Risperidone and Desipramine in Alcohol Use and Schizophrenia
Condition: Schizophrenia; Alcoholism; Dual Diagnosis
MeSH terms: Alcoholism; Schizophrenia
Study type: Interventional
Phase: Phase 2

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Risperidone + Desipramine
Intervention type(s): Drug
Other intervention name(s): Norpramin
Intervention MeSH terms: Risperidone; Desipramine
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Schizophrenia; Alcoholism; Dual Diagnosis; Desipramine; Risperidone