Drug & supplement interaction

Indian Snakeroot + Amitriptyline, Perphenazine

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

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

Amitriptyline, Perphenazine falls into 4 drug categories that Indian Snakeroot can interact with; the most serious is rated major. Theoretically, concomitant use might increase the risk of adverse effects.

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

Indian Snakeroot and Amitriptyline, Perphenazine

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

Why Are There 4 Interactions?

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

Major

ANTIPSYCHOTIC DRUGS

1 of 4

Why this applies to Amitriptyline, Perphenazine

Amitriptyline, Perphenazine falls under ANTIPSYCHOTIC DRUGS — the group Indian Snakeroot interacts with.

Theoretically, concomitant use might increase the risk of adverse effects.
Concomitant use of neuroleptics with Indian snakeroot may potentiate the effects of these drugs, as well as the alkaloid constituents of Indian snakeroot.
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

Triavil combines amitriptyline (an older antidepressant) with perphenazine (an antipsychotic). Indian snakeroot contains reserpine, which lowers blood pressure and has its own sedating, mood-dampening effects on the brain and nerves. Stacking these together can pile on similar effects. The concern here is mostly theoretical, based on how these compounds act rather than strong studies, but the overlap is real.

What that could look like in everyday terms: heavier drowsiness, dizziness or fainting when you stand up (from blood pressure dropping too low), and a possible worsening of mood or low feelings. Both this medicine and snakeroot can also affect heart rhythm. Please don't start or stop anything on your own. Run this by your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Blumenthal M, ed. The Complete German Commission E Monographs: Therapeutic Guide to Herbal Medicines. Trans. S. Klein. Boston, MA: American Botanical Council, 1998.
  2. Gruenwald J, Brendler T, Jaenicke C. PDR for Herbal Medicines. 1st ed. Montvale, NJ: Medical Economics Company, Inc., 1998.
Moderate

CNS DEPRESSANTS

2 of 4

Amitriptyline, Perphenazine also falls under CNS DEPRESSANTS.

Theoretically, taking Indian snakeroot might cause additive sedative effects.
Sedation and drowsiness have been reported in clinical trials using Indian snakeroot.
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

Triavil combines amitriptyline (an older antidepressant) with perphenazine (an antipsychotic). Both of these already tend to make people feel drowsy, foggy, and a little lightheaded, especially when you first start them. Indian snakeroot carries its own sedative punch and can also lower blood pressure on its own.

Put them together and the sleepiness can stack up. You might feel more groggy than usual, have trouble concentrating, or feel dizzy when you stand up too fast. This concern is theoretical, based on how these ingredients behave rather than on direct studies, so it isn't a guaranteed problem. Still, please don't start or stop anything on your own. Have a quick chat with your pharmacist or doctor before combining them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Sheldon MB, Kotte JH. Effect of Rauwolfia serpentina and reserpine on the blood pressure in essential hypertension; a long-term double-blind study. Circulation. 1957 Aug;16(2):200-6.
  2. Vakil RJ. A clinical trial of Rauwolfia serpentina in essential hypertension. Br Heart J. 1949 Oct;11(4):350-5. PubMed
  3. Achor RW, Hanson NO, Gifford RW Jr. Hypertension treated with Rauwolfia serpentina (whole root) and with reserpine; controlled study disclosing occasional severe depression. J Am Med Assoc. 1955 Oct 29;159(9):841-5. PubMed
  4. Wilkins RW, Judson WE. The use of Rauwolfia serpentina in hypertensive patients. N Engl J Med. 1953 Jan 8;248(2):48-53.
Moderate

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES

3 of 4

Amitriptyline, Perphenazine also falls under CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES.

Theoretically, Indian snakeroot might inhibit CYP2D6 enzymes and reduce the metabolism of CYP2D6 substrates.
Indian snakeroot contains small amounts of the drug yohimbine. In vitro research shows that yohimbine inhibits CYP2D6 enzyme activity.
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

Triavil combines two medicines, amitriptyline (an antidepressant) and perphenazine (an antipsychotic), and both are partly cleared by a liver enzyme called CYP2D6. Lab studies suggest Indian snakeroot may slow that enzyme down a bit. If that happens, these drugs could clear more slowly and build up, which might mean stronger side effects like drowsiness, dry mouth, constipation, blurred vision, dizziness when standing, or a faster heartbeat.

