CNS Drugs

, Volume 33, Issue 11, pp 1087–1099 | Cite as

Effects of Fampridine in People with Multiple Sclerosis: A Systematic Review and Meta-analysis

  • Maxime ValetEmail author
  • Mélanie Quoilin
  • Thierry Lejeune
  • Gaëtan Stoquart
  • Vincent Van Pesch
  • Souraya El Sankari
  • Christine Detrembleur
  • Thibault Warlop
Systematic Review



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.


Author Contributions

MV initiated and designed the study, registered the protocol, performed the data collection and analysis, interpreted the results, designed the figures, and wrote the manuscript; MQ performed the data collection and analysis, interpreted the results, drafted the manuscript, and revised the final version; TL, GS, VVP, and SES initiated and designed the study, participated in the interpretation of the results, and critically revised the manuscript; CD designed and helped with the statistical analyses, interpreted the results, and critically revised the manuscript; TW initiated and designed the study, performed the data collection and analysis, interpreted the results, designed the figures, and critically revised the manuscript. All the authors approved the final version to be published.


Maxime Valet was partly funded by the Fondation pour l’aide à la recherche sur la sclérose en plaques (ARSEP), the Fondation Saint-Luc, Bourse de mobilité Sofmer-Allergan, and the Fonds de la Recherche Scientifique-FNRS while designing, conducting, and reporting the present work. These funders did not interfere with the present work.

Compliance with Ethical Standards

Conflicts of Interest

Thierry Lejeune, Gaëtan Stoquart, Vincent Van Pesch, and Souraya El Sankari have received a research grant from Biogen. We certify that Biogen did not interfere with the present study. Maxime Valet, Mélanie Quoilin, Christine Detrembleur, and Thibault Warlop have no conflict of interest to disclose.

Supplementary material

40263_2019_671_MOESM1_ESM.pdf (212 kb)
Supplementary material 1 (PDF 212 kb)


