Effects of haloperidol on antioxidant defense system enzymes in schizophrenia

Dysregulation of free radical metabolism as reflected by abnormal erythrocyte activities of three critical enzymes of the antioxidant defense system (AODS), i.e. superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT), has been reported in schizophrenic patients. The present study examined the effects of haloperidol, a standard antipsychotic agent, on the AODS enzymes, using a within-subject, repeated-measures, on–off haloperidol treatment design. The mean drug free period was 40 days. At baseline, there were no significant differences for all three enzymes between patients and age and sex-matched normal volunteers. During the drug-free condition, SOD activity, but not GSH-Px and CAT activities, was significantly higher relative to normal control subjects. However, within-subjects both SOD and GSH-Px activities, but not CAT activity, were higher in the drug-free condition compared to the treatment condition. No significant correlation was observed between SOD activity and plasma haloperidol (or daily haloperidol dose) levels. Smoking status, as assessed by the cotinine level, was unrelated to enzyme activities. In addition, none of the major AODS enzymes showed significant differences between relapsed and clinically stable patients. These findings suggest that haloperidol may not have direct regulatory effect on AODS enzyme activities and that SOD and GSH-Px activities may change in response to other factors such as change in symptom severity.