Kratom + Amitriptyline, Perphenazine
Amitriptyline, Perphenazine brand names: Triavil, Etrafon, Etrafon-A, Etrafon-Forte.
Amitriptyline, Perphenazine falls into 6 drug categories that Kratom can interact with; the most serious is rated moderate. Theoretically, concomitant use might increase the risk for adverse CNS depressant effects.
Read the full interaction reportKratom and Amitriptyline, Perphenazine
These two interact in 6 distinct ways. Each one is explained separately below.
Why Are There 6 Interactions?
Kratom interacts with whole categories of medication. Amitriptyline, Perphenazine falls into 6 of those categories, so it can interact with Kratom in 6 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).
CNS DEPRESSANTS
1 of 6Why this applies to Amitriptyline, Perphenazine
Amitriptyline, Perphenazine falls under CNS DEPRESSANTS — the group Kratom interacts with.
Kratom contains mitragynine, a mu-receptor agonist that may cause respiratory depression. Although results from animal research suggest that mitragynine causes less respiratory depression than the CNS depressant codeine, fatalities have been reported for patients who ingested a combination of kratom and O-desmethyltramadol, another mu-receptor agonist. Additionally, observational research suggests that adverse effects such as drowsiness and coma are more likely to occur in individuals taking kratom in combination with agents such as opioids and sedatives. Theoretically, ingesting kratom along with other CNS depressants can increase the risk of adverse effects, including drowsiness, coma, and/or severe or fatal respiratory depression.
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.
This combination pill pairs amitriptyline (a sedating antidepressant) with perphenazine (an antipsychotic). Both already tend to make people sleepy and slow things down in the brain. Kratom acts on your opioid receptors and can add its own sedating, breathing-slowing effects on top of that.
So the worry here is overlap. Stacking kratom with this medication could deepen drowsiness, confusion, low blood pressure, and in a worst case, dangerously slowed breathing. To be honest, this is a theoretical concern based on how these drugs work rather than solid human studies, but real-world reports of kratom mixed with sedatives have ended badly. Please don't change anything on your own. Talk with your pharmacist or doctor before using kratom with this medicine.
- Backstrom BG, Classon G, Lowenhielm P, Thelander G. [Krypton--new, deadly Internet drug. Since October 2009 have nine young persons died in Sweden]. Lakartidningen 2010;107(50):3196-3197.
- Kronstrand R, Roman M, Thelander G, Eriksson A. Unintentional fatal intoxications with mitragynine and O-desmethyltramadol from the herbal blend Krypton. J Anal Toxicol 2011;35(4):242-247. PubMed
- Jansen KL, Prast CJ. Ethnopharmacology of kratom and the Mitragyna alkaloids. J Ethnopharmacol 1988;23(1):115-119. PubMed
- Davidson C, Cao D, King T, et al. A comparative analysis of kratom exposure cases in Thailand and the United States from 2010-2017. Am J Drug Alcohol Abuse. 2020:1-10. PubMed
CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES
2 of 6Amitriptyline, Perphenazine also falls under CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES.
In vitro research suggests that kratom extract inhibits CYP2D6 enzyme activity. However, human research shows that a single low dose of kratom tea 2 grams does not inhibit CYP2D6 activity. However, this kratom dose is lower than what is normally taken for psychoactive effects. In one case report, a 63-year-old male presented with possible serotonin syndrome after taking an unknown dose of kratom for up to 3 months along with serotonergic prescription medications bupropion, buspirone, desvenlafaxine, trazodone, and ziprasidone. It was hypothesized that kratom inhibited CYP2D6-mediated metabolism of buspirone and consequently increased systemic exposure to serotonin. In another case, a 37-year-old male stable for 15 years on amitriptyline presented with anticholinergic symptoms including xerostomia, dry eyes, and constipation, along with mildly elevated bilirubin and liver enzymes after taking progressively higher doses of up to 14 grams of kratom daily for 12 weeks. It was hypothesized that the adverse effects of amitriptyline were precipitated by CYP2D6 inhibition by kratom.
