NutriStack
Duloxetine and L-Tryptophan, contraindicated.
Duloxetine blocks both serotonin and norepinephrine reuptake, and L-tryptophan provides extra substrate for serotonin synthesis. The combination can raise serotonin tone beyond the therapeutic range and precipitate serotonin syndrome. Risk rises if you also use tramadol, triptans, MDMA, St. John's Wort, or other antidepressants.
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
- Duloxetine and L-Tryptophan
- Pair type
- Contraindicated
- Evidence (highest tier)
- Moderate
- Source citations
- 3 sources
- Stack Score effect
- −25 to your Stack Score (per scored contraindication row).
- Scope
- Supplement × Prescription
- Last verified
- May 30, 2026
Contraindicated · Moderate evidence
Contraindicated
What is happening. Duloxetine blocks both serotonin and norepinephrine reuptake, and L-tryptophan provides extra substrate for serotonin synthesis. The combination can raise serotonin tone beyond the therapeutic range and precipitate serotonin syndrome. Risk rises if you also use tramadol, triptans, MDMA, St. John's Wort, or other antidepressants.
Mechanism. L-Tryptophan increases the pool of serotonin precursor available to serotonergic neurons. Duloxetine inhibits SERT and NET, so increased serotonin synthesis is combined with impaired reuptake.
Recommendation. Do not take L-tryptophan supplements with duloxetine. Food tryptophan is fine; avoid concentrated sleep or mood products containing L-tryptophan. Get urgent help for clonus, high fever, severe restlessness, confusion, or muscle rigidity.
Sources (3)
- Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352(11):1112-1120. PMID 15784664
- Young SN. Use of tryptophan in combination with other antidepressant treatments: a review. J Psychiatry Neurosci. 1991;16(5):241-246. PMID 1797098
- Bymaster FP, Dreshfield-Ahmad LJ, Threlkeld PG, et al. Comparative affinity of duloxetine and venlafaxine for serotonin and norepinephrine transporters in vitro and in vivo, human serotonin receptor subtypes, and other neuronal receptors. Neuropsychopharmacology. 2001;25(6):871-880. PMID 11750180
Stack Score
How this pair moves the number.
Effect on the composite score
If both Duloxetine and L-Tryptophan 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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