FX Medicine

Home of integrative and complementary medicine

Review supports efficacy of SAMe in Depression

Melissa_Peterson's picture
  • Natural antidepressants - mood disorders

Melissa Peterson ● 2 min read

On analysing the scientific basis for the efficacy of S-Adenosylmethionine (SAMe), a recent comprehensive review shows the beneficial effect of supplemental SAMe as a potential alternative to or adjunctive therapy for use with antidepressants.

SAMe is a naturally occurring molecule, which when made commercially available became one of the most widely used natural antidepressants.

The literature review carried out an analysis of all MEDLINE/PubMed results of human randomised controlled and open clinical trials in any language, which used SAME as a therapeutic agent in Major Depressive Disorder (MDD) and Treatment-Resistant Depression (TRD). These studies included all preparations: intravenous (IV), intramuscular (IM) and oral. In cases of MDD, doses of between 200 to 1600mg daily, oral or parenterally, seemed to be superior to placebo and superior or equivalent to antidepressants, although some individuals required higher doses to achieve a sufficient clinical response. Additionally, the reviewers stated that SAMe may be a beneficial adjunctive strategy in those who do not respond to antidepressants by accelerating and enhancing their effects. They also recommended that oral doses should be taken on an empty stomach, and stated oral dosing has a half-life of approximately 100 minutes with peak plasma concentrations reached three to five hours after ingestion.

Overall, the review showed SAMe significantly improved depressive symptoms and the reviewers recommended it as both a monotherapy in mildly symptomatic patients and as an adjunctive strategy for MDD. It appeared to be safe and effective, especially as a complementary therapy in paediatric depressive disorders and in pregnant and nursing women. It is well tolerated and has few side effects. However, SAMe should be used with caution in patients with a history of hypomania or mania, and those taking it alongside antidepressants should be monitored for symptoms of serotonergic syndrome.

The effectiveness of SAMe in neurological conditions, such as depression, may be attributed to its role in several metabolic pathways. It is a substrate for methylation, transulfuration and transamino-propylation. As part of these pathways, it is integral in glutathione production, the formation of analgesic, anti-inflammatory and cell growth regulating polyamines and their resultant modulation of N-methyl-D-aspartate (NMDA) receptor excitability, and metabolism/ catabolism of monoamine neurotransmitters, such as seritonin, dopamine and noradrenaline. It is also synthesised
as part of a metabolic pathway called the one-carbon metabolism and it is suggested that MDD is associated with a dysregulation in this complex metabolic process.

‘In summary, based on the retrieved studies here evaluated, available evidence suggests that SAMe may be a therapeutic agent in MDD and also owns a pro-cognitive activity.’


  1. De Berardis D, Orsolini L, Serroni N, et al. A comprehensive review on the efficacy of S-Adenosyl-L-Methionine in major depressive disorder. CNS Neurol Disord Drug Targets. 2016;15(1):35-44. [Abstract]
  2. Carpenter DJ. St. John’s wort and S-adenosyl methionine as “natural” alternatives to conventional antidepressants in the era of the suicidality boxed warning: what is the evidence for clinically relevant benefit? Altern Med Rev 2011;16(1):17-39. [Full text]


The information provided on FX Medicine is for educational and informational purposes only. The information provided on this site is not, nor is it intended to be, a substitute for professional advice or care. Please seek the advice of a qualified health care professional in the event something you have read here raises questions or concerns regarding your health.

Share / Print: 
Melissa_Peterson's picture

Melissa Peterson has been a writer and educator in the health and medical science fields for over 15 years. Naturopathically trained, Melissa also has postgraduate qualifications in literature research and reviewing. Her business, Words On Therapy, provides many services to industry including technical articles, white papers, blogs, SEO content, copywriting and research collation.