Risperidone and Desipramine in Alcohol Use and Schizophrenia (RADIAUS)

• Timeline Followback [ Time Frame: Weekly for 14 weeks ] [ Designated as safety issue: No ]
  Alcohol/other substance use (including tobacco) will be assessed primarily by weekly self-report using the Timeline Followback (TLFB) method enhanced by procedures to strengthen the reliability and validity of this measure. Our data and Carey's suggest that the TLFB is useful for assessing alcohol use in persons diagnosed with SCZ. We will use well delineated procedures to minimize response bias,e.g., and we will obtain a Certificate of Confidentiality. The self-report data will be buttressed with other data.
  
  

Alcohol use disorder (AUD) is at least three times more common in schizophrenia (SCZ) than in the general population, and worsens the course of SCZ. 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 (CLOZ) limits alcohol and cannabis use in "dual diagnosis" patients with SCZ much more effectively than other antipsychotics that have been assessed, however, the side effects produced by CLOZ severely limit its use.

The investigators have hypothesized that CLOZ 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 CLOZ can be duplicated in rodents when medications with CLOZ-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 (DMI), significantly decreases alcohol consumption in alcohol drinking rodents.

This translational study is a pilot "proof of concept" 14-week double-blind investigation of 40 participants who have co-occurring diagnoses of SCZ and AUD. Patients not treated with RISP at the time of consent will be switched to RISP in the first two weeks of the study. At Week 3, all participants will be randomized to treatment with risperidone (RISP) with placebo or RISP plus desipramine (DMI) 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). Exploratory aims will assess whether the addition of DMI alters symptoms (of SCZ and of depression), and increases side effects as compared to treatment with RISP and placebo. The investigators anticipate that data from this study will support a larger trial of RISP + DMI in patients with SCZ and AUD.