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Neuropsychopharmacology (1997) 17 317-325.
Effects of Clozapine on Plasma Catecholamines and Relation to Treatment Response in Schizophrenia: A Within-Subject Comparison with Haloperidol
Alan S Brown MD 1, George Gewirtz MD1, Jill Harkavy-Friedman Ph.D1, Thomas Cooper MA2, Gildas Brébion Ph.D1, Xavier F Amador Ph.D1, Dolores Malaspina MD1 and Jack M Gorman MD1 |
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1From the Department of Psychiatry, College of Physicians and Surgeons of Columbia University, New York State Psychiatric Institute, New York, New York, U.S.A
2Nathan Kline Institute, Orangeburg, New York
Correspondence: Dr Alan S Brown, New York State Psychiatric Institute, 722 W. 168th Street, Unit 2, New York, NY 10032
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ABSTRACT
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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 2¾4 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. Ó 1997 American College of Neuropsyphopharmacology
Keywords: Clozapine; Schizophrenia; Norepinephrine; Homovanillic acid; Symptomatology |
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