Risperidone and Desipramine in Alcohol Use and Schizophrenia
| Status: | Completed |
|---|---|
| Conditions: | Schizophrenia, Psychiatric |
| Therapuetic Areas: | Psychiatry / Psychology |
| Healthy: | No |
| Age Range: | 18 - 65 |
| Updated: | 4/17/2018 |
| Start Date: | December 2011 |
| End Date: | September 2014 |
Alcoholism and Schizophrenia: A Translational Approach to Treatment
Note: In June 2013, the study design was changed from a randomized controlled study of
risperidone + despiramine vs. risperidone vs. placebo to an open label pre-post study of
risperidone (or risperidone-like drug) + desipramine. The aims of the study were revised to
read:
1. To determine whether participants treated with risperidone in combination with
desiprmaine have less alcohol use (fewer drinking days; fewer heavy drinking days)
during the final 8 weeks on these medications as compared to pre-baseline. The primary
hypothesis is that compared to pre-baseline, participants will demonstrate fewer days of
drinking (per week), as well as fewer days of heavy drinking (per week) in the final
eight weeks they are taking risperidone and desipramine, as recorded on the Timeline
Follow-Back assessment
2. To explore changes in symptoms (of schizophrenia and of depression) in the final eight
weeks of treatment with risperidone + desipramine compared to the period before baseline
3. To assess the side effect burden associated with the combination of these two
medications in participants.
The original aims of the study were:
The purpose of this study is to determine whether participants who are treated with
risperidone in combination with desipramine have less alcohol use (fewer drinking days; fewer
heavy drinking days) than do participants who are treated with RISP with placebo. The primary
hypothesis is that compared to treatment with risperidone, participants randomized to a
combination of risperidone plus desipramine will have fewer days of drinking, as well as
fewer days of heavy drinking. The study will also compare the effects of risperidone as
compared to risperidone plus desipramine on participants' symptoms and side effects.
risperidone + despiramine vs. risperidone vs. placebo to an open label pre-post study of
risperidone (or risperidone-like drug) + desipramine. The aims of the study were revised to
read:
1. To determine whether participants treated with risperidone in combination with
desiprmaine have less alcohol use (fewer drinking days; fewer heavy drinking days)
during the final 8 weeks on these medications as compared to pre-baseline. The primary
hypothesis is that compared to pre-baseline, participants will demonstrate fewer days of
drinking (per week), as well as fewer days of heavy drinking (per week) in the final
eight weeks they are taking risperidone and desipramine, as recorded on the Timeline
Follow-Back assessment
2. To explore changes in symptoms (of schizophrenia and of depression) in the final eight
weeks of treatment with risperidone + desipramine compared to the period before baseline
3. To assess the side effect burden associated with the combination of these two
medications in participants.
The original aims of the study were:
The purpose of this study is to determine whether participants who are treated with
risperidone in combination with desipramine have less alcohol use (fewer drinking days; fewer
heavy drinking days) than do participants who are treated with RISP with placebo. The primary
hypothesis is that compared to treatment with risperidone, participants randomized to a
combination of risperidone plus desipramine will have fewer days of drinking, as well as
fewer days of heavy drinking. The study will also compare the effects of risperidone as
compared to risperidone plus desipramine on participants' symptoms and side effects.
Alcohol use disorder is at least three times more common in schizophrenia than in the general
population, and worsens the course of schizophrenia. Typical antipsychotic agents are of
limited value in controlling alcohol use in these "dual diagnosis" patients. Data from our
group and others suggest that the atypical antipsychotic drug clozapine limits alcohol and
cannabis use in "dual diagnosis" patients with schizophrenia much more effectively than other
antipsychotics that have been assessed, however, the side effects produced by clozapine
severely limit its use.
