SAMe Augmentation in Major Depressive Disorder: Clinical Trial
Does SAMe help when antidepressants don’t work?
Yes. SAMe augmentation produces approximately 2 times greater response rates (36.1% vs. 17.6%) and more than 2 times greater remission rates (25.8% vs. 11.7%) compared to placebo in patients with treatment-resistant depression. A randomized controlled trial of 73 patients who failed prior SSRI treatment found that adding SAMe to ongoing antidepressants provided clinically meaningful improvements comparable to FDA-approved augmentation medications.
SAMe works by increasing the synthesis of brain neurotransmitters like serotonin, dopamine, and norepinephrine through its role as a major methyl donor in the one-carbon cycle, addressing underlying biochemical imbalances that may limit antidepressant effectiveness.