Amitriptyline and St. John's Wort: what the research found
PubMed indexes 7 records that name Amitriptyline and St. John's Wort together, either in the title or in an interaction, co-administration, or pharmacokinetic context. The key findings come first, in the authors’ own words, followed by every study with its design and PubMed link.
A summary of published research, not medical advice. A pharmacist can check any combination against your full list of medicines and supplements.
Reviews and human studies first. Each quote is the authors’ own conclusion about their study, not a NutriStack assessment, and a single study is not a consensus.
“Numerous interactions between herbal medicines and conventional drugs have been documented. While the significance of many interactions is uncertain, several interactions, particularly those with St John's wort, may have serious clinical consequences.”
“In contrast, SR was diminished and the dilation phase of VR was prolonged following multiple dosing with amitriptyline (P < 0.05). Decreased electrodermal reactivity observed with amitriptyline reflects inhibition of acetylcholine at peripheral m3-cholinoreceptors, whereas prolongation of VR induced by the tricyclic drug may be due to sustained activation of central and/or peripheral sympathetic neurons.”
“Multiple doses of St John's wort extract do not affect heart rate variability nor cognitive function. Chronic administration of amitriptyline causes a decrement of HRV and subjective sedation but it does not impair cognitive performance.”
The research
7 studies naming Amitriptyline and St. John's Wort.
Strongest relevance first: papers naming both substances in the title, then human trials and systematic reviews.
“In contrast, SR was diminished and the dilation phase of VR was prolonged following multiple dosing with amitriptyline (P < 0.05). Decreased electrodermal reactivity observed with amitriptyline reflects inhibition of acetylcholine at peripheral m3-cholinoreceptors, whereas prolongation of VR induced by the tricyclic drug may be due to sustained activation of central and/or peripheral sympathetic neurons.”
Names both Amitriptyline and St. John's Wort in its title.
British journal of clinical pharmacology · 2002 · PMID 12236848
Clinical TrialRandomized Controlled Trial
“Multiple doses of St John's wort extract do not affect heart rate variability nor cognitive function. Chronic administration of amitriptyline causes a decrement of HRV and subjective sedation but it does not impair cognitive performance.”
Names both Amitriptyline and St. John's Wort in its title.
“Thus, 37% of the LI 160 treated patients reported adverse events, compared to 64% in the amitriptyline group. This considerable superiority in tolerability for LI 160 in relation to amitriptyline, could confer an advantage in improving compliance for antidepressant pharmacotherapy.”
Names both Amitriptyline and St. John's Wort in its title.
Journal of clinical psychopharmacology · 2002 · PMID 11799342
Human subjects
“John's wort extract may explain this pharmacokinetic interaction. Physicians should be aware of this interaction when treating patients with amitriptyline.”
Names both Amitriptyline and St. John's Wort in its title.
“Numerous interactions between herbal medicines and conventional drugs have been documented. While the significance of many interactions is uncertain, several interactions, particularly those with St John's wort, may have serious clinical consequences.”
Names Amitriptyline and St. John's Wort together in an interaction, co-administration, or pharmacokinetic context.
European journal of clinical pharmacology · 2006 · PMID 16477470
Comparative StudyReviewHuman subjects
Names Amitriptyline and St. John's Wort together in an interaction, co-administration, or pharmacokinetic context.
Limitations
What this evidence cannot tell you.
Search-based evidence indexes have real limits, and it is worth being explicit about them:
Selection. These records were found by searching PubMed titles and abstracts for both substance names alongside interaction and pharmacokinetic terms. Relevant work that phrases things differently, or is not indexed in PubMed, will be missing.
No effect size. The quoted conclusions are the authors’ words about their own study. We have not extracted effect direction or magnitude, and a single study’s conclusion is not a consensus.
Population mismatch. Findings in healthy volunteers, animals, or a specific patient group may not transfer to you, your dose, or your formulation.
Absence is not safety. Few published studies means the combination is under-studied, which is not the same as established as safe.
How to read this page
A literature summary, not guidance.
A study listed here is not proof that Amitriptyline and St. John's Wort interact. Two substances can be named together in a paper that never tested them in combination, and a source listed as background may cover only one of them.
Findings are quoted from each abstract as the authors wrote them. NutriStack has not re-analysed, pooled, or reconciled them, and they may disagree with each other.
Decisions about prescription medication and supplements belong with your prescriber or pharmacist, who can see your full regimen. Our timing guide and forms guide explain the general mechanisms.
Nearby evidence
Other pairs with published research.
Pages covering Amitriptyline or St. John's Wort alongside a different substance.
NutriStack is a free iPhone app for organising a supplement routine: what you take, when, and what the published record says about it. Its exploratory interaction checker covers Amitriptyline, St. John's Wort, and several hundred other substances.
Log your routine, get reminders at the times you choose, and scan a label to add a product. The checker is a research and organisation tool, not a clinical decision aid.
NutriStack is an informational and organizational tool, not a medical service, and not a substitute for professional advice. Always consult a qualified healthcare professional before starting, stopping, or changing any supplement or medication.
