NutriStack
Fluoxetine and Tramadol, contraindicated.
Fluoxetine combined with tramadol creates dual serotonin syndrome risk. Additionally, fluoxetine inhibits CYP2D6, reducing tramadol conversion to its active metabolite (O-desmethyltramadol), potentially reducing analgesic efficacy while increasing serotonergic toxicity risk.
One pair, every claim cited. The two substances, the type, the mechanism, the recommendation, and the primary literature.
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At a glance
- Substances
- Fluoxetine and Tramadol
- Pair type
- Contraindicated
- Evidence (highest tier)
- Strong
- Source citations
- 1 source
- Stack Score effect
- −25 to your Stack Score (per scored contraindication row).
- Scope
- Supplement × Prescription
- Last verified
- May 30, 2026
Contraindicated · Strong evidence
Contraindicated
What is happening. Fluoxetine combined with tramadol creates dual serotonin syndrome risk. Additionally, fluoxetine inhibits CYP2D6, reducing tramadol conversion to its active metabolite (O-desmethyltramadol), potentially reducing analgesic efficacy while increasing serotonergic toxicity risk.
Mechanism. Fluoxetine potently inhibits CYP2D6 and serotonin reuptake. Tramadol also inhibits serotonin reuptake. The combination produces additive serotonergic activity and altered tramadol metabolism.
Recommendation. Avoid concurrent use. The CYP2D6 interaction compounds the serotonin syndrome risk, making this combination particularly dangerous.
Stack Score
How this pair moves the number.
Effect on the composite score
If both Fluoxetine and Tramadol are in the same stack, this pair applies −25 to your Stack Score (per scored contraindication row).
The full algorithm, the clamping rules, and four worked stacks are documented at /methodology/stack-score.
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