The effect of aminopyridine for the treatment of several symptoms in people with multiple sclerosis

Solari A, Uitdehaag BMJ, Giuliani G, Pucci E, Taus C

Published Online:

January 21, 2009

Multiple sclerosis (MS) is a disease that affects young and middle-aged adults, causing different symptoms in individuals. It is caused by damage to the myelin sheaths (fibres that wrap around and protect the nerves and spinal cord). Potassium (a mineral) is important for nerve function, but may become too active when there is not enough myelin. Potassium blocking drugs (4-aminopyridine AP, and 3,4-daminopyridine DAP) may be able to improve nerve function in nerves without enough myelin. However, the review of trials found there is not enough evidence about the safety of these drugs or whether benefits are certain.

Abstract (click to read)

Background:

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).

Objectives:

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 (December 2004), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 4, 2004), MEDLINE (January 1966 to December 2004) and EMBASE (1974 to December 2004). 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).

Authors' 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.

This record should be cited as:

Solari A, Uitdehaag BMJ, Giuliani G, Pucci E, Taus C. Aminopyridines for symptomatic treatment in multiple sclerosis. Cochrane Database of Systematic Reviews 2001, Issue 4. Art. No.: CD001330. DOI: 10.1002/14651858.CD001330

Assessed as up to date:

December 29, 2004

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Primary Review Group:

Multiple Sclerosis and Rare Diseases of the Central Nervous System Group

Health topics:

Neurology > Multiple sclerosis > Pharmacological treatments by drug type

Cochrane Summaries^beta

Independent high-quality evidence for health care decision making

The effect of aminopyridine for the treatment of several symptoms in people with multiple sclerosis

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