Facilitation of NMDA Receptor Function in Patients With Schizophrenia and Co-morbid Alcoholism
| Status: | Completed |
|---|---|
| Conditions: | Schizophrenia, Psychiatric |
| Therapuetic Areas: | Psychiatry / Psychology |
| Healthy: | No |
| Age Range: | 21 - 60 |
| Updated: | 1/19/2018 |
| Start Date: | June 2003 |
| End Date: | December 2015 |
This placebo-controlled study is designed to evaluate the efficacy of glycine, an agonist of
the glycine-B co-agonist site of the NMDA receptor, on alcohol consumption and craving as
well as negative symptoms in schizophrenia.
Glycine will decrease the rewarding action of ethanol and reduce ethanol consumption. Also,
glycine will improve negative symptoms and cognitive deficits in schizophrenia.
the glycine-B co-agonist site of the NMDA receptor, on alcohol consumption and craving as
well as negative symptoms in schizophrenia.
Glycine will decrease the rewarding action of ethanol and reduce ethanol consumption. Also,
glycine will improve negative symptoms and cognitive deficits in schizophrenia.
OBJECTIVE: Schizophrenia affects about 1% of the general population and is a highly disabling
disease. Additionally, the rate of alcohol dependency for patients with schizophrenia is very
high. There are no established treatments for alcohol dependency and negative symptoms in
schizophrenia. This study will examine whether the addition of glycine to neuroleptic
medications will help patients with schizophrenia and alcoholism decrease their drinking as
well as improve negative symptoms.
RESEARCH PLAN: An abnormality of the glutamate neurotransmitter system has been hypothesized
for both alcoholism and schizophrenia. Studies suggest that the amino acid glycine may
improve alcohol dependency and symptoms of schizophrenia by acting on the N methyl D
aspartate (NMDA) glutamate receptor. Glycine causes reversal of the effects of ethanol in
animal studies and improves mood, social withdrawal and other so called "negative symptoms"
of schizophrenia. Consequently, the use of glycine by patients with schizophrenia and alcohol
dependency may potentially decrease alcohol craving and alcohol consumption and also improve
certain symptoms of schizophrenia. The potential of glycine to improve both alcohol
dependency and negative symptoms could represent an important step in the improvement of the
quality of life for patients with schizophrenia.
METHODOLOGY/FINDINGS/RESULTS: In order to test this hypothesis, we will use a double blind,
placebo controlled study and measure the number of drinks, the degree of craving for alcohol
and symptoms of schizophrenia among other parameters. Our principal approach to analyses of
medication effectiveness will be the application of the linear mixed effect model. The linear
mixed effect model permits a flexible approach for studying change in individuals through
time as a random effect, and does not require all patients to have data at all measured
points. Our principal model of analysis includes treatment (placebo or glycine), as between
subject factor, and time, as within subject factor. Compliance will be also included as a
time varying independent variable. This project continues to recruit subjects.
disease. Additionally, the rate of alcohol dependency for patients with schizophrenia is very
high. There are no established treatments for alcohol dependency and negative symptoms in
schizophrenia. This study will examine whether the addition of glycine to neuroleptic
medications will help patients with schizophrenia and alcoholism decrease their drinking as
well as improve negative symptoms.
RESEARCH PLAN: An abnormality of the glutamate neurotransmitter system has been hypothesized
for both alcoholism and schizophrenia. Studies suggest that the amino acid glycine may
improve alcohol dependency and symptoms of schizophrenia by acting on the N methyl D
aspartate (NMDA) glutamate receptor. Glycine causes reversal of the effects of ethanol in
animal studies and improves mood, social withdrawal and other so called "negative symptoms"
of schizophrenia. Consequently, the use of glycine by patients with schizophrenia and alcohol
dependency may potentially decrease alcohol craving and alcohol consumption and also improve
certain symptoms of schizophrenia. The potential of glycine to improve both alcohol
dependency and negative symptoms could represent an important step in the improvement of the
quality of life for patients with schizophrenia.
METHODOLOGY/FINDINGS/RESULTS: In order to test this hypothesis, we will use a double blind,
placebo controlled study and measure the number of drinks, the degree of craving for alcohol
and symptoms of schizophrenia among other parameters. Our principal approach to analyses of
medication effectiveness will be the application of the linear mixed effect model. The linear
mixed effect model permits a flexible approach for studying change in individuals through
time as a random effect, and does not require all patients to have data at all measured
points. Our principal model of analysis includes treatment (placebo or glycine), as between
subject factor, and time, as within subject factor. Compliance will be also included as a
time varying independent variable. This project continues to recruit subjects.
Inclusion Criteria:
- DSM-IV diagnosis of schizophrenia or schizoaffective disorder
- DSM-IV diagnosis of alcohol dependence
- Stable treatment with typical or atypical antipsychotics
Exclusion Criteria:
- Axis I diagnosis other than alcohol dependence, schizophrenia, schizoaffective
disorder, OCD, and PTSD.
- current drug dependence
- evidence of significant hepatocellular injury evidence by abnormal SGOT or SGPT levels
- history of seizures
- diabetes and medical conditions that would alter glycine metabolism
- positive pregnancy test
- treatment with clozapine, naltrexone or disulfiram
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