Elliott E S, Marken P A, Ruehter V L
Pharmacy Practice Resident, Western Missouri Mental Health Center, Kansas City, USA.
Ann Pharmacother. 2000 May;34(5):615-8. doi: 10.1345/aph.19213.
To report a case of extrapyramidal reaction associated with a dosage increase of clozapine.
A 44-year-old white man with a 20-year history of chronic paranoid schizophrenia was admitted to an inpatient psychiatric facility. His prior medications restarted on admission were clozapine 650 mg at bedtime, haloperidol 10 mg at bedtime, clonazepam 2 mg/d, and aspirin 325 mg/d. Two days after admission (hospital day 3), clozapine and clonazepam were discontinued, and he was prescribed haloperidol 5 mg every morning and 10 mg every evening. Stabilization occurred over the following 24 days, with progressively lower dosages of haloperidol and increasing dosages of clozapine. Haloperidol was discontinued on day 24. On day 47, the patient was agitated and making bizarre statements; thus, the morning dose of clozapine was increased by 50 mg (total 450 mg/d). On day 48 at 2200, a dystonic reaction was diagnosed; he received intramuscular diphenhydramine 50 mg, which caused the reaction to subside. At the time of the adverse reaction, he was prescribed clozapine 450 mg/d, vitamin E 400 IU three times daily, aspirin 325 mg/d, and acetaminophen, milk of magnesia, and Maalox as needed.
Although the risk of extrapyramidal symptoms (EPS) is significantly lower with clozapine than with conventional agents, elevated clozapine blood concentrations have been reported to cause EPS; other reports have cited severe dystonias and dyskinesias on abrupt clozapine withdrawal. Considering the medications prescribed at the time and the discontinuation of haloperidol 24 days before the event, clozapine was the most likely cause of the extrapyramidal reaction.
Regardless of anticipated safety associated with novel antipsychotics such as clozapine, reports of dystonic reactions must be taken into account and patients monitored appropriately.
报告1例与氯氮平剂量增加相关的锥体外系反应病例。
一名44岁白人男性，有20年慢性偏执型精神分裂症病史，入住一家住院精神科机构。入院时重新开始服用的既往药物包括睡前服用氯氮平650 mg、睡前服用氟哌啶醇10 mg、氯硝西泮2 mg/d以及阿司匹林325 mg/d。入院后两天（住院第3天），停用氯氮平和氯硝西泮，给他开了每天早上5 mg、晚上10 mg的氟哌啶醇。在接下来的24天里病情稳定，氟哌啶醇剂量逐渐降低，氯氮平剂量逐渐增加。氟哌啶醇在第24天停用。在第47天，患者烦躁不安并胡言乱语；因此，氯氮平的 morning dose 增加了50 mg（总量达450 mg/d）。在第48天22:00，诊断出肌张力障碍反应；他接受了50 mg肌内注射苯海拉明，反应消退。在发生不良反应时，他正在服用氯氮平450 mg/d、维生素E 400 IU每日三次、阿司匹林325 mg/d以及按需服用的对乙酰氨基酚、氢氧化镁乳剂和氢氧化铝镁。
虽然氯氮平引起锥体外系症状（EPS）的风险明显低于传统药物，但有报道称氯氮平血药浓度升高会导致EPS；其他报告提到突然停用氯氮平会出现严重肌张力障碍和运动障碍。考虑到事件发生时所开的药物以及事件发生前24天停用了氟哌啶醇，氯氮平最有可能是锥体外系反应的原因。
无论新型抗精神病药物如氯氮平预期的安全性如何，都必须考虑肌张力障碍反应的报告并对患者进行适当监测。
