SAM-e with SSRIs: Serotonin syndrome risk
SAM-e increases serotonin synthesis and activity. Combined with SSRIs, increases serotonin syndrome risk. Some psychiatrists do combine carefully under supervision, but not without monitoring.
Do not combine without psychiatric supervision. Risk of serotonin syndrome.
Requires medical supervision if combined
SAM-e with SSRIs: Serotonin syndrome risk. Do not combine without psychiatric supervision. Risk of serotonin syndrome.
Requires medical supervision if combined
This interaction is rated “Danger” by Formulate. SAM-e increases serotonin synthesis and activity. Combined with SSRIs, increases serotonin syndrome risk. Some psychiatrists do combine carefully under supervision, but not without monitoring.
Studies from our registry that mention sam-e or ssri. Each links to the primary source and the other Formulate pages citing it.
Mentions ssri · 2024
St. John's Wort — StatPearls
Primary literature · Monograph
Identifies SSRIs (sertraline, paroxetine, fluoxetine, citalopram) as high-concern co-administration targets due to serotonin syndrome risk. Typical SJW doses implicated: 600-900 mg/day standardized extract. Typical SSRI doses in case reports: 20-75 mg/day.
Mentions ssri · 2015
Rhodiola rosea versus sertraline for major depressive disorder: a randomized placebo-controlled trial
Mao JJ, Xie SX, Zee J, et al. · Phytomedicine
12-week three-arm RCT (n=57) found rhodiola produced smaller antidepressant effect than sertraline but with significantly fewer adverse events, supporting it as an option for milder depression.
Mentions sam-e · 1996
Muscle creatine loading in men
Hultman et al. · Journal of Applied Physiology
Showed that 3g/day for 28 days reaches the same muscle creatine saturation as the classical 20g × 6 day loading protocol.
Other interactions to know
Combining St John's wort with any SSRI risks serotonin syndrome — a potentially fatal hyperserotonergic state.
Risk of serotonin syndrome
Melatonin may enhance SSRI side effects
Rhodiola may have mild MAOI effects
Ashwagandha may enhance SSRI effects
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Medical disclaimer. This page is for educational purposes only and does not replace advice from a qualified healthcare provider.
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