Amantadine Influences Cognitive Processing in Patients with Multiple Sclerosis

We investigated the effect of amantadine on cognitive processing in patients with multiple sclerosis (MS) and fatigue with objective electrophysiological measures. Behavioral methods (Reaction Time, RT) and two different Event Related Potential (ERP) components measuring i) stimulus selection (Selection Negativity, SN) and ii) response selection (Lateralized Readiness Potential, LRP) were employed. Twentyfour patients with clinical definite MS (10 relapsing remitting and 14 secondary progressive) and confirmed fatigue in the past three months (Fatigue Severity Scale (FSS) > 4) were included. Patients were randomized in a double-blind, placebo-controlled cross-over design. We found a difference between the two treatments for ERP measures to stimuli with relevant colour starting at about 200 ms. This negativity had a higher amplitude during amantadine treatment regardless of treatment order. The RT did not differ significantly between the treated and untreated groups. Additional analysis indicated that patients with a disease duration of less than 7 years had a significant test position (practice effect), but no treatment effect, while patients with a longer MS duration showed no practice effect, but rather an improved reaction speed and increased ERP amplitude effects when treated with amantadine. The present findings suggest that amantadine exerts beneficial effects on early cognitive processes in patients with MS, but appears to be limited to subjects with a longer duration of the disease.

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