Objective. To review the antidepressant efficacy of S-Adenosyl-L-Methionine (SAMe) both in monotherapy
and/or in augmentation with antidepressants to better understand its potential role in the treatment of patients with Major
Depressive Disorder (MDD) and Treatment-Resistant Depression (TRD).
Data Sources: A MEDLINE/PubMed search was carried out by using the following set of keywords: ((SAMe OR SAdenosyl-
L-Methionine) AND (major depressive disorder OR depression)).
Data Selection and Data Extraction: No language or time restrictions were placed on the electronic searches. Randomized
controlled trials and open trials involving humans were here included and analyzed. The references of published articles
identified in the initial search process were also examined for any additional studies appropriate for the review.
Data Synthesis: SAMe is an important physiologic compound, playing a central role as precursor molecule in several
biochemical reactions. Numerous studies have shown that SAMe may affect the regulation of various critical components
of monoaminergic neurotransmission involved in the pathophysiology of MDD. Some findings have suggested its
antidepressant efficacy in treating MDD. Several randomized controlled trials have supported that the antidepressant
efficacy of SAMe in monotherapy is superior to placebo and tricyclic antidepressants. Recent findings have also
demonstrated its efficacy in patients nonresponsive to selective serotonin reuptake inhibitors and serotonin-norepinephrine
Conclusion: Overall, SAMe is a well-tolerated medication, which may offer considerable advantages as an alternative to
antidepressant drugs or as an add-on therapy in the treatment of MDD and TRD. More large-scale controlled trials are
needed to gain a better understanding of the relative efficacy of this drug.