SAM-e is the primary methyl donor in the central nervous system. SAM-e increases the action of several neurotransmitters such as dopamine, serotonin and norepinephrine by facilitating the binding of these to cell receptors (Cohen BM, et al., 1989). A number of neurotransmitters, fatty acids, phospholipids, and other chemicals must accept methyl groups from SAM-e for activation. Thus, it is believed that the observed antidepressant effect of SAM-e is due to its influence on neurotransmitter metabolism and on membrane fluidity and receptor activity (Bottiglieri and Hyland, 1994).

Serum and cerebrospinal fluid levels of SAM-e are reported to be low in depressed patients (Bottiglieri, Chary, Laundy, et al., 1988; Bottiglieri, Godfrey, Flynn, et al., 1990), although reports of depressed serum SAM-e levels were not consistent (Bottiglieri and Hyland, 1994).

An increase in SAM-e serum levels has been shown to be positively correlated with responses to both SAM-e and imipramine therapy (Bell, Potkin, Carreon, et al., 1994), as defined by a 50 percent lower score on the Hamilton Depression Rating Scale.