Role of betaine in improving the antidepressant effect of S-adenosyl-methionine in patients with mild-to-moderate depression

Background: S-adenosyl-methionine (SAMe) is a common add-on treatment used to counteract depressive symptoms in subjects with mild-to-moderate depression, who are low responders to other antidepressant drugs. However, there is some concern about the possible impact of SAMe therapy on homocysteine levels. Betaine is known both to counteract high level of homocysteine in plasma and to increase liquor and plasma levels of SAMe, thus potentiating its effect.

Aim: To evaluate the role played by betaine, administered along with SAMe, in potentiating the antidepressive role played by SAMe administered as such.

Methods: The study enrolled 46 subjects with a diagnosis of mild-to-moderate depression according to the Beck Depression Inventory Scale II. All the subjects had a suboptimal control of their symptoms. After randomization, they were treated with adjunctive treatment with either Samyr(®) (enteric-coated SAMe) or DDM Metile(®) (enteric-coated SAMe plus betaine) for 90 days.

Results: Both treatments acted similarly in improving symptoms such as anxiety, psychomotor agitation, feelings of helplessness and worthlessness, physical efficiency, and somatization, but treatment with DDM Metile(®) determined better statistically significant results following a 90-day therapy. Tolerability and compliance were overlapping in both the treatments.

Conclusion: The association of SAMe plus betaine seemed to demonstrate more effectiveness than SAMe alone when administered as an add-on therapy to subjects, affected by mild-to-moderate depression, who were low responders to conventional antidepressants.