DOPAMINE TURNOVER IN SCHIZOPHRENIA BEFORE AND AFTER HALOPERIDOL WITHDRAWAL - CSF, PLASMA, AND URINE STUDIES

The dopamine hypotheses of schizophrenia and antipsychotic drug action suggest that the dopamine metabolite homovanillic acid (HVA) should c hange with drug withdrawal and change in clinical state. We designed a study of cerebrospinal fluid (CSF), plasma, and urinary HVA on and of f haloperidol to examine the effects of drug withdrawal. CSF and plasm a HVA samples were obtained in 72 healthy schizophrenic (DSM-III-R) ma les (age: 36 +/- 7.4 years), before and after haloperidol withdrawal, which was after 6 weeks on placebo or sooner if they met specific crit eria for relapse. We collected three 24-hour urine samples in 34 of th ese patients. In addition, CSF HVA was obtained in 24 well-screened ag e-matched male normal controls. HVA was measured with high-pressure li quid chromatography (HPLC). CSF HVA decreased significantly after drug withdrawal, particularly in those who met relapse criteria; drug-free CSF HVA levels were not significantly different from those of normals . Plasma HVA increased significantly after haloperidol withdrawal in r elapsing patients, but not in clinically stable patients. Urinary HVA excretion decreased after withdrawal with decreased HVA clearance. We conclude that haloperidol withdrawal had a strong effect on dopamine t urnover whereas the patient's clinical state had only a weak central e ffect, without affecting total body production of HVA. Conceivably, do pamine involvement in schizophrenia reflects the failure of the homeos tatic mechanisms that allow for integration of different functional br ain components Its needed.