Alcohol use disorder is the most common co-morbid condition in patients with schizophrenia, and the problems resulting from the use of alcohol by these patients contribute strikingly to the overall morbidity of schizophrenia-to clinical (anti-psychotic) medications are helpful for the treatment of psychosis, they do not appear to have a role in preventing alcohol use disorders in these patients. However, preliminary data from our group and others suggest that clozapine (CLOZ), an atypical anti-psychotic, may be effective in decreasing alcohol use in the population. The literature suggests that in patients with schizophrenia, the use of alcohol may decrease negative symptoms and transiently ameliorate a presumed defect in the dopamine-rich brain reward system. We have hypothesize that CLOZ lessens alcohol use in patients because of its unique mechanism of action that includes release of dopamine (DA) in the prefrontal cortex. We further hypothesize that through its diverse effects on many neurotransmitter systems, including DA and norepinephrine, CLOZ will decrease negative symptoms, and help to normalize dysfunctional brain reward circuits in these patients. Within this revised application, the PI and colleagues propose to begin a line of investigation aimed at delineating the effects of CLOZ on alcohol use in patients with schizophrenia, and at elucidating the process by which CLOZ produces these effects. As a first step, we propose to begin a line of investigation aimed at delineating the effects of CLOZ on alcohol use in patients with Schizophrenia, and at elucidating the process by which CLOZ produces these effects. As a first step, we propose a double-blind, controlled 12-week trial of the short- term effects of CLOZ on alcohol use in this population. Our primary aim is to test the hypothesis that patients switched from typical neuroleptics to CLOZ will have decreased in alcohol use during CLOZ treatment as compared to patients who are switched to CLOZ but remain on their current antipsychotic drug. A secondary aim is to begin to investigate the process by which CLOZ produces its effects on alcohol use by determining: (a) how differences in alcohol use between the two groups will depend on changes in negative symptoms; and (b) whether decreases in alcohol use within the group of CLOZ patients will relate to changes in negative symptoms. A subsidiary aim is to begin address changes in quality of life, a key measure of the effects of CLOZ in patients with alcohol use disorder and schizophrenia. Confirmation that CLOZ decreases alcohol use in this population would have important public health implications and could lead to a new use for CLOZ.
| Green, Alan I (2007) Pharmacotherapy for schizophrenia and co-occurring substance use disorders. Neurotox Res 11:33-40 |
| Roth, Robert M; Brunette, Mary F; Green, Alan I (2005) Treatment of substance use disorders in schizophrenia: a unifying neurobiological mechanism? Curr Psychiatry Rep 7:283-91 |
| Green, Alan I; Chau, David T; Keung, Wing Ming et al. (2004) Clozapine reduces alcohol drinking in Syrian golden hamsters. Psychiatry Res 128:9-20 |
| Noordsy, Douglas L; Green, Alan I (2003) Pharmacotherapy for schizophrenia and co-occurring substance use disorders. Curr Psychiatry Rep 5:340-6 |
| Green, Alan I; Burgess, Ellen S; Dawson, Ree et al. (2003) Alcohol and cannabis use in schizophrenia: effects of clozapine vs. risperidone. Schizophr Res 60:81-5 |
| Green, Alan I; Canuso, Carla M; Brenner, Mark J et al. (2003) Detection and management of comorbidity in patients with schizophrenia. Psychiatr Clin North Am 26:115-39 |
