Supplements and Amitriptyline.
Amitriptyline is a tricyclic antidepressant: it inhibits reuptake of both serotonin and noradrenaline, with significant antimuscarinic effect.
Amitriptyline is a tricyclic antidepressant. It was originally prescribed for depression. UK use is now mainly at low doses (10 to 50mg) for neuropathic pain, migraine prevention, and chronic tension headache. The full antidepressant dose (75 to 150mg) is uncommon outside specialist practice. Mechanism is mixed: serotonin and noradrenaline reuptake inhibition, plus significant antimuscarinic, antihistaminic, and alpha-1 blockade. Those off-target effects drive the side effect profile. Dry mouth, constipation, daytime sedation, postural hypotension. Cardiac conduction effects matter at higher doses, with QT prolongation especially in overdose. A few supplement interactions warrant care. Anything serotonergic on top (St John's Wort, 5-HTP, SAMe). Anything sedating at bedtime (valerian, kava, magnesium at high doses). And anything anticholinergic, which adds to the dry mouth and constipation load. The pain indication at low dose has a milder risk profile than the historical antidepressant dose, but the mechanism stays the same.
Below are the 7 documented pairs we have explicitly assessed against Amitriptyline in the Distil database: 7 amber. The pairs cluster around 3 mechanisms: Cholinergic vs anticholinergic (opposing), CYP induction, and Additive serotonergic activity. Every call is cited to either a clinical reference (PMID) or the British National Formulary. Anything not on this list is either still to be assessed or beyond our database scope. The checker beneath surfaces assessments by supplement, and the missing-item form at the bottom of the page routes any uncatalogued supplement into our next curation pass.
Documented interactions
Cholinergic vs anticholinergic (opposing)
Huperzine A raises acetylcholine, while amitriptyline has a strong anticholinergic effect that blocks it. The two can work against each other, and amitriptyline may blunt any benefit from huperzine A. It is worth mentioning the huperzine A to your prescriber.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
CYP induction
St John's Wort can speed up how the body clears amitriptyline, lowering the drug level in your blood and making it work less well for low mood or pain. In a study, it cut amitriptyline levels by about a fifth. If you take amitriptyline, mention St John's Wort to your GP or pharmacist rather than starting it on your own, and watch for symptoms returning.
Additive serotonergic activity
Amitriptyline has weak serotonin-reuptake-inhibiting activity. Combined with 5-HTP, the serotonergic effect is additive. Watch for restlessness, sweating, or muscle twitching, and discuss with your GP before stacking.
Tryptophan is the building block your body uses to make serotonin, and amitriptyline raises serotonin and noradrenaline. Taking them together raises serotonin from both directions and the effect can add up. Watch for agitation, sweating, tremor, shivering, or muscle twitching, and discuss with your GP before stacking.
Rhodiola has a mild effect on serotonin pathways, and amitriptyline raises serotonin as part of how it works. In theory, taking them together could add to that effect. Most people tolerate the combination, but watch for restlessness, sweating, tremor, or a racing heart, and talk to your GP before stacking them, especially if your dose has recently changed.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
SAMe has its own antidepressant, serotonin-related activity, which may add to amitriptyline's. Most people tolerate the combination, but watch for restlessness, sweating, tremor, shivering, or a racing heart, and tell your GP before stacking them, especially if your amitriptyline dose has recently changed.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
Saffron has its own mild antidepressant effect that appears to act on serotonin, and amitriptyline raises serotonin too. Taking them together may add up. Most people tolerate it, but discuss it with your GP before stacking, especially if your dose has recently changed.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
What this list does not say. Pairs not flagged here are not implicitly safe. They are either not yet in our database, or fall outside our inclusion scope (food-supplement interactions only; for drug-drug interactions, the BNF is authoritative). Use the checker below to surface any supplement, and submit a missing item if you take something we have not catalogued.
How we grade severity, choose what's in scope, and what we exclude.
Every call on this page is reasoned. We publish the full rubric for severity tiers, the medication inclusion logic, the evidence grades we accept, and what we deliberately leave out. About three thousand words. Worth reading once if you use this tool more than occasionally.
Read the full methodologyWant this checked across everything you take?
This page checks the pairs you enter. The personalised Distil report goes further:
- the same graded, cited interaction check across your whole stack, not just the pairs you thought to type in
- where your current routine may be leaving you short of your goals
- the evidence-backed compounds worth adding, and the ones worth dropping
It's a paid report: £79, or £49 for the first 25 customers. The interactions check is one section of it, and you can read a real one in full before you buy.
See a real sample reportSomething missing?
If a supplement or medication you take isn't in our autocomplete, tell us. We go through what people flag every week and add what's missing.