Assessing the Safety and Efficacy of Lamotrigine as Anti-myotonic Agent in Myotonic Dystrophy Type 1 (DM1): A Longitudinal, Open-Label, Pilot Study

Abstract

Introduction: Myotonia, defined as impaired relaxation of skeletal muscles after voluntary contraction or electrical stimulation, is a core feature of myotonic dystrophy type 1 (DM1) and can be highly disabling. The most used anti-myotonic drug, mexiletine, has limited availability and is associated with several side effects. Lamotrigine (LTG), an anti-epileptic drug that reduces voltage-sensitive sodium channel activity, has shown efficacy in treating myotonia in both in vitro models and patients with non-dystrophic myotonias. We aimed to investigate in a cohort of patients with DM1 the use of LTG as an anti-myotonic treatment in a real-world setting.

Methods: We enrolled 14 consecutive adult patients with genetically confirmed DM1 and clinically significant myotonia impacting daily living (Myotonia Behaviour Scale, MBS > 1). LTG was administered in escalating doses, starting from 50 mg/day up to 200 mg/day. Efficacy was assessed using a linear mixed-effects model. Two functional timed tests [the 9-Hole Peg Test (9HPT) and the preparation of a coffee pot, devised by us and called the "Coffee Task" test] were performed at baseline (pre-treatment) and at each dose level. Safety data was also collected.

Results: The mean age at enrollment was 40 years, and the mean disease duration was 12 years. LTG dosage had a significant positive effect on 9HPT performance at the maximum dose compared to baseline. Age and disease duration significantly influenced 9HPT results. No significant changes were observed in the other functional timed test. No serious adverse events were reported.

Conclusion: This pilot, open-label study provides preliminary evidence for the efficacy and safety of LTG as an anti-myotonic treatment in patients with DM1. These findings support the need for larger, placebo-controlled trials to confirm its clinical utility.

Keywords: DM1; Lamotrigine; Myotonia; Myotonic dystrophy; Therapy.

Fig. 1

9HPT-R and 9HPT-L values at baseline and at each LTG dose increase. The timepoints representing the increasing daily dose of LTG (mg) are shown on the x-axis. On the y-axis, the values of 9HPT-R (a) and 9HPT-L (b) are shown as the time taken to perform the test in seconds. 9HPT-R and 9HPT-L are reported as mean ± SEM and have been log₁₀-transformed prior to analysis. The number of patients at each timepoint is illustrated at the bottom of the graph. 9HPT-R was significantly lower at T200 compared to BSL (p = 0.018) (a). 9HPT-L was significantly lower at T150 compared to BSL (p = 0.015) and at T200 compared to BSL (p = 0.016) (b). BSL baseline, LTG lamotrigine, sec seconds, T50 50 mg daily dose, T100 100 mg daily dose, T150 150 mg daily dose, T200 200 mg daily dose, 9HPT-L Nine-Hole Peg Test on left side, 9HPT-R Nine-Hole Peg Test on right side