The incidence and characteristics of clozapine- induced fever in a local psychiatric unit in Hong Kong.
OBJECTIVE
To determine the incidence, characteristics, and predictors of clozapine-induced fever in a sample of patients in a local psychiatric unit.


METHODS
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 degrees 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).


CONCLUSIONS
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.
Pui-yin Chung
Joseph
J
Department of Psychiatry, Pamela Youde Nethersole Eastern Hospital, Chai Wan, Hong Kong.
Shiu-yin Chong
Catherine
C
Chung
Ka-fai
KF
Lai-wah Dunn
Eva
E
Wai-nang Tang
Orlando
O
Chan
Wah-fat
WF
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000927:Anticonvulsants / Q000008:administration & dosage / Q000009:adverse effects; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001714:Bipolar Disorder / Q000188:drug therapy*; D003024:Clozapine / Q000008:administration & dosage / Q000009:adverse effects*; D003430:Cross-Sectional Studies; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005334:Fever / Q000139:chemically induced* / Q000453:epidemiology*; D006723:Hong Kong; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D011567:Psychiatric Department, Hospital / Q000706:statistics & numerical data; D011618:Psychotic Disorders / Q000188:drug therapy*; D012189:Retrospective Studies; D012307:Risk Factors; D012559:Schizophrenia / Q000188:drug therapy*; D014635:Valproic Acid / Q000008:administration & dosage / Q000009:adverse effects; D055815:Young Adult
D000927:Anticonvulsants; D014150:Antipsychotic Agents; D014635:Valproic Acid; D003024:Clozapine