NutriStack
SAMe and Tramadol, contraindicated.
SAMe has antidepressant activity and serotonergic relevance, while tramadol inhibits serotonin reuptake and is a known serotonin syndrome risk drug. A published case report describes toxicity when SAMe was combined with the serotonergic antidepressant clomipramine, so adding SAMe to tramadol is a clinically plausible serotonergic stacking risk. Symptoms can include restlessness, sweating, tremor, diarrhea, fever, clonus, confusion, and seizure.
One pair, every claim cited. The two substances, the type, the mechanism, the recommendation, and the primary literature.
Same shape as the other 1,729 pairs in the public database.
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What the row says.
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At a glance
- Pair type
- Contraindicated
- Evidence (highest tier)
- Moderate
- Source citations
- 2 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. SAMe has antidepressant activity and serotonergic relevance, while tramadol inhibits serotonin reuptake and is a known serotonin syndrome risk drug. A published case report describes toxicity when SAMe was combined with the serotonergic antidepressant clomipramine, so adding SAMe to tramadol is a clinically plausible serotonergic stacking risk. Symptoms can include restlessness, sweating, tremor, diarrhea, fever, clonus, confusion, and seizure.
Mechanism. Tramadol increases synaptic serotonin by inhibiting serotonin reuptake. SAMe participates in methylation reactions relevant to monoamine metabolism and has clinical antidepressant activity, so concurrent use can add serotonergic pressure even though direct tramadol-SAMe cases are sparse.
Recommendation. Avoid SAMe while taking tramadol unless your prescriber specifically approves and monitors the combination. Do not add SAMe for mood support during tramadol treatment. Seek urgent care for high fever, muscle rigidity, clonus, severe agitation, or seizure.
Sources (2)
- Beakley BD, Kaye AM, Kaye AD. Tramadol, Pharmacology, Side Effects, and Serotonin Syndrome: A Review. Pain Physician. 2015;18(4):395-400. PMID 26218943
- Iruela LM, Minguez L, Merino J, Monedero G. Toxic interaction of S-adenosylmethionine and clomipramine. Am J Psychiatry. 1993;150(3):522. PMID 8434674
Stack Score
How this pair moves the number.
Effect on the composite score
If both SAMe 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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