S-Adenosyl-L-Methionine (SAMe) for Neuropsychiatric Disorders: Latest Clinical and Mechanistic Evidence

Dr. David Mischoulon   DMISCHOULON@mgh.harvard.edu



S-adenosyl methionine (SAMe) is a natural antidepressant that has been supported as effective and safe in more than 40 published clinical trials. SAMe has been effectively and safely combined with standard antidepressants. A recent double blind study showed no advantage for SAMe or escitalopram over placebo for adults with major depressive disorder (MDD). This presentation will review the evidence for SAMe as an antidepressant, and present new data examining whether combination therapy with SAMe and escitalopram following nonresponse to either therapy alone or to placebo is effective for persistent MDD.


Patients who completed the acute phase of treatment in a 12-week randomized double blind clinical trial comparing SAMe vs escitalopram vs placebo monotherapy were followed in a second 12-week period where responders continued on their originally assigned treatment, and nonreponders were switched to open therapy with SAMe 3200mg/day plus escitalopram 20mg/day. Efficacy was determined based on the Hamilton Depression Rating Scale (HAM-D-17), the Inventory of Depressive Symptomatology-Self Rated (IDS-SR), and Clinical Global Improvement Scales for severity (CGI-S) and improvement (CGI-I).


Continuation on the original treatments (Placebo, SAMe, escitalopram) for 12 more weeks produced no significant additional improvement relative to each other. Subjects who were crossed over to combination therapy following nonresponse showed significantly greater improvements in HAM-17 compared to those who continued on SAMe (p=0.049) or escitalopram (p=0.049), but only a trend compared to placebo (p=0.098); CGI-S and CGI-I scores improved significantly more for the combination therapy group than for SAMe (p<0.001), escitalopram (p<0.001), or placebo (p=0.006). IDS-SR scores did not improve significantly for the combination group compared to SAMe, ESC, or placebo (all p>0.2). Tolerability of the combination was good, with the combination group reporting fewer adverse effects than the monotherapies or placebo.


Combining SAMe with escitalopram may be an effective approach for patients who fail to fully respond to either treatment alone. While the literature as a whole supports SAMe's antidepressant effect, controlled studies examining this and other treatment combinations with SAMe are needed.



5th MBI symposium