关键词: Clozapine/administration and dosage clozapine/adverse effects lamotrigine mortality/drug effects myocarditis/chemically induced myocarditis/etiology myocarditis/pathology myocarditis/prevention and control valproic acid

Mesh : Antipsychotic Agents / administration & dosage adverse effects Clozapine / administration & dosage adverse effects Fatal Outcome Humans Male Middle Aged Myocarditis / chemically induced Psychotic Disorders / drug therapy

来  源:   DOI:10.1177/0091217415621269   PDF(Sci-hub)

Abstract:
Clozapine-induced myocarditis is a poorly understood, rare, potentially fatal adverse drug reaction with absolute risks ranging from 7 to 34 per 1000 in Australia and 0.07-0.6 per 1000 in other countries. Hypersensitivity reactions have been postulated including some cases probably associated with rapid titrations. This case describes a 50-year-old African-American man with schizoaffective disorder, naïve to clozapine, who probably died from clozapine-induced myocarditis. He was started on 25 mg/day of clozapine and received 1625 mg over 14 days, prior to his death on day 15. The autopsy found predominantly lymphocytic infiltrate of the perivascular soft tissue and myocardium of the ventricles, with occasional eosinophils. Using the Liverpool ADR Causality Assessment Tool, it was deemed probable that the patient\'s death was secondary to myocarditis. The patient had fulminant death with no obvious changes in vital signs. Neither C-reactive protein nor troponin was measured, but it is unlikely that the results would have arrived in time to prevent the patient\'s death. Age, rapid titration, and concomitant use of valproate contributed to this case, which was probably an idiosyncratic adverse drug reaction associated with rapid titration. Lamotrigine-induced Stevens-Johnson syndrome also appears to be an idiosyncratic adverse drug reaction associated with rapid titration, but its incidence has been remarkably reduced since the recommended starting lamotrigine dose was reduced and corrected by the effect of inhibitors such as valproate. Similarly, clozapine-induced myocarditis incidence probably can be reduced with the use of slow titrations, including even slower titrations for patients with lower ability to metabolize clozapine, such as those taking valproate.
摘要:
氯氮平引起的心肌炎知之甚少,罕见,潜在的致命药物不良反应,在澳大利亚,绝对风险为7至34/1000,在其他国家为0.07-0.6/1000。已经推测超敏反应,包括一些可能与快速滴定有关的病例。这个案例描述了一个50岁的非洲裔美国人患有分裂情感障碍,天真的氯氮平,可能死于氯氮平诱发的心肌炎.他开始服用25毫克/天的氯氮平,并在14天内接受1625毫克,在他15天去世之前.尸检发现主要是血管周围软组织和心室心肌的淋巴细胞浸润,偶尔伴有嗜酸性粒细胞。使用利物浦ADR因果关系评估工具,据认为,患者的死亡可能是继发于心肌炎。患者暴发性死亡,生命体征无明显变化。既不测量C反应蛋白也不测量肌钙蛋白,但它是不可能的结果会及时到达,以防止病人的死亡。年龄,快速滴定,同时使用丙戊酸盐导致了这种情况,这可能是与快速滴定相关的特殊不良反应。拉莫三嗪诱导的Stevens-Johnson综合征似乎也是一种与快速滴定相关的特异性药物不良反应。但自拉莫三嗪的推荐起始剂量减少并通过丙戊酸盐等抑制剂的作用得到纠正后,其发病率已显著降低.同样,氯氮平诱导的心肌炎发病率可能可以通过使用慢滴定降低,包括代谢氯氮平能力较低的患者的滴定速度甚至更慢,比如那些服用丙戊酸盐的人。
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