EFFECTS OF CLOZAPINE ON PLASMA-CATECHOLAMINES AND RELATION TO TREATMENT RESPONSE IN SCHIZOPHRENIA - A WITHIN-SUBJECT COMPARISON WITH HALOPERIDOL

We conducted a within-subject comparison of the effects of clozapine a nd haloperidol on plasma levels of neurotransmitters and metabolites, and related changes in specific plasma neurochemicals with clozapine r esponse. The subjects were 14 inpatients with schizophrenia or schzoaf fective disorder, who were refractory to haloperidol and at least one other typical antipsychotic medication. Subjects underwent, in the fol lowing order: a 6-week ''fixed, flexible dose'' haloperidol trial, fol lowed by a 2-4 week medication-free phase, and a 6-week clozapine tria l. Plasma levels of norepinephrine (NE), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG), and objective clinical ratings of total, positive, negative, and depressive symptoms wee obtained at the end of each phase. As expected, we found a substantial increase o f plasma NE with clozapine but not with haloperidol. However, the incr ease in NE was not associated with improvement in total or positive sy mptomatology. There was some evidence for an association between impro vement in negative symptoms and increased HVA on clozapine, as well as diminished HVA during the medication-free phase. The implications of these data for understanding the mechanisms of action of clozapine are discussed. (C) 1997 American College of Neuropsychopharmacology. Publ ished by Elsevier Science Inc.