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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; p < 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. [Display omitted] [ABSTRACT FROM AUTHOR]

An influenza pandemic occurred in 2009. We performed a retrospective national questionnaire survey about H1N1pdm2009 myocarditis to compare influenza A H1N1pdm2009 myocarditis in the pandemic (2009/2010) and postpandemic seasons (2010/2011) by collecting data from 360 hospitals. The diagnosis of myocarditis was performed using the guidelines for Diagnosis and Treatment of Myocarditis published by the Japanese Circulation Society (JCS 2009). Twenty-nine patients with influenza A H1N1pdm2009 myocarditis were reported, with 25 from the 2009/2010 season and only 4 patients from the 2010/2011 season. Morbidity and mortality was 28 % (8/29) among all the myocarditis patients. Six patients with myocarditis were complicated by pneumonia. Myocarditis was proved by endomyocardial biopsy or autopsy in 9 patients, although histological findings showed mild myocarditis even in clinically defined fulminant myocarditis cases. Seventeen patients were diagnosed with fulminant H1N1pdm2009 myocarditis with fatal arrhythmias or varying degrees of cardiogenic shock. Fifteen fulminant myocarditis patients were seen in the 2009/2010 season and only 2 in the 2010/2011 season. Ventilators were used in 16 patients. Mechanical circulatory support with intraaortic balloon pumping or percutaneous cardiopulmonary support (IABP/PCPS) was emergently inserted in 13 patients. Of these, 9 patients were rescued with mechanical circulatory support, and 4 patients died. Four fulminant myocarditis patients treated without IABP/PCPS died. We described the clinical features of patients with myocarditis associated with influenza H1N1pdm2009 in the pandemic and postpandemic seasons and demonstrated the high prevalence of fulminant myocarditis (17/29, 59 %). The number of patients with myocarditis associated with influenza A virus seemed to increase in the pandemic season. [ABSTRACT FROM AUTHOR]