Full Text View
Tabular View
No Study Results Posted
Related Studies
Risperidone Long-Acting Versus Oral Risperidone in Patients With Schizophrenia and Alcohol Use Disorder
This study is ongoing, but not recruiting participants.
First Received: August 15, 2005   Last Updated: March 4, 2009   History of Changes
Sponsors and Collaborators: Dartmouth-Hitchcock Medical Center
Janssen, LP
Information provided by: Dartmouth-Hitchcock Medical Center
ClinicalTrials.gov Identifier: NCT00130923
  Purpose

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.


Condition Intervention Phase
Schizophrenia
Psychotic Disorders
Substance Abuse
Alcohol Abuse
Drug: risperidone long-acting
Drug: oral risperidone
Phase IV

MedlinePlus related topics: Alcohol Psychotic Disorders Schizophrenia
Drug Information available for: Ethanol Risperidone
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study
Official Title: Risperidone Long-Acting for Alcohol and Schizophrenia Treatment (R-LAST)

Further study details as provided by Dartmouth-Hitchcock Medical Center:

Primary Outcome Measures:
  • Alcohol use assessed by the Timeline Followback scale [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Other substance use as assessed by the Timeline Followback scale [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Clinical symptoms, global functioning, cognition, and extrapyramidal system effects [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 100
Study Start Date: September 2005
Estimated Study Completion Date: June 2010
Estimated Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
1: Experimental
Risperidone Long Acting
Drug: risperidone long-acting
Dose 25.00, 37.50 or 50.00 mg q two weeks
2: Active Comparator
Oral Risperidone aka Risperdal
Drug: oral risperidone
0.50-6.00 mg oral risperidone qd

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00130923

Locations
United States, Florida
JMH Mental Health Center, University of Miami
Miami, Florida, United States, 33136
United States, Missouri
School of Pharmacy, Univ. of Missouri Kansas City
Kansas City, Missouri, United States, 64108
Washington University School of Medicine
St. Louis, Missouri, United States, 63110
United States, New Hampshire
Mental Health Center of Greater Manchester
Manchester, New Hampshire, United States, 03101
West Central Behavioral Health
Lebanon, New Hampshire, United States, 03766
Center for Psychiatric Advancement
Nashua, New Hampshire, United States, 03060
United States, South Carolina
University of South Carolina
Columbia, South Carolina, United States, 29203
United States, Vermont
White River Junction Veterans Admininistration Medical Center
White River Junction, Vermont, United States, 05009
Sponsors and Collaborators
Dartmouth-Hitchcock Medical Center
Janssen, LP
Investigators
Principal Investigator: Alan I. Green, MD Dartmouth Medical School, Dartmouth College
  More Information

