Department of Psychiatry, Texas Tech University Health Sciences Center, School of Medicine, Lubbock, TX.
Department of Psychiatry, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
Am J Ther. 2019 May/Jun;26(3):e406-e416. doi: 10.1097/MJT.0000000000000894.
Clozapine is a second-generation antipsychotic typically used for refractory schizophrenia or otherwise psychotic pathology. There are no FDA or manufacturer guidelines for use of clozapine in pediatric population. We investigated the current state of research concerning the use of clozapine in pediatric patients.
We describe consistent calls for more research into the long-term and short-term effects of clozapine use in a young patient population. Despite the strongly supported efficacy, questions concerning clear indications for use and risk-benefit analysis persist. We acknowledge that a more comprehensive meta-analysis would greatly benefit the field. However, this is the first article of its kind for clozapine in recent history, and therefore, serves as a focus and reference point for future, more in-depth analyses.
We conducted a search of PubMed, ClinicalKey, PsycINFO, and MEDLINE databases. Keywords used included, in varying combinations: clozapine, off-label, indications, children and adolescent, pediatric, behavioral, suicidality, psychosis, early and very-early onset schizophrenia, side-effect profile, and long-term use. Further criteria and selection are described in Methods below.
We describe the documented efficacy of clozapine for the management of refractory psychotic and nonpsychotic symptoms in the pediatric population. The authors highlight the risk of unmanaged early-onset schizophrenia, aggressive or suicidal behavior, and severe nonpsychotic pathology. Unfortunately, these studies are generally small. There is little consistency in when clozapine is prescribed, how long it is administered, and how long patients are followed. Despite the lack of FDA and manufacturer guidelines, clozapine continues to be used for the benefit of young patients.
Indications for prescription of clozapine should be revisited, given the data presented in this manuscript of a low risk-benefit ratio for properly chosen patients. Larger studies should be conducted to provide more statistical power and determine clear guidelines for use, risk of side effects, and long-term adverse events that may arise.
氯氮平是一种第二代抗精神病药，通常用于治疗难治性精神分裂症或其他精神病性疾病。美国食品药品监督管理局（FDA）或制造商均没有关于氯氮平在儿科人群中使用的指南。我们调查了目前有关氯氮平在儿科患者中使用的研究状况。
我们描述了一致呼吁进行更多研究，以了解氯氮平在年轻患者群体中的长期和短期影响。尽管氯氮平的疗效得到了强有力的支持，但关于明确使用指征和风险效益分析的问题仍然存在。我们承认，更全面的荟萃分析将极大地有益于该领域。然而，这是氯氮平在最近历史上的第一篇此类文章，因此，它是未来更深入分析的重点和参考点。
我们对 PubMed、ClinicalKey、PsycINFO 和 MEDLINE 数据库进行了搜索。使用的关键词包括但不限于：氯氮平、超适应证用药、适应证、儿童和青少年、儿科、行为、自杀意念、精神病、早期和极早发性精神分裂症、副作用谱、长期使用。下文的方法部分进一步描述了具体的标准和选择过程。
我们描述了氯氮平在儿科人群中管理难治性精神病性和非精神病性症状的已记录疗效。作者强调了未管理的早发性精神分裂症、攻击性或自杀行为以及严重非精神病性疾病的风险。不幸的是，这些研究通常规模较小。氯氮平的处方时间、给药时间和患者随访时间没有一致性。尽管缺乏 FDA 和制造商的指南，但氯氮平仍继续用于年轻患者。
鉴于本文提供的关于适当选择的患者风险效益比较低的数据，应重新考虑氯氮平的处方适应证。应进行更大规模的研究，以提供更多的统计效力，并确定明确的使用指南、副作用风险以及可能出现的长期不良事件。
