A sample of 40 chronic schizophrenics and 20 normal controls will be studied. Patients will be selected for clinical non- responsiveness in at least 3 trials of different classes of neuroleptic medication in the last 5 years. Patients who show substantial clinical improvement during any phase of the study will be dropped and replaced. To be included, patients must have a duration of illness greater than 5 years and persistent psychosis and impaired social, vocational, or interpersonal functioning for 3 years. All subjects will be between 25 and 40 years of age. Patients will be treated with haloperidol in an initial medication phase of at least 2 weeks at steady state plasma levels between 8 to 20 ng/ml. Patients will then enter a 4-week discontinuation phase, free of all medications. In the case of marked clinical deterioration, minimal discontinuation will be 2 weeks. Following this, patients enter a standardized 5-week haloperidol treatment phase, reaching a 10 day steady dosage level of 60 mg (or maximum tolerated dose) by the end of this phase. rCBF patinet measurements will be conducted at the end of the initial treatment phase, 7, 14, and 28 days drug free, and during the 5th week of the prospective treatment phase. An acute test dose response study will be done at 28 days drug free. Normal controls will undergo comparable rCBF resting condition measurements at time points comparable to end of initial treatment phase, end of discontinuation phase and end of prospective treatment phase. Controls will also be administered the acute test dose (5 mg PO) rCBF evaluation with haloperiodol. Plasma and RBC haloperidol levels, reduced haloperidol and plasma HVA will be assessed repeatedly. The study will address effects of neuroleptic treatment and discontinuation on rCBF, abnormalities in the rCBF levels and topography in chronic schizophrenics, the relations between effects of acute and chronic neuroleptic administration of rCBF and the temporal course of neuroleptic discontinuation effects. rCBF measurements will be conducted during both resting state and while subjects perform a continuous performance task (activated state). To our knowledge, such systemic examination of both neuroleptic treatment and discontinuation effects on human brain functions has never been performed.
Showing the most recent 10 out of 14 publications
