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Logigian, E.L. et al.

E.L. Logigian, W.B. Martens, R.T. Moxley, M.P. McDermott, N. Dilek, A.W. Wiegner, A.T. Pearson, C.A. Barbieri, C.L. Annis, C.A. Thornton, R.T. Moxley,

Mexiletine is an effective antimyotonia treatment in myotonic dystrophy type 1.

OBJECTIVE: To determine if mexiletine is safe and effective in reducing myotonia in myotonic dystrophy type 1 (DM1). BACKGROUND: Myotonia is an early, prominent symptom in DM1 and contributes to decreased dexterity, gait instability, difficulty with speech/swallowing, and muscle pain. A few preliminary trials have suggested that the antiarrhythmic drug mexiletine is useful, symptomatic treatment for nondystrophic myotonic disorders and DM1. METHODS: We performed 2 randomized, double-blind, placebo-controlled crossover trials, each involving 20 ambulatory DM1 participants with grip or percussion myotonia on examination. The initial trial compared 150 mg of mexiletine 3 times daily to placebo, and the second trial compared 200 mg of mexiletine 3 times daily to placebo. Treatment periods were 7 weeks in duration separated by a 4- to 8-week washout period. The primary measure of myotonia was time for isometric grip force to relax from 90% to 5% of peak force after a 3-second maximum grip contraction. EKG measurements and adverse events were monitored in both trials. RESULTS: There was a significant reduction in grip relaxation time with both 150 and 200 mg dosages of mexiletine. Treatment with mexiletine at either dosage was not associated with any serious adverse events, or with prolongation of the PR or QTc intervals or of QRS duration. Mild adverse events were observed with both placebo and mexiletine treatment. CONCLUSIONS: Mexiletine at dosages of 150 and 200 mg 3 times daily is effective, safe, and well-tolerated over 7 weeks as an antimyotonia treatment in DM1. Classification of Evidence: This study provides Class I evidence that mexiletine at dosages of 150 and 200 mg 3 times daily over 7 weeks is well-tolerated and effective in reducing handgrip relaxation time in DM1.[1]

References

Mexiletine is an effective antimyotonia treatment in myotonic dystrophy type 1. Logigian, E.L., Martens, W.B., Moxley, R.T., McDermott, M.P., Dilek, N., Wiegner, A.W., Pearson, A.T., Barbieri, C.A., Annis, C.L., Thornton, C.A., Moxley, R.T. Neurology (2010) [Pubmed]

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