Sultan Ryan S, Olfson Mark, Correll Christoph U, Duncan Erica J
New York State Psychiatric Institute/Department of Psychiatry, College of Physicians and Surgeons of Columbia University, 1051 Riverside Dr, New York, NY 10032.
Department of Psychiatry, College of Physicians and Surgeons, Columbia University; and the New York State Psychiatric Institute, New York, New York, USA.
J Clin Psychiatry. 2017 Sep/Oct;78(8):e933-e939. doi: 10.4088/JCP.16m11152.
Concerns exist that clozapine is underutilized in the management of treatment-resistant schizophrenia. Although a 2015 change in the US Food and Drug Administration (FDA) monitoring recommendations lowered the threshold of the absolute neutrophil count for treatment interruption from 1,500/μL to 1,000/μL and removed white blood cell count thresholds from the monitoring algorithm, the implications of this policy change on clozapine interruptions remain unknown.
We analyzed outpatient prescribing records for antipsychotic medications in the Veterans Integrated Service Network 7 (VISN 7) database between 1999 and 2012 to assess the potential impact of the recent changes in FDA neutropenia monitoring recommendations on clozapine treatment discontinuation. We evaluated results of complete blood count monitoring to compare percentages of patients who developed or would have developed ≥ 1 hematologic event under the previous and current FDA guidelines in the first year following initiation of clozapine.
From a cohort of 14,620 patients with schizophrenia (ICD-9-295.x), 246 patients received clozapine treatment (1.7%). No agranulocytosis was observed during the study period. Under the former recommendations, 5 patients in the clozapine initiation cohort (n = 160, 3.1%; 95% CI, 0.43-5.83) qualified for treatment interruption during the first year of clozapine treatment, while only 1 patient (0.6%) qualified under the current recommendations. Under the former recommendations, hematologic events occurred at a similar rate for individuals taking and not taking clozapine.
While clozapine remains an underused medication, the new FDA monitoring guidelines are likely to substantially reduce the percentage of patients who meet criteria for clozapine-associated hematologic events requiring treatment interruption. This decrease may reduce the clinical burden of managing patients on clozapine and therefore increase the number of individuals treated with this uniquely effective medication. However, prospective studies of individuals treated under the new guidelines are needed to fully assess safety of the FDA's change.
人们担心氯氮平在难治性精神分裂症的治疗中未得到充分利用。尽管2015年美国食品药品监督管理局（FDA）监测建议的变更将治疗中断的绝对中性粒细胞计数阈值从1500/μL降至1000/μL，并从监测算法中删除了白细胞计数阈值，但这一政策变更对氯氮平中断治疗的影响仍不明确。
我们分析了1999年至2012年退伍军人综合服务网络7（VISN 7）数据库中抗精神病药物的门诊处方记录，以评估FDA中性粒细胞减少监测建议的近期变更对氯氮平治疗停药的潜在影响。我们评估了全血细胞计数监测结果，以比较在氯氮平治疗开始后的第一年中，根据之前和当前FDA指南发生或本会发生≥1次血液学事件的患者百分比。
在14620例精神分裂症患者（ICD-9-295.x）队列中，246例患者接受了氯氮平治疗（1.7%）。研究期间未观察到粒细胞缺乏症。根据之前的建议，氯氮平起始队列中的5例患者（n = 160，3.1%；95% CI，0.43 - 5.83）在氯氮平治疗的第一年有资格中断治疗，而根据当前建议只有1例患者（0.6%）有资格。根据之前的建议，服用和未服用氯氮平的个体发生血液学事件的发生率相似。
虽然氯氮平仍然是一种未得到充分使用的药物，但新的FDA监测指南可能会大幅降低符合氯氮平相关血液学事件标准而需要中断治疗的患者百分比。这种降低可能会减轻管理氯氮平治疗患者的临床负担，从而增加接受这种独特有效药物治疗的个体数量。然而，需要对在新指南下接受治疗的个体进行前瞻性研究，以全面评估FDA变更的安全性。
