The sex-dependent impact of chronic clozapine and haloperidol treatment on characteristics of the metabolic syndrome in a rat model.
BACKGROUND
An increased risk for metabolic syndrome has been described for patients with psychotic disorders. Antipsychotic drugs possibly contribute to metabolic changes.


METHODS
Haloperidol or clozapine was orally fed to male and female Sprague Dawley rats for 12 weeks, and body weight gain, food and water intake were measured. The serum levels of fasting glucose, HbA1c, triglycerides, cholesterol, HDL and LDL, insulin, leptin, adiponectin and ghrelin were determined. Gonadal and perirenal fat pads were removed and weighed.


RESULTS
We found increased body weight in the male clozapine group, but decreased ones in the male haloperidol group. Clozapine-treated male and female animals had higher fasting glucose, adiponectin, leptin, ghrelin, cholesterol, HDL and LDL levels, whereas haloperidol caused increased levels of insulin and decreased values of HbA1c, cholesterol, HDL and LDL.


CONCLUSIONS
Both antipsychotic drugs cause sex-dependent metabolic changes, which are risk factors for the metabolic syndrome, be it hyperinsulinemia under haloperidol treatment or hyperglycemia, hyperleptinemia and hyperlipidemia under clozapine.
Department of Psychiatry and Psychotherapy, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany.
M
M
von Wilmsdorff
M L
ML
Bouvier
U
U
Henning
A
A
Schmitt
T
T
Schneider-Axmann
W
W
Gaebel
D050154:Adiposity / Q000187:drug effects; D000818:Animals; D014150:Antipsychotic Agents / Q000097:blood / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D003024:Clozapine / Q000097:blood / Q000494:pharmacology*; D004326:Drinking / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D005260:Female; D006220:Haloperidol / Q000097:blood / Q000494:pharmacology*; D006728:Hormones / Q000097:blood; D007328:Insulin / Q000378:metabolism; D008055:Lipids / Q000097:blood; D008297:Male; D024821:Metabolic Syndrome / Q000378:metabolism*; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics; D015430:Weight Gain / Q000187:drug effects
D014150:Antipsychotic Agents; D001786:Blood Glucose; D006728:Hormones; D007328:Insulin; D008055:Lipids; D003024:Clozapine; D006220:Haloperidol