Mike J Crawford, Verity C Leeson, Rachel Evans, Barbara Barrett, Aisling McQuaid, Jack Cheshire, Rahil Sanatinia, Gary Lamph, Piyal Sen, Katina Anagnostakis, Louise Millard, Inti Qurashi, Fintan Larkin, Nusrat Husain, Paul Moran, Thomas R E Barnes, Carol Paton, Zoe Hoare, Marco Picchioni, Simon Gibbon
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We randomly allocated participants on a 1:1 ratio to receive up to 400 mg of clozapine per day or an inert placebo using a remote web-based randomisation service. The primary outcome was total score on the Zanarini Rating scale for Borderline Personality Disorder (ZAN-BPD) at 6 months. Secondary outcomes included self-harm, aggression, resource use and costs, side effects and adverse events. We used a modified intention to treat analysis (mITT) restricted to those who took one or more dose of trial medication, using a general linear model fitted at 6 months adjusted for baseline score, allocation group and site.</p><p><strong>Results: </strong>The study closed early due to poor recruitment and the impact of the COVID-19 pandemic. Of 29 study participants, 24 (83%) were followed up at 6 months, of whom 21 (72%) were included in the mITT analysis. At 6 months, 11 (73%) participants assigned to clozapine and 6 (43%) of those assigned to placebo were still taking trial medication. 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引用次数: 0
摘要
背景:来自病例系列的数据表明氯氮平可能对边缘性人格障碍(BPD)的住院患者有益，但尚未进行随机试验。方法:多中心、双盲、安慰剂对照试验。我们的目标是招募222名18岁或以上的重度BPD住院患者，他们对其他抗精神病药物没有反应。我们使用基于网络的远程随机化服务，以1:1的比例随机分配参与者，每天接受高达400mg氯氮平或惰性安慰剂。主要结果是6个月时扎纳里尼边缘型人格障碍(Zanarini Rating scale for Borderline Personality Disorder, ZAN-BPD)的总分。次要结果包括自残、攻击、资源使用和成本、副作用和不良事件。我们使用改良的治疗意向分析(mITT)，仅限于服用一剂或多剂试验药物的患者，使用6个月时拟合的一般线性模型，调整基线评分、分配组和地点。结果:受新冠肺炎疫情影响和招募不力影响，本研究提前结束。在29名研究参与者中，24名(83%)随访6个月，其中21名(72%)纳入了mITT分析。6个月时，11名(73%)氯氮平组参与者和6名(43%)安慰剂组参与者仍在服用试验药物。6个月时，平均总ZAN-BPD评分的调整差为-3.86(95%置信区间= -10.04至2.32)。严重不良事件14例;氯氮平组6例，安慰剂组8例。两组之间的护理费用几乎没有差别。解释:我们招募的参与者不足以检验主要假设。研究结果强调了氯氮平安慰剂对照试验的问题，以及氯氮平在BPD患者中使用的问题。试验注册ISRCTN18352058。https://doi.org/10.1186/ISRCTN18352058
The clinical effectiveness and cost effectiveness of clozapine for inpatients with severe borderline personality disorder (CALMED study): a randomised placebo-controlled trial.
Background: Data from case series suggest that clozapine may benefit inpatients with borderline personality disorder (BPD), but randomised trials have not been conducted.
Methods: Multicentre, double-blind, placebo-controlled trial. We aimed to recruit 222 inpatients with severe BPD aged 18 or over, who had failed to respond to other antipsychotic medications. We randomly allocated participants on a 1:1 ratio to receive up to 400 mg of clozapine per day or an inert placebo using a remote web-based randomisation service. The primary outcome was total score on the Zanarini Rating scale for Borderline Personality Disorder (ZAN-BPD) at 6 months. Secondary outcomes included self-harm, aggression, resource use and costs, side effects and adverse events. We used a modified intention to treat analysis (mITT) restricted to those who took one or more dose of trial medication, using a general linear model fitted at 6 months adjusted for baseline score, allocation group and site.
Results: The study closed early due to poor recruitment and the impact of the COVID-19 pandemic. Of 29 study participants, 24 (83%) were followed up at 6 months, of whom 21 (72%) were included in the mITT analysis. At 6 months, 11 (73%) participants assigned to clozapine and 6 (43%) of those assigned to placebo were still taking trial medication. Adjusted difference in mean total ZAN-BPD score at 6 months was -3.86 (95% Confidence Intervals = -10.04 to 2.32). There were 14 serious adverse events; 6 in the clozapine arm and 8 in the placebo arm of the trial. There was little difference in the cost of care between groups.
Interpretation: We recruited insufficient participants to test the primary hypothesis. The study findings highlight problems in conducting placebo-controlled trials of clozapine and in using clozapine for people with BPD, outside specialist inpatient mental health units.
期刊介绍：
Therapeutic Advances in Psychopharmacology delivers the highest quality peer-reviewed articles, reviews, and scholarly comment on pioneering efforts and innovative studies across all areas of psychopharmacology. The journal has a strong clinical and pharmacological focus and is aimed at clinicians and researchers in psychopharmacology, providing a forum in print and online for publishing the highest quality articles in this area.
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