Three medications used off-label for fatigue in multiple sclerosis (MS) have performed no better than placebo, according to results from a randomised crossover trial.

But the drugs — amantadine, modafinil and methylphenidate — produced more adverse effects than placebo, leading the US specialists to advise against their use for fatigue in MS.

In the four-arm, double-blinded, crossover, placebo-controlled trial, known as TRIUMPHANT-MS, 141 participants were randomised to receive the three drugs and placebo, but in different orders.

Each drug was given to the participants for six weeks, with two-week wash-outs after each treatment, the authors wrote in The Lancet Neurology.