Mexiletine for Myotonia: A New Use for an Old Heart Drug?

A generic cardiovascular drug called mexiletine, initially developed to treat heart rhythm abnormalities, appears to hold some potential for treating muscle stiffness and other symptoms of non-dystrophic myotonias (NDMs), a rare group of disorders without progressive muscle wasting and weakness, that have abnormalities in the function of ion channels in the muscle cells (chloride or sodium channels).  The abnormal ion channel function leads to stiffness and delayed relaxation of muscle following grip or tight closing of the eyes (myotonia).  Myotonic dystrophy (DM) has as one of its alterations abnormal function of the chloride channel.  This causes myotonia and stiffness, and, like the patients with non-dystrophic myotonia, DM patients show a beneficial response to treatment with mexiletine.

A study published in the Journal of the American Medical Association (JAMA) in early October evaluated the drug in 59 people with NDMs. The study, sponsored by the National Institutes of Health’s Rare Disease Clinical Research Network, randomized patients with one of the rare forms of non-dystrophic myotonia to either the study drug (one capsule of mexiletine three times a day for four weeks) or placebo. After four weeks, patients stopped taking either for a week then switched to the opposite treatment for four weeks. 
 
When patients took the study drug, their muscle stiffness improved up to 40 percent and their pain scores fell by 17%. Objective tests also found that mexiletine reduced abnormal electrical activity (myotonic discharges) in the muscles that led to the spasms and stiffness. Patients also experienced significant improvements in their overall quality of life. The most common side effects were gastrointestinal, such as diarrhea, nausea, and heartburn. Click here to read an abstract of the article.
 
This study echoes findings on mexiletine and its beneficial effects on myotonia published in 2010 by Drs. Moxley, Logigian, Martens, Thornton et al.  The 2010 study, conducted at the University of Rochester with a group of 20 DM1 patients, found that grip relaxation time improved by 50% and muscle stiffness decreased when patients took mexiletine compared to placebo. Click here to read an abstract on the 2010 Rochester study.
 
Mexiletine works by slowing the rate of movement of sodium ions into muscle cells, reducing or eliminating the tendency of the muscle to maintain a prolonged contraction.  This enables the muscle cell to relax properly and be ready for the next contraction.  Mexiletine works for several hours and it needs to be taken two or three times daily to exert continued beneficial effects.
 
The drug is not approved for treating either NDM or DM, but doctors can prescribe it “off label.” However, as with any drug, there are risks and benefits and only your doctor, with your input, can decide if it might work for you.
 
10/23/2012

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