氯氮平是治疗难治性精神分裂症的金标准。严重甚至危及生命的不良反应,主要是粒细胞减少症,心肌炎,便秘,引起了极大的临床关注,并构成了处方氯氮平的障碍,从而剥夺了许多符合条件的患者的救生治疗选择。有趣的是,氯氮平呈现受众多参数影响的可变药代动力学,导致显著的个体间和个体内差异。因此,通过增加处方医生对药物的信心和患者对治疗的依从性,血浆氯氮平水平的治疗药物监测在日常临床实践中具有显着的益处,主要通过确保有效的治疗和有限的剂量相关的副作用。在本系统综述中,我们的目的是确定一系列不良反应与血浆氯氮平水平的关系,使用Jadad分级系统评估现有临床证据的质量。我们的发现表明脑电图减慢,强迫症状,心率变异性,高胰岛素血症,代谢综合征,便秘与血浆氯氮平水平相关,而QTc,心肌炎,猝死,白细胞减少症,中性粒细胞减少症,流涎,相当不相关。治疗开始时的快速剂量增加可能导致心肌炎的出现,或者白细胞减少症.在这些情况下,管理不利影响的策略是不同的,并进行了相应的讨论。
Clozapine is the gold standard for treatment-resistant schizophrenia. Serious and even life-threatening adverse effects, mostly granulocytopenia, myocarditis, and constipation, are of great clinical concern and constitute a barrier to prescribing clozapine, thus depriving many eligible patients of a lifesaving treatment option. Interestingly, clozapine presents variable pharmacokinetics affected by numerous parameters, leading to significant inter- and intra-individual variation. Therefore, therapeutic drug monitoring of plasma clozapine levels confers a significant benefit in everyday clinical practice by increasing the confidence of the prescribing doctor to the drug and the adherence of the patient to the treatment, mainly by ensuring effective treatment and limited dose-related side effects. In the present systematic review, we aimed at identifying how a full range of adverse effects relates to plasma clozapine levels, using the Jadad grading system for assessing the quality of the available clinical evidence. Our findings indicate that EEG slowing, obsessive-compulsive symptoms, heart rate variability, hyperinsulinemia, metabolic syndrome, and constipation correlate to plasma clozapine levels, whereas QTc, myocarditis, sudden death, leucopenia, neutropenia, sialorrhea, are rather unrelated. Rapid dose escalation at the initiation of treatment might contribute to the emergence of myocarditis, or leucopenia. Strategies for managing adverse effects are different in these conditions and are discussed accordingly.