This resubmission proposes a study for testing the efficacy of remoxipride a putative atypical antipsychotic drug for efficacy in neuroleptic treatment resistant schizophrenic patients. It will also provide support for a significant public and academic liaison initiative; the Treatment Resistant Unit of the University of Maryland at Baltimore. We propose that it will also lead to the development of a standard clinical protocol to test other candidate atypical drugs in the future. The drugs will be tested in a drug-drug double-blind parallel group design versus chlorpromazine, with clozapine used at the study end to describe the response level of the study population. Patients will be selected for poor neuroleptic response with a history of at least one year of persistent symptoms accompanied by failure to respond to at least three adequate trials of neuroleptics. Patients who enter the 12-week remoxipride trial will also have failed to respond to six weeks of haloperidol therapy on our study unit. Remoxipride is a potent D2 dopamine receptor blocking agent which has a low in vivo affinity for the D2 receptor, similar to clozapine. Future candidate drugs will be selected based on the outcome of the first rial and will be the subject of future submissions. This design provides substantial power for testing the remoxipride superiority hypothesis. Results will be analyzed with regard to improvement in total BPRS score and psychotic symptoms. Negative symptoms and side effect changes will be assessed. 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).

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
Project #
Application #
Study Section
Treatment Assessment Review Committee (TA)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Maryland Baltimore
Schools of Medicine
United States
Zip Code
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

Showing the most recent 10 out of 20 publications