Drug & supplement interaction

Yohimbe + 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 6 drug categories that Yohimbe can interact with; the most serious is rated moderate. Theoretically, yohimbe might increase the levels and adverse effects of CYP2D6 substrates.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions6
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Yohimbe and Amitriptyline, Perphenazine

These two interact in 6 distinct ways. Each one is explained separately below.

Why Are There 6 Interactions?

Yohimbe interacts with whole categories of medication. Amitriptyline, Perphenazine falls into 6 of those categories, so it can interact with Yohimbe in 6 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES

1 of 6

Why this applies to Amitriptyline, Perphenazine

Amitriptyline, Perphenazine falls under CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES — the group Yohimbe interacts with.

Theoretically, yohimbe might increase the levels and adverse effects of CYP2D6 substrates.
In vitro research suggests that yohimbine, a constituent of yohimbe bark, 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

This combination pill pairs amitriptyline (an antidepressant) with perphenazine (an antipsychotic), and both rely on the liver enzyme CYP2D6 to be cleared from your body. Lab studies hint that yohimbine, the active part of yohimbe, may slow this enzyme down. If that happens, levels of both medicines could creep up, which can mean more drowsiness, dry mouth, constipation, blurred vision, dizziness on standing, or a faster heartbeat.

Keep in mind this is only theoretical, based on test-tube work, not real patient cases, so I don't want to alarm you. That said, yohimbe itself can spike blood pressure and heart rate, which is a poor mix with these drugs. Please check 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

CYTOCHROME P450 2D6 (CYP2D6) INHIBITORS

2 of 6

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

CYP2D6 inhibitors may increase the levels and adverse effects of yohimbine, a constituent of yohimbe.
In vitro and clinical research shows that the yohimbe bark constituent, yohimbine, is metabolized by CYP2D6 isoenzymes. Paroxetine, a cytochrome P450 (CYP) 2D6 inhibitor, increases the maximum serum concentration of yohimbine and reduces the clearance of yohimbine compared to yohimbine alone in patients who are extensive CYP2D6 metabolizers..
Severity Moderate Likelihood Probable Evidence B

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

Here's the key thing to understand: this combo pill (the antidepressant amitriptyline plus the antipsychotic perphenazine) actually slows down a liver enzyme called CYP2D6. Yohimbe's active compound, yohimbine, leans on that same enzyme to get cleared from your body. So when you pair them, yohimbine can pile up to higher levels than expected.

Practically, that means a stronger dose of yohimbine's stimulant-like effects, things like a racing or pounding heart, spikes in blood pressure, jitteriness, and anxiety. That's a real concern when you're already on a medicine that affects mood and heart rhythm. This is rated a probable, moderate interaction with decent supporting research. Over-the-counter yohimbe products are also wildly inconsistent in strength, which adds risk. Please check with your pharmacist or doctor before combining these.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Le Corre P, Parmer RJ, Kailasam MT, et al. Human sympathetic activation by alpha2-adrenergic blockade with yohimbine: Bimodal, epistatic influence of cytochrome P450-mediated drug metabolism. Clin Pharmacol Ther. 2004;76(2):139-53.
  2. Mueller-Schoell A, Michelet R, Weinelt F, Kloft C, Mikus G. CYP2D6 phenotype explains reported yohimbine concentrations in four severe acute intoxications. Arch Toxicol. 2021. PubMed
  3. Bharucha AE, Skaar T, Andrews CN, et al Relationship of cytochrome P450 pharmacogenetics to the effects of yohimbine on gastrointestinal transit and catecholamines in healthy subjects. Neurogastroenterol Motil. 2008;20(8):891-9. PubMed
  4. Vay M, Meyer MJ, Blank A, et al. Oral yohimbine as a new probe drug to predict CYP2D6 activity: results of a fixed-sequence phase I trial. Clin Pharmacokinet. 2020;59(7):927-939. PubMed
Moderate

PHENOTHIAZINES

3 of 6

Amitriptyline, Perphenazine also falls under PHENOTHIAZINES.

Theoretically, using yohimbine with phenothiazines might have additive effects.
Yohimbine, a constituent of yohimbe, has alpha-2 adrenergic antagonist effects. Theoretically, combining it with phenothiazines can cause additive alpha-2 adrenergic antagonism.
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 combo pill pairs amitriptyline (an antidepressant) with perphenazine (a phenothiazine). Both of these already nudge those same alpha adrenergic receptors that yohimbine acts on. The concern here is more of an overlapping action than a true metabolism clash, and honestly the evidence is theoretical, based on how these compounds behave on paper rather than real patient reports.

In practice, layering yohimbe on top could push your blood pressure and heart rate around in unpredictable ways, on top of the dizziness, lightheadedness, fast heartbeat, or jitteriness this medication can already cause. Since yohimbe products vary so much in strength and can be hard on the heart, please check with your pharmacist or doctor before adding it.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Brinker F. Herb Contraindications and Drug Interactions. 2nd ed. Sandy, OR: Eclectic Medical Publications, 1998.
Moderate

TRICYCLIC ANTIDEPRESSANTS (TCAs)

4 of 6

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

Theoretically, taking yohimbe with TCAs can increase adverse effects.
A small clinical study in patients taking TCAs for at least 4 weeks shows that receiving doses of intravenous yohimbine 2.5-20 mg daily for up to 7 days precipitates severe anxiety, agitation, and tremor. The effects of yohimbe bark itself are unclear; oral yohimbe bark contains 0.6% to 1.38% yohimbine, but it is unclear how much is absorbed.
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 antipsychotic). Here's the concern with yohimbe: it revs up your body's adrenaline-type signaling, and that can stack on top of the stimulating side of tricyclics. In one small study, people on TCAs who got yohimbine ended up with noticeable anxiety, agitation, and tremor. With your combo, I'd also keep an eye out for a racing or pounding heartbeat and higher blood pressure.

