Effects of clozapine and olanzapine on cytokine systems are closely linked to weight gain and drug-induced fever.
The second generation antipsychotics clozapine and olanzapine are known to cause weight gain. However, only clozapine is associated with drug-induced fever. Cytokines have been linked to the induction of both weight gain and drug-induced fever. We investigated these potential side effects of clozapine and olanzapine and studied their differential effects on cytokine secretion. Thirty patients suffering from schizophrenia, schizophreniform disorder or schizoaffective disorder were treated with either clozapine (mean modal dose: 266.7+/-77.9mg) or olanzapine (21.2+/-2.5mg) in a randomized, double-blind, 6-week study. Body mass index (BMI), tympanic temperature, and plasma levels of leptin and cytokines (tumor necrosis factor-alpha (TNF-alpha), soluble TNF receptor 1 and 2 (sTNFR-1/2), soluble interleukin-2 receptors (sIL-2R), interleukin-6) were determined weekly. BMI, leptin and cytokines significantly increased over time, except interleukin-6 and sTNFR-1 in the olanzapine group. All cytokines numerically increased compared to baseline already during the first week of treatment in both groups. Leptin, TNF-alpha, sTNFR-1, sTNFR-2 and sIL-2R levels correlated with the BMI. Five patients who received clozapine (33%) developed drug-induced fever (>/=38 degrees C). In these, interleukin-6 peak levels were significantly (p<0.01) higher than in those patients treated with clozapine who did not develop fever. In conclusion, increase of BMI appears to be related to clozapine's and olanzapine's similar effects on cytokine systems, whilst drug-induced fever appears to be related to clozapine's differential effects on interleukin-6.
Max Planck Institute of Psychiatry, Munich, Germany.
Michael
M
Kluge
Andreas
A
Schuld
Alexander
A
Schacht
Hubertus
H
Himmerich
Mira A
MA
Dalal
Peter M
PM
Wehmeier
Dunja
D
Hinze-Selch
Thomas
T
Kraus
Ralf W
RW
Dittmann
Thomas
T
Pollmächer
D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000494:pharmacology*; D001569:Benzodiazepines / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D015992:Body Mass Index; D003024:Clozapine / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D016207:Cytokines / Q000097:blood*; D004311:Double-Blind Method; D005260:Female; D005334:Fever / Q000139:chemically induced*; D006801:Humans; D020738:Leptin / Q000097:blood; D008297:Male; D008875:Middle Aged; D000077152:Olanzapine; D011569:Psychiatric Status Rating Scales; D011618:Psychotic Disorders / Q000188:drug therapy / Q000378:metabolism; D012559:Schizophrenia / Q000188:drug therapy / Q000378:metabolism; D015430:Weight Gain / Q000187:drug effects*
D014150:Antipsychotic Agents; D016207:Cytokines; D020738:Leptin; D001569:Benzodiazepines; D003024:Clozapine; D000077152:Olanzapine