The Incidence and Characteristics of Clozapine-Induced Fever in a Local Psychiatric Unit in Hong Kong

• Published in: Canadian journal of psychiatry Vol. 53; no. 12; pp. 857 - 862
• Main Authors: Chung, Joseph Pui-Yin, Chong, Catherine Shiu-Yin, Chung, Ka-Fai, Dunn, Eva Lai-Wah, Tang, Orlando Wai-Nang, Chan, Wah-Fat
• Format: Journal Article
• Language: English
• Published: Los Angeles, CA SAGE Publications 01.12.2008; Canadian Psychiatric Association; SAGE PUBLICATIONS, INC
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Anticonvulsants - administration & dosage; Anticonvulsants - adverse effects; Antipsychotic Agents - administration & dosage; Antipsychotic Agents - adverse effects; Biological and medical sciences; Bipolar Disorder - drug therapy; Clozapine - administration & dosage; Clozapine - adverse effects; Cross-Sectional Studies; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Fever; Fever - chemically induced; Fever - epidemiology; Hong Kong; Humans; Incidence; Infections; Influenza; Kinases; Male; Medical records; Medical sciences; Middle Aged; Neuropharmacology; Pharmacology. Drug treatments; Physical examinations; Plasma; Psychiatric Department, Hospital - statistics & numerical data; Psychiatry; Psycholeptics: tranquillizer, neuroleptic; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychopharmacology; Psychotic Disorders - drug therapy; Retrospective Studies; Risk Factors; Sample size; Schizophrenia - drug therapy; Side effects; Standard deviation; Urine; Valproic Acid - administration & dosage; Valproic Acid - adverse effects; Young Adult; Hong Kong; Asia; China; clozapine; fever; Chinese; Hong Kong; Atypical antipsychotic; Neuroleptic; Psychotropic; Clozapine; Epidemiology; Fever; Incidence; D2 Dopamine receptor; Hospital ward; Antagonist; Psychiatry; Public health
• ISSN: 0706-7437; 1497-0015
• DOI: 10.1177/070674370805301211

Objective: To determine the incidence, characteristics, and predictors of clozapine-induced fever in a sample of patients in a local psychiatric unit. Method: A retrospective review of case notes of 227 inpatients newly started on clozapine from March 2003 to December 2006 was conducted. Demographic characteristics, presence of fever, investigations carried out, fever characteristics, and complications of fever were recorded and analyzed. Patients with clozapine-induced fever were compared with their fever-free counterparts on demographic and clinical factors. Multivariate logistic regression was performed to identify predictors of clozapine-induced fever. Results: Thirty-one out of 227 patients (13.7%) developed clozapine-induced fever. The means for day of onset of clozapine-induced fever after clozapine initiation and duration of fever were 13.7 and 4.7 days, respectively. The mean highest body temperature was 38.8 °C. Fever resolved within 48 hours after clozapine discontinuation in 79% of the patients with clozapine-induced fever. One out of 7 patients (14.3%) had fever on re-challenge. Clozapine-induced fever was associated with rate of titration more than 50 mg/wk (OR 18.9; 95% CI 5.3 to 66.7; P < 0.01), concomitant use of valproate (OR 3.6; 95% CI 1.5 to 8.9; P = 0.01), and presence of physical illnesses (OR 3.2; 95% CI 1.2 to 8.3; P = 0.02). Conclusion: Clozapine-induced fever is common. Temporary withdrawal of clozapine may result in resolution of fever, and clozapine re-challenge may be considered after fever subsides. Slower rate of clozapine titration may be helpful in patients with underlying physical illness and concomitant valproate treatment.