S-Adenosylmethionine (SAM-e) has good evidence as a treatment for osteoarthritis pain. Some studies have found that oral SAM-e is as effective as NSAID painkillers. SAM-e takes longer to act than drugs do, but it also has fewer side effects than NSAIDs.

SAM-e has also been used to treat depression for many years. Some studies have found that SAM-e might work as well as tricyclic antidepressants in relieving symptoms.

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