Cardiac drug combats muscle cramps in ALS

By Eleanor McDermid

A phase II study shows that the sodium channel blocker mexiletine has no specific safety concerns in patients with amyotrophic lateral sclerosis (ALS) and, moreover, markedly reduces muscle cramps.

"While it remains of uncertain benefit in regard to effects on disease progression, mexiletine could potentially become a first-line therapy for this frequently debilitating complication", say Michael Weiss (University of Washington Medical Center, Seattle, USA) and study co-authors.

Mexiletine is approved as an anti-arrhythmic agent, but the team tested it in ALS patients because of its recently demonstrated in vitro effects against neuronal hyperexcitability. Although riluzole - the only approved drug for delaying ALS progression - is also a sodium channel blocker, it has no reported effect on muscle cramps.

In the current study, the frequency of muscle cramp fell from 2.50 per week in the 20 patients taking placebo, to 0.78 and 0.40 per week in the 20 patients taking mexiletine 300 mg/day and the 19 patients taking 900 mg/day, respectively.

The effect was most striking among patients who had experienced at least 10 muscle cramps in the 30 days prior to baseline, with corresponding values of 8.56, 1.90 and 0.60.

The pain of muscle cramp also significantly reduced, the team reports in Neurology. Among all patients, the average pain score on a scale of 0-10 was reduced from 0.54 with placebo to 0.24 and 0.14 with mexiletine 300 and 900 mg/day, respectively.

The researchers describe this dose-dependent reduction as "dramatic". The higher mexiletine dose was not well tolerated, however, with 32% of patients discontinuing treatment, compared with 5% of those taking the lower dose or placebo. But the most common adverse effects were dizziness, falls, tremor and nausea - as expected for a sodium-channel blocker.

Weiss et al therefore suggest that mexiletine for muscle cramps could be initiated at a dose of 300 mg/day and gradually increased as needed and tolerated.

Mexiletine had no significant effect on ALS progression during the 12 weeks of treatment, with average revised ALS Functional Rating Scale scores falling by 0.66 in the placebo group and by 0.90 and 0.85 in the mexiletine 300 and 900 mg/day groups, respectively.

But the researchers stress that the study was small and of short duration, so benefits for progression cannot yet be ruled out.

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