Lipid status, anti-oxidant enzyme defence and haemoglobin content in the blood of long-term clozapine-treated schizophrenic patients.
OBJECTIVE
Despite clozapine's unique effectiveness in patients with schizophrenia, a number of adverse effects have been recognised including abnormalities in lipid and glucose metabolisms. A high clozapine level in red blood cells (RBCs) and disturbed anti-oxidant enzyme activities in blood from schizophrenic patients prompted us to investigate lipid status and anti-oxidant enzyme defence in the blood of chronic schizophrenic patients on long-term clozapine therapy.


METHODS
Plasma lipids, RBC anti-oxidant enzyme activities and haemoglobin (Hb) content were measured using established procedures in a group of eighteen chronically-medicated (average 630 days of therapy) schizophrenic patients receiving clozapine (average dose of 295 mg/day) and data were compared with those from a group of eighteen well-matched normal controls.


RESULTS
Significantly higher levels of plasma triglycerides (by 47%, p<0.01) and total cholesterol and phospholipids (by 8% and 11%, respectively p<0.05) in patients were found. CuZn-superoxide dismutase (SOD1) activity was markedly higher (by 35%, p<0.001) while selenium-dependent glutathione peroxidase (GSH-Px1) activity was markedly lower (by 41%, p<0.001) in patients. In addition, metHb and HbA1c levels in patients were significantly higher (by 58% and 25%, respectively p<0.001). SOD1 activity was negatively correlated (p<0.001) to GSH-Px1 activity in patients.


CONCLUSIONS
The findings support the view that ongoing oxidative stress may be a mechanism by which clozapine induces some adverse effects that increase the risk of diabetes and metabolic syndrome. If valid, this would indicate that in parallel with long-term clozapine treatment, schizophrenic patients could be encouraged to make some lifestyle changes to limit the detrimental effects of the medication.
Miljevic
Cedo
C
Institute of Mental Health, Belgrade, Serbia.
Nikolic
Milan
M
Nikolic-Kokic
Aleksandra
A
Jones
David R
DR
Niketic
Vesna
V
Lecic-Tosevski
Dusica
D
Spasic
Mihajlo B
MB
D000328:Adult; D000886:Anthropometry / Q000379:methods; D014150:Antipsychotic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001823:Body Composition / Q000187:drug effects; D015992:Body Mass Index; D002374:Catalase / Q000097:blood; D003024:Clozapine / Q000494:pharmacology* / Q000627:therapeutic use; D004912:Erythrocytes / Q000187:drug effects* / Q000201:enzymology; D005260:Female; D005979:Glutathione Peroxidase / Q000097:blood; D005980:Glutathione Reductase / Q000097:blood; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D008055:Lipids / Q000097:blood*; D008137:Longitudinal Studies; D008297:Male; D012559:Schizophrenia / Q000097:blood* / Q000188:drug therapy; D013482:Superoxide Dismutase / Q000097:blood
D014150:Antipsychotic Agents; D006454:Hemoglobins; D008055:Lipids; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D003024:Clozapine