Pharmacodynamic studies on the central mode of action of S-adenosyl-L-methionine (SAMe) infusions in elderly subjects, utilizing EEG mapping and psychometry

In a double-blind, placebo-controlled cross-over study, the acute and subacute effects of S-adenosyl-L-methionine (SAMe), or ademetionine, on brain function and behavior of 10 elderly normal healthy volunteers (5 males and 5 females, aged 56-71 years, mean: 59.3 years) were investigated by means of EEG mapping and psychometry. In random order they received infusions of 800 mg SAMe and placebo, administered over 30 minutes for 7 days, with a wash-out period of 3 weeks in between. EEG recordings and psychometric tests were carried out 0, 1, 3 and 6 hours after drug administration on days 1 and 7. Multivariate analysis based on MANOVA/Hotelling T-2 tests demonstrated significant central effects of SAMe as compared with placebo after acute, subacute and superimposed drug administration. Acute SAMe-induced changes were characterized by a decrease in total power, an increase in absolute delta and a decrease in absolute alpha power, further by an increase in relative delta and a decrease in relative alpha power, a slowing of the delta/theta centroid as well as a slowing of the centroid of the total power spectrum. These changes are typical of classical antidepressants of the thymoleptic type such as imipramine and amitriptyline. After one week of daily infusions there was a marked increase in total power, reminiscent of nootropic drug effects. One additional superimposed dosage mitigated these effects in the direction of an antidepressant profile, with the inter-drug differences waning in the 6(th) hour. Our pharmaco-EEG findings suggest both inhibitory and excitatory drug effects underlying the antidepressant properties of SAMe well-documented in clinical trials. Psychometric tests concerning noopsychic and thymopsychic measures as well as critical flicker frequency generally demonstrated a lack of differences between SAMe and placebo, which again reflects a good tolerability of the drug in elderly subjects.