Prolonged-release (PR) fampridine is a potassium channel blocker used as a symptomatic treatment for walking disability in patients with multiple sclerosis (MS). Its clinical effects in such patients have not been systematically reviewed, and may be more wide-ranging than expected. To summarize the evidence on the effects of PR fampridine in patients with MS. A systematic search of Pubmed, Scopus (including EMBASE), and PsycINFO (completed in 01/2019) was carried out to identify randomized controlled trials (RCT) that compared PR fampridine to placebo. When appropriate, data were pooled using a random-effects model, and standardized mean differences (SMD) were computed. Study quality was assessed using the Downs and Black checklist. PRISMA guidelines were followed. All retrieved functional outcomes were categorized according to the International Classification of Functioning, Disability and Health (ICF). A total of 706 articles were screened for inclusion. Twenty RCTs involving 2616 patients met the eligibility criteria. Most studies were of good-to-excellent quality. PR fampridine administration resulted in significant benefits in relation to walking short distances (SMD: 1.23 (95% IC 0.65–1.81)) and perceived walking capacity (0.64 (0.27–1.02)). Its effects on muscle strength and middle-distance walking were not significant (0.53 (− 0.04 to 1.10) and 0.31 (− 0.18 to 0.80), respectively). No effect on higher-level cognitive functions (− 0.07 (− 0.58 to 0.45)) or hand and arm use (0.16 (− 0.33 to 0.64)) was observed. Individual studies reported effects on other outcomes across the ICF domains. There is strong evidence that PR fampridine exerts strong effects on the ability to walk short distances and on perceived walking capacity. Other effects of PR fampridine according to the ICF are possible but still unclear.
