title: Effects of clozapine on plasma catecholamines and relation to treatment response in schizophrenia: a within-subject comparison with haloperidol.
abstract: We conducted a within-subject comparison of the effects of clozapine and haloperidol on plasma levels of neurotransmitters and metabolites, and related changes in specific plasma neurochemicals with clozapine response. The subjects were 14 inpatients with schizophrenia or schzoaffective disorder, who were refractory to haloperidol and at least one other typical antipsychotic medication. Subjects underwent, in the following order: a 6-week "fixed, flexible dose" haloperidol trial, followed by a 2-4 week medication-free phase, and a 6-week clozapine trial. 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 were obtained at the end of each phase. As expected, we found a substantial increase of plasma NE with clozapine but not with haloperidol. However, the increase in NE was not associated with improvement in total or positive symptomatology. There was some evidence for an association between improvement 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.
authors.affiliation: Department of Psychiatry, College of Physicians and Surgeons of Columbia University, New York State Psychiatric Institute, New York, USA.
authors.forename: A S
authors.initials: AS
authors.lastname: Brown
authors.forename: G
authors.initials: G
authors.lastname: Gewirtz
authors.forename: J
authors.initials: J
authors.lastname: Harkavy-Friedman
authors.forename: T
authors.initials: T
authors.lastname: Cooper
authors.forename: G
authors.initials: G
authors.lastname: Brébion
authors.forename: X F
authors.initials: XF
authors.lastname: Amador
authors.forename: D
authors.initials: D
authors.lastname: Malaspina
authors.forename: J M
authors.initials: JM
authors.lastname: Gorman
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D003024:Clozapine / Q000627:therapeutic use*; D006220:Haloperidol / Q000627:therapeutic use*; D006719:Homovanillic Acid / Q000097:blood*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008734:Methoxyhydroxyphenylglycol / Q000097:blood*; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood*; D011388:Prolactin / Q000097:blood; D011618:Psychotic Disorders / Q000097:blood / Q000188:drug therapy; D012559:Schizophrenia / Q000097:blood* / Q000188:drug therapy*
chemical_list: D014150:Antipsychotic Agents; D008734:Methoxyhydroxyphenylglycol; D011388:Prolactin; D003024:Clozapine; D006220:Haloperidol; D006854:Hydrocortisone; D009638:Norepinephrine; D006719:Homovanillic Acid