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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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.</p><p><strong>Trial registration: </strong>ISRCTN18352058. https://doi.org/10.1186/ISRCTN18352058.</p>","PeriodicalId":3,"journal":{"name":"ACS Applied Electronic Materials","volume":" ","pages":"20451253221090832"},"PeriodicalIF":4.3000,"publicationDate":"2022-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9058570/pdf/","citationCount":"0","resultStr":"{\"title\":\"The clinical effectiveness and cost effectiveness of clozapine for inpatients with severe borderline personality disorder (CALMED study): a randomised placebo-controlled trial.\",\"authors\":\"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\",\"doi\":\"10.1177/20451253221090832\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Data from case series suggest that clozapine may benefit inpatients with borderline personality disorder (BPD), but randomised trials have not been conducted.</p><p><strong>Methods: </strong>Multicentre, double-blind, placebo-controlled trial. 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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：
ACS Applied Electronic Materials is an interdisciplinary journal publishing original research covering all aspects of electronic materials. The journal is devoted to reports of new and original experimental and theoretical research of an applied nature that integrate knowledge in the areas of materials science, engineering, optics, physics, and chemistry into important applications of electronic materials. Sample research topics that span the journal's scope are inorganic, organic, ionic and polymeric materials with properties that include conducting, semiconducting, superconducting, insulating, dielectric, magnetic, optoelectronic, piezoelectric, ferroelectric and thermoelectric.
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