The investigators have hypothesized that clozapine will lessen alcohol/substance use in such
dual diagnosis patients in part because of its mechanism of action that includes release of
dopamine (DA) in the prefrontal cortex which will help to normalize dysfunctional brain
reward circuits that may underlie the co- occurring alcohol/substance use in patients with
schizophrenia. Our data suggest that the effect of clozapine can be duplicated in rodents
when medications with clozapine-like activity (DA D2 antagonism, potent norepinephrine (NE)
α2 receptor antagonism and NE reuptake inhibition) are combined together. The investigators
have demonstrated that RISP (a medication that is both a DA D2 receptor antagonist, and a
potent NE α2 receptor antagonist), in combination with the specific NE reuptake inhibitor
desipramine, significantly decreases alcohol consumption in alcohol drinking rodents.
This translational study is a pilot "proof of concept" 14-week double-blind investigation of
participants who have co-occurring diagnoses of schizophrenia and an alcohol use disorder.
Patients not treated with risperidone (or a risperidone-like agent, including risperidone
long-acting, paliperidone and paliperidone palmitate) at the time of consent will be switched
to oral risperidone in the first two weeks of the study. At Week 3, all participants will
begin treatment with risperidone risperidone plus desipramine and followed for 12 weeks. The
primary outcome measure will be days of drinking (per week), as well as days of heavy
drinking (per week). The investigators anticipate that data from this study will support a
larger trial of risperidone + desipramine in patients with schizophrenia and an alcohol use
disorder.
population, and worsens the course of schizophrenia. Typical antipsychotic agents are of
limited value in controlling alcohol use in these "dual diagnosis" patients. Data from our
group and others suggest that the atypical antipsychotic drug clozapine limits alcohol and
cannabis use in "dual diagnosis" patients with schizophrenia much more effectively than other
antipsychotics that have been assessed, however, the side effects produced by clozapine
severely limit its use.
The investigators have hypothesized that clozapine will lessen alcohol/substance use in such
dual diagnosis patients in part because of its mechanism of action that includes release of
dopamine (DA) in the prefrontal cortex which will help to normalize dysfunctional brain
reward circuits that may underlie the co- occurring alcohol/substance use in patients with
schizophrenia. Our data suggest that the effect of clozapine can be duplicated in rodents
when medications with clozapine-like activity (DA D2 antagonism, potent norepinephrine (NE)
α2 receptor antagonism and NE reuptake inhibition) are combined together. The investigators
have demonstrated that RISP (a medication that is both a DA D2 receptor antagonist, and a
potent NE α2 receptor antagonist), in combination with the specific NE reuptake inhibitor
desipramine, significantly decreases alcohol consumption in alcohol drinking rodents.
This translational study is a pilot "proof of concept" 14-week double-blind investigation of
participants who have co-occurring diagnoses of schizophrenia and an alcohol use disorder.
Patients not treated with risperidone (or a risperidone-like agent, including risperidone
long-acting, paliperidone and paliperidone palmitate) at the time of consent will be switched
to oral risperidone in the first two weeks of the study. At Week 3, all participants will
begin treatment with risperidone risperidone plus desipramine and followed for 12 weeks. The
primary outcome measure will be days of drinking (per week), as well as days of heavy
drinking (per week). The investigators anticipate that data from this study will support a
larger trial of risperidone + desipramine in patients with schizophrenia and an alcohol use
disorder.
Inclusion Criteria:
1. Meets the diagnostic criteria of schizophrenia or schizoaffective disorder
2. Meets the diagnostic criteria for a current alcohol use disorder (abuse or dependence)
3. Recent alcohol use as documented on the Timeline Followback
4. Receives outpatient treatment with oral antipsychotic medication (including
risperidone.
5. Is willing to switch to risperidone treatment at the beginning of the study.
Exclusion Criteria:
1. Other substance use disorder other than alcohol, caffeine and nicotine, and cannabis
abuse, as defined by DSM-IV criteria.
2. Receives current treatment with Clozapine
3. Continues to use alcohol despite current adequate treatment with medication to
decrease alcohol use(e.g. naltrexone, acamprosate, disulfiram or topiramate)
4. Is determined to be a "slow metabolizer" of CYP2D6
5. Is currently pregnant, trying to become pregnant, or nursing
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