  1. 1.
    Thompson AJ, Baranzini SE, Geurts J, Hemmer B, Ciccarelli O. Multiple sclerosis. Lancet. 2018;391(10130):1622–36. Scholar
  2. 2.
    Montalban X, Gold R, Thompson AJ, Otero-Romero S, Amato MP, Chandraratna D, et al. ECTRIMS/EAN guideline on the pharmacological treatment of people with multiple sclerosis. Mult Scler J. 2018;24(2):96–120. Scholar
  3. 3.
    Hayes KC. The use of 4-aminopyridine (fampridine) in demyelinating disorders. CNS Drug Rev. 2004;10(4):295–316.CrossRefGoogle Scholar
  4. 4.
    Food and Drug Administration. Drugs@FDA: FDA approved drug products. 2018. Accessed 26 Sept 2018.
  5. 5.
    Jensen HB, Ravnborg M, Dalgas U, Stenager E. 4-Aminopyridine for symptomatic treatment of multiple sclerosis: a systematic review. Ther Adv Neurol Disord. 2014;7(2):97–113. Scholar
  6. 6.
    Lecat M, Decavel P, Magnin E, Lucas B, Gremeaux V, Sagawa Y. Multiple sclerosis and clinical gait analysis before and after fampridine: a systematic review. Eur Neurol. 2017;78(5–6):272–86. Scholar
  7. 7.
    World Health Organization. International Classification of Functioning, Disability and Health: ICF. Geneva: World Health Organization; 2001.Google Scholar
  8. 8.
    Conrad A, Coenen M, Kesselring J, Cieza A. What explains functioning from the perspective of people with multiple sclerosis? J Neurol. 2014;261(12):2283–95. Scholar
  9. 9.
    Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med. 2009;151(4):264–9. Scholar
  10. 10.
    Covidence systematic review software. Melbourne, Australia: Veritas Health Innovation.
  11. 11.
    Downs SH, Black N. The feasibility of creating a checklist for the assessment of the methodological quality both of randomised and non-randomised studies of health care interventions. J Epidemiol Community Health. 1998;52(6):377–84.CrossRefGoogle Scholar
  12. 12.
    Deeks JJ, Higgins JP, Altman. Analysing data and undertaking meta-analyses. In: Higgins JP, Green S, editors. Cochrane Handbook for Systematic Reviews of Interventions. London: Cochrane; 2008. p. 243–96.CrossRefGoogle Scholar
  13. 13.
    O’Connor SR, Tully MA, Ryan B, Bradley JM, Baxter GD, McDonough SM. Failure of a numerical quality assessment scale to identify potential risk of bias in a systematic review: a comparison study. BMC Res Notes. 2015;8:224. Scholar
  14. 14.
    Trac MH, McArthur E, Jandoc R, Dixon SN, Nash DM, Hackam DG, et al. Macrolide antibiotics and the risk of ventricular arrhythmia in older adults. CMAJ. 2016;188(7):E120–9. Scholar
  15. 15.
    Rauch A, Cieza A, Stucki G. How to apply the International Classification of Functioning, Disability and Health (ICF) for rehabilitation management in clinical practice. Eur J Phys Rehabil Med. 2008;44(3):329–42.PubMedGoogle Scholar
  16. 16.
    Brown TR, Simnad VI. A randomized crossover trial of dalfampridine extended release for effect on ambulatory activity in people with multiple sclerosis. Int J MS Care. 2016;18(4):170–6. Scholar
  17. 17.
    Satchidanand N, Drake A, Smerbeck A, Hojnacki D, Kolb C, Patrick K, et al. Dalfampridine benefits ambulation but not cognition in multiple sclerosis. Mult Scler. 2018. Scholar
  18. 18.
    Goodman AD, Brown TR, Cohen JA, Krupp LB, Schapiro R, Schwid SR, et al. Dose comparison trial of sustained-release fampridine in multiple sclerosis. Neurology. 2008;71(15):1134–41. Scholar
  19. 19.
    Broicher SD, Filli L, Geisseler O, Germann N, Zorner B, Brugger P, et al. Positive effects of fampridine on cognition, fatigue and depression in patients with multiple sclerosis over 2 years. J Neurol. 2018;265(5):1016–25. Scholar
  20. 20.
    Jensen HB, Nielsen JL, Ravnborg M, Dalgas U, Aagaard P, Stenager E. Effect of slow release-fampridine on muscle strength, rate of force development, functional capacity and cognitive function in an enriched population of MS patients. A randomized, double blind, placebo controlled study. Mult Scler Relat Disord. 2016;10:137–44. Scholar
  21. 21.
    Goodman AD, Cohen JA, Cross A, Vollmer T, Rizzo M, Cohen R, et al. Fampridine-SR in multiple sclerosis: a randomized, double-blind, placebo-controlled, dose-ranging study. Mult Scler. 2007;13(3):357–68. Scholar
  22. 22.
    Morrow SA, Rosehart H, Johnson AM. The effect of fampridine-SR on cognitive fatigue in a randomized double-blind crossover trial in patients with MS. Mult Scler Relat Disord. 2017;11:4–9. Scholar
  23. 23.
    Horton L, Conger A, Conger D, Remington G, Frohman T, Frohman E, et al. Effect of 4-aminopyridine on vision in multiple sclerosis patients with optic neuropathy. Neurology. 2013;80(20):1862–6. Scholar
  24. 24.
