Real-World Study Provides Support for Lamotrigine in Treating Non-Dystrophic Myotonias

A recently published, single-center, prospective, real-world study found a significant reduction in Myotonia Behavior Score (MBS) in patients with non-dystrophic myotonias (NDM) treated with lamotrigine (Lamictal), further supporting the treatment as a viable treatment option for genetically confirmed NDM.

Recently published in Neuromuscular Disorders, the study featured 37 patients with genetically confirmed NDM who were prescribed lamotrigine as part of routine clinical care. Patients were followed for a mean of 26 months, with 26 individuals included in the efficacy analysis.

All told, results showed that mean MBS improved substantially with lamotrigine treatment, with mean MBS decreasing from 3.3 (SD, 1.0) prior to treatment to 1.8 (SD, 1.1) at follow-up. When categorized by genotype, patients with CLCN1 variants (n = 16) experienced a reduction in mean MBS from 3.6 to 1.8, while those with SCN4A variants (n = 10) saw scores decline from 2.9 to 1.8. Overall, the mean reduction in MBS was 1.5 points (SD, 1.3, 95% CI, 1.0-2.1), representing a statistically significant improvement in myotonia symptoms (t(25) = 5.9; P < .001).

In terms of safety, adverse events (AEs) were reported in 14 of 37 patients, leading to treatment discontinuation in 9 cases. The most common AEs prompting cessation were rash (n = 5) and headache (n = 2). One patient discontinued lamotrigine during an inpatient admission for an unrelated ischemic stroke. Among patients who continued treatment despite mild AEs, reported symptoms included tremor, nausea, anxiety, insomnia, and headache. No severe or cardiac adverse events were observed during the study.

Led by Murva Asad, MB, BCh, BAO, neurologist at the National Hospital for Neurology and Neurosurgery in London and PhD candidate, this UK National Referral Centre study had a mean age cohort of 51.5 years. Participants received an average daily dose of 200 mg of lamotrigine, with a maximum of 400 mg. Follow-up appointments were conducted in a nursing telephone clinic every 3–6 months, with yearly consultant-led visits, over an average of 26 months. In addition to the primary outcome of MBS reduction, the study recorded gene variants, reasons for choosing lamotrigine, prior NDM treatments, maintenance doses, and adverse events, including reasons for discontinuation.

Lamotrigine was selected as a treatment option for patients with NDM in this study due to its favorable safety profile and potential efficacy. According to the study authors, it was particularly appealing for individuals who experienced AEs or had contraindications to first-line therapy, such as mexiletine. Coming into the study, several participants had previously tried mexiletine or other anti-myotonic agents but discontinued due to treatment-related AEs, including gastrointestinal issues, cardiac concerns, or other comorbidities.

“Lamotrigine may represent a more practical and accessible alternative in certain settings,” noted study authors. “Following a recent trial directly comparing lamotrigine to mexiletine, Vivekanandam et al. proposed a personalized treatment algorithm factoring in patient comorbidities, family planning considerations, side effects, lifestyle preferences, and health-economic implications when selecting first-line therapy between these two medications.”

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A previous randomized study published in 2017 evaluated lamotrigine using a similar treatment rationale. That randomized, double-blind, placebo-controlled, two-period crossover trial (NCT02159963) enrolled adults in Denmark with clinical myotonia and genetically confirmed myotonia congenita or paramyotonia congenita. All in all, the investigators found that lamotrigine significantly reduced myotonia severity, with consistent improvements observed across both patient-reported outcomes and objective measures.²

The primary endpoint of the 2017 study was change in MBS, similar to Asad et al’s work. Patients had a mean baseline MBS score of 3.2 (SD, 1.1), which fell by 1.3 points (SD, 0.2) after lamotrigine treatment (P < .001), whereas placebo was associated with a nonsignificant 0.2-point change (SD, 0.1; P = .4). The estimated treatment effect size was 1.0 (SD, 0.2, 95% CI, 0.5-1.5; P < .001; n = 22), with a standardized effect size of 1.5 (95% CI, 1.2-1.8).

For that study, a pharmacy manufactured the medication and matching placebo and performed block randomization with a block size of 10. Both participants and investigators remained blinded to treatment allocation until completion of the trial. Each participant received oral lamotrigine and placebo during two separate 8-week treatment periods, administered once daily with a stepwise dose escalation every second week from 25 mg to 50 mg, 150 mg, and a maximum of 300 mg.

REFERENCES
1. Asad M., Skorupinska I., James N., Jayaseelan D., Hanna M., Vivekanandam V. Long term safety and efficacy of lamotrigine in patients with non-dystrophic myotonia, a single-centre prospective study. Neuromuscular Disorders. 2025;56–57(106222): ISSN 0960-8966. Doi: 10.1016/j.nmd.2025.106222.
2. Andersen G, Hedermann G, Witting N, Duno M, Andersen H, Vissing J. The antimyotonic effect of lamotrigine in non-dystrophic myotonias: a double-blind randomized study. Brain. 2017;140(9):2295-2305. doi:10.1093/brain/awx192