A Treatment Comparison Trial for Multiple Sclerosis–Related Fatigue

Fatigue is a major symptom and source of disability in multiple sclerosis (MS). Off-label therapies include modafinil, amantadine, and methylphenidate. Investigators enrolled 141 patients with fatigue into this double-blind, placebo-controlled, four-sequence, four-period, crossover trial. Each treatment lasted 6 weeks, with a 2-week washout in between.

The estimated mean modified fatigue impact scale (MFIS) score was 51.3 at baseline, 40.6 with placebo, 41.3 with amantadine, 39.0 with modafinil, and 38.6 with methylphenidate. Treatment was not significantly different from placebo. In post-hoc analyses, a small benefit of half a point or less was observed with methylphenidate for the MFIS psychosocial subscale. Also, a trend for mild benefit …