S‐Adenosyl Methionine in the Therapy of Depression and Other Psychiatric Disorders

ABSTRACT Preclinical Research S‐adenosyl methionine (SAM) is a major methyl donor and as such exerts its influence on CNS function through methylation reactions, such as methylation of several catecholamine moiety‐containing neurotransmitters, epigenetic changes through methylation of DNA, RNA, RNA‐binding proteins and histones, and phospholipid methylation. Based on available evidence, SAM is currently recommended as a next‐step (second‐line) treatment option following inadequate treatment response to a first‐line antidepressant. It shows significant promise in the treatment of pediatric and perinatal depression, as well as Alzheimer's disease, but to make this a recommendation further clinical trials are needed. SAM is safe to use in most patients, but is contraindicated in those with bipolar disorder. Concerns considering the possible increase of homocysteine levels (and cardiovascular complications) due to long‐term SAM therapy need to be further addressed in clinical trials taking into account individual`s ability to metabolize homocysteine and his/her folate status. Drug Dev Res 77 : 336–346, 2016. © 2016 Wiley Periodicals, Inc.