Sam-E Interactions

SAM-e has independent antidepressant and serotonergic activity, and combining it with fluoxetine can additively raise serotonergic tone, increasing the risk of serotonin syndrome and hypomania. Fluoxetine's long half-life means this risk persists for weeks after the last dose.

SAM-e (S-adenosyl-L-methionine) has its own antidepressant and serotonergic effects, and combining it with the SSRI sertraline can additively raise serotonergic activity and increase the risk of serotonin syndrome. Case reports describe mania and serotonin-toxicity-like presentations in patients combining SAM-e with SSRIs.