SYSTEMATIC REVIEW article
Front. Neurol.
Sec. Multiple Sclerosis and Neuroimmunology
This article is part of the Research TopicThe hidden burden of multiple sclerosis: Exploring depression, fatigue, pain, and cognitive impairmentsView all articles
The effects of fampridine on MS-related fatigue, a systematic review
Provisionally accepted
- 1Tehran University of Medical Sciences, Tehran, Iran
- 2University of San Francisco, San Francisco, United States
- 3Washington University Center for Cellular Imaging, Saint Louis, United States
- 4James Hope University, Lagos, Nigeria
- 5Johns Hopkins University, Baltimore, United States
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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 2675 records; after removing duplicates, we had 1504 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 thirteen randomized, placebo-controlled studies showed that fampridine improved fatigue better than a placebo. Conclusions: 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.
Keywords: dalfampridine, fampridine, Fatigue, Multiple Sclerosis, Systematic review
Received: 07 Oct 2025; Accepted: 10 Dec 2025.
Copyright: © 2025 Rastkar, Cordano, Ghajarzadeh and Nourbakhsh. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Mahsa Ghajarzadeh
Bardia Nourbakhsh
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