氯氮平治疗重度边缘型人格障碍住院患者的临床疗效和成本效益（CALMED研究）：一项随机安慰剂对照试验

The clinical effectiveness and cost effectiveness of clozapine for inpatients with severe borderline personality disorder (CALMED study): a randomised placebo-controlled trial.

作者信息

Crawford Mike J, Leeson Verity C, Evans Rachel, Barrett Barbara, McQuaid Aisling, Cheshire Jack, Sanatinia Rahil, Lamph Gary, Sen Piyal, Anagnostakis Katina, Millard Louise, Qurashi Inti, Larkin Fintan, Husain Nusrat, Moran Paul, Barnes Thomas R E, Paton Carol, Hoare Zoe, Picchioni Marco, Gibbon Simon

机构信息

Division of Psychiatry, Imperial College London, The Commonwealth Building, The Hammersmith Hospital, Du Cane Road, London W12 0NN, UK.

Division of Psychiatry, Imperial College London, London, UK.

出版信息

Ther Adv Psychopharmacol. 2022 Apr 29;12:20451253221090832. doi: 10.1177/20451253221090832. eCollection 2022.

DOI:10.1177/20451253221090832

PMID:35510087

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9058570/

Abstract

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.

TRIAL REGISTRATION

ISRCTN18352058. https://doi.org/10.1186/ISRCTN18352058.

摘要

背景

病例系列数据表明，氯氮平可能对边缘型人格障碍（BPD）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岁及以上的重度BPD住院患者，这些患者对其他抗精神病药物治疗无效。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，使其每天接受高达400毫克的氯氮平或惰性安慰剂。主要结局是6个月时边缘型人格障碍赞纳里尼评定量表（ZAN-BPD）的总分。次要结局包括自我伤害、攻击行为、资源使用和成本、副作用及不良事件。我们采用了一种改良的意向性分析（mITT），该分析仅限于那些服用了一剂或多剂试验药物的患者，使用在6个月时拟合的一般线性模型，并根据基线分数、分配组和研究地点进行调整。

结果

由于招募困难和COVID-19大流行的影响，该研究提前结束。在29名研究参与者中，24名（83%）在6个月时接受了随访，其中21名（72%）被纳入mITT分析。在6个月时，分配到氯氮平组的11名（73%）参与者和分配到安慰剂组的6名（43%）参与者仍在服用试验药物。6个月时ZAN-BPD总分的调整差异为-3.86（95%置信区间=-10.04至2.32）。共有14起严重不良事件；试验中氯氮平组6起，安慰剂组8起。两组之间的护理成本差异不大。