The purpose of the study is to assess the effectiveness of long-acting injectable risperidone on psychiatric inpatient hospitalization, schizophrenia symptoms, quality of life, medication adherence, side effects, and health care costs.

Primary Objective: To evaluate the impact of long-acting intramuscular (IM) risperidone on risk of inpatient psychiatric hospitalization in comparison to standard oral antipsychotic treatment in a randomized controlled trial to be conducted with 600 veterans diagnosed with schizophrenia or schizoaffective disorder at 17 VA medical centers over three years.

Secondary Objective: To evaluate adherence, health benefits, and costs of long-acting IM risperidone as compared to standard oral antipsychotic treatment as measured by: a) symptom reduction over 12 months, b) time to all-cause medication discontinuation, c) quality of life, d) VA and non-VA health service use and related costs, e) medication side effects, f) violent behavior, g) use of concomitant medication, and h) the incremental cost-effectiveness ratio.

In the proposed study 600 veterans with a primary diagnosis of schizophrenia who had at least one psychiatric hospitalization for schizophrenia in the previous year would be randomly assigned at 17 VA medical centers to long-acting injectible risperidone or doctor''''s choice of oral antipsychotic medication (i.e., excluding other long-acting injectable medications, but not specifying any particular oral agents or dosages). Recruitment would take 2 years to complete, and the study would continue for a third year to allow a full year of follow-up for the last patient recruited. All patients would be treated from the time of entry up to the end of the three-year study period. Follow-up assessments would continue quarterly. Treatments would not be blinded since giving placebo injections to the comparison group would interfere with the goal of comparing the acceptability of two different methods of medication administration. However, end points will be blindly rated.

Condition	Intervention	Phase
Schizophrenia Schizoaffective Disorder	Drug: IM risperidone	Phase IV

Further Study Details: 

Primary Outcomes: Time to rehospitalization during the first year following randomization; Poor symptom and functional response; Cost; Psychiatric inpatient admission.
Secondary Outcomes: Symptoms of schizophrenia; Retention and compliance; General psychiatric symptoms; Quality of life; Medication side effects; Violent behavior; Substance use; Neurocognitive status; Cost; Cost-effectiveness
Expected Total Enrollment:  600

The purpose of the study is to assess the effectiveness of long-acting injectable risperidone on psychiatric inpatient hospitalization, schizophrenia symptoms, quality of life, medication adherence, side effects, and health care costs.

Objectives:

Primary: To evaluate the impact of long-acting intramuscular (IM) risperidone on risk of inpatient psychiatric hospitalization in comparison to standard oral antipsychotic treatment in a randomized controlled trial to be conducted with 600 veterans diagnosed with schizophrenia or schizoaffective disorder at 17 VA medical centers over three years.

Secondary: To evaluate adherence, health benefits, and costs of long-acting IM risperidone as compared to standard oral antipsychotic treatment as measured by: a) symptom reduction over 12 months, b) time to all-cause medication discontinuation, c) quality of life, d) VA and non-VA health service use and related costs, e) medication side effects, f) violent behavior, g) use of concomitant medication, and h) the incremental cost-effectiveness ratio.

Study Design:

In the proposed study 600 veterans with a primary diagnosis of schizophrenia who had at least one psychiatric hospitalization for schizophrenia in the previous year would be randomly assigned at 17 VA medical centers to long-acting injectible risperidone or doctor''''s choice of oral antipsychotic medication (i.e., excluding other long-acting injectable medications, but not specifying any particular oral agents or dosages). Recruitment would take 2 years to complete, and the study would continue for a third year to allow a full year of follow-up for the last patient recruited. All patients would be treated from the time of entry up to the end of the three-year study period. Follow-up assessments would continue quarterly. Treatments would not be blinded since giving placebo injections to the comparison group would interfere with the goal of comparing the acceptability of two different methods of medication administration. However, end points will be blindly rated.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

1. Age 18 years or older.
2. Diagnosed with schizophrenia or schizoaffective disorder by the Structured Clinical Interview for Diagnosis (SCID) (Spitzer and First et al., 1996).
3. At least one hospitalization in a VA or non-VA psychiatric unit in the past year (i.e., excluding care in Domiciliaries, halfway houses, psychosocial rehabilitation programs, or incarceration).
4. Adequate transportation is available and the participant lives within a travel time of less than 1.5 hours, allowing attendance at all scheduled visits.
5. Use of an acceptable method of birth control by female patients who have a possibility of becoming pregnant (safety concerns).
6. Able to give informed consent as assessed by the MacArthur Competence Assessment Tool (MacCAT) (Appelbaum and Grisso, 1996).
7. Dually diagnosed patients with both schizophrenia and addictive disorders would be included in this study but should not be in need of acute detoxification for physiologic substance dependence (excluding nicotine) in the past 30 days.

Exclusion Criteria:

1. Physiologic substance dependence requiring detoxification (excluding nicotine) in the past 30 days (substance abuse is not an exclusion).
2. Intolerance of risperidone.
3. Intolerance of intramuscular injection.
4. Current treatment with depot antipsychotic medication.
5. Current treatment with oral clozapine or presence of refractory schizophrenia that, in the treating psychiatrist’s opinion, requires clozapine.
6. Hepatic or renal problems AST or ALT (>800); elevated bilirubin (>1.2), BUN (>24), creatinine (>1.7).
7. Unstable, serious medical condition or one requiring acute medical treatment, or anticipation of hospitalization for extended care.
8. Dementia, epilepsy, insulin-dependent diabetes, anticoagulation with coumadin.
9. Unstable living arrangements or not planning to remain in the area for the next year.
10. Legal entanglements or pending legal charges with potential of incarceration.
11. Assault or suicide gesture currently needing acute intervention.
12. Concurrent participation in another clinical trial with an investigational drug during the last 30 days.
13. Pregnant or lactating women or women planning to become pregnant.

Please refer to this study by ClinicalTrials.gov identifier  NCT00132314

Study chairs or principal investigators

Robert Rosenheck, MD,  Study Chair,  VA Connecticut Healthcare System   
John Krystal, MD,  Study Chair,  VA Connecticut Healthcare System   

Study ID Numbers:  555
Last Updated:  August 22, 2005
Record first received:  August 17, 2005
ClinicalTrials.gov Identifier:  NCT00132314
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-08-23