Channelopathies: beneficial effects of lamotrigine

Like mexiletine, lamotrigine is a sodium channel blocker that reduces myotonia. However, it is less expensive and appears to cause fewer adverse effects than mexiletine.

A short-term Danish trial

A Danish team therefore conducted a phase II trial of lamotrigine in 26 adults with non-dystrophic myotonia (congenital myotonia and paramyotonia congenita), representing approximately one third of all adults diagnosed with non-dystrophic myotonia in Denmark, between November 2013 and July 2015.

In this randomised, double-blind, crossover trial, half of the participants received lamotrigine for two months followed, after a two- to four-week washout period, by placebo for two months. The other half received placebo first and then lamotrigine according to the same protocol.

The results showed good treatment tolerability. Lamotrigine significantly reduced myotonia and was associated with improved quality of life in treated participants.

The authors concluded that lamotrigine could represent an alternative to mexiletine and may be considered a first-line treatment for myotonia in patients with non-dystrophic myotonia.

A longer British study

A more recent study confirmed the beneficial effects of lamotrigine over approximately two years. At the end of follow-up, the 37 patients with non-dystrophic myotonia included in the study showed significant improvement in myotonia. Overall, treatment was well tolerated, although nine patients discontinued treatment due to headaches or skin rashes.

Sources
The antimyotonic effect of lamotrigine in non-dystrophic myotonias: a double-blind randomized study.
Andersen G, Hedermann G, Witting N, Duno M, Andersen H, Vissing J.
Brain. 2017 Sept.
On ClinicalTrials.gov: NCT01939561

Long term safety and efficacy of lamotrigine in patients with non-dystrophic myotonia, a single-centre prospective study.
Asad M, Skorupinska I, James N et al.
Neuromuscul Disord. 2025 Nov