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.
Both medicines in this combo pill, amitriptyline and perphenazine, are cleared by a liver enzyme called CYP2D6. Kratom may slow that enzyme down. If it does, these drugs can build up in your body and their effects get stronger. With amitriptyline especially, that usually means more of the classic "anticholinergic" side effects: a dry mouth, blurry vision, constipation, drowsiness, and feeling lightheaded. There was even a real case of someone stable on amitriptyline for years who developed exactly these symptoms after using high daily doses of kratom.
I'll be honest, this is mostly theoretical and the evidence is thin, and tiny amounts may not matter. But because both medicines can also add to kratom's sedation, please run this by your pharmacist or doctor before mixing them.
- Kong WM, Chik Z, Ramachandra M, et al. Evaluation of the effects of Mitragyna speciosa alkaloid extract on cytochrome P450 enzymes using a high throughput assay. Molecules. 2011;16(9):7344-7356. PubMed
- Eudaley ST, Brooks SP, Hamilton LA. Case Report: Possible Serotonin Syndrome in a Patient Taking Kratom and Multiple Serotonergic Agents. J Pharm Pract 2022. PubMed
- Tanna RS, Nguyen JT, Hadi DL, et al. Clinical Assessment of the Drug Interaction Potential of the Psychotropic Natural Product Kratom. Clin Pharmacol Ther 2023;113(6):1315-1325. PubMed
- Vanani NB, Stevanovic SG, Stevanovic N. Adverse Drug Interaction Between Kratom and Amitriptyline With Gastrointestinal and Mild Hepatic Effects. Cureus 2023;15(1):e33809. PubMed
CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES
3 of 6Amitriptyline, Perphenazine also falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES.
In vitro research suggests that kratom extract inhibits the activity of CYP1A2. In one case report, a 63-year-old male presented with possible serotonin syndrome after taking an unknown dose of kratom for up to 3 months along with serotonergic prescription medications bupropion, buspirone, desvenlafaxine, trazodone, and ziprasidone. It was hypothesized that kratom inhibited CYP1A2-mediaed metabolism of ziprasidone which consequently increased systemic exposure to serotonin.
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.
Here's the gist for this combination pill, which pairs amitriptyline (a tricyclic antidepressant) with perphenazine (an antipsychotic). Amitriptyline is partly handled by a liver enzyme called CYP1A2. Lab studies suggest kratom can slow that enzyme down, so in theory the amitriptyline could clear out of your body more slowly and build up. That can mean stronger effects like heavy drowsiness, dry mouth, constipation, blurry vision, dizziness on standing, and in some cases heart rhythm changes.
There's also a separate worry: both kratom and amitriptyline affect serotonin and the brain, so stacking them could raise the risk of serotonin-related problems or deep sedation. To be fair, this is mostly theoretical, based on lab work and a single case report, not solid human studies. Still, please don't mix these without talking to your pharmacist or doctor first.
- Kong WM, Chik Z, Ramachandra M, et al. Evaluation of the effects of Mitragyna speciosa alkaloid extract on cytochrome P450 enzymes using a high throughput assay. Molecules. 2011;16(9):7344-7356. PubMed
- Eudaley ST, Brooks SP, Hamilton LA. Case Report: Possible Serotonin Syndrome in a Patient Taking Kratom and Multiple Serotonergic Agents. J Pharm Pract 2022. PubMed
CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES
4 of 6Amitriptyline, Perphenazine also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.
