Official Title: “Risperidone Long-Acting for Alcohol and Schizophrenia Treatment (R-LAST)”

The purpose of this study is to compare the efficacy of oral risperidone (Risperdal) to risperidone long-acting (Consta) in reducing alcohol use in persons diagnosed with schizophrenia or schizoaffective disorder.

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study

Study Primary Completion Date: June 2009

Comorbid alcohol/substance use disorder (SUD) in people with schizophrenia is a major concern, both in view of the high frequency of SUD among patients with schizophrenia and the difficulty in managing such patients. Though antipsychotic medications are effective in reducing symptoms and impairment in persons with schizophrenia, the typical antipsychotic agents are of limited value in controlling alcohol/substance use in these patients.

Extrapyramidal, dysphoric side effects of conventional neuroleptics may actually promote the use of substances in an attempt to counteract these effects. In addition, medication non-compliance is common among patients with schizophrenia.

Novel antipsychotics have altered treatment expectations and outcomes for patients with severe forms of schizophrenia. A growing number of studies have assessed the effects of oral risperidone in persons with dual disorders. Potential mechanisms of action by which risperidone and other atypical antipsychotics could decrease substance use include being less likely to cause extrapyramidal side effects than typical agents, improving negative symptoms and ameliorating a dysfunction of the brain reward system. Risperidone long-acting injectable medication addresses issues of noncompliance, while avoiding peak blood levels of oral preparations, thereby minimizing EPS and improving negative symptoms of schizophrenia.

Risperidone may also facilitate dopamine neurotransmission in the prefrontal cortex and correct a hypothesized dysfunction of the brain reward system.

This study is an open, randomized, controlled study to compare intramuscular long-acting risperidone to oral risperidone with blinded ratings to determine whether the long-acting form of risperidone has greater efficacy in reducing substance use. Patients with schizophrenia or schizoaffective disorder, age 18 to 65, who are taking any single oral antipsychotic medication except clozapine or risperidone long-acting may be enrolled.

Intervention(s) in this Clinical Trial

• Drug: risperidone long-acting
  • Dose 25.00, 37.50 or 50.00 mg q two weeks
• Drug: oral risperidone
  • 0.50-6.00 mg oral risperidone qd

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • Risperidone Long Acting
• Active Comparator: 2
  • Oral Risperidone aka Risperdal

Primary Measures

• Alcohol use assessed by the Timeline Followback scale
  • Time Frame: 6 months
    Safety Issue?: No

Secondary Measures

• Other substance use as assessed by the Timeline Followback scale
  • Time Frame: 6 months
    Safety Issue?: No
• Clinical symptoms, global functioning, cognition, and extrapyramidal system effects
  • Time Frame: 6 months
    Safety Issue?: Yes

Inclusion Criteria:

• Ages 18-65
• Schizophrenia or schizoaffective disorder
• Meets the Structured Clinical Interview for DSM-IV (SCID) criteria for an alcohol use disorder
• Alcohol use on at least 5 days during the 4 weeks prior to randomization
• Patient is medically stable to start either form of risperidone.

Exclusion Criteria:

• Current treatment with clozapine.
• Current treatment with injectable risperidone long-acting.
• Currently pregnant, planning to become pregnant, or unwilling to use an acceptable form of birth control.
• Change in medications (dose of current medication, discontinuation of medication, or new medication) in past 30 days.
• History of or current breast cancer.
• History of intolerance of or allergy to risperidone or risperidone long-acting.
• Currently residing in a residential program designed to treat substance use disorders.
• Current treatment with long-acting, injectable antipsychotic medication will require a review by the medication adjustment group before entering the client into the study.
• Past treatment with risperidone long-acting will require a review by the medication adjustment group before entering the client into the study.
• Treatment at baseline with a second antipsychotic medication will require a review by the medication adjustment group before entering the client into the study.
• Treatment at baseline with a psychotropic agent proposed to curtail substance use will require a review by the medication adjustment group before entering the client into the study.
• Patients who, in the opinion of the investigator, are judged unsuitable to participate in the study.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 65 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Dartmouth-Hitchcock Medical Center

Overall Clinical Trial Officials and Contacts

Alan I. Green, MD Principal Investigator Dartmouth Medical School, Dartmouth College  

Overall Contact: Christopher D. O'Keefe, MA 603-271-5747 christopher.d.o'keefe@dartmouth.edu

Information obtained from ClinicalTrials.gov on November 18, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00130923

Study ID Number: 17359

ClinicalTrials.gov Identifier: NCT00130923

Health Authority: United States: Institutional Review Board