Yuan-Pin Hung1, Carol S-M Wang2,3, Chia-Nan Yen2, Hsun-Cheng Chang2, Po See Chen4,5, I Hui Lee4,5, Kao Chin Chen4,5, Yen Kuang Yang4,5,6,7, Ru-Band Lu4,5,6,8,9, Tzu-Yun Wang4. 1. Department of Internal Medicine, Tainan Hospital, Ministry of Health and Welfare, Tainan, Taiwan. 2. Department of Psychiatry, Tainan Hospital, Ministry of Health and Welfare, Tainan, Taiwan. 3. Department of BioMedical Engineering, National Cheng Kung University Hospital, College of Medicine, Tainan, Taiwan. 4. Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, Tainan, Taiwan. 5. Addiction Research Center, National Cheng Kung University, Tainan, Taiwan. 6. Institute of Behavioral Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan. 7. Department of Psychiatry, National Cheng Kung University Hospital, Dou-Liou Branch, Yunlin, Taiwan. 8. Institute of Allied Health Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan. 9. Center for Neuropsychiatric Research, National Health Research Institutes, Miaoli, Taiwan.
Abstract
AIM: Clozapine-associated fever is common but the specific cytokine changes and treatment durations that may cause fever remain unknown. We investigated the association between inflammatory cytokine changes and clozapine-induced fever in patients who were treated with clozapine. METHODS: Forty-three patients with schizophrenia or schizoaffective disorder, diagnosed by using the Chinese Version of the Mini International Neuropsychiatric Interview, were treated with clozapine for the first time (first-time use group, n = 22) or for more than 6 months (long-term use group, n = 21). The Positive and Negative Syndrome Scale, tympanic temperature, and levels of tumor necrosis factor-α (TNF-α), interferon-γ (INF-γ), interleukin-2 (IL-2), and interleukin-6 (IL-6) were determined at baseline and weeks 1, 2, 3, 4, and 6. A multiple linear regression with generalized estimating equation methods was used to analyze the association between the changes in the cytokine levels and clozapine-induced fever in the different groups. RESULTS: The IL-6 level changes were significantly different between the two groups (P = 0.04). In the first-time use group, the fever rate was increased (47.1%) compared with the long-term use group (5.6%, P = 0.005). Moreover, in these patients, the TNF-α, INF-γ, IL-2, and IL-6 levels were significantly (P < 0.001) different from patients who did not develop a fever. An interaction effect with the different treatment duration groups and fever development was only significant for IL-6 (P < 0.001). CONCLUSION: Patients who were treated with clozapine for the first time have an increased rate of developing a fever, and IL-6 might have a specific role in the interaction effect between treatment duration and fever development.
AIM: Clozapine-associated fever is common but the specific cytokine changes and treatment durations that may cause fever remain unknown. We investigated the association between inflammatory cytokine changes and clozapine-induced fever in patients who were treated with clozapine. METHODS: Forty-three patients with schizophrenia or schizoaffective disorder, diagnosed by using the Chinese Version of the Mini International Neuropsychiatric Interview, were treated with clozapine for the first time (first-time use group, n = 22) or for more than 6 months (long-term use group, n = 21). The Positive and Negative Syndrome Scale, tympanic temperature, and levels of tumor necrosis factor-α (TNF-α), interferon-γ (INF-γ), interleukin-2 (IL-2), and interleukin-6 (IL-6) were determined at baseline and weeks 1, 2, 3, 4, and 6. A multiple linear regression with generalized estimating equation methods was used to analyze the association between the changes in the cytokine levels and clozapine-induced fever in the different groups. RESULTS: The IL-6 level changes were significantly different between the two groups (P = 0.04). In the first-time use group, the fever rate was increased (47.1%) compared with the long-term use group (5.6%, P = 0.005). Moreover, in these patients, the TNF-α, INF-γ, IL-2, and IL-6 levels were significantly (P < 0.001) different from patients who did not develop a fever. An interaction effect with the different treatment duration groups and fever development was only significant for IL-6 (P < 0.001). CONCLUSION:Patients who were treated with clozapine for the first time have an increased rate of developing a fever, and IL-6 might have a specific role in the interaction effect between treatment duration and fever development.