EFFECTS OF HALOPERIDOL ON ANTIOXIDANT DEFENSE SYSTEM ENZYMES IN SCHIZOPHRENIA

Dysregulation of free radical metabolism as reflected by abnormal eryt hrocyte activities of three critical enzymes of the antioxidant defens e system (AODS), i.e. superoxide dismutase (SOD), glutathione peroxida se (GSH-Px) and catalase (CAT), has been reported in schizophrenic pat ients. The present study examined the effects of haloperidol, a standa rd antipsychotic agent, on the AODS enzymes, using a within-subject, r epeated-measures, on-off haloperidol treatment design. The mean drug f ree period was 40 days. At baseline, there were no significant differe nces for all three enzymes between patients and age and sex-matched no rmal volunteers. During the drug-free condition, SOD activity, but not GSH-Px and CAT activities, was significantly higher relative to norma l control subjects. However, within-subjects both SOD and GSH-Px activ ities, but not CAT activity, were higher in the drug-free condition co mpared to the treatment condition. No significant correlation was obse rved 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 en zymes showed significant differences between relapsed and clinically s table patients. These findings suggest that haloperidol may not have d irect 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. (C) 1998 Elsevier Science Ltd. All rights reserve d.