In vitro research shows that kratom extract inhibits CYP3A4 enzyme activity. A pharmacokinetic study in adults shows that taking kratom tea 2 grams modestly increases the plasma concentration time-curve (AUC) and maximum concentration (Cmax) of CYP3A4 probe midazolam by 40-50% and its CYP3A4-mediated metabolites 18-27%. However, a lack of change in the half-life of midazolam and a simulation of the kratom-midazolam interaction suggest that kratom inhibits CYP3A4 enzymes in the small intestine but not the liver. Additionally, there is one case report of a 27-year-old male who died from neuroleptic malignant-like symptoms after concomitant use of kratom and quetiapine, a CYP3A4 substrate. Although it did not appear that the patient had consumed large quantities of quetiapine, postmortem plasma levels were in the lethal range, indicating possible inhibition of CYP3A4 by kratom. In another case report, a 63-year-old male presented with possible serotonin syndrome after taking an unknown dose of kratom for up to 3 months along with serotonergic prescription medications bupropion, buspirone, desvenlafaxine, trazodone, and ziprasidone. It is hypothesized that CYP3A4 inhibition by kratom reduced metabolism of desvenlafaxine, trazodone, and ziprasidone and consequently increased systemic exposure to serotonin.
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.
Triavil combines two medicines: amitriptyline (an older antidepressant) and perphenazine (an antipsychotic). Both are partly cleared by a liver and gut enzyme called CYP3A4. Kratom appears to block that enzyme, mostly in the gut, so these drugs could clear a bit more slowly and build up in your system.
If levels climb, you may notice stronger side effects: deep drowsiness, dizziness, dry mouth, constipation, a fast or irregular heartbeat, or confusion. Because both kratom and this combo can also affect serotonin and the nervous system, there is added concern about over-sedation or rare but serious reactions. Honestly, the evidence here is mostly theoretical and from lab work, but it is worth taking seriously. Please talk with your pharmacist or doctor before mixing these.
- Kong WM, Chik Z, Ramachandra M, et al. Evaluation of the effects of Mitragyna speciosa alkaloid extract on cytochrome P450 enzymes using a high throughput assay. Molecules. 2011;16(9):7344-7356. PubMed
- Hughes RL. Fatal combination of mitragynine and quetiapine - a case report with discussion of a potential herb-drug interaction. Forensic Sci Med Pathol. 2019 Mar;15(1):110-113. PubMed
- Eudaley ST, Brooks SP, Hamilton LA. Case Report: Possible Serotonin Syndrome in a Patient Taking Kratom and Multiple Serotonergic Agents. J Pharm Pract 2022. PubMed
- Tanna RS, Nguyen JT, Hadi DL, et al. Clinical Assessment of the Drug Interaction Potential of the Psychotropic Natural Product Kratom. Clin Pharmacol Ther 2023;113(6):1315-1325. PubMed
SEROTONERGIC DRUGS
5 of 6Amitriptyline, Perphenazine also falls under SEROTONERGIC DRUGS.
A 63-year-old male presented with possible serotonin syndrome after taking an unknown dose of kratom for up to 3 months along with serotonergic prescription medications bupropion, buspirone, desvenlafaxine, trazodone, and ziprasidone. It was hypothesized that kratom inhibited the cytochrome P450 3A4-, 2C9-, 2D6-, and 1A2-mediated metabolism of several of these serotonergic medications, consequently increasing systemic exposure to serotonin.
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.
This combination pill pairs amitriptyline (a tricyclic antidepressant that raises serotonin) with perphenazine (an antipsychotic). Kratom acts on opioid receptors and may add its own serotonin-like activity. Putting them together could nudge serotonin too high, raising the small but real risk of serotonin syndrome, which can show up as agitation, sweating, fast heartbeat, shivering, muscle twitching, or confusion.
There's also a second concern: kratom may slow the liver enzymes that clear amitriptyline, so the drug could build up. That can mean more drowsiness, dry mouth, constipation, dizziness, and in larger buildups, heart rhythm changes. Honestly, this is based on a single case report and theory, so it's not proven. Still, please talk with your pharmacist or doctor before mixing them.
