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Medication · tricyclic antidepressant

Supplements and Imipramine.

Every documented pair, every citation. Below: 3 documented pairs grouped by mechanism.

Imipramine is a tricyclic antidepressant: it inhibits reuptake of both serotonin and noradrenaline, with significant antimuscarinic effect.

Imipramine 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 3 documented pairs we have explicitly assessed against Imipramine in the Distil database: 3 amber. The pairs cluster around 2 mechanisms: Cholinergic vs anticholinergic (opposing) 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)

Amber Huperzine A

Huperzine A raises acetylcholine, while imipramine has a strong anticholinergic effect that blocks it. The two can work against each other, and imipramine may blunt any benefit from huperzine A. It is worth mentioning the huperzine A to your prescriber.

PMID 29350336 · PMID 18425924 · BNF: Imipramine

Reviewer-flagged: awaiting clinical-reviewer sign-off.

Additive serotonergic activity

Amber 5-HTP

Imipramine has 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.

BNF: Imipramine

Saffron has its own mild antidepressant effect that appears to act on serotonin, and imipramine raises 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.

PMID 15852492 · PMID 36678554 · BNF: Imipramine

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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For adults over 18. This tool gives evidence-graded information, not medical advice. Always discuss changes with your GP, especially if you take any medication, are pregnant, breastfeeding, or have a serious health condition.
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How we decide

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.

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Distil's interactions database is reviewed and updated every quarter. We grade evidence transparently and publish our methodology, including every database change, at /about/methodology. This tool is information, not a substitute for clinical judgement. If you take medication and supplements together, your GP or pharmacist can review your full regimen against your medical history. If you want a full personalised stack reasoned against this same database, the Distil report is the next step up.