Risperidone Long-acting Versus Oral Risperidone in Patients With Schizophrenia and Alcohol Use Disorder

Phase 4

Completed

• Conditions: Schizophrenia; Psychotic Disorders; Substance Abuse; Alcohol Abuse
• Interventions: Drug: Risperidone Long Acting; Drug: oral risperidone

• Registration Number: NCT00130923
• Lead Sponsor: Dartmouth-Hitchcock Medical Center

Brief Summary

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.

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.

Study Timeline

• Study First Submitted: 2005-08-15
• Study First Submitted QC: 2005-08-15
• Study First Posted: 2005-08-16
• Study Start: 2005-09
• Primary Completion: 2009-06
• Study Completion: 2010-07
• Results First Submitted: 2012-07-23
• Results First Submitted QC: 2012-09-23
• Results First Posted: 2012-10-24
• Status Verified: 2019-04
• Last Update Submitted: 2019-04-16
• Last Update Posted: 2019-05-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 95

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Risperidone Long Acting	Risperidone Long Acting	Risperidone Long Acting; aka Risperdal Consta; injectable form
Oral Risperidone	oral risperidone	Oral Risperidone; aka Risperdal; oral form

Primary Outcome Measures

Name	Time	Method
Change Over Time in Frequency of Heavy Drinking Days (Used to Evaluate Treatment Efficacy)	6 months	Frequency of heavy drinking days is obtained each week retrospectively as the number of heavy drinking days during the prior week (assessed by the Timeline Followback Scale). A heavy drinking day is defined as 4 or more drinks per day for a female and 5 or more drinks per day for a male. Mixed models are used to obtain estimates of efficacy from the partial data provided by each subject while adherent to assigned treatment (under the 'missing at random' assumption). The 'explanatory' estimands (target of the mixed model estimation) are defined in terms of population quantities that would have occurred had all subjects remained on assigned treatment throughout the study. The point estimate for each arm is reported under Number.

Secondary Outcome Measures

Name	Time	Method
Average Over Time of Frequency of Drinking Days (Used to Evaluate Treatment Efficacy)	6 months	Frequency of drinking days is obtained each week retrospectively as the number of drinking days during the prior week (assessed using the Timeline Followback). Mixed models are used to obtain estimates of efficacy from the partial data provided by each subject while adherent to assigned treatment (under the 'missing at random' assumption). The 'explanatory' estimands (target of the mixed model estimation) are defined in terms of population quantities that would have occurred had all subjects remained on assigned treatment throughout the study. The point estimate for each arm is reported under Number.
Average Over Time of Positive and Negative Symptoms (Used to Evaluate Treatment Efficacy)	6 months	A rater assesses positive and negative symptoms of schizophrenia using a 30-item scale (Positive and Negative Symptom Score) Scores range from 30 to 210, where higher values represent a worse outcome. Mixed models are used to obtain estimates of efficacy from the partial data provided by each subject while adherent to assigned treatment (under the 'missing at random' assumption). The 'explanatory' estimands (target of the mixed model estimation) are defined in terms of population quantities that would have occurred had all subjects remained on assigned treatment throughout the study. The point estimate for each arm is reported under Number.
Average Over Time of Global Functioning (Used to Evaluate Treatment Efficacy)	6 months	A rater assesses social, occupational and psychological functioning on a hypothetical continuum of mental health - illness (using Global Assessment of Functioning); scores range from 100 to 1, where higher values represent a better outcome. Mixed models are used to obtain estimates of efficacy from the partial data provided by each subject while adherent to assigned treatment (under the 'missing at random' assumption). The 'explanatory' estimands (target of the mixed model estimation) are defined in terms of population quantities that would have occurred had all subjects remained on assigned treatment throughout the study. The point estimate for each arm is reported under Number.
Number of Participants With Medication Adherence	6 months	Number of participants with medication adherence (defined as taking medication at least 75% of the days in the treatment period).
Average Over Time of Severity of Illness and Global Improvement (Used to Evaluate Treatment Efficacy)	6 months	A rater assesses the severity of illness and global impression using a scale from 1 to 7 (Clinical Global Impression), where higher values represent a worse outcome. Mixed models are used to obtain estimates of efficacy from the partial data provided by each subject while adherent to assigned treatment (under the 'missing at random' assumption). The 'explanatory' estimands (target of the mixed model estimation) are defined in terms of population quantities that would have occurred had all subjects remained on assigned treatment throughout the study. The point estimate for each arm is reported under Number.

Trial Locations

Locations (8)

University of South Carolina; 🇺🇸 Columbia, South Carolina, United States

Washington University School of Medicine; 🇺🇸 Saint Louis, Missouri, United States

West Central Behavioral Health; 🇺🇸 Lebanon, New Hampshire, United States

White River Junction Veterans Admininistration Medical Center; 🇺🇸 White River Junction, Vermont, United States

Center for Psychiatric Advancement; 🇺🇸 Nashua, New Hampshire, United States

School of Pharmacy, Univ. of Missouri Kansas City; 🇺🇸 Kansas City, Missouri, United States

Mental Health Center of Greater Manchester; 🇺🇸 Manchester, New Hampshire, United States

JMH Mental Health Center, University of Miami; 🇺🇸 Miami, Florida, United States