Pharmacy Department, South London and Maudsley NHS Foundation Trust, London, UK; Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Pharmacy Department, South London and Maudsley NHS Foundation Trust, London, UK; National Psychosis Service, South London and Maudsley NHS Foundation Trust, London, UK; Institute of Pharmaceutical Science, King's College, London, UK.
Lancet Psychiatry. 2022 Aug;9(8):636-644. doi: 10.1016/S2215-0366(22)00188-2. Epub 2022 Jun 27.
Clozapine is uniquely effective in treatment-resistant psychosis. In the UK, patients must discontinue clozapine indefinitely if they are placed on the Central Non-Rechallenge Database (CNRD) after their haematological parameters fall below particular thresholds. Under exceptional circumstances, patients can be rechallenged on clozapine under an off-licence agreement. In the USA in 2015, restrictive practice was discontinued to allow greater flexibility for clozapine maintenance. The absolute neutrophil count leading to treatment interruption was lowered from less than 1·5 × 10/L to less than 1·0 × 10/L and platelet and white cell count monitoring were ceased. We aimed to investigate the implications of a similar policy change on clozapine use in the UK.
This was a modelling study of all patients registered on the UK CNRD. First, we determined the proportion of patients placed on the database in the UK who would have had to discontinue clozapine treatment under the US Food and Drug Administration (FDA) criteria. Second, we compared the haematological characteristics of patients who did or did not meet FDA criteria for discontinuing clozapine, including the time to registration from clozapine initiation and the proportion of cases of severe neutropenia at registration. Third, we investigated the success rates of clozapine re-challenge for patients that had been placed on the CNRD. Successful rechallenge was defined as no recurrence of CNRD registration.
Between May 2, 2002 and March 1, 2021, 3731 patients were placed on the CNRD, with a mean age of 47 years (SD 15), including 1420 (38%) women and 2311 (62%) men, of whom 3089 (83%) were White, 360 (10%) were Black, 190 (5%) were Asian, and 92 (2%) were classified as other. 566 (15%) of 3731 patients met the equivalent criteria for clozapine discontinuation under the FDA guidelines. The median time to CNRD registration from clozapine initiation was 1·6 years (IQR 0·2-4·9). Data for 519 rechallenged patients were examined; 419 (81%) were successful. Clozapine rechallenge success rates were broadly similar between individuals who did not meet the US CNRD registration criteria (36 [78%] of 46) and those who did meet the criteria (383 [81%] of 473).
Implementing the revised FDA monitoring criteria in the UK would substantially reduce clozapine discontinuation for haematological reasons, which would greatly improve the mental health outcomes of these patients without having a major effect on their physical health.
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氯氮平在治疗抵抗性精神病方面具有独特的疗效。在英国，如果患者的血液参数低于特定阈值后被列入中央非重挑战数据库（CNRD），则必须无限期停止氯氮平治疗。在特殊情况下，患者可以根据非许可协议重新接受氯氮平治疗。2015 年，美国停止了限制性做法，以增加氯氮平维持治疗的灵活性。导致治疗中断的中性粒细胞绝对计数从<1.5×10/L 降低至<1.0×10/L，并且停止了血小板和白细胞计数监测。我们旨在研究英国类似政策变化对氯氮平使用的影响。
这是一项针对所有在英国 CNRD 登记的患者的建模研究。首先，我们确定了在英国，根据美国食品和药物管理局（FDA）标准，有多少被列入数据库的患者必须停止氯氮平治疗。其次，我们比较了符合或不符合 FDA 停止氯氮平治疗标准的患者的血液学特征，包括从氯氮平开始到登记的时间以及登记时严重中性粒细胞减少症的比例。第三，我们调查了被列入 CNRD 的患者重新接受氯氮平治疗的成功率。重新挑战成功的定义是没有重新登记 CNRD。
2002 年 5 月 2 日至 2021 年 3 月 1 日，3731 名患者被列入 CNRD，平均年龄为 47 岁（标准差 15），包括 1420 名（38%）女性和 2311 名（62%）男性，其中 3089 名（83%）为白人，360 名（10%）为黑人，190 名（5%）为亚洲人，92 名（2%）被归类为其他。在符合 FDA 指南的情况下，3731 名患者中有 566 名（15%）符合氯氮平停药的等效标准。从氯氮平开始到 CNRD 登记的中位时间为 1.6 年（IQR 0.2-4.9）。共检查了 519 名重新接受治疗的患者的数据；419 名（81%）成功。未达到美国 CNRD 登记标准的患者（46 名中的 36 名[78%]）与达到标准的患者（473 名中的 383 名[81%]）的氯氮平重新挑战成功率大致相似。
在英国实施修订后的 FDA 监测标准将大大减少因血液学原因而停止氯氮平治疗，这将极大地改善这些患者的精神健康状况，而对他们的身体健康没有重大影响。
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