Supplements and Fluoxetine hydrochloride.
Fluoxetine hydrochloride, sold under the brand names Prozac, Olena, Oxactin, is a selective serotonin reuptake inhibitor (SSRI): it raises synaptic serotonin by blocking its reuptake.
Fluoxetine was the original SSRI. It remains widely prescribed in the UK and has the longest plasma half life of the class. The active metabolite norfluoxetine persists for one to two weeks after stopping. The long persistence is clinically useful for patients who struggle with adherence, and it matters for drug interactions. Fluoxetine is a strong CYP2D6 inhibitor and a moderate CYP3A4 inhibitor, so it raises plasma levels of drugs that depend on those enzymes when given alongside (some beta-blockers, antipsychotics, tricyclics). The supplement profile is the standard SSRI shape. Serotonergic concerns with St John's Wort (hard exclude), 5-HTP (hard exclude), tryptophan, rhodiola, saffron extract, and SAMe. The slow clearance also extends the MAOI washout after stopping fluoxetine to five weeks, against two weeks for sertraline or citalopram. Any planned supplement change ideally accounts for it.
Below are the 7 documented pairs we have explicitly assessed against Fluoxetine hydrochloride in the Distil database: 2 severe and 5 caution. 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 11 October 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 Fluoxetine hydrochloride?
5-HTP is the precursor your body uses to make serotonin. Combined with an SSRI like fluoxetine, it can cause serotonin syndrome (agitation, sweating, tremor, confusion). Do not combine.
Evidence: Supported by human study data.
Severe Does St John's Wort interact with Fluoxetine hydrochloride?
St John's Wort and fluoxetine both raise serotonin levels. Combined, they can cause serotonin syndrome (agitation, sweating, tremor, raised heart rate, confusion). Do not combine.
Evidence: Supported by human study data.
Caution Does Ashwagandha interact with Fluoxetine hydrochloride?
Ashwagandha may interact with fluoxetine. In people taking other SSRI antidepressants, side effects that eased once ashwagandha was stopped have been reported, and one person on escitalopram developed serotonin toxicity after a large dose of ashwagandha. No report involves fluoxetine itself, but it works the same way, so speak to your GP or pharmacist before starting ashwagandha and get urgent help if you notice twitching, agitation, fever or a racing heart. Fluoxetine stays in the body for weeks after stopping, so this applies for a while afterwards too.
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 Fluoxetine hydrochloride?
Tryptophan is the building block your body uses to make serotonin, so adding it to fluoxetine 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: Supported by human study data.
Caution Does Rhodiola Rosea interact with Fluoxetine hydrochloride?
Rhodiola has mild effects on serotonin pathways that can add to fluoxetine's. 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, from small studies or case reports.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
Caution Does SAMe interact with Fluoxetine hydrochloride?
SAMe has its own antidepressant, serotonin-related activity, which may add to fluoxetine'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 fluoxetine dose has recently changed. Fluoxetine also stays in your system for weeks after stopping, so the caution applies for a while after a dose change.
Evidence: Limited human data, from small studies or case reports.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
Caution Does Saffron Extract interact with Fluoxetine hydrochloride?
Saffron has its own antidepressant effect, possibly via serotonin-receptor modulation. Combined with fluoxetine, the serotonergic effect may stack. Most people tolerate the combination 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.
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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