Supplements and Duloxetine hydrochloride.
Duloxetine hydrochloride, sold under the brand names Cymbalta, Yentreve, is an antidepressant: depending on the agent, it acts on serotonin, noradrenaline, or both.
Duloxetine hydrochloride sits in the BNF "other antidepressants" group. The group includes the SNRIs (venlafaxine, duloxetine), the atypicals (mirtazapine, agomelatine, vortioxetine), and the older tetracyclics. The clinical class matters more than the BNF group, because the supplement profile differs sharply across it. SNRIs share the SSRI serotonergic concerns. Mirtazapine sits closer to the sedating, appetite-stimulating profile. Agomelatine is heavily liver-metabolised with mandatory LFT monitoring. Where these antidepressants share a supplement surface, it is St John's Wort (hard exclude across the class), 5-HTP (hard exclude on serotonergic grounds), rhodiola, and any supplement with significant sedating or activating effect depending on the agent. Discontinuation profiles differ too. Venlafaxine has the heaviest withdrawal syndrome of common antidepressants. Agomelatine probably the lightest.
Below are the 6 documented pairs we have explicitly assessed against Duloxetine hydrochloride in the Distil database: 2 red and 4 amber. The pairs cluster around 1 mechanism: 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
Last reviewed 21 June 2026. Each interaction below is assessed against PubMed-indexed evidence.
Additive serotonergic activity
Red Does 5-HTP interact with ?
5-HTP raises serotonin levels. Combined with an SNRI like duloxetine, it can cause serotonin syndrome. Do not combine.
Evidence: Supported by human study data.
Red Does St John's Wort interact with ?
St John's Wort and duloxetine both raise serotonin levels. Combined, they can cause serotonin syndrome. Do not combine.
Evidence: Supported by human study data.
Amber Does L-Tryptophan interact with ?
Tryptophan is the building block your body uses to make serotonin, so adding it to duloxetine raises serotonin from both directions. The combination can cause agitation, sweating, tremor, shivering, muscle twitching, or a racing heart. Do not stack them without your GP's involvement.
Evidence: Limited human data, based on case reports and a known mechanism.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
Amber Does Rhodiola Rosea interact with ?
Rhodiola has mild effects on serotonin pathways, and duloxetine raises serotonin as part of how it works. Taking them together may 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: Limited human data, based on case reports and a known mechanism.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
Amber Does SAMe interact with ?
SAMe has its own antidepressant, serotonin-related activity, which may add to duloxetine'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 duloxetine dose has recently changed.
Evidence: Limited human data, based on case reports and a known mechanism.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
Amber Does Saffron Extract interact with ?
Saffron has its own antidepressant effect that may stack with duloxetine's serotonergic component. Most people tolerate the combination but discuss it with your GP, especially if your dose has recently changed.
Evidence: Limited human data, based on case reports and a known mechanism.
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 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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- the same graded, cited interaction check across your whole stack, not just the pairs you thought to type in
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- the evidence-graded compounds worth adding, and the ones worth dropping
It's a paid report: £79, or £49 founder pricing while we earn our first reviews. The interactions check is one section of it, and you can read a real one in full before you decide.
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