Tolerability and safety of mexiletine in patients with myotonia dystrophy type 1 over time

Objectives: Although mexiletine is accepted as an antimyotonic agent in the non-dystrophic myotonias, there is still no general consensus S128 123 regarding safety in the dystrophic myotonias. In this study our primary aim was to assess tolerability and safety in patients with myotonic dystrophy type 1 (DM 1) over time. In addition our secondary aims were to determine of the effects of the drug on myotonia and muscle strength in these same patients. Methods: 36 patients with moderately-severe adult DM1 were treated with mexiletine 200 mg tid and compared to age-, diseaseduration and MRC- matched 34 untreated patients with moderatelysevere DM1. Manual muscle strength (MRC), myotonia self-assessment scales (0–5 scale) and cardiac parameters (PR interval; QRS duration,QRSD; heart rate, HR;ejection fraction, EF) were determined before and after long-term mexiletine treatment (DM1: mean treatment duration 7.5 years ± 3.7; DM2: 5.2 ± 3.5 years). All patients filled in a form of reporting on tolerability and side-effects of treatment. In a subgroup of patients fulfilling criteria for electrophysiological study. Results: Preliminary data suggest that initial and final PR, QRSD, HR, EF were similar in the treated and untreated DM1 groups. Sideeffects were minimal. Myotonia improved significantly in the treated DM1 compared to the untreated patients (p[0.0001).MRC decreased significantly in both treated and untreated DM1 patients Conclusion: Although preliminary, our data suggest that mexiletine is safe and well-tolerated in DM1 patients. There are indications that myotonia but not muscle strength may improve with prolonged treatment. To further confirm or refute our data, we are extending the study to a larger group of patients. In addition, the effects of intravenous mexiletine on the main electrophysiological functional parameters and on the arrhytmia inducibility will also be determined.