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Research Letter |

Long-term Safety and Efficacy of Mexiletine for Patients With Skeletal Muscle Channelopathies

Karen Joan Suetterlin, MRCP1; Enrico Bugiardini, MD1; Juan P. Kaski, MRCPCH, MD(Res)2; Jasper M. Morrow, MRCP1; Emma Matthews, MRCP, PhD1; Michael G. Hanna, FRCP, MD(Res)1; Doreen Fialho, MRCP, PhD1
[+] Author Affiliations
1MRC Centre for Neuromuscular Diseases, Department of Molecular Neuroscience, University College London Institute of Neurology, London, England
2University College London Institute of Cardiovascular Science, London, England
JAMA Neurol. 2015;72(12):1531-1533. doi:10.1001/jamaneurol.2015.2338.
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This retrospective review of a large skeletal muscle channelopathy patient cohort examines the long-term safety and efficacy of mexiletine for treating myotonia.

The skeletal muscle channelopathies include the nondystrophic myotonias and the periodic paralyses. Myotonia is the core clinical feature of the nondystrophic myotonias and may be a feature of hyperkalemic periodic paralysis. It is caused by mutations in the skeletal muscle voltage-gated chloride channel gene CLCN1 or sodium channel gene SCN4A. Adequate treatment of myotonia is important for quality of life, mobility, and functional independence.1 Mexiletine acts on voltage-gated sodium channels. Its most frequent adverse effect is gastrointestinal2,3 but minor neurological effects (eg, tremor) are also reported.4,5 Two randomized clinical trials have demonstrated the efficacy of mexiletine for the short-term treatment of myotonia2,3 but long-term safety and efficacy data outside a trial setting are lacking. We performed a retrospective review of our large skeletal muscle channelopathy patient cohort to address this.

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Figure 1.
Percentage of Patients Reporting Adverse Events While Taking Mexiletine

A, Any symptom or adverse event reported while taking mexiletine was included unless there was a clear alternative precipitant. Because some patients reported more than 1 adverse event, the total exceeds 100%. B, Distribution of adverse events by genotype. Because some patients reported more than 1 adverse event, in some cases, the total exceeds the total number of patients in that category. CLCN1 missense indicates all patients with CLCN1 missense mutations only (dominant or recessive myotonia congenita); heterozygous (Het) NMD, patients with recessive myotonia congenita with 1 CLCN1 missense mutation and 1 CLCN1 mutation associated with nonsense mediated decay; homozygous (Hom) NMD, patients with recessive myotonia congenita with 2 mutations associated with nonsense mediated decay; and SCN4A missense, all patients with SCN4A mutations.

aOther adverse effects were breathlessness (3.1%), vivid dreams (1.5%), tremor and dizziness (1.5%), loose stool, change in ejaculate and fatigue (1.5%), blepharospasm, and the inability to focus (1.5%).

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Figure 2.
Mexiletine Efficacy and Mean Effective Dose by Genotype

Efficacy was classified based on subjective patient report as documented by the clinician. A, Patient-reported mexiletine efficacy according to genotype. B, Mean effective dose of mexiletine by genotype. In A and B, patients were excluded if the effective dose was unknown (n = 1, CLCN1 missense) or mexiletine was stopped because of concern over potential but not actual adverse events (n = 1, Hom NMD). B, To enable analysis of effective dose, those patients who found mexiletine ineffective (n = 12) were also excluded. CLCN1 missense indicates all patients with CLCN1 missense mutations only (dominant or recessive myotonia congenita); heterozygous (Het) NMD, patients with recessive myotonia congenita with 1 CLCN1 missense mutation and 1 CLCN1 mutation associated with nonsense mediated decay; homozygous (Hom) NMD, patients with recessive myotonia congenita with 2 mutations associated with nonsense mediated decay; and SCN4A missense, all patients with SCN4A mutations. One-way analysis of variance P = .007.

aPost hoc unpaired t test P = .001.

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