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Recent advances and better understanding of neurobiology provide a rational basis for individualizing treatment of patients with major depression.

Objective A systematic review on S-adenosylmethionine (SAMe) for treatment of neuropsychiatric conditions and co-morbid medical conditions. Data Sources Searches were conducted between 7/15/2015 and 9/28/2016 by combining search terms for SAMe (s-adenosyl methionine or s-adenosyl-l-methionine) with terms for relevant disease states including (major depressive disorder, MDD, depression, perinatal depression, human immunodeficiency virus, HIV, Parkinson's, Alzheimer's, dementia, anxiety, Schizophrenia, psychotic, 22q11.2, substance abuse, fibromyalgia, osteoarthritis, hepatitis, or cirrhosis). Additional studies were identified from prior literature. Ongoing clinical trials were identified through clinical trial registries. Study Selection Of the 174 records retrieved, 21 were excluded, as they were not original investigations. An additional 21 records were excluded, for falling outside of the scope of this review. Of the 132 studies included in this review, 115 were clinical trials and 17 were preclinical studies. Data Extraction A wide range of studies was included in this review in order to capture information that would be of interest to psychiatrists in clinical practice. Results This review of SAMe in the treatment of major depressive disorder found promising but limited evidence of efficacy and safety to support the use of SAMe as a monotherapy and as an augmentation for other antidepressants. Additionally, preliminary evidence suggests that SAMe may ameliorate symptoms in certain neurocognitive, substance use and psychotic disorders and co-morbid medical conditions. Conclusions SAMe holds promise as a treatment for multiple neuropsychiatric conditions, but the body of evidence has limitations. The encouraging findings support further study of SAMe in both psychiatric and co-morbid medical illnesses.

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