Supplements and Trazodone hydrochloride.
Trazodone hydrochloride, sold under the brand names Molipaxin, Desyrel, is an antidepressant: depending on the agent, it acts on serotonin, noradrenaline, or both.
Trazodone 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 7 documented pairs we have explicitly assessed against Trazodone hydrochloride in the Distil database: 1 red and 6 amber. The pairs cluster around 2 mechanisms: Additive serotonergic activity and Additive CNS depression. 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
Red Does 5-HTP interact with Trazodone hydrochloride?
5-HTP is turned into serotonin in the body, and trazodone is an antidepressant that acts on serotonin, so taking the two together can cause serotonin syndrome (agitation, sweating, tremor, a racing heart, confusion). Do not take 5-HTP with trazodone; if you already take both, tell the prescriber who manages your trazodone, and do not stop trazodone on your own.
Evidence: Limited human data, from small studies or case reports.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
Amber Does L-Tryptophan interact with Trazodone hydrochloride?
Tryptophan is the building block your body uses to make serotonin, so adding it to trazodone 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, from small studies or case reports.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
Amber Does Rhodiola Rosea interact with Trazodone hydrochloride?
Rhodiola has a mild effect on serotonin pathways, and trazodone 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.
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.
Amber Does SAMe interact with Trazodone hydrochloride?
SAMe has its own antidepressant, serotonin-related activity, and trazodone is a serotonergic antidepressant too. Taking them together may add to that serotonin effect. 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 trazodone dose has recently changed.
Evidence: Limited human data, from small studies or case reports.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
Amber Does Saffron Extract interact with Trazodone hydrochloride?
Saffron has its own mild antidepressant effect that appears to act on serotonin, and trazodone is a serotonergic antidepressant. Taking them together may add to that serotonin effect. 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.
Amber Does St John's Wort interact with Trazodone hydrochloride?
St John's Wort and trazodone both act on serotonin, so combining them may raise the risk of serotonin syndrome (agitation, sweating, tremor, confusion). Talk to your GP or pharmacist before taking them together.
Evidence: Limited human data, from small studies or case reports.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
Additive CNS depression
Amber Does Ginkgo Biloba interact with Trazodone hydrochloride?
There is a published report of an older person with Alzheimer's disease falling into a coma after taking ginkgo with a low dose of trazodone. If you take trazodone, it is safer not to add ginkgo without discussing it with your GP first, especially in older adults.
Evidence: Limited human data, from small studies or case reports.
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 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 methodologyA 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.
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