More MS news articles for Nov 2001

Aminopyridines for symptomatic treatment in multiple sclerosis (Cochrane Review)

The Cochrane Libary, Issue 4, 2001
Solari A, Uitdehaag B, Giuliani G, Pucci E, Taus C

A substantive amendment to this systematic review was last made on 20 September 2000. Cochrane reviews are regularly checked and updated if necessary.


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


To determine the efficacy and safety of aminopyridines in improving neurological deficits in people with MS.

Search strategy:

Computerised general (MEDLINE, EMBASE) and specialised databases (Cochrane MS Group's trials register, CCTR). Hand search of bibliographic references from retrieved studies and recent MS symposia reports. Contact with principal investigators of known studies.

Selection criteria:

Trials were included if they fulfilled 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:

We identified 26 potentially pertinent studies. Three reviewers independently extracted data and assessed trial quality [~~Jadad 1996~~] from the 16 studies available as full papers.

Main results:

Five studies (six publications) and 144 participants were considered in this review. Two more abstracts are awaiting assessment.
All five studies were single-centre, double-blind, crossover trials. Four studies assessed the efficacy of AP versus placebo, one compared DAP with active placebo. The duration of treatment ranged from hours to three months. The median quality score of the studies was 3 (range 2-5). The heterogeneity of outcome assessment and the absence of information on individual study periods, allowed quantitative pooling of results for few categorical variables.

Of the 144 treated patients, there were six major side effects: one acute encephalopathy, three episodes of confusion, and two seizures.

Manual muscle testing was assessed in three studies (54 patients), with 29 patients (54%) improving in at least one muscular district during study treatment versus four patients (7%) during placebo (odds ratio [OR] 14.5, 95% confidence interval [CI] 4.7-43.7). Ambulation was assessed in three studies (54 patients): 9 patients (17%) improved during study treatment versus none during placebo (p <0.001). An improvement in EDSS score was found in 13 of the 144 participants during study treatment (9%) versus none during placebo (p <0.001). No improvement in neuropsychological tests was found in the two trials that evaluated cognitive function. Finally, 47 of 136 people with MS (35%) felt improved when receiving the study drug, against 7(5%) on placebo (OR 9.7, 95% CI 4.3-22.0).

Reviewers' conclusions:

Based on currently available information, no unbiased statement can be made about the safety or efficacy of aminopyridines for treating MS symptoms. Furthermore, we could not obtain any data on three unpublished RCTs involving 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, 4, 2001. Oxford: Update Software.

This is an abstract of a regularly updated, systematic review prepared and maintained by the Cochrane Collaboration. The full text of the review is available in The Cochrane Library (ISSN 1464-780X).

The Cochrane Library is prepared and published by Update Software Ltd. All rights reserved