The effects of fampridine on MS-related fatigue: a systematic review

Background: Slow-release 4-aminopyridine (fampridine) has been shown to improve walking function in people with multiple sclerosis (MS). Its effect on other MS symptoms, such as fatigue, remains controversial. We performed this systematic review to summarize the evidence of the effect of fampridine on fatigue in patients with MS. Methods: PubMed, Scopus, EMBASE, Web of Science, google scholar, and ProQuest were searched for randomized trials or observational studies reporting fatigue scores before and after the treatment with fampridine. We summarized the findings of all relevant reports. Results: A literature search revealed 2,675 records; after removing duplicates, we had 1,504 records. Ninety-seven full texts were evaluated, and finally, 33 studies remained for systematic review. Most studies were done in USA, France, Germany, and Italy. The participants' age and the duration of studies ranged between 39 and 54 years and 2 and 48 weeks, respectively. Out of 20 non-randomized or observational studies, 19 reported a benefit of fampridine in improving MS fatigue; however, only three out of 13 randomized, placebo-controlled studies showed that fampridine improved fatigue better than a placebo. Conclusion: Overwhelmingly positive results of fampridine on fatigue reported in non-randomized and observational studies are compatible with the placebo-responsiveness of fatigue in MS. Randomized, placebo-controlled studies have provided inconsistent results on the effects of fampridine on MS fatigue. Although it is possible that fatigue, at least in a subgroup of people with MS, might respond to fampridine, high-quality, placebo-controlled, blinded, randomized trials are needed to show the efficacy of this medication in improving MS fatigue.