Schizophrenia is a serious mental disease that costs $30 billion annually in the U.S. Treatment refractory patients account for the majority of these expenditures. Standard antipsychotic drugs are clinically effective in only 50% of the patients. The atypical antipsychotic clozapine (CLO) is the only treatment with proven efficacy in refractory patients. However, its use has been limited by its high cost and capacity to cause agranulocytosis. A second atypical drug risperidone (RIS) has not been adequately tested in refractory patients. Major questions facing the field are what should be the role of RIS in the treatment of refractory schizophrenia and what is its comparative efficacy to CLO. These questions are important in terms of clinical care and public health care allocation. Recent experience has demonstrated the poor understanding that clinicians and patients have concerning the appropriate uses of CLO and RIS, and the need for a study to determine their comparative efficacies in severely ill patients. The R-10 application to be conducted at three sites - Bronx Psychiatric Center (AECOM; J. Lieberman, P.I.); Rockland Psychiatric Center, and Manhattan Psychiatric Center in association with the Nathan S. Kline Institute for Psychiatric Research under the direction of Jan Volavka (P.I.) - describes a project that will address these questions. We will examine the comparative efficacy of CLO, RIS 6 mg/day, RIS 16 mg/day, and a standard agent, haloperidol (HAL) in severely ill treatment resistant patients with schizophrenia. Approximately 75 patients from each site (224 combined sample of all sites) will enter a 12-week clinical trial in which they are randomized to one of four treatments under double blind conditions. Doses of CLO and HAL will be titrated to target blood levels. Doses of RIS will be fixed at 6 or 16 mg/day. Patients' response in terms of symptom reduction will be assessed by PANSS, CGI, and Overt Aggression Scale, social functioning and activities of daily living by NOSIE, quality of life by the Quality of Life Interview, cognitive effects by a test battery, and side effects by ESRS. We hypothesize that the antipsychotic and the antiaggressive effects of CLO will be superior to RIS and HAL, and that RIS will be superior to HAL. RIS 16 mg/day will have more antiaggressive effect than 6 mg/day. The results of this study will provide the evidentiary basis for clinical practice and health care policy decisions.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Unknown (R10)
Project #
5R10MH053550-03
Application #
2675288
Study Section
Special Emphasis Panel (SRCM (21))
Project Start
1995-09-30
Project End
2000-03-31
Budget Start
1998-04-15
Budget End
1999-03-31
Support Year
3
Fiscal Year
1998
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
Hoptman, Matthew J; Volavka, Jan; Czobor, Pal et al. (2006) Aggression and quantitative MRI measures of caudate in patients with chronic schizophrenia or schizoaffective disorder. J Neuropsychiatry Clin Neurosci 18:509-15
Muller, Daniel J; Klempan, Tim A; De Luca, Vincenzo et al. (2005) The SNAP-25 gene may be associated with clinical response and weight gain in antipsychotic treatment of schizophrenia. Neurosci Lett 379:81-9
Volavka, Jan; Nolan, Karen A; Kline, Linda et al. (2005) Efficacy of clozapine, olanzapine, risperidone, and haloperidol in schizophrenia and schizoaffective disorder assessed with nurses observation scale for inpatient evaluation. Schizophr Res 76:127-9
Muller, Daniel J; De Luca, Vincenzo; Sicard, Tricia et al. (2005) Suggestive association between the C825T polymorphism of the G-protein beta3 subunit gene (GNB3) and clinical improvement with antipsychotics in schizophrenia. Eur Neuropsychopharmacol 15:525-31
Nolan, Karen A; Volavka, Jan; Czobor, Pal et al. (2005) Aggression and psychopathology in treatment-resistant inpatients with schizophrenia and schizoaffective disorder. J Psychiatr Res 39:109-15
De Luca, Vincenzo; Vincent, John B; Muller, Daniel J et al. (2005) Identification of a naturally occurring 21 bp deletion in alpha 2c noradrenergic receptor gene and cognitive correlates to antipsychotic treatment. Pharmacol Res 51:381-4
Hoptman, Matthew J; Volavka, Jan; Weiss, Elisabeth M et al. (2005) Quantitative MRI measures of orbitofrontal cortex in patients with chronic schizophrenia or schizoaffective disorder. Psychiatry Res 140:133-45
Volavka, Jan; Czobor, Pal; Cooper, Thomas B et al. (2004) Prolactin levels in schizophrenia and schizoaffective disorder patients treated with clozapine, olanzapine, risperidone, or haloperidol. J Clin Psychiatry 65:57-61
Lindenmayer, Jean-Pierre; Czobor, Pal; Volavka, Jan et al. (2004) Effects of atypical antipsychotics on the syndromal profile in treatment-resistant schizophrenia. J Clin Psychiatry 65:551-6
Volavka, Jan; Kennedy, James L; Ni, Xingqun et al. (2004) COMT158 polymorphism and hostility. Am J Med Genet B Neuropsychiatr Genet 127B:28-9

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