Neuroleptics represent the mainstay of the pharmacologic treatment of schizophrenia; however, the large number of treatment-resistant schizophrenic patients has prompted efforts at augmenting their therapeutic effects. In this study we will evaluate the clinical efficacy of alprazolam augmentation of neuroleptic treatment in treatment-resistant schizophrenic patients. Fifty-two treatment-resistant schizophrenic patients will be studied as inpatients for six weeks. During the first two weeks, patients will be stabilized on fluphenazine following which either alprazolan or placebo will be added in a double-blind manner for four weeks. Clinical response will be assessed by weekly double-blind ratings of """"""""positive"""""""" and """"""""negative"""""""" psychotic symptoms. In addition, plasma levels of homovanillic acid will be obtained three times weekly for assessment of alprazolan effects on plasma measures of dopamine turnover. All patients will additionally receive magnetic resonance imaging brain scans to assess the possible relationship of estimates of prefrontal cortex atrophy to favorable clinical response to alprazolam (as suggested by pilot data). This study may lead to the development of novel therapeutic approaches to the treatment-resistant schizophrenic patient as well as to a delineation of biological predictors or concomitants of favorable clinical response.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29MH043612-03
Application #
3474823
Study Section
Treatment Development and Assessment Research Review Committee (TDA)
Project Start
1987-09-30
Project End
1992-08-31
Budget Start
1989-09-01
Budget End
1990-08-31
Support Year
3
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Type
Overall Medical
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Wolkowitz, O M (1993) Rational polypharmacy in schizophrenia. Ann Clin Psychiatry 5:79-90
Wolkowitz, O M; Turetsky, N; Reus, V I et al. (1992) Benzodiazepine augmentation of neuroleptics in treatment-resistant schizophrenia. Psychopharmacol Bull 28:291-5
Wolkowitz, O M; Pickar, D (1991) Benzodiazepines in the treatment of schizophrenia: a review and reappraisal. Am J Psychiatry 148:714-26