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Aminopyridines for symptomatic treatment in multiple sclerosis

Updated April 1, 2004
Solari A, Uitdehaag B, Giuliani G, Pucci E, Taus C.
Cochrane Review Abstracts

A substantive amendment to this systematic review was last made on 15 July 2002. Cochrane reviews are regularly checked and updated if necessary.


The potassium channel blockers 4-aminopyridine (AP) and 3,4-diaminopyridine (DAP) increase nerve conduction in demyelinated nerve fibers, and have been proposed as a symptomatic therapy for people with multiple sclerosis (MS).


To determine the efficacy and safety of aminopyridines for neurological deficits in adults with MS.

Search strategy:

We searched the Cochrane MS Group trials register (July 2002), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 2, 2002), MEDLINE (January 1966 to July 2002) and EMBASE (1974 to July 2002). We hand searched bibliographic references from retrieved studies and recent MS symposia reports, and contacted known studies' investigators.

Selection criteria:

We included trials fulfilling all following criteria: randomised controlled trials (RCTs); adults with MS, out of exacerbation; AP or DAP treatment versus placebo; clinical endpoints.

Data collection and analysis:

Three reviewers independently extracted data and assessed trial quality from 17 full-paper studies.

Main results:

Six studies (eight publications, 198 participants, all crossover trials) were considered. Five studies assessed the efficacy of AP versus placebo, one compared DAP with active placebo. Treatment duration ranged from hours to six months. Median quality score of the studies was three. Of the 198 treated participants, there were six major side effects: one acute encephalopathy, three episodes of confusion, and two seizures. Three studies (54 participants) assessed manual muscle testing, with 29 participants (54%) improving in at least one muscular district during study treatment versus four participants (7%) during placebo (odds ratio [OR] 14.5, 95% confidence interval [CI] 4.7 to 43.7). Nine out of 54 participants (17%) improved in ambulation during study treatment versus none during placebo (p < 0.001). A lower Expanded Disability Status Scale (EDSS) score was found in 13/198 participants during study treatment (7%) versus none during placebo (p < 0.001). No improvement in neuropsychological tests was found in three trials assessing cognitive function. Finally, 47/136 adults with MS (35%) felt better when receiving the study drug, against 7(5%) on placebo (OR 9.7, 95% CI 4.3 to 22.0).

Reviewers' conclusions:

Currently available information allows no unbiased statement about safety or efficacy of aminopyridines for treating MS symptoms. Furthermore, we could not obtain any data on three unpublished RCTs (more than 300 participants). We conclude that publication bias remains a pervasive problem in this area, and that until the results of these unpublished studies are available to the scientific community, no confident estimate of effectiveness of aminopyridines in the management of MS symptoms is possible.


Solari A, Uitdehaag B, Giuliani G, Pucci E, Taus C. Aminopyridines for symptomatic treatment in multiple sclerosis (Cochrane Review). In: The Cochrane Library, Issue 2, 2004. Chichester, UK: John Wiley & Sons, Ltd.

Copyright © 2004, The Cochrane Collaboration