Lamotrigine useful alternative to Mexiletine for Non-dystrophic Myotonias: Lancet
A recent groundbreaking trial conducted in London United Kingdom
revealed that lamotrigine is as effective as mexiletine and can be used as
an alternative drug for non-dystrophic myotonias. The trial results were
published in the journal The Lancet Neurology.
Non-dystrophic myotonias are a group of rare genetic
neuromuscular disorders stemming from ion channel dysfunction. They
predominantly occur in the first two decades of life leading to lifelong
morbidity. They affect skeletal muscle relaxation and typically affect the legs.
There is no cure for this condition except for symptomatic management which
includes usage of sodium channel blockers. Research done in the past has shown
that Mexiletine which is a sodium channel blocker can be used symptomatically
to improve the quality of life. Recent research has also shown the
effectiveness of lamotrigine for the symptomatic management of myotonias.
Hence, researchers conducted a head-to-head trial to compare mexiletine and
lamotrigine and the non-inferiority of lamotrigine.
A randomized, double-blind, crossover, non-inferiority,
phase 3 trial was carried out at the National Hospital for Neurology and
Neurosurgery (London, UK) by including individuals aged ≥18 years who had
genetically confirmed symptomatic non-dystrophic myotonia. The participants
were randomly assigned (1:1), employing a block randomization schedule created
by a computer program, to receive either mexiletine for 8 weeks followed by
lamotrigine for 8 weeks, or lamotrigine followed by mexiletine, with a 7-day
washout period in between.
Masking of the investigators and participants was done
during treatment allocation. The primary outcome measure was the mean
interactive voice response (IVR) diary stiffness score (0–9 scale) over the
participant’s final 2 weeks of diary reporting in each treatment period. A
mixed-effects model was used to assess the non-inferiority with a predefined
margin of 0·5 and included all randomly assigned participants who contributed
at least 7 days of IVR-diary data in either treatment period.
Findings:
- About 60 participants were screened (24 females
and 36 males) and randomly assigned between Aug 1, 2021, and Dec 12, 2022, to
either the mexiletine–lamotrigine sequence (n=30) or the lamotrigine–mexiletine
sequence (n=30). - Among them, 53 participants contributed data to
the primary analysis. - Post-treatment with the drugs, the mean IVR
stiffness score with mexiletine was 2·54 versus 2·77 with lamotrigine (mean
mexiletine–lamotrigine difference −0·23). - Indigestion–reflux was the most common adverse
event reported (eight participants, 208 participant-days receiving mexiletine;
seven participants, 130 participant-days receiving lamotrigine). - No serious adverse events were reported.
Thus, the trial concluded that lamotrigine was as effective
as mexiletine. Despite the lack of definitive evidence for non-inferiority both
the medications displayed similar efficacy. This suggests that lamotrigine can
be used as an alternative to mexiletine. This trial offers critical insights for
clinicians to offer therapeutic options to patients based on patient’s
acceptance.
Further reading: Vivekanandam V, Skorupinska I, Jayaseelan
DL, et al. Mexiletine versus lamotrigine in non-dystrophic myotonias: a
randomised, double-blind, head-to-head, crossover, non-inferiority, phase 3
trial. Lancet Neurol. 2024;23(10):1004-1012.
doi:10.1016/S1474-4422(24)00320-X
