Centre for Psychiatry, Imperial College London, London, UK.
Centre for the Economics of Mental and Physical Health, King's College London, London, UK.
Health Technol Assess. 2018 Apr;22(17):1-68. doi: 10.3310/hta22170.
No drug treatments are currently licensed for the treatment of borderline personality disorder (BPD). Despite this, people with this condition are frequently prescribed psychotropic medications and often with considerable polypharmacy. Preliminary studies have indicated that mood stabilisers may be of benefit to people with BPD.
To examine the clinical effectiveness and cost-effectiveness of lamotrigine for people with BPD.
A two-arm, double-blind, placebo-controlled individually randomised trial of lamotrigine versus placebo. Participants were randomised via an independent and remote web-based service using permuted blocks and stratified by study centre, the severity of personality disorder and the extent of hypomanic symptoms.
Secondary care NHS mental health services in six centres in England.
Potential participants had to be aged ≥ 18 years, meet diagnostic criteria for BPD and provide written informed consent. We excluded people with coexisting psychosis or bipolar affective disorder, those already taking a mood stabiliser, those who spoke insufficient English to complete the baseline assessment and women who were pregnant or contemplating becoming pregnant.
Up to 200 mg of lamotrigine per day or an inert placebo. Women taking combined oral contraceptives were prescribed up to 400 mg of trial medication per day.
Outcomes were assessed at 12, 24 and 52 weeks after randomisation. The primary outcome was the total score on the Zanarini Rating Scale for Borderline Personality Disorder (ZAN-BPD) at 52 weeks. The secondary outcomes were depressive symptoms, deliberate self-harm, social functioning, health-related quality of life, resource use and costs, side effects of treatment and adverse events. Higher scores on all measures indicate poorer outcomes.
Between July 2013 and October 2015 we randomised 276 participants, of whom 195 (70.6%) were followed up 52 weeks later. At 52 weeks, 49 (36%) of those participants prescribed lamotrigine and 58 (42%) of those prescribed placebo were taking it. At 52 weeks, the mean total ZAN-BPD score was 11.3 [standard deviation (SD) 6.6] among those participants randomised to lamotrigine and 11.5 (SD 7.7) among those participants randomised to placebo (adjusted mean difference 0.1, 95% CI -1.8 to 2.0; = 0.91). No statistically significant differences in secondary outcomes were seen at any time. Adjusted costs of direct care for those prescribed lamotrigine were similar to those prescribed placebo.
Levels of adherence in this pragmatic trial were low, but greater adherence was not associated with better mental health.
The addition of lamotrigine to the usual care of people with BPD was not found to be clinically effective or provide a cost-effective use of resources.
Future research into the treatment of BPD should focus on improving the evidence base for the clinical effectiveness and cost-effectiveness of non-pharmacological treatments to help policy-makers make better decisions about investing in specialist treatment services.
Current Controlled Trials ISRCTN90916365.
Funding for this trial was provided by the Health Technology Assessment programme of the National Institute for Health Research (NIHR) and will be published in full in ; Vol. 22, No. 17. See the NIHR Journals Library website for further project information. The Imperial Biomedical Research Centre Facility, which is funded by NIHR, also provided support that has contributed to the research results reported within this paper. Part of Richard Morriss' salary during the project was paid by NIHR Collaboration for Leadership in Applied Health Research and Care East Midlands.
目前尚无药物治疗被批准用于治疗边缘型人格障碍（BPD）。尽管如此，患有这种疾病的人经常被开精神药物，而且通常是多种药物并用。初步研究表明，心境稳定剂可能对 BPD 患者有益。
研究拉莫三嗪治疗 BPD 的临床疗效和成本效益。
一项为期 52 周的双盲、安慰剂对照、个体随机试验，比较拉莫三嗪与安慰剂。参与者通过独立的远程网络服务进行随机分组，使用置换块和分层方法，分层因素包括研究中心、人格障碍严重程度和轻躁狂症状程度。
英格兰六个中心的二级保健 NHS 心理健康服务。
潜在参与者必须年龄≥18 岁，符合 BPD 诊断标准，并提供书面知情同意书。我们排除了同时患有精神病或双相情感障碍的患者、已经服用心境稳定剂的患者、英语水平不足以完成基线评估的患者以及正在怀孕或计划怀孕的女性。
每天服用拉莫三嗪 200 毫克或安慰剂。服用复方口服避孕药的女性每天最多可服用 400 毫克试验药物。
在随机分组后 12、24 和 52 周进行评估。主要结局是 52 周时 ZAN-BPD 总分。次要结局是抑郁症状、蓄意自伤、社会功能、健康相关生活质量、资源使用和成本、治疗副作用和不良事件。所有测量指标得分越高，表明结果越差。
在 2013 年 7 月至 2015 年 10 月期间，我们随机分配了 276 名参与者，其中 195 名（70.6%）在 52 周后进行了随访。在 52 周时，服用拉莫三嗪的参与者中有 49 人（36%）和服用安慰剂的参与者中有 58 人（42%）正在服用。在 52 周时，随机分配到拉莫三嗪组的参与者的 ZAN-BPD 总分平均为 11.3（标准差 6.6），随机分配到安慰剂组的参与者平均为 11.5（标准差 7.7）（调整后的平均差异 0.1，95%CI-1.8 至 2.0； = 0.91）。在任何时间点都没有观察到次要结局的统计学显著差异。服用拉莫三嗪的参与者的直接护理成本调整后与服用安慰剂的参与者相似。
这项实用试验的依从性水平较低，但更高的依从性与更好的心理健康状况无关。
在 BPD 患者的常规治疗中添加拉莫三嗪并未发现具有临床疗效或提供具有成本效益的资源利用。
未来对 BPD 治疗的研究应集中于提高非药物治疗的临床疗效和成本效益的证据基础，以帮助决策者更好地决定投资于专科治疗服务。
当前对照试验 ISRCTN90916365。
本试验的资金由英国国家卫生研究院（NIHR）的卫生技术评估计划提供，并将在 中全文发表；第 22 卷，第 17 期。请访问 NIHR 期刊库网站以获取更多项目信息。帝国生物医学研究中心设施由 NIHR 资助，该设施也为本文报告的研究结果提供了支持。理查德·莫里斯的部分工资是由 NIHR 合作的东米德兰应用健康研究和护理领导提供的。
