This is a competitive continuation of an on going series of studies to test the efficacy and effectiveness of novel antipsychotic in neuroleptic treatment resistant schizophrenic patients. Support for this proposal will also continue support for a significant Public and Academic Liaison initiative the Treatment Research Unit of the University of Maryland at Baltimore. In our initial work, we have develop[ed a standard clinical protocol to test candidate drugs for differential effect in neuroleptic treatment resistant schizophrenic inpatients. The study proposed in this application will test the efficacy of sertindole, quetiapine, and risperidone versus fluphenazine in this population. The drugs will be tested in a drug-drug double-blind parallel group design. The study will last 24-weeks. Patients will be selected for poor neuroleptic response because of a history of a least one year of persistent symptoms, a history of failure to respond to at least two adequate trials of neuroleptics over the past five years and poor global functioning for the past five years. Patients who enter the trial will also have failed to respond to six seeks of prospective haloperidol therapy. The current drugs that will be studied, along with olanzapine, whose evaluation we are completing now, represent all of the new antipsychotic drug that will be available in the near future. Future candidate drugs will be selected based on the outcome of this trial and will be the subject of future submissions. This design provides substantial power for testing superiority of a candidate drug. Results will be analyzed with regard to improvement in total BPRS score and psychotic symptoms. We will also assess improvements to quality of life, living skills and dischargability. This study size is based on a predicted effect of 11% difference in total symptoms and a 22% difference in positive symptoms with a power of 0.80 and alpha of 0.05 (two-tailed).

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH047311-06
Application #
2674997
Study Section
Treatment Assessment Review Committee (TA)
Project Start
1993-01-01
Project End
2002-03-31
Budget Start
1998-04-15
Budget End
1999-03-31
Support Year
6
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of Maryland Baltimore
Department
Psychiatry
Type
Schools of Medicine
DUNS #
003255213
City
Baltimore
State
MD
Country
United States
Zip Code
21201
Conley, Robert R; Ascher-Svanum, Haya; Zhu, Baojin et al. (2007) The burden of depressive symptoms in the long-term treatment of patients with schizophrenia. Schizophr Res 90:186-97
Carpenter, William T; Conley, Robert R (2007) Challenge to atypical antipsychotic drug effect on cognition. Am J Psychiatry 164:1910-1;author reply 1911-2
Kelly, Deanna L; Richardson, Charles M; Yu, Yang et al. (2006) Plasma concentrations of high-dose olanzapine in a double-blind crossover study. Hum Psychopharmacol 21:393-8
Kelly, Deanna L; Conley, Robert R (2006) A randomized double-blind 12-week study of quetiapine, risperidone or fluphenazine on sexual functioning in people with schizophrenia. Psychoneuroendocrinology 31:340-6
Conley, Robert R; Kelly, Deanna L (2005) Second-generation antipsychotics for schizophrenia: a review of clinical pharmacology and medication-associated side effects. Isr J Psychiatry Relat Sci 42:51-60
McMahon, Robert P; Arndt, Stephan; Conley, Robert R (2005) More powerful two-sample tests for differences in repeated measures of adverse effects in psychiatric trials when only some patients may be at risk. Stat Med 24:11-21
Conley, Robert R; Shim, Joo-Cheol; Kelly, Deanna L et al. (2005) Cardiovascular disease in relation to weight in deceased persons with schizophrenia. Compr Psychiatry 46:460-7
Kelly, Deanna L; Conley, Robert R (2005) Thyroid function in treatment-resistant schizophrenia patients treated with quetiapine, risperidone, or fluphenazine. J Clin Psychiatry 66:80-4
Conley, Robert R; Kelly, Deanna L; Nelson, Matthew W et al. (2005) Risperidone, quetiapine, and fluphenazine in the treatment of patients with therapy-refractory schizophrenia. Clin Neuropharmacol 28:163-8
Wilk, Christopher M; Gold, James M; Humber, Kathy et al. (2004) Brief cognitive assessment in schizophrenia: normative data for the Repeatable Battery for the Assessment of Neuropsychological Status. Schizophr Res 70:175-86

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