    Goodman AD, Brown TR, Krupp LB, Schapiro RT, Schwid SR, Cohen R, et al. Sustained-release oral fampridine in multiple sclerosis: a randomised, double-blind, controlled trial. Lancet. 2009;373(9665):732–8. Scholar
  25. 25.
    Goodman AD, Brown TR, Edwards KR, Krupp LB, Schapiro RT, Cohen R, et al. A phase 3 trial of extended release oral dalfampridine in multiple sclerosis. Ann Neurol. 2010;68(4):494–502. Scholar
  26. 26.
    Schwid SR, Petrie MD, McDermott MP, Tierney DS, Mason DH, Goodman AD. Quantitative assessment of sustained-release 4-aminopyridine for symptomatic treatment of multiple sclerosis. Neurology. 1997;48(4):817–21.CrossRefGoogle Scholar
  27. 27.
    Pickering H, Murray J, Lin CS, Cormack C, Martin A, Kiernan MC, et al. Fampridine treatment and walking distance in multiple sclerosis: a randomised controlled trial. Clin Neurophysiol. 2017;128(1):93–9. Scholar
  28. 28.
    Jacques F, Schembri A, Nativ A, Paquette C, Kalinowski P. Prolonged-release fampridine as adjunct therapy to active motor training in MS patients: a pilot, double-blind, randomized, placebo-controlled study. Mult Scler J. 2018;4(1):2055217318761168. Scholar
  29. 29.
    Zorner B, Filli L, Reuter K, Kapitza S, Lorincz L, Sutter T, et al. Prolonged-release fampridine in multiple sclerosis: improved ambulation effected by changes in walking pattern. Mult Scler. 2016;22(11):1463–75. Scholar
  30. 30.
    Applebee A, Goodman AD, Mayadev AS, Bethoux F, Goldman MD, Klingler M, et al. Effects of dalfampridine extended-release tablets on 6-minute walk distance in patients with multiple sclerosis: a post hoc analysis of a double-blind, placebo-controlled trial. Clin Ther. 2015;37(12):2780–7. Scholar
  31. 31.
    Yapundich R, Applebee A, Bethoux F, Goldman MD, Hutton GJ, Mass M, et al. Evaluation of dalfampridine extended release 5 and 10 mg in multiple sclerosis: a randomized controlled trial. Int J MS Care. 2015;17(3):138–45. Scholar
  32. 32.
    Filli L, Zorner B, Kapitza S, Reuter K, Lorincz L, Weller D, et al. Monitoring long-term efficacy of fampridine in gait-impaired patients with multiple sclerosis. Neurology. 2017;88(9):832–41. Scholar
  33. 33.
    Gasperini C, Hupperts R, Lycke J, Short C, McNeill M, Zhong J, et al. Prolonged-release fampridine treatment improved subject-reported impact of multiple sclerosis: item-level analysis of the MSIS-29. J Neurol Sci. 2016;370:123–31. Scholar
  34. 34.
    Hupperts R, Lycke J, Short C, Gasperini C, McNeill M, Medori R, et al. Prolonged-release fampridine and walking and balance in MS: randomised controlled MOBILE trial. Mult Scler. 2016;22(2):212–21. Scholar
  35. 35.
    Limone BL, Sidovar MF, Coleman CI. Estimation of the effect of dalfampridine-ER on health utility by mapping the MSWS-12 to the EQ-5D in multiple sclerosis patients. Health Qual Life Outcomes. 2013;11:105. Scholar
  36. 36.
    Korsen M, Kunz R, Schminke U, Runge U, Kohlmann T, Dressel A. Dalfampridine effects on cognition, fatigue, and dexterity. Brain Behav. 2017;7(1):e00559. Scholar
  37. 37.
    Magnin E, Sagawa Y, Chamard L, Berger E, Moulin T, Decavel P. Verbal fluencies and fampridine treatment in multiple sclerosis. Eur Neurol. 2015;74(5–6):243–50. Scholar
  38. 38.
    Triche EW, Ruiz JA, Olson KM, Lo AC. Changes in cognitive processing speed, mood, and fatigue in an observational study of persons with multiple sclerosis treated with dalfampridine-ER. Clin Neuropharmacol. 2016;39(2):73–80. Scholar
  39. 39.
    Espejo C, Montalban X. Dalfampridine in multiple sclerosis: from symptomatic treatment to immunomodulation. Clin Immunol. 2012;142(1):84–92. Scholar
  40. 40.
    Huynh W, Pickering H, Howells J, Murray J, Cormack C, Lin CS, et al. Effect of fampridine on axonal excitability in multiple sclerosis. Clin Neurophysiol. 2016;127(7):2636–42. Scholar
  41. 41.
    Sherratt RM, Bostock H, Sears TA. Effects of 4-aminopyridine on normal and demyelinated mammalian nerve fibres. Nature. 1980;283(5747):570–2.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Service de Médecine Physique et de RéadaptationCliniques universitaires Saint-LucBrusselsBelgium
  2. 2.Neuromusculoskeletal Lab (NMSK), Secteur des Sciences de la Santé, Institut de Recherche Expérimentale et CliniqueUniversité catholique de LouvainBrusselsBelgium
  3. 3.Service de NeurologieCliniques universitaires Saint-LucBrusselsBelgium
  4. 4.Institute of Neuroscience (IoNS) - Pôle CEMO (Cellular and Molecular), Secteur des Sciences de la Santé, Université catholique de LouvainBrusselsBelgium
  5. 5.Institute of Neuroscience (IoNS) - Pôle NEUR (Clinical Neuroscience), Secteur des Sciences de la Santé, Université catholique de LouvainBrusselsBelgium

Personalised recommendations