NutriStack
SAMe and SSRIs/SNRIs, contraindicated.
SAMe increases serotonin synthesis. Combined with SSRIs: serotonin syndrome and/or manic switch risk. 9/11 bipolar patients developed mania on SAMe.
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
- SAMe and SSRIs/SNRIs
- Pair type
- Contraindicated
- Evidence (highest tier)
- Moderate
- Source citations
- 1 source
- Stack Score effect
- −25 to your Stack Score (per scored contraindication row).
- Scope
- Supplement × Supplement
- Last verified
- May 30, 2026
Contraindicated · Moderate evidence
Contraindicated
What is happening. SAMe increases serotonin synthesis. Combined with SSRIs: serotonin syndrome and/or manic switch risk. 9/11 bipolar patients developed mania on SAMe.
Mechanism. SAMe donates methyl groups in serotonin synthesis. SSRIs block reuptake. Combined effect risks serotonergic excess.
Recommendation. Do NOT combine without close psychiatric supervision. Risk of mania especially high in patients with bipolar disorder.
Sources (1)
- SAMe-induced mania case report PMID 29950497
Stack Score
How this pair moves the number.
Effect on the composite score
If both SAMe and SSRIs/SNRIs 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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