• In a double-blind placebo-controlled crossover study of ten patients with multiple sclerosis, we found amantadine hydrochloride therapy to be effective in improving fatigability in six. Administration of the drug was associated with significantly higher levels of β-endorphinβ-lipotropin and responders had significantly higher levels than nonresponders. Lactate levels were significantly higher and pyruvate levels lower in nonresponders. Amantadine given for fatigue to patients with multiple sclerosis is associated with measurable changes in levels of metabolites and peptides in the circulation.
Rosenberg GA, Appenzeller O. Amantadine, Fatigue, and Multiple Sclerosis. Arch Neurol. 1988;45(10):1104-1106. doi:10.1001/archneur.1988.00520340058012