Department of Epidemiology and Preventive Medicine, Monash University, The Alfred Centre, 99 Commercial Road, Melbourne, VIC 3004, Australia.
Schizophr Res. 2012 Nov;141(2-3):173-8. doi: 10.1016/j.schres.2012.08.018. Epub 2012 Sep 23.
Despite the implementation of cardiac monitoring guidelines, clozapine-induced myocarditis continues to cause deaths in Australia, and the risk is a barrier to prescription of this effective drug for the treatment of schizophrenia. This study was designed to identify clinical and phenotypic risk factors for clozapine-induced myocarditis.
Possible cases of clozapine related myocarditis occurring between June 1993 and November 2009 and a comparative group of controls taking clozapine for at least 45days without cardiac disease were documented from the patients' medical records.
105 cases, with time to onset of 10-33days, and 296 controls were included in the study. In multivariate analysis, the risk of myocarditis increased by 26% for each additional 250mg of clozapine administered in the first nine days of clozapine titration (odds ratio 1.26; 95% confidence interval 1.02-1.55; p=0.03) and concomitant sodium valproate more than doubled the risk (2.59; 1.51-4.42; 0.001). Further, each successive decade in age was associated with a 31% increase in risk (1.31; 1.07-1.60; 0.009). Nevertheless, 33 cases received less than 920mg of clozapine during the first nine days of dose titration, did not take sodium valproate and were aged less than 40years; and nine control patients received sodium valproate and more than 920mg of clozapine in the first nine days without developing myocarditis.
Clozapine should be initiated by slow dose titration and sodium valproate is best avoided, if clinically feasible, during this period. All patients commencing clozapine should be monitored for myocarditis up to Day 28.
尽管已经实施了心脏监测指南，但氯氮平诱发的心肌炎仍在澳大利亚导致死亡，而这种风险是限制将这种有效药物用于治疗精神分裂症的一个因素。本研究旨在确定氯氮平诱导心肌炎的临床和表型危险因素。
从患者的病历中记录了 1993 年 6 月至 2009 年 11 月期间发生的可能与氯氮平相关的心肌炎病例和至少服用氯氮平 45 天而无心脏病的对照组。
共纳入 105 例病例（发病时间为 10-33 天）和 296 例对照组。多变量分析显示，在前 9 天氯氮平滴定过程中每增加 250mg 氯氮平，心肌炎的风险增加 26%（比值比 1.26；95%置信区间 1.02-1.55；p=0.03），同时服用丙戊酸钠使风险增加两倍以上（2.59；1.51-4.42；0.001）。此外，每增加 10 岁，风险增加 31%（1.31；1.07-1.60；0.009）。尽管如此，仍有 33 例患者在前 9 天的剂量滴定过程中接受的氯氮平少于 920mg，未服用丙戊酸钠且年龄小于 40 岁；9 例对照患者在前 9 天内接受了丙戊酸钠和超过 920mg 的氯氮平，但未发生心肌炎。
氯氮平应缓慢开始剂量滴定，在这段时间内如果临床可行，最好避免使用丙戊酸钠。所有开始使用氯氮平的患者应在第 28 天之前监测心肌炎。
