Drug & supplement interaction

5-htp + Amitriptyline, Perphenazine

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

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

Amitriptyline, Perphenazine falls into 2 drug categories that 5-htp can interact with; the most serious is rated moderate. Theoretically, concomitant use of 5-HTP with medications that cause sedation might have additive effects.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions2
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

5-htp and Amitriptyline, Perphenazine

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

Why Are There 2 Interactions?

5-htp interacts with whole categories of medication. Amitriptyline, Perphenazine falls into 2 of those categories, so it can interact with 5-htp in 2 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 2

Why this applies to Amitriptyline, Perphenazine

Amitriptyline, Perphenazine falls under CNS DEPRESSANTS — the group 5-htp interacts with.

Theoretically, concomitant use of 5-HTP with medications that cause sedation might have additive effects.
In clinical trials, 5-HTP has been associated with drowsiness and somnolence.
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

The combo of Triavil (which pairs amitriptyline with perphenazine) and 5-HTP comes down to overlapping calming effects. Amitriptyline is already a sedating antidepressant, and perphenazine adds its own drowsiness. Since 5-HTP has been linked to sleepiness in studies, stacking it on top could leave you feeling extra groggy, foggy, or unsteady on your feet.

I'll be honest with you: this concern is mostly theoretical, based on how these ingredients behave rather than strong proof. There's also a separate point worth flagging since amitriptyline raises serotonin too, and 5-HTP boosts serotonin, so adding them together is something I'd want your doctor or pharmacist to look at before you start. Please check in with them first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Cangiano C, Ceci F, Cancino A, et al. Eating behavior and adherence to dietary prescriptions in obese adult subjects treated with 5-hydroxytryptophan. Am J Clin Nutr 1992;56:863-7. PubMed
  2. den Boer JA, Westenberg HG. Behavioral, neuroendocrine, and biochemical effects of 5-hydroxytryptophan administration in panic disorder. Psychiatry Res 1990;31:267-78. PubMed
  3. Titus F, Dávalos A, Alom J, Codina A. 5-Hydroxytryptophan versus methysergide in the prophylaxis of migraine. Randomized clinical trial. Eur Neurol 1986;25:327-9. PubMed
  4. De Benedittis G, Massei R. Serotonin precursors in chronic primary headache. A double-blind cross-over study with L-5-hydroxytryptophan vs. placebo. J Neurosurg Sci 1985;29:239-48.
Moderate

SEROTONERGIC DRUGS

2 of 2

Amitriptyline, Perphenazine also falls under SEROTONERGIC DRUGS.

Combining serotonergic drugs with 5-HTP might cause additive serotonergic effects.
5-HTP can increase serotonin levels and cause serotonergic effects. Theoretically, combining serotonergic drugs with 5-HTP might increase the risk of serotonergic side effects, including serotonin syndrome and cerebral vasoconstrictive disorders. However, serotonin syndrome with 5-HTP has not yet been reported in humans. Monitor patients for signs of serotonin syndrome and other serotonergic side effects if using 5-HTP with serotonergic drugs.
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

This combination pill pairs amitriptyline, a tricyclic antidepressant, with perphenazine, an older antipsychotic. The amitriptyline part already nudges serotonin levels upward, and 5-HTP is a direct building block your body turns into more serotonin. Stacking the two could, in theory, push serotonin too high. That's the concern here.

If serotonin climbs too far, you can get what's called serotonin syndrome: agitation, a racing heart, sweating, shivering, muscle twitching, or confusion. I'll be honest, this is a theoretical worry based on how these work, and it hasn't actually been reported with 5-HTP in people. Still, since amitriptyline is already a serotonin-active drug, it's smart to check with your pharmacist or doctor before adding 5-HTP rather than combining them on your own.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Birdsall TC. 5-Hydroxytryptophan: A Clinically-Effective Serotonin Precursor. Altern Med Rev 1998;3:271-80.
  2. Singhal AB, Caviness VS, Begleiter AF, et al. Cerebral vasoconstriction and stroke after use of serotonergic drugs. Neurology 2002;58:130-3. PubMed
  3. Maffei ME. 5-Hydroxytryptophan (5-HTP): Natural Occurrence, Analysis, Biosynthesis, Biotechnology, Physiology and Toxicology. Int J Mol Sci. 2020;22(1):181. 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

5-htp Also Interacts With Other Medications

5-htp has 397 moderate known drug interactions in our database — the Amitriptyline, Perphenazine one above is among them. If you take anything else, check it against the full list below.

Moderate 397 No known interaction 2,433 (incl. Amitriptyline, Perphenazine)
Taking anything else?

Check Another of Your Medications Against 5-htp

Covers the 2,830 medications we’ve checked against 5-htp. Pick one to open its full report.

From our Q&A

Questions About 5-htp or Amitriptyline, Perphenazine

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers 5-htp or Amitriptyline, Perphenazine, 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 Amitriptyline, Perphenazine

This page covers 5-htp 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: 1,4-butanediol (major), Activated Charcoal (major), American Hellebore (major), Arsenic (major) and Beer (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

One more smart check

Taking 5-htp as Part of a Dietary Supplement Product? Check It for Interactions

We hold 1,651 real supplement products containing 5-htp, each one broken down to its full ingredient list — and combination products often carry several ingredients besides 5-htp. Your product may carry other ingredients that interact with Amitriptyline, Perphenazine too, on top of 5-htp — 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 5-htp 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 5-htp
Top 10%

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

29 days ago today
Medication Amitriptyline, Perphenazine
Top half

#1,276 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 5-htp

What is 5-htp?

5-htp
  • Low mood or depression
  • Anxiety and stress
  • Sleep problems
  • Migraine headaches
  • Fibromyalgia
  • Appetite or weight management

5-HTP is a compound your body uses to make serotonin, and people take it as a supplement hoping to improve mood, sleep, and headaches. Some early research is promising, but the overall evidence is limited and not conclusive. Because it can affect serotonin and may interact with medicines, talk to your pharmacist or doctor before using it.

Read the full 5-htp monograph & all interactions
Keep checking

Other Drugs & 5-htp

Browse every other medication we’ve checked against 5-htp — both the ones with a known interaction and the ones without. Select any drug for the full detail.

0Major
397Moderate
0Minor
2,432No known interaction
397 Moderate 2,432 No interaction
Moderate

397 interactions

Showing 60 of 397 moderate interactions — see all 397 on the 5-htp page.

No interaction 2,432 drugs checked — show the list

We also checked 5-htp against these medications and found no known interaction in our sources. Open any page to confirm.

Showing the 60 most looked-up of 2,432 medications checked with no known interaction — see the full 5-htp list.

See the full 5-htp 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
5-htp monograph › Uses, safety, and every drug interaction in one place Amitriptyline, Perphenazine supplement interactions › Every supplement checked against Amitriptyline, Perphenazine, ranked by severity 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 5-htp and Amitriptyline, Perphenazine Together: Common Questions

Can you take 5-htp with Amitriptyline, Perphenazine?
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 2 interactions listed for 5-htp and Amitriptyline, Perphenazine?
Amitriptyline, Perphenazine belongs to more than one drug category, and 5-htp 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 5-htp and Amitriptyline, Perphenazine 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

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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.