Higher frequencies of inflammatory adverse effects of clozapine have been reported in Japan. As the international titration protocol for Asians has set slower dose titration than the Japanese package insert, we hypothesized that a dose titration speed slower than the recommendation of the guideline would be associated with fewer inflammatory-related adverse events. The medical records of all 272 patients who were first started on clozapine at seven hospitals between 2009 and 2023 were studied retrospectively. Of those, 241 were included in the analysis. The patients were divided into two groups regarding whether the titration speed was faster or slower than the guideline for Asians. The incidence of inflammatory adverse events with clozapine was compared between the groups. The frequency of inflammatory adverse events was 34 % (37/110) in the faster titration group and 13 % (17/131) in the slower titration group, and a significant difference was observed by Fisher exact test (odds ratio 3.38; 95 % confidence interval 1.71–6.91; < 0.001). Serious adverse effects, fever for more than five days, and clozapine discontinuation were significantly more frequent in the faster titration group. Logistic regression analysis indicated significantly more inflammatory adverse events in the faster titration group (adjusted odds ratio 4.01; 95 % confidence interval 2.02–7.87; p < 0.001) considering age, sex, body mass index, concomitant valproic acid, and smoking as confounding factors. Clozapine-induced inflammatory adverse events were less frequent in Japanese individuals when a titration rate was more gradual than the protocol recommended in the Japanese package insert.

中文翻译：

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氯氮平滴定速度比日本官方方案慢，可减少炎症不良反应：对七家医院的回顾性图表审查


日本报道氯氮平引起炎症不良反应的频率较高。由于亚洲人的国际滴定方案设定的剂量滴定速度比日本包装说明书慢，我们假设剂量滴定速度慢于指南的建议将与较少的炎症相关不良事件相关。回顾性研究了 2009 年至 2023 年间在 7 家医院首次开始使用氯氮平的所有 272 名患者的医疗记录。其中 241 个被纳入分析。根据滴定速度是否比亚洲人的指南快或慢，将患者分为两组。比较各组之间氯氮平炎症不良事件的发生率。快速滴定组的炎症不良事件发生率为 34% (37/110)，慢滴定组为 13% (17/131)，Fisher 精确检验观察到显着差异（比值比 3.38；95%）置信区间 1.71–6.91；< 0.001)。在快速滴定组中，严重不良反应、发烧超过五天和氯氮平停药的发生率明显更高。 Logistic 回归分析表明，考虑到年龄、性别、体重指数、伴随丙戊酸和吸烟作为混杂因素，快速滴定组的炎症不良事件明显增多（调整后优势比 4.01；95% 置信区间 2.02–7.87；p < 0.001） 。当滴定速度比日本包装说明书中推荐的方案更渐进时，氯氮平引起的炎症不良事件在日本人中较少发生。