NutriStack
Paroxetine and SAMe, a caution.
SAMe has independent serotonergic and antidepressant activity. Combined with paroxetine, the additive serotonergic effect raises the risk of serotonin syndrome — agitation, sweating, tremor, hyperreflexia, clonus, and hyperthermia.
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.
From the interaction database
What the row says.
Every entry follows the same shape: what is happening, the mechanism, the recommendation, and the primary literature.
At a glance
- Substances
- Paroxetine and SAMe
- Pair type
- Caution
- Evidence (highest tier)
- Emerging
- Source citations
- 2 sources
- Stack Score effect
- −5 to your Stack Score (per scored caution row).
- Scope
- Supplement × Prescription
- Last verified
- May 30, 2026
Caution · Emerging evidence
Caution
What is happening. SAMe has independent serotonergic and antidepressant activity. Combined with paroxetine, the additive serotonergic effect raises the risk of serotonin syndrome — agitation, sweating, tremor, hyperreflexia, clonus, and hyperthermia.
Mechanism. SAMe modulates monoamine neurotransmission with measurable antidepressant activity. Combined with paroxetine's SERT blockade, the additive serotonergic effect can drive postsynaptic toxicity.
Recommendation. Avoid starting SAMe alongside paroxetine without explicit prescriber approval. If used together, start SAMe at the lowest effective dose and watch for tremor, restlessness, sweating, or rapid heart rate.
Sources (2)
- Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352(11):1112-20. PMID 15784664
- Sarris J, Murphy J, Mischoulon D, et al. Adjunctive S-adenosylmethionine (SAMe) in treating non-remittent major depressive disorder: An 8-week double-blind, randomized, controlled trial. Eur Neuropsychopharmacol. 2018;28(10):1126-1136. PMID 30115553
Stack Score
How this pair moves the number.
Effect on the composite score
If both Paroxetine and SAMe are in the same stack, this pair applies −5 to your Stack Score (per scored caution row).
The full algorithm, the clamping rules, and four worked stacks are documented at /methodology/stack-score.
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