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

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.