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

Abstract

BackgroundS-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.AimTo evaluate the role played by betaine, administered along with SAMe, in potentiating the antidepressive role played by SAMe administered as such.MethodsThe 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.ResultsBoth 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.ConclusionThe 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.

Betaine enhances antidepressant-like, but blocks psychotomimetic effects of ketamine in mice

“…It appears that betaine plays a critical role in the regulation of brain functions. A recent clinical study has shown that the combined action of SAMe and betaine is more effective than the administration of SAMe alone in patients with mild to moderate depression (Di Pierro et al 2015). The present animal study revealed that betaine has acute and sustained antidepressant-like effects.…”

“…A recent clinical study has demonstrated that S-adenosylmethionine (SAMe) plus betaine is more effective 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 (Di Pierro et al 2015). Although a betaine-alone treatment group was not included in this clinical report and the exact mechanisms underlying the antidepressant effects of betaine remain to be further investigated, apparently betaine has beneficial effects for patients with treatment-resistant depression.…”

S‐Adenosyl Methionine in the Therapy of Depression and Other Psychiatric Disorders

“…A recent meta-analysis showed that SAM increases the efficiency of conventional antidepressants when used together in the treatment of nonresponsive MDD patients [Sarris et al, 2016]. One study demonstrated that the combination of SAM and betaine as an add-on therapy in depressed patients, who did not respond to conventional antidepressants, was more effective than SAM alone [Di Pierro et al, 2015]. Betaine is an alternative methyl group donor in remethylation of methionine (a SAM precursor) from Overall, SAM was comparable to other antidepressants in a therapy of depression.…”

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“…Betaine serves as organic osmolytes and is taken up by cells in situations of environmental stress such as high temp, salinity, osmotic stress, etc. Role of betaine has been well established in treating depression 38 . The lowered concentration of betaine signifies cellular stress in PTSD.…”