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

Dartmouth-Hitchcock Medical Center95 enrolled

Overview

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.

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Schizophrenia Psychotic Disorders Substance Abuse Alcohol Abuse

Interventions

Risperidone Long ActingDRUG

Dose 25.00, 37.50 or 50.00 mg q two weeks

oral risperidoneDRUG

0.50-6.00 mg oral risperidone daily

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

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.

Locations (8)

JMH Mental Health Center, University of Miami

Miami, Florida, United States

School of Pharmacy, Univ. of Missouri Kansas City

Kansas City, Missouri, United States

Washington University School of Medicine

St Louis, Missouri, United States

Outcomes

Primary Outcomes

Change Over Time in Frequency of Heavy Drinking Days (Used to Evaluate Treatment Efficacy)

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.

Time frame: 6 months

Secondary Outcomes

Average Over Time of Frequency of Drinking Days (Used to Evaluate Treatment Efficacy)

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.

Time frame: 6 months

Average Over Time of Severity of Illness and Global Improvement (Used to Evaluate Treatment Efficacy)

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.

Data from ClinicalTrials.gov

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