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Mexiletine reduced stiffness related to nondystrophic myotonias
Use of the antiarrhythmic drug mexiletine improved self-reports of stiffness during 4 weeks of treatment among patients with nondystrophic myotonias, according to findings from a preliminary, phase 2 study.
Researchers for the Consortium of Clinical Investigation of Neurologic Channelopathies conducted a study to determine the effects of mexiletine for symptoms of myotonia. Data on treatment of nondystrophic myotonias (NDMs) are largely anecdotal and consist of case series, a single blind, controlled trial and a 2006 Cochrane review that concluded there are no sufficient data to consider any treatment safe and effective for myotonia, according to background information in the study.
The current study, part of the NIH-funded Rare Disease Clinical Research Network, included 57 patients with NDMs (33 men; mean age, 43 years). Patients were randomly assigned to oral mexiletine 200 mg or placebo three times daily for 4 weeks, followed by the opposite intervention for 4 weeks, with a 1-week washout in between. The study was conducted at seven neuromuscular referral centers in four countries from December 2008 to March 2011.
The main outcome was patient-reported severity score of stiffness recorded on an interactive voice response diary. A score of 1 corresponded to minimal stiffness and a score of 9 corresponded to the worst ever experienced. Mexiletine was associated with significantly improved stiffness as reported on the interactive voice response diary in both treatment periods. For period 1, the treatment effect was 2.53 for mexiletine vs. 4.21 for placebo (P<.001); for period 2, 1.6 for mexiletine vs. 5.27 for placebo (P=.04).
Mexiletine was also associated with significant improvements in patient-reported outcomes, quality-of-life scales and quantitative measures of myotonia measured on clinical examination by overall handgrip times in seconds.
“Our study provides preliminary evidence of the effectiveness of mexiletine for symptoms and signs of myotonia in NDMs,” the researchers wrote. “The clinical significance of the improvement in stiffness score on the [interactive voice response] diary is supported by the broad improvement in clinical, quantitative, and electrophysiological measures of myotonia.”
Treatment was well tolerated. The most common adverse events were gastrointestinal related, with nine events in the mexiletine group and one in the placebo group. Two patients experienced transient cardiac events, but did not require stopping or withdrawal from the study.
Disclosure: See the full study for the researchers’ relevant financial disclosures.