Just as important here, both Indian snakeroot and this medicine lower blood pressure and can be sedating, so stacking them could leave you feeling lightheaded or overly sleepy. Keep in mind this enzyme concern is theoretical, based only on test-tube data, not real patients. Still, I'd talk with your pharmacist or doctor before combining them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. VandenBrink, B. M., Foti, R. S., Rock, D. A., Wienkers, L. C., and Wahlstrom, J. L. Prediction of CYP2D6 drug interactions from in vitro data: evidence for substrate-dependent inhibition. Drug Metab Dispos. 2012;40(1):47-53. PubMed
Moderate

TRICYCLIC ANTIDEPRESSANTS (TCAs)

4 of 4

Amitriptyline, Perphenazine also falls under TRICYCLIC ANTIDEPRESSANTS (TCAs).

Theoretically, concomitant use might alter the effects of Indian snakeroot and increase the risk of adverse effects.
A small clinical study in patients taking TCAs for at least 4 weeks shows that receiving doses of intravenous yohimbine, a constituent of Indian snakeroot, 2.5-20 mg daily for up to 7 days precipitates severe anxiety, agitation, and tremor. Also, concomitant use of TCAs with Indian snakeroot may decrease the effects of other rauwolfia alkaloids.
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

Your medication combines amitriptyline, a tricyclic antidepressant, with perphenazine, an older antipsychotic. Indian snakeroot is a potent plant that lowers nerve chemicals like norepinephrine, and it isn't something to take lightly on its own. When paired with this drug, there's a theoretical concern that things could pull in two directions: the snakeroot's blood-pressure-lowering and calming effects may be blunted, while the risk of side effects could climb.

In a small study, one snakeroot component (yohimbine) triggered severe anxiety, agitation, and tremor in people on tricyclics. You might also notice low blood pressure or dizziness. This is based on pharmacology, not strong proof, but given how unpredictable snakeroot is, please check with your pharmacist or doctor before combining them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. McEvoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 1998.
  2. Schmauss M, Laakmann G, Dieterle D. Effects of alpha 2-receptor blockade in addition to tricyclic antidepressants in therapy-resistant depression. J Clin Psychopharmacol. 1988;8(2):108-11.

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

Indian Snakeroot Also Interacts With Other Medications

Indian Snakeroot has 82 major, 760 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.

Major 82 Moderate 760 No known interaction 1,988 (incl. Amitriptyline, Perphenazine)
Taking anything else?

Check Another of Your Medications Against Indian Snakeroot

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

Everything else you take

See Every Supplement That Interacts With Amitriptyline, Perphenazine

This page covers Indian Snakeroot 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 Indian Snakeroot as Part of a Dietary Supplement Product? Check It for Interactions

We hold 70 real supplement products containing Indian Snakeroot, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Indian Snakeroot. Your product may carry other ingredients that interact with Amitriptyline, Perphenazine too, on top of Indian Snakeroot — 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 Indian Snakeroot 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 Indian Snakeroot
Top half

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

29 days ago today
Medication Amitriptyline, Perphenazine
Top half

#1,316 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 Indian Snakeroot

What is Indian Snakeroot?

Indian Snakeroot
  • High blood pressure
  • Anxiety and stress
  • Insomnia
  • Agitation
  • Fever (traditional use)

Indian snakeroot is a traditional Ayurvedic plant that contains reserpine, a compound with real blood-pressure-lowering and sedative effects. Because its potent alkaloids can cause serious side effects like depression and very low blood pressure, it should never be used without medical supervision. It is not a safe or simple home remedy, and many countries restrict its use.

Read the full Indian Snakeroot monograph & all interactions
Keep checking

Other Drugs & Indian Snakeroot

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

82Major
760Moderate
0Minor
1,987No known interaction
82 Major 760 Moderate 1,987 No interaction
Major

82 interactions

Showing 60 of 82 major interactions — see all 82 on the Indian Snakeroot page.

Moderate

760 interactions

Showing 60 of 760 moderate interactions — see all 760 on the Indian Snakeroot page.

No interaction 1,987 drugs checked — show the list

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

Showing the 60 most looked-up of 1,987 medications checked with no known interaction — see the full Indian Snakeroot list.

See the full Indian Snakeroot 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
Indian Snakeroot 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 Indian Snakeroot and Amitriptyline, Perphenazine Together: Common Questions

Can you take Indian Snakeroot 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.
Why are there 4 interactions listed for Indian Snakeroot and Amitriptyline, Perphenazine?
Amitriptyline, Perphenazine belongs to more than one drug category, and Indian Snakeroot 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 Indian Snakeroot 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

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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.