Honestly, the evidence here is mostly theoretical and based on how these drugs work, not strong proof. Still, yohimbe supplements vary wildly in strength and can be hard on the heart on their own. Please check with your pharmacist or doctor before adding it, rather than stopping or changing anything yourself.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Betz, J. M., White, K. D., and der Marderosian, A. H. Gas chromatographic determination of yohimbine in commercial yohimbe products. J AOAC Int 1995;78(5):1189-1194. DOI
  2. Cohen PA, Wang YH, Maller G, DeSouza R, Khan IA. Pharmaceutical quantities of yohimbine found in dietary supplements in the USA. Drug Test Anal. 2015 Sep 22. PubMed
  3. 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.
Minor

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

5 of 6

Amitriptyline, Perphenazine also falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES.

Theoretically, yohimbe might decrease the levels and clinical effects of CYP1A2 substrates.
In vitro research shows that yohimbe extract induces CYP1A2 enzymes.
Severity Minor 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 blends amitriptyline (a tricyclic antidepressant) with perphenazine (an antipsychotic). Some lab research hints that yohimbe may speed up a liver enzyme called CYP1A2, which helps clear part of this medication. In theory, that could lower the drug levels a bit and make it work less well, meaning your mood, sleep, or anxiety symptoms might not be as well controlled.

I want to be honest though: this is rated minor and rests only on test-tube data, not real people, so it may not amount to much in practice. The bigger worry is yohimbe itself, since it can raise blood pressure and speed up your heart, which is a real concern alongside this medicine. Please check with your pharmacist or doctor before combining them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Haron MH, Dale O, Martin K, et al. Evaluation of the Herb-Drug Interaction Potential of Commonly Used Botanicals on the US Market with Regard to PXR- and AhR-Mediated Influences on CYP3A4 and CYP1A2. J Diet Suppl 2022. PubMed
Minor

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

6 of 6

Amitriptyline, Perphenazine also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.

Theoretically, yohimbe might decrease the levels and clinical effects of CYP3A4 substrates.
In vitro research shows that yohimbe extract induces CYP3A4 enzymes.
Severity Minor 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 active medicines: amitriptyline (a tricyclic antidepressant) and perphenazine (an antipsychotic). The lab-based concern here is that yohimbe may speed up a liver enzyme called CYP3A4, which helps break these medicines down. If that happened, your body might clear them a little faster, which could make them work less well, so depression or anxiety symptoms might creep back.

Honestly, this is a theoretical worry pulled from test-tube research, not from real patients, and it's rated as a minor interaction. So I wouldn't lose sleep over it. The bigger real-world issue is that yohimbe itself can raise blood pressure and heart rate, which doesn't mix well with these drugs. Please check with your pharmacist or doctor before combining them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Haron MH, Dale O, Martin K, et al. Evaluation of the Herb-Drug Interaction Potential of Commonly Used Botanicals on the US Market with Regard to PXR- and AhR-Mediated Influences on CYP3A4 and CYP1A2. J Diet Suppl 2022. 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

Yohimbe Also Interacts With Other Medications

Yohimbe has 9 major, 679 moderate, 436 minor 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 9 Moderate 679 Minor 436 No known interaction 1,706 (incl. Amitriptyline, Perphenazine)
Taking anything else?

Check Another of Your Medications Against Yohimbe

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

Everything else you take

See Every Supplement That Interacts With Amitriptyline, Perphenazine

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

We hold 1,054 real supplement products containing Yohimbe, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Yohimbe. Your product may carry other ingredients that interact with Amitriptyline, Perphenazine too, on top of Yohimbe — 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 Yohimbe 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 Yohimbe
Top 25%

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

29 days ago today
Medication Amitriptyline, Perphenazine
Top half

#1,335 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 Yohimbe

What is Yohimbe?

Yohimbe
  • Erectile dysfunction
  • Low sex drive
  • Sexual performance
  • Weight loss
  • Athletic performance

Yohimbe is a West African tree bark that contains yohimbine, a compound mainly promoted for erectile dysfunction and as an aphrodisiac. A prescription form of yohimbine has some evidence for erectile dysfunction, but over-the-counter yohimbe supplements vary widely in content and can cause serious side effects like high blood pressure and fast heart rate. Because of these safety concerns, talk to your pharmacist or doctor before using it.

Read the full Yohimbe monograph & all interactions
Keep checking

Other Drugs & Yohimbe

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

9Major
679Moderate
436Minor
1,705No known interaction
9 Major 679 Moderate 436 Minor 1,705 No interaction
Major

9 interactions

Moderate

679 interactions

Showing 60 of 679 moderate interactions — see all 679 on the Yohimbe page.

Minor

436 interactions

Showing 60 of 436 minor interactions — see all 436 on the Yohimbe page.

No interaction 1,705 drugs checked — show the list

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

Showing the 60 most looked-up of 1,705 medications checked with no known interaction — see the full Yohimbe list.

See the full Yohimbe 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
Yohimbe 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 Yohimbe and Amitriptyline, Perphenazine Together: Common Questions

Can you take Yohimbe 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 6 interactions listed for Yohimbe and Amitriptyline, Perphenazine?
Amitriptyline, Perphenazine belongs to more than one drug category, and Yohimbe 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 Yohimbe 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

Still Have a Question About Amitriptyline, Perphenazine and Yohimbe?

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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.