Lamotrigine as Treatment of Myotonia

In order to document that Lamotrigine is an effective treatment of myotonia investigators have chosen a 20-weeks double-blind randomized and placebo-controlled cross-over design.

Participants are randomized to receive either Lamotrigine or placebo in the first period (8 weeks) and the opposite in the second period (8 weeks). Between the two periods, a drug free period of minimum two weeks is included to ensure that participants receiving Lamotrigine in the first period, is no longer affected by the drug at the beginning of the second period.

Participants are schedules for six evaluations in the clinic, three in each period. At each evaluation, the degree of myotonia is determined and a blood sample is taken and analyzed, after study closure, to determine Lamotrigine level. Before each evaluation participants evaluate myotonia at home by the Myotonia Behavior Scale (MBS). Furthermore, participants had to complete the validated life quality questionnaire SF-36, before first period, in the drug free period, and after the second period.

Treatment: Participants are treated with escalating dosages (25/50/150/300 mg)of Lamotrigine/placebo once daily in two periods of eight weeks. Patients who prior to the study receive treatment, with drugs that can potentially influence myotonia, must stop the treatment during the study. Participants, who experience severe myotonia as defined by the MBS, are allowed to use escape medicine (Mexiletine) up until 60 hours before evaluation. Any use of Mexiletine will be noted and assessed as a part of the efficacy estimation. If Mexiletine is taken under 60 hours before evaluation blood concentration of Mexiletine is measured, to exclude data with blood concentration in the therapeutic level.

Disadvantage, Side effects and Safety: During the study participants cannot take their usual medications against myotonia. This can cause symptoms of myotonia, which can be a nuisance in the patient's everyday life.

Side effects of Lamotrigine treatment are usually mild. The most common are headaches and skin rash (2). All events and inconveniences will be registered and side effects will be reported to Health Authorities in accordance with current regulations.

The study will be stopped if there is a suspicion of a previously unknown side effect of Lamotrigine that can have an impact on the participant's life or feasibility.

Inclusion criteria

• Clinical myotonia: Myotonia affecting patients daily life, such as chewing function, handshake, initiation of walking and running, or dropping objects. Patients in antimyotonic treatment.
• Gen-verified diagnosis: Myotonia Congenita, Paramyotonia Congenita, Potassium-aggravated Myotonia or Dystrophia Myotonica type 1.

Exclusion criteria

• In treatment with medicines affecting the study results, estimated by investigators.
• Participated in other drug-trials within 30 days prior to study start.
• Known intolerance or allergy to Lamotrigine.
• Significant renal or liver function, epilepsy, or long QT interval on the ECG.
• Pregnancy and breast-feeding.
• After the investigators discretion