SAMe holds promise for depression, studies find

Published: 20-Mar-2024

Two novel studies have suggested S-Adenosylmethionine (SAMe) could be a beneficial monotherapy for patients with depression

A new systematic review and meta-analysis highlights SAMe as a potential supplemental therapy for depression.

Gnosis offers the premier, patented brand of SAMe, Adonat® Premium SAMe, with an established presence on the market.

Two novel papers that examine the evidence connecting SAMe (S-Adenosylmethionine) and its efficacy, as well as acceptability for depressed patients have been recently released.

They were published in General Hospital Psychiatry and Progress in Neuropsychopharmacology & Biological Psychiatry.

In one meta-analysis, entitled: S-Adenosylmethionine (SAMe) as an adjuvant therapy for patients with depression1, researchers evaluated 14 trials with 1,522 subjects and examined the evidence concerning the efficacy of SAMe (at doses ranging from 200 to 3,200 mg and durations of 2 to 12 weeks) as a monotherapy or in combination with antidepressants. 

Depression impacts nearly 280 million people worldwide

(Statstic from the World Health Organization (WHO)

Another meta-analysis, titled ‘Efficacy and acceptability of S-adenosyl-L-methionine (SAMe) for depressed patients: A systematic review and meta-analysis’ examined 23 trials with a total of 2,183 participants compared SAMe, ranging from 45 to 3,200 mg, with either placebo or antidepressants.

According to the World Health Organization (WHO), depression impacts nearly 280 million people worldwide, leading to persistent feelings of sadness and affecting daily life. 

The condition is about 50% more prevalent among women than men3, and despite the increased availability of antidepressants, many with major depressive disorder (MDD) still have symptoms—as many as 29% to 46% of patients with MDD show only partial or no response to an adequate course of an antidepressant.4 

This emphasises the need to find better-tolerated and more effective therapies and led researchers to explore SAMe.

Several studies have found that people with MDD tend to have lower levels of SAMe in their cerebrospinal fluid.5

Administration of SAMe increases its concentrations in the cerebrospinal fluid, indicating its ability to cross the blood-brain barrier. SAMe plays a beneficial role in biochemical mechanisms that have been associated with depression, regulating key components of neurotransmission related to MDD.[5]


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The combined findings from a meta-analysis and a systematic review confirm the potential of SAMe in alleviating depression symptoms, revealing its comparable efficacy to conventional antidepressants. 

The analysis by Limveerprajak et al. is significant, being the first and largest quantitative review affirming SAMe’s efficacy as a monotherapy for depression. Both studies show SAMe’s safety and tolerability. 

Overall, these studies highlight SAMe as a beneficial option for patients seeking alternatives to traditional antidepressants, suggesting consultation with healthcare providers for incorporating SAMe into treatment plans.

The publication of these new meta-analyses is significant for the healthcare industry and patients alike. 

The findings of these studies could have a significant impact on the way healthcare providers approach depression, potentially changing the course of treatment for many patients.

“Exploring new natural solutions is important for enhancing mental health care,” says Jean-François Jeanne, Substantiation and Applications Manager at Gnosis by Lesaffre. “In the realm of depression management, where conventional approaches encounter obstacles such as treatment discontinuation and low success rates, there is a growing acknowledgment of the significance of exploring alternatives to overcome challenges with traditional methods.


1 Peng T-R, Cheng H-Y, Wu T-W. “S-Adenosylmethionine (SAMe) as an adjuvant therapy for patients with
depression: An updated systematic review and meta-analysis.” Gen Hosp Psychiatry. 2024 Jan-Feb:86:118-126.
2 Limveeraprajak et al. Efficacy and acceptability of S-adenosyl-L-methionine (SAMe) for depressed patients:
A systematic review and meta-analysis. Progress in Neuropsychopharmacology & Biological Psychiatry 132 (2024)110985
5 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.

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