Demler Tammie Lee, Trigoboff Eileen
Buffalo Psychiatric Center, Buffalo, New York, USA.
Innov Clin Neurosci. 2011 Apr;8(4):35-41.
Clozapine is an atypical antipsychotic agent used for refractory schizophrenia. It has a relatively low affinity for D2 receptors and thus is associated with a lower incidence of extrapyramidal side effects when compared with typical antipsychotics. Clozapine as monotherapy can induce a rare, but serious, blood dyscrasia called agranulocytosis; however, some concomitant medications may contribute to the risk. Examples of these medications are mood-stabilizing antiepileptic drugs, such as carbamazepine, and sulfonamide antibiotics, such as sulfamethoxazole. There were no studies at the writing of this article examining the effect of concomitant medications on clozapine blood dyscrasias, and few published reports describing enhanced bone marrow suppression in those taking clozapine. The primary objective of this study was to evaluate the effect of concomitant medications used in a state psychiatric hospital on clozapine-induced blood dyscrasias. This was a retrospective record review of adverse drug reactions reported at an adult inpatient state psychiatric center. The records for a pilot sample of 26 patients with reported clozapine-related adverse drug reactions between January 1, 2007, and June 30, 2009, were reviewed. Fundamental to this study were reported adverse drug reactions defined as 1) substantial drops in white blood cell or absolute neutrophil count (a substantial drop in white blood cell is >3,000 or absolute neutrophil count is >1,500 over a 3-week period); 2) mild leukopenia/granulocytopenia; and 3) moderate-severe leukopenia/granulocytopenia. Concomitant medications were examined for contributions to an increased potential for clozapine-induced blood dyscrasias. Other data collected included demographic information (age, gender, ethnicity), medical and psychiatric diagnoses, dose and duration of medications, and changes in medications. Medications that had a statistically significant impact on the incidence of clozapine-induced blood dyscrasias are reported in this article, as well as the possible duration of medication use prior to induction of an adverse drug reaction.
氯氮平是一种用于难治性精神分裂症的非典型抗精神病药物。它对D2受体的亲和力相对较低，因此与典型抗精神病药物相比，锥体外系副作用的发生率较低。氯氮平作为单一疗法可诱发一种罕见但严重的血液系统疾病，称为粒细胞缺乏症；然而，一些同时使用的药物可能会增加这种风险。这些药物包括情绪稳定的抗癫痫药物，如卡马西平，以及磺胺类抗生素，如磺胺甲恶唑。在撰写本文时，没有研究考察同时使用的药物对氯氮平所致血液系统疾病的影响，也很少有已发表的报告描述服用氯氮平者骨髓抑制增强的情况。本研究的主要目的是评估一家州立精神病医院使用的同时服用的药物对氯氮平所致血液系统疾病的影响。这是一项对一家成人住院州立精神病中心报告的药物不良反应进行的回顾性记录审查。对2007年1月1日至2009年6月30日期间报告有氯氮平相关药物不良反应的26例患者的试点样本记录进行了审查。本研究的基础是报告的药物不良反应，定义为：1）白细胞或绝对中性粒细胞计数大幅下降（在3周内白细胞大幅下降>3000或绝对中性粒细胞计数>1500）；2）轻度白细胞减少/粒细胞减少；3）中度至重度白细胞减少/粒细胞减少。检查同时服用的药物对氯氮平所致血液系统疾病潜在风险增加的影响。收集的其他数据包括人口统计学信息（年龄、性别、种族）、医学和精神科诊断、药物剂量和用药时间以及药物变化。本文报告了对氯氮平所致血液系统疾病发生率有统计学显著影响的药物，以及在诱发药物不良反应之前可能的用药持续时间。
