The relationship between blood levels and clinical efficacy of neuroleptics remains undetermined. Haloperidol (HAL) lacks multiple active metabolites and is therefore a suitable drug for studies of such a relationship. Several small studies claimed that optimal therapeutic results in schizophrenia can be obtained when HAL blood levels were in a """"""""therapeutic range"""""""". Levels below and above the range were associated with poorer outcomes. Other workers were unable to confirm the existence of a therapeutic range. The principal goal of this project is to define how HAL and reduced haloperidol (RHAL) blood levels interact with clinical variables in determining the short-term outcome of treatment in schizophrenia and schizoaffective disorder. The subjects will be 135 acutely decompensated new admissions to inpatient services. Patients will be assigned to one of three plasma level ranges of HAL (rather than to a fixed dose), and those who fail to improve after 6 weeks on that plasma level will be either continued in the same range or moved to one of the two other plasma level ranges for another six weeks. Assignment of plasma level ranges will be randomized, and double-blind procedures will be used. The patient evaluations will include the Brief Psychiatric Rating Scale, scales for the assessment of positive and negative symptoms (Andreasen), Simpson-Angus Scale, and special ratings for akathisia. Blood for HAL and RHAL assays will be drawn weekly; HAL plasma levels will be reported on the same day and used for dose adjustment which may be needed to keep the patients within their assigned plasma level ranges. We hypothesize that patients' history and clinical presentation will co-determine the relationship between HAL (and RHAL) blood levels and the outcome. The relationship will be either curvilinear (implying a therapeutic range) or linear. The proposed study will resolve the controversy surrounding the relation between blood levels of HAL and clinical effects. The results will indicate which patients do best at which blood levels of HAL; this will be a major contribution to the clinical practice of psychiatry.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH041772-02
Application #
3380542
Study Section
(TDAB)
Project Start
1987-02-01
Project End
1990-01-31
Budget Start
1988-02-01
Budget End
1989-01-31
Support Year
2
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Nathan Kline Institute for Psychiatric Research
Department
Type
DUNS #
167204762
City
Orangeburg
State
NY
Country
United States
Zip Code
10962
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Czobor, P; Volavka, J (1996) Dimensions of the Brief Psychiatric Rating Scale: an examination of stability during haloperidol treatment. Compr Psychiatry 37:205-15
Czobor, P; Volavka, J (1996) Positive and negative symptoms: is their change related? Schizophr Bull 22:577-90
Volavka, J; Cooper, T B; Czobor, P et al. (1996) Effect of varying haloperidol plasma levels on negative symptoms in schizophrenia and schizoaffective disorder. Psychopharmacol Bull 32:75-9
Volavka, J; Cooper, T B; Laska, E M et al. (1996) Placebo washout in trials of antipsychotic drugs. Schizophr Bull 22:567-76
Volavka, J; Cooper, T B; Czobor, P et al. (1995) Plasma haloperidol levels and clinical effects in schizophrenia and schizoaffective disorder. Arch Gen Psychiatry 52:837-45
Convit, A; Volavka, J; Czobor, P et al. (1994) Effect of subtle neurological dysfunction on response to haloperidol treatment in schizophrenia. Am J Psychiatry 151:49-56
Krakowski, M I; Kunz, M; Czobor, P et al. (1993) Long-term high-dose neuroleptic treatment: who gets it and why? Hosp Community Psychiatry 44:640-4
Czobor, P; Volavka, J (1993) Quantitative electroencephalogram examination of effects of risperidone in schizophrenic patients. J Clin Psychopharmacol 13:332-42
Czobor, P; Volavka, J (1992) Level of haloperidol in plasma is related to electroencephalographic findings in patients who improve. Psychiatry Res 42:129-44

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