- Eudaley ST, Brooks SP, Hamilton LA. Case Report: Possible Serotonin Syndrome in a Patient Taking Kratom and Multiple Serotonergic Agents. J Pharm Pract 2022. PubMed
CYTOCHROME P450 2C19 (CYP2C19) SUBSTRATES
6 of 6Amitriptyline, Perphenazine also falls under CYTOCHROME P450 2C19 (CYP2C19) SUBSTRATES.
In vitro research shows that kratom extract weakly inhibits CYP2C19 enzyme activity.
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.
Here's the gist with Triavil (the amitriptyline plus perphenazine combo). Lab studies suggest kratom can weakly slow down a liver enzyme called CYP2C19, which helps clear amitriptyline from your body. If that enzyme is blocked, a little more of the drug could linger, in theory nudging up its usual effects like drowsiness, dry mouth, constipation, blurry vision, or feeling lightheaded when you stand.
I want to be honest, though: this is a theoretical concern based only on test-tube data, and the effect looks weak. The bigger worry I'd flag is that both kratom and this medicine can be sedating and affect the heart, so stacking them isn't something to take lightly. Please check with your doctor or pharmacist before combining them.
- Kong WM, Chik Z, Ramachandra M, et al. Evaluation of the effects of Mitragyna speciosa alkaloid extract on cytochrome P450 enzymes using a high throughput assay. Molecules. 2011;16(9):7344-7356. PubMed
What These Ratings Mean
Every interaction above is graded three ways — here’s the key to each label.
Clinically significant. Avoid the combination, or use only under close professional supervision.
Usually worth avoiding or managing — may need monitoring, a dose change, or timing apart.
Generally not serious. Be aware of it and mention it to your pharmacist.
- 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.
- 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.
Kratom Also Interacts With Other Medications
Kratom has 982 moderate, 12 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.
Check Another of Your Medications Against Kratom
We haven’t checked that one against Kratom yet — ask our pharmacists directly.
Covers the 2,830 medications we’ve checked against Kratom. Pick one to open its full report.
Questions About Kratom 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 Kratom 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.
See Every Supplement That Interacts With Amitriptyline, Perphenazine
This page covers Kratom 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
Taking Kratom as Part of a Dietary Supplement Product? Check It for Interactions
We hold 8 real supplement products containing Kratom, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Kratom. Your product may carry other ingredients that interact with Amitriptyline, Perphenazine too, on top of Kratom — and those would not show on this page. Find your product and we’ll check every ingredient on its label:
Where Kratom 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.
#328 of 1,452 supplements looked up here in the last 7 days
#1,276 of 2,830 medications looked up here in the last 7 days
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.
About Kratom
What is Kratom?
- Pain relief
- Opioid withdrawal symptoms
- Anxiety and stress
- Low energy or fatigue
- Mood enhancement
Kratom is a Southeast Asian plant whose leaves act on the brain's opioid receptors and can produce both stimulant-like and opioid-like effects. It is not approved or proven safe by health regulators, carries real risks of dependence and serious harm, and its legal status varies widely. Talk to a pharmacist or doctor before considering it.
Other Drugs & Kratom
Browse every other medication we’ve checked against Kratom — both the ones with a known interaction and the ones without. Select any drug for the full detail.
No drugs match “”.
982 interactions
- Diltiazem ›
- Theophylline ›
- Nifedipine ›
- Metronidazole ›
- Diphenhydramine ›
- Hydrocortisone ›
- Methylphenidate ›
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- Propranolol ›
- Lidocaine ›
- Norethindrone ›
- Testosterone ›
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- Prednisone ›
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- Dexamethasone ›
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- Zopiclone ›
- Ciprofloxacin ›
- Colchicine ›
- Fentanyl ›
- Oxybutynin ›
- Oxycodone ›
- Phenytoin ›
- Prednisolone ›
- Tacrolimus ›
- Temazepam ›
- Budesonide ›
- Carbamazepine ›
- Clindamycin ›
- Dextromethorphan ›
- Doxorubicin ›
- Fluticasone ›
- Formoterol ›
- Miconazole ›
- Morphine Sulfate ›
- Nitrazepam ›
- Phenylephrine ›
- Trimipramine ›
- Acetaminophen ›
- Amphetamine ›
- Buprenorphine ›
- Conjugated Estrogens ›
- Diazepam ›
- Everolimus ›
- Ivabradine ›
- Lofepramine ›
- Medroxyprogesterone ›
- Medroxyprogesterone Acetate ›
- Meprobamate ›
- Nortriptyline ›
- Oxymorphone ›
- Propoxyphene ›
- Rifampin ›
- Selegiline ›
Showing 60 of 982 moderate interactions — see all 982 on the Kratom page.