Publications:
Albanese MJ, Khantzian EJ, Murphy SL, Green AI. Decreased substance use in chronically psychotic patients treated with clozapine. Am J Psychiatry. 1994 May;151(5):780-1. No abstract available.
Albanese M. Risperidone in substance abusers with bipolar disorder. Presented at the 39th Annual Meeting of the American College of Neuropsychopharmacology. Sa Juan, PR, 2000.
Akaike, H, Information theory and an extension of the maximum likelihood principle., in 2nd International Symposium on Information Theory and Control., EBN Petrovand & C. Csaki, Editors. 1973, Akademia Kiado: Budapest, p. 267-281.
Bartels SJ, Teague GB, Drake RE, Clark RE, Bush PW, Noordsy DL. Substance abuse in schizophrenia: service utilization and costs. J Nerv Ment Dis. 1993 Apr;181(4):227-32.
Birkett MA, Day SJ. Internal pilot studies for estimating sample size. Stat Med. 1994 Dec 15-30;13(23-24):2455-63.
Bowers MB Jr, Mazure CM, Nelson JC, Jatlow PI. Psychotogenic drug use and neuroleptic response. Schizophr Bull. 1990;16(1):81-5.
Buckley P, Thompson P, Way L, Meltzer HY. Substance abuse among patients with treatment-resistant schizophrenia: characteristics and implications for clozapine therapy. Am J Psychiatry. 1994 Mar;151(3):385-9.
Buckley P, Thompson PA, Way L, Meltzer HY. Substance abuse and clozapine treatment. J Clin Psychiatry. 1994 Sep;55 Suppl B:114-6.
Buckley PF. Novel antipsychotic medications and the treatment of comorbid substance abuse in schizophrenia. J Subst Abuse Treat. 1998 Mar-Apr;15(2):113-6.
Buckley PF. Substance abuse in schizophrenia: a review. J Clin Psychiatry. 1998;59 Suppl 3:26-30. Review.
Buckley PF, Miller A, Chiles JA, Sajatovic M. Implementing effectiveness research and improving care for schizophrenia in real-world settings. Am J Manag Care. 1999 Jun 25;5 Spec No:SP47-56.
Buckley P, McCarthy M, Chapman P, Richman C, Yamamoto B. Clozapine treatment of comorbid substance abuse in patients with schizophrenia. Schizophr Res 1999, 36:272.
Coldham EL, Addington J, Addington D. Medication adherence of individuals with a first episode of psychosis. Acta Psychiatr Scand. 2002 Oct;106(4):286-90.
Drake RE, Xie H, McHugo GJ, Green AI. The effects of clozapine on alcohol and drug use disorders among patients with schizophrenia. Schizophr Bull. 2000;26(2):441-9.
Frison L, Pocock SJ. Repeated measures in clinical trials: analysis using mean summary statistics and its implications for design. Stat Med. 1992 Sep 30;11(13):1685-704.
Green AI, Zimmet SV, Strous RD, Schildkraut JJ. Clozapine for comorbid substance use disorder and schizophrenia: do patients with schizophrenia have a reward-deficiency syndrome that can be ameliorated by clozapine? Harv Rev Psychiatry. 1999 Mar-Apr;6(6):287-96. Review.
Green AI, Salomon MS, Brenner MJ, Rawlins K. Treatment of schizophrenia and comorbid substance use disorder. Curr Drug Targets CNS Neurol Disord. 2002 Apr;1(2):129-39. Review.
Green AI, Burgess ES, Dawson R, Zimmet SV, Strous RD. Alcohol and cannabis use in schizophrenia: effects of clozapine vs. risperidone. Schizophr Res. 2003 Mar 1;60(1):81-5.
Hunt GE, Bergen J, Bashir M. Medication compliance and comorbid substance abuse in schizophrenia: impact on community survival 4 years after a relapse. Schizophr Res. 2002 Apr 1;54(3):253-64.
Khantzian EJ. The self-medication hypothesis of addictive disorders: focus on heroin and cocaine dependence. Am J Psychiatry. 1985 Nov;142(11):1259-64. Review.
Khantzian EJ. The self-medication hypothesis of substance use disorders: a reconsideration and recent applications. Harv Rev Psychiatry. 1997 Jan-Feb;4(5):231-44. Review.
Lacro JP, Dunn LB, Dolder CR, Leckband SG, Jeste DV. Prevalence of and risk factors for medication nonadherence in patients with schizophrenia: a comprehensive review of recent literature. J Clin Psychiatry. 2002 Oct;63(10):892-909. Review.
Laird NM, Ware JH. Random-effects models for longitudinal data. Biometrics. 1982 Dec;38(4):963-74.
Lee, ET. Statistical Methods for Survival Analysis. 1992, New York: John Wiley & Sons.
Newton TF, Ling W, Kalechstein AD, Uslaner J, Tervo K. Risperidone pre-treatment reduces the euphoric effects of experimentally administered cocaine. Psychiatry Res. 2001 Jul 24;102(3):227-33.
Salyers MP, Mueser KT. Social functioning, psychopathology, and medication side effects in relation to substance use and abuse in schizophrenia. Schizophr Res. 2001 Mar 1;48(1):109-23.
Siris SG. Pharmacological treatment of substance-abusing schizophrenic patients. Schizophr Bull. 1990;16(1):111-22. Review.
Smelson DA, Losonczy MF, Davis CW, Kaune M, Williams J, Ziedonis D. Risperidone decreases craving and relapses in individuals with schizophrenia and cocaine dependence. Can J Psychiatry. 2002 Sep;47(7):671-5.
Tukey, JW. Exploratory Data Analysis. 1977, Reading, MA: Addison Wesley Publ. Co.
Waternaux, C, Laird, N, Ware, J. Methods for the analysis of longitudinal data: Blood concentrations and cognitive development. J.Amer. Stat. Assoc. 1989: 84, p.33-41.
Weiss RE, Lazaro CG. Residual plots for repeated measures. Stat Med. 1992 Jan 15;11(1):115-24.
Zimmet SV, Strous RD, Burgess ES, Kohnstamm S, Green AI. Effects of clozapine on substance use in patients with schizophrenia and schizoaffective disorder: a retrospective survey. J Clin Psychopharmacol. 2000 Feb;20(1):94-8.

Responsible Party: Dartmouth Medical School ( Alan I. Green, MD )
Study ID Numbers: 17359, RIS-EMR-4032
Study First Received: August 15, 2005
Last Updated: March 4, 2009
ClinicalTrials.gov Identifier: NCT00130923     History of Changes
Health Authority: United States: Institutional Review Board

Keywords provided by Dartmouth-Hitchcock Medical Center:
Risperidone
Schizophrenia
Substance Use Disorder
Alcohol Use Disorder
Treatment
Schizoaffective Disorder

Study placed in the following topic categories:
Neurotransmitter Agents
Tranquilizing Agents
Psychotropic Drugs
Risperidone
Central Nervous System Depressants
Disorders of Environmental Origin
Antipsychotic Agents
Alcohol Drinking
Serotonin
Schizophrenia
Dopamine
Mental Disorders
Alcoholism
Substance-Related Disorders
Dopamine Agents
Psychotic Disorders
Alcohol-Related Disorders
Schizophrenia and Disorders with Psychotic Features
Ethanol

Additional relevant MeSH terms:
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Psychotropic Drugs
Disorders of Environmental Origin
Schizophrenia
Serotonin Antagonists
Pathologic Processes
Mental Disorders
Therapeutic Uses
Substance-Related Disorders
Alcohol-Related Disorders
Psychotic Disorders
Schizophrenia and Disorders with Psychotic Features
Disease
Tranquilizing Agents
Risperidone
Central Nervous System Depressants
Dopamine Antagonists
Antipsychotic Agents
Pharmacologic Actions
Serotonin Agents
Alcoholism
Dopamine Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on May 06, 2009