Supplements and Doxepin.
Doxepin, sold under the brand names Sinepin, Silenor, is a tricyclic antidepressant: it inhibits reuptake of both serotonin and noradrenaline, with significant antimuscarinic effect.
Doxepin is a tricyclic antidepressant (TCA). The class blocks reuptake of both serotonin and noradrenaline. It also has significant antimuscarinic, antihistaminic, and alpha-1 blockade. In current UK prescribing, TCAs are used mostly at low doses (10 to 50mg) for neuropathic pain, migraine prophylaxis, and chronic tension headache. The full antidepressant dose (75 to 150mg) is uncommon outside specialist practice. The 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 higher doses). And anything anticholinergic that adds to the dry mouth and constipation load. The pain indication at low dose has a lower risk profile than the historical antidepressant dose, but the mechanism is the same.
Below are the 6 documented pairs we have explicitly assessed against Doxepin in the Distil database: 1 severe and 5 caution. The pairs cluster around 2 mechanisms: Additive serotonergic activity and CYP induction. 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
Last reviewed 13 September 2026. Each interaction below lists the evidence its assessment drew on: some rest on studies of the exact pair, others on mechanism evidence, where a citation may support one part of the reasoning rather than the exact combination. The evidence line on each entry says which.
Additive serotonergic activity
Severe Does 5-HTP interact with Doxepin?
5-HTP is turned into serotonin in the body, and doxepin is a tricyclic antidepressant that can add to serotonin activity, so taking the two together can cause serotonin syndrome (agitation, sweating, tremor, a racing heart, confusion). Do not take 5-HTP with doxepin; if you already take both, tell the prescriber who manages your doxepin, and do not stop doxepin on your own.
Evidence: No direct study of this exact combination yet; the caution rests on a plausible mechanism or on reports involving a related medicine.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
Caution Does L-Tryptophan interact with Doxepin?
Tryptophan is the building block your body uses to make serotonin, and doxepin 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.
Evidence: Limited human data, from small studies or case reports.
Caution Does Rhodiola Rosea interact with Doxepin?
Rhodiola has a mild effect on serotonin pathways, and doxepin can raise 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.
Evidence: No direct study of this exact combination yet; the caution rests on a plausible mechanism or on reports involving a related medicine.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
Caution Does SAMe interact with Doxepin?
SAMe has its own antidepressant, serotonin-related activity, which may add to doxepin'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 doxepin dose has recently changed.
Evidence: Limited human data, from small studies or case reports.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
Caution Does Saffron Extract interact with Doxepin?
Saffron has its own mild antidepressant effect that appears to act on serotonin, and doxepin acts on serotonin and noradrenaline 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.
Evidence: Limited human data, from small studies or case reports.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
CYP induction
Caution Does St John's Wort interact with Doxepin?
Doxepin is a tricyclic antidepressant broken down by the same liver enzymes that St John's Wort speeds up, so St John's Wort may lower its level and make it work less well. If you take doxepin, mention St John's Wort to your GP or pharmacist rather than starting it on your own, and watch for symptoms returning.
Evidence: No direct study of this exact combination yet; the caution rests on a plausible mechanism or on reports involving a related medicine.
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.
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How the checker decides
Every result has a source
Each pair we have assessed is cited to a published study (PMID) or the British National Formulary, so you can read the source yourself.
Four kinds of answer
Severe, caution, no known interaction, and not yet assessed. A pair we have not assessed is never shown as clear.
- Severe
- Caution
- No known interaction
- Not yet assessed
Nothing in our data is not a clearance
When nothing in our data records a problem with a pair, the result says no known interaction at typical doses, which is not a clearance: your pharmacist or GP can check the pair against your full medical history.
A full supplement review, built around you, not a generic stack.
The free checker answers one interaction question at a time. A Distil report reviews the bigger picture: your goals, diet, medications, current supplements and any blood results you provide, then shows what appears worth keeping, changing, adding or leaving out.
- what your diet already covers, so you are not adding a capsule for something food is already handling
- which evidence-graded compounds are worth considering for your goals, and which were considered but left out
- what to keep, change or stop from what you already take, plus the order to introduce anything new
- how your medications and complete supplement stack fit together, with daily timing and a clear point for reassessment
The interaction check is one section of the full report. You also get the reasoning behind each recommendation and the evidence references used.
£49 until 30 June 2027 · £79 from 1 July 2027.
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