Mexiletine is the only drug with proven effect for treatment of non-dystrophic myotonia, but mexiletine is expensive, has limited availability and several side effects. There is therefore a need to identify other pharmacological compounds that can alleviate myotonia in non-dystrophic myotonias. Like mexiletine, lamotrigine is a sodium channel blocker, but unlike mexiletine, lamotrigine is available, inexpensive, and well tolerated. We investigated the potential of using lamotrigine for treatment of myotonia in patients with non-dystrophic myotonias. In this, randomized double-blind, placebo-controlled, two-period cross-over study, we included adult outpatients recruited from all of Denmark with clinical myotonia and genetically confirmed myotonia congenita and paramyotonia congenita for investigation at the Copenhagen Neuromuscular Center. A pharmacy produced the medication and placebo, and randomized patients in blocks of 10. Participants and investigators were all blinded to treatment until the end of the trial. In two 8-week periods, oral lamotrigine or placebo capsules were provided once daily, with increasing doses (from 25 mg, 50 mg, 150 mg to 300 mg) every second week. The primary outcome was a severity score of myotonia, the Myotonic Behaviour Scale ranging from asymptomatic (score 1) to invalidating myotonia (score 6), reported by the participants during Weeks 0 and 8 in each treatment period. Clinical myotonia was also measured and side effects were monitored. The study was registered at ClinicalTrials.gov (NCT02159963) and EudraCT (2013-003309-24). We included 26 patients (10 females, 16 males, age: 19–74 years) from 13 November 2013 to 6 July 2015. Twenty-two completed the entire study. One patient withdrew due to an allergic reaction to lamotrigine. Three patients withdrew for reasons not related to the trial intervention. The Myotonic Behaviour Scale at baseline was 3.2 ± 1.1, which changed after treatment with lamotrigine by 1.3 ± 0.2 scores (P < 0.001), but not with placebo (0.2 ± 0.1 scores, P = 0.4). The estimated effect size was 1.0 ± 0.2 (95% confidence interval = 0.5–1.5, P < 0.001, n = 22). The standardized effect size of lamotrigine was 1.5 (confidence interval: 1.2–1.8). Number needed to treat was 2.6 (P = 0.006, n = 26). No adverse or unsuspected event occurred. Common side effects occurred in both treatment groups; number needed to harm was 5.2 (P = 0.11, n = 26). Lamotrigine effectively reduced myotonia, emphasized by consistency between effects on patient-related outcomes and objective outcomes. The frequency of side effects was acceptable. Considering this and the high availability and low cost of the drug, we suggest that lamotrigine should be used as the first line of treatment for myotonia in treatment-naive patients with non-dystrophic myotonias.

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拉莫三嗪对非营养性肌强直的抗强直性作用：一项双盲随机研究

美西律汀是唯一一种对非营养不良性肌强直具有有效疗效的药物，但美西律汀价格昂贵，可用性有限且具有多种副作用。因此，需要鉴定可以减轻非营养性肌强直性肌强直的其他药理化合物。像美西律一样，拉莫三嗪是一种钠通道阻滞剂，但与美西律不同，拉莫三嗪市售，便宜且耐受性好。我们调查了非营养性肌强直患者使用拉莫三嗪治疗肌强直的潜力。在这项随机，双盲，安慰剂对照，两期交叉研究中，我们纳入了从丹麦全国招募来的具有临床肌强直和遗传学证实的先天性肌强直和副肌强直的成人门诊患者，用于哥本哈根神经肌肉中心的研究。一家药房生产药物和安慰剂，将患者随机分为10组，直到试验结束，所有参与者和研究者均不接受治疗。在两个8周的时间里，口服拉莫三嗪或安慰剂胶囊每天一次，每第二周增加一次剂量（从25 mg，50 mg，150 mg到300 mg）。主要结局是肌强直的严重程度评分，该肌强直行为量表的范围从无症状（得分1）到无效肌强直（得分6），由参与者在每个治疗期间的第0周和第8周报告。还测量了临床肌强直，并监测了副作用。该研究已在ClinicalTrials.gov（NCT02159963）和EudraCT（2013-003309-24）上注册。我们纳入了2013年11月13日至2015年7月6日的26位患者（10位女性，16位男性，年龄：19-74岁）。22个完成了整个研究。一名患者因对拉莫三嗪的过敏反应而退出治疗。三名患者由于与试验干预无关的原因退出。基线时的强直性行为量表为3.2±1.1，经拉莫三嗪治疗后变化为1.3±0.2分（P <0.001），但不使用安慰剂（0.2±0.1评分，P = 0.4）。估计的效应大小为1.0±0.2（95％置信区间= 0.5–1.5，P <0.001，n = 22）。拉莫三嗪的标准化作用量为1.5（置信区间：1.2–1.8）。需要治疗的人数为2.6（P = 0.006，n = 26）。没有发生不利或意外的事件。两个治疗组均发生常见的副作用。伤害所需的数字是5.2（P = 0.11，n =26）。拉莫三嗪可有效减少肌强直，强调患者相关结果与客观结果之间的一致性。副作用的频率是可以接受的。考虑到这一点以及该药物的高可用性和低成本，我们建议拉莫三嗪应作为初治非营养不良性肌强直患者的肌强直治疗的第一线。