S-adenosyl methionine (SAMe) A high-quality Cochrane review of the effectiveness and safety of SAMe supplementation on depression severity revealed two randomized clinical trials of low risk of bias that showed no significant pooled effects for SAMe monotherapy versus placebo.
One trial, also of low risk of bias, showed a significant medium short-term effect as adjunctive to standard antidepressant medication, both for depression severity.
Further five RCTs, which were rated as having overall unclear risk of bias, showed similar pooled effects of SAMe monotherapy on depression severity compared with standard antidepressant medications.