A recent study published in The Lancet Neurology reveals that lamotrigine, a commonly used drug for epilepsy and mood disorders, is a viable alternative to mexiletine for treating non-dystrophic myotonia. The head-to-head, phase 3 trial demonstrated that lamotrigine is equally effective in reducing muscle stiffness, the hallmark symptom of this rare muscle disorder.
The trial, conducted at the UCL Queen Square Multidisciplinary Centre for Neuromuscular Diseases, involved 60 adults diagnosed with non-dystrophic myotonia. Participants were randomly assigned to receive either mexiletine followed by lamotrigine, or lamotrigine followed by mexiletine, each for eight weeks with a one-week washout period. The double-blind design ensured that neither the participants nor the researchers were aware of the treatment sequence.
Comparable Efficacy and Tolerability
The study's primary outcome was the reduction in muscle stiffness. Results indicated that lamotrigine was non-inferior to mexiletine in alleviating this symptom. Moreover, lamotrigine was well-tolerated by patients, with no serious side effects reported. This is a significant advantage, as mexiletine is associated with gastrointestinal side effects in approximately one-third of patients and is contraindicated during pregnancy.
Clinical Implications and Global Impact
Dr. Vino Vivekanandam (UCL Queen Square Institute of Neurology), the chief investigator, emphasized the importance of head-to-head trials for rare diseases, stating, "Head-to-head trials comparing drugs are important in order to allow us to identify which treatments are ideal. The trial results are very exciting and important for patients with this muscle channelopathy."
Non-dystrophic myotonias are characterized by muscle stiffness, pain, weakness, and fatigue, significantly impacting patients' quality of life and employability. While mexiletine has been the first-line treatment since 2012, its limitations necessitate alternative options. Lamotrigine's favorable profile makes it an attractive choice, particularly in developing countries where mexiletine is often inaccessible or expensive.
Personalized Treatment Algorithm
Based on the trial data, Dr. Vivekanandam's team has already developed a personalized treatment algorithm for clinical practice. This algorithm considers the mechanisms of action of both drugs, as well as local economic factors, to optimize treatment decisions for individual patients.
Professor Michael Hanna (UCL Queen Square Institute of Neurology), a senior author of the study, highlighted the significance of drug repurposing for rare diseases: "Drug repurposing is an important strategy in developing treatments for rare diseases. This is the first head-to-head trial on this rare muscle disease and the results will directly inform patient care and provide more 'real-world' options for patients."
