Role of cytokine changes in clozapine-induced fever: A cohort prospective study

Yuan Pin Hung, Carol S.M. Wang, Chia Nan Yen, Hsun Cheng Chang, Po See Chen, I. Hui Lee, Kao Chin Chen, Yen Kuang Yang, Ru Band Lu, Tzu Yun Wang

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)395-402
Number of pages8
JournalPsychiatry and Clinical Neurosciences
Issue number6
Publication statusPublished - 2017 Jun

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Neurology
  • Clinical Neurology
  • Psychiatry and Mental health


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