Abstract

The Non-Dystrophic Myotonias (NDM) are a group of skeletal muscle channelopathies caused by mutations in the chloride channel gene, CLCN1 or sodium channel gene, SCN4A. They can cause disabling stiffness, fatigue and weakness. There is anecdotal evidence that mexiletine may reduce stiffness but no randomised, double-blind, placebo-controlled trials have been done to date. We conducted an international, randomised, double-blind, placebo-controlled, crossover trial of 59 subjects with NDM. Participants were randomised to mexiletine 200 mg tds or placebo for 4 weeks, followed by a 1-week wash out, and then crossover to the alternate treatment for 4 weeks. Efficacy of the drug was monitored by daily patient reported symptom severity (stiffness, pain, weakness, tiredness) on a scale of 1–9. Improvement in stiffness was the primary outcome measure. Secondary outcome measures included a clinical assessment, quality of life, quantitative grip myotonia assessment and neurophysiological measurements of short and long exercise testing and myotonia on needle EMG. Mexiletine was found to significantly improve stiffness compared with placebo with a mean difference of 2.73 (p<0.0001) compared with placebo. It also significantly improved pain, weakness, fatigue and quality of life. It was well tolerated with no serious cardiac events. Gastrointestinal side effects were reported by 15%. Mexiletine is therefore an effective and safe drug in the treatment of stiffness in NDM.