Mexiletine for nondystrophic myotonia

Christine Ma, University of New South Wales, Australia

Nondystrophic myotonias are a group of rare skeletal muscle ion channel disorders, with prevalence of one in a million [1] causing stiffness and, depending on the channelopathy, pain, weakness and fatigue [2]. Despite significant effects on quality of life and function, there is insufficient data to recommend a safe and effective treatment. In recent times, mexiletine, a class 1b antiarrhythmic drug with high affinity for muscle sodium channels has been found to reduce stiffness, although effectiveness is largely unknown [2, 3].

This paper describes a multi-centre, randomised, double blind, placebo-controlled crossover study enrolling 59 patients with any form of nondystrophic myotonia. 200mg mexiletine or placebo was administered over a 4 week period, each with a one week washout period confirmed by blood levels of the drug. The primary end-point was the severity score of stiffness reported by patients in the 3rd and 4th week of treatment in either period, and secondary end-points included objective and subjective, clinical and physiological measures of myotonia and other symptoms, as well as quality of life measures [3].

Mexiletine was associated with significantly improved stiffness in both treatment groups, and also showed superiority in secondary end-points. This study contributes preliminary evidence to the efficacy of mexiletine these types of myotonias. From this, larger studies would be required to confirm preliminary findings, as well as the safety of mexiletine (which has been linked with arrhythmia [2]). This study also included a heterogenous group with different channelopathies, and separate studies into distinct disease entities may yield more specific findings. Of course, the rarity of these disorders is the major barrier to further research.


1. Emery AE. Population Frequencies of Inherited Neuromuscular Diseases – a World Survey. Neuromuscular Disorders. 1991;1(1):19-29. Doi 10.1016/0960-8966(91)90039-U
2. Greenberg DA, Aminoff MJ, Simon RP. Motor Disorders. Clinical Neurology, 8e. McGraw Hill 2012.
3. Statland JM, Bundy BN, Wang Y, Rayan DR, Trivedi JR, Sansone VA, Salajegheh MK, Venance SL, Ciafaloni E, Matthews E, Meola G, Herbelin L, Griggs RC, Barohn RJ, Hanna MG. Mexiletine for Symptoms and Signs of Myotonia in Nondystrophic Myotonia. JAMA 2012; 308(13):1357-1365. Doi 10.1001/jama.2012.12607

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