A recent study led by Dr. Bjorn Oskarsson from the Mayo Clinic Jacksonville and supported by The ALS Association demonstrated that mexiletine, a drug approved by the U.S. Food and Drug Administration, reduced the frequency and severity of muscle cramps in people with ALS compared to a placebo.
This could lead to an improved therapeutic treatment of people with ALS. More than 90 percent of people with ALS experience muscle cramping and how clinicians currently treat cramps varies widely.
Mexiletine is approved by the FDA for the treatment of cardiac arrhythmias (irregular heartbeats) with a typical dosage between 200 and 400 mg at three times a day. It is a sodium channel blocker, meaning it impairs the movement of sodium ions (Na+) through sodium channels in the body’s cells. The main mechanism behind muscle cramping is largely unknown. In motor neurons, the cells that die in ALS, mexiletine is thought to reduce the influx of sodium ions into the distal part of axons, thereby reducing muscle cramps.
Oskarsson and colleagues conducted a multi-center, double-blind, placebo-controlled crossover trial of mexiletine at 150 mg twice daily over a 2-week period. They enrolled 20 people with ALS who wanted medication to treat muscle cramping and applied few exclusion criteria to increase enrollment.
They found that people on mexiletine experienced the following:
- Four people became completely cramp free.
- 18 out of 20 people recorded fewer muscle cramps.
- Cramp severity was significantly reduced.
- No change in fasciculations (small, involuntary muscle twitching) were reported.
- Dose was well tolerated with infrequent adverse effects.
In a small study exploring impact on muscle cramping, mexiletine was well tolerated and shown to reduce muscle cramp frequency and severity. To date, mexiletine is the only medication to demonstrate such an effect.
B. Oskarsson, et al. Mexiletine for Muscle Cramps in Amyotrophic Lateral Sclerosis: A Randomized, Double-Blind Crossover Trial. Muscle Nerve. 2018 March 6. DOI:10.1002/mus.26117.
Paper is not open access.
For trial information, click here.