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 6 documented pairs we have explicitly assessed against Fluoxetine 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 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 ?
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.
Red Does St John's Wort interact with ?
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.
Amber Does L-Tryptophan interact with ?
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.
Amber Does Rhodiola Rosea interact with ?
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, alongside 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 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, alongside a known mechanism.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
Amber Does Saffron Extract interact with ?
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, alongside 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.
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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