Clinical Trials Logo

Clinical Trial 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.


Clinical Trial 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. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT01411085
Study type Interventional
Source Dartmouth-Hitchcock Medical Center
Contact
Status Completed
Phase Phase 2
Start date December 2011
Completion date September 2014

See also
  Status Clinical Trial Phase
Recruiting NCT05039489 - A Study on the Brain Mechanism of cTBS in Improving Medication-resistant Auditory Hallucinations in Schizophrenia N/A
Completed NCT05321602 - Study to Evaluate the PK Profiles of LY03010 in Patients With Schizophrenia or Schizoaffective Disorder Phase 1
Completed NCT05111548 - Brain Stimulation and Cognitive Training - Efficacy N/A
Completed NCT04503954 - Efficacy of Chronic Disease Self-management Program in People With Schizophrenia N/A
Completed NCT02831231 - Pilot Study Comparing Effects of Xanomeline Alone to Xanomeline Plus Trospium Phase 1
Completed NCT05517460 - The Efficacy of Auricular Acupressure on Improving Constipation Among Residents in Community Rehabilitation Center N/A
Completed NCT03652974 - Disturbance of Plasma Cytokine Parameters in Clozapine-Resistant Treatment-Refractory Schizophrenia (CTRS) and Their Association With Combination Therapy Phase 4
Recruiting NCT04012684 - rTMS on Mismatch Negativity of Schizophrenia N/A
Recruiting NCT04481217 - Cognitive Factors Mediating the Relationship Between Childhood Trauma and Auditory Hallucinations in Schizophrenia N/A
Completed NCT00212784 - Efficacy and Safety of Asenapine Using an Active Control in Subjects With Schizophrenia or Schizoaffective Disorder (25517)(P05935) Phase 3
Completed NCT04092686 - A Clinical Trial That Will Study the Efficacy and Safety of an Investigational Drug in Acutely Psychotic People With Schizophrenia Phase 3
Completed NCT01914393 - Pediatric Open-Label Extension Study Phase 3
Recruiting NCT03790345 - Vitamin B6 and B12 in the Treatment of Movement Disorders Induced by Antipsychotics Phase 2/Phase 3
Recruiting NCT05956327 - Insight Into Hippocampal Neuroplasticity in Schizophrenia by Investigating Molecular Pathways During Physical Training N/A
Terminated NCT03209778 - Involuntary Memories Investigation in Schizophrenia N/A
Terminated NCT03261817 - A Controlled Study With Remote Web-based Adapted Physical Activity (e-APA) in Psychotic Disorders N/A
Completed NCT02905604 - Magnetic Stimulation of the Brain in Schizophrenia or Depression N/A
Recruiting NCT05542212 - Intra-cortical Inhibition and Cognitive Deficits in Schizophrenia N/A
Completed NCT04411979 - Effects of 12 Weeks Walking on Cognitive Function in Schizophrenia N/A
Terminated NCT03220438 - TMS Enhancement of Visual Plasticity in Schizophrenia N/A