12 interactions
No interaction 1,835 drugs checked — show the list
We also checked Kratom against these medications and found no known interaction in our sources. Open any page to confirm.
- Levothyroxine ›
- Ivermectin ›
- Aspirin ›
- Rosuvastatin ›
- Docusate ›
- Valacyclovir ›
- Hydroxyurea ›
- Ibuprofen ›
- Semaglutide ›
- Tirzepatide ›
- Bupropion ›
- Metformin ›
- Amoxicillin ›
- Acyclovir ›
- Lisinopril ›
- Doxycycline ›
- Methotrexate ›
- Azithromycin ›
- Isotretinoin ›
- Levothyroxine, Liothyronine ›
- Cyclopentolate ›
- Candesartan Cilexetil ›
- Cephalexin ›
- Mannitol ›
- Pegunigalsidase Alfa-iwxj ›
- Daptomycin ›
- Hexobarbitone ›
- Valsartan ›
- Levothyroxine Sodium ›
- Spironolactone ›
- Factor 7a ›
- Carbidopa, Levodopa ›
- Thyroid Hormone ›
- Minoxidil ›
- Mitomycin ›
- Levodopa ›
- Ezetimibe ›
- Cefaclor ›
- Lenvatinib ›
- Vancomycin ›
- Hethylphenidate Hcl ›
- Bentoquatam ›
- Dirithromycin ›
- Procainamide ›
- Tenecteplase ›
- Hydroxychloroquine ›
- Amoxicillin, Clavulanate Potassium ›
- Digoxin ›
- Azelaic Acid ›
- Dextrothyroxine ›
- Triptorelin ›
- Lomustine ›
- Acetylsalicylic Acid ›
- Diclofenac Sodium ›
- Hydrochlorothiazide ›
- Tocainide ›
- Pizotifen ›
- Rocuronium ›
- Succimer ›
- Mitomycin C ›
Showing the 60 most looked-up of 1,835 medications checked with no known interaction — see the full Kratom list.
Sources & How We Checked
Interaction details are evidence-graded and sourced from the Natural Medicines database. The medication overview comes from MedlinePlus.
- Natural Medicines (Therapeutic Research Center) — Evidence-graded clinical reference for vitamins, herbs and supplements — the basis for our interaction data.
- MedlinePlus, U.S. National Library of Medicine — NIH consumer drug information, used for the medication overviews.
- NIH Dietary Supplement Label Database (DSLD) — Official supplement product labels.
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
Amitriptyline, Perphenazine Is Linked to Lower Levels of 3 Nutrients
Natural Medicines records Amitriptyline, Perphenazine as a medicine that can lower these. This is not an interaction with Kratom — it is a separate effect of the medicine, and it is a reason some people are advised to supplement rather than to avoid one:
Read the full Amitriptyline, Perphenazine nutrient depletion report ›
Depletion records come from the licensed Natural Medicines database. Do not start a supplement on the strength of this page — ask your pharmacist or doctor whether it applies to you.
Taking Kratom and Amitriptyline, Perphenazine Together: Common Questions
Can you take Kratom with Amitriptyline, Perphenazine?
Why are there 6 interactions listed for Kratom and Amitriptyline, Perphenazine?
How serious is the Kratom and Amitriptyline, Perphenazine interaction?
Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy
Still Have a Question About Amitriptyline, Perphenazine and Kratom?
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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.