
0Minor
2,559No known interaction
249 Major 21 Moderate 2,559 No interaction
Major

249 interactions

Showing 60 of 249 major interactions — see all 249 on the 1,4-butanediol page.

Moderate

21 interactions

No interaction 2,559 drugs checked — show the list

We also checked 1,4-butanediol against these medications and found no known interaction in our sources. Open any page to confirm.

Showing the 60 most looked-up of 2,559 medications checked with no known interaction — see the full 1,4-butanediol list.

See the full 1,4-butanediol interactions page
See every supplement checked against Amitriptyline, Perphenazine, 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
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Pharmacist Counseling Corner

Taking 1,4-butanediol and Amitriptyline, Perphenazine Together: Common Questions

Can you take 1,4-butanediol with Amitriptyline, Perphenazine?
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.
How serious is the 1,4-butanediol and Amitriptyline, Perphenazine 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 Amitriptyline, Perphenazine and 1,4-butanediol?

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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.