Potassium Channel Blocker Not Helpful in MS Fatigue

Placebo did better than promising drug in treating MS fatigue.

The first study of a treatment directed at cognitive fatigue in persons with multiple sclerosis (MS) found greater improvement with placebo than with the investigated potassium channel blocker, fampridine-SR (Ampyra/Acorda Therapeutics).

Despite the results, the investigators remain intrigued with the possibility that an agent can be found to improve the cognitive fatigue that is experienced in an estimated 43 to 60 percent of persons with MS.

"Although this small pilot study does not suggest that fampridine-SR results in a statistically significant improvement of cognitive function in MS patients as compared to placebo, individuals demonstrated an improvement in both information processing speed and cognitive fatigue, suggesting further studies are warranted," indicated Sarah Morrow, MD, MS, University of Western Ontario, Department of Clinical Neurological Sciences, Western University, Ontario, Canada, and colleagues.

The potassium channel blocker is an approved adjunct in MS treatment, having been shown to improve ambulation, fatigue and endurance. The effects are attributed to improvement of potassium currents in the demyelinated axons characteristic of MS, and improving nerve impulse propagation.

Morrow and colleagues reasoned that the drug effects of enhancing action potential formation, improving conduction and preventing conduction block that have been associated with improvement in generalized, motor-muscle fatigue could lead to improvement of cognitive fatigue as well.

The study randomized 60 persons with MS of any type to four weeks of double-blind treatment with placebo or fampridine-SR 10mg twice daily, followed by one week of drug/placebo wash-out and cross over to four weeks in the other treatment arm. Pre-study medications were maintained if the dosing had been stable for at least 28 days prior to enrollment. Forty-eight persons completed the study, with no significant demographic differences between the groups.

Cognitive fatigue, a decline in cognitive performance during a task requiring sustained cognitive activity, was measured at baseline and at completion of the four week treatment periods with the Paced Auditory Serial Addition Test (PASAT). The presence of cognitive fatigue was indicated by a PASAT score of negative three or less (PASAT CF), referring to at least three fewer correct responses in the last third of the PASAT testing than in the initial portion.

The mean PASAT CF score of those on placebo was -5.3 (± 1.9) at baseline and -2.2 (± 2.8) after four weeks, while the baseline score of those receiving fampridine-SR was -3.3 (± 2.7) and -2.2 (± 2,7) after four weeks. The results indicate that subjects improved while on placebo, and showed no benefit from active medication.

Morrow and colleagues suggest that the results may reflect limitations in the study, rather than an absence of drug effect. They note that the study may have been underpowered from a small sample size, and that it was conducted at a single site.

"Further studies are needed to address potential treatment options for this common MS symptom," the investigators indicated.

The study of fampridine SR for cognitive fatigue in MS was published in the January issue of Multiple Sclerosis and Related Disorders.

The Effect of Fampridine-SR on Cognitive Fatigue in a Randomized Double-Blind Crossover Trial in Patients with MS

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