S-adenosylmethionine
SAMe
Pronunciation: SAM-ee
What it isThe body’s principal methyl donor, sold over the counter as a dietary supplement in enteric-coated 200 and 400 mg tablets.
Why this oneThe supplement with the strongest antidepressant evidence, best as an adjunct to an SSRI in partial responders. It supports monoamine synthesis rather than blocking reuptake, so its MAOI risk is far smaller than tryptophan’s.
What limits itCan induce mania or hypomania in bipolar disorder; serotonin toxicity reported with MAOIs and SSRIs. Activating (dose in the morning), expensive at effective doses, and destroyed by stomach acid unless enteric-coated.
Used for
- depression (monotherapy or, better, adjunct to an antidepressant)
- osteoarthritis
- liver disease
NO BOXED WARNINGS
Principal riskCan induce mania in bipolar disorder; serotonin toxicity reported with MAOIs
Classes and tags
Clinical profile
Serotonin and MAOI
Provisional washout figures
Elevating mechanismIndirect (supports monoamine synthesis)
Evidence confidenceLow
InterpretationSerotonin toxicity has been reported with MAOIs and SSRIs (case reports); avoid with an MAOI.