Oral Versus Injectable Risperidone for Treating First-Episode Schizophrenia

Study Overview
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Brief Summary
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This study will determine the effectiveness of oral risperidone versus long-acting injectable risperidone in treating people with first-episode schizophrenia.

Detailed Description
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Schizophrenia is a severely disabling brain disorder. People with schizophrenia often experience hallucinations, delusions, thought disorders, and movement disorders. Proper treatment of first-episode schizophrenia may increase the chances of controlling disease progression on a long-term basis. People experiencing their first episode of schizophrenia are more responsive to treatment than those with chronic schizophrenia, but are also more susceptible to adverse treatment side effects. Atypical antipsychotic medications have been shown to produce fewer adverse side effects than older typical antipsychotics. Risperidone is a type of atypical antipsychotic medication that is used to control the symptoms of schizophrenia. This study will determine the effectiveness of oral risperidone versus long-acting injectable risperidone in treating people with first-episode schizophrenia. Participants in this open label study will be randomly assigned to receive either orally administered risperidone or long-acting risperidone administered via injection. Participants assigned to oral risperidone will receive medication in doses that are determined to be optimal by the study psychiatrist. Participants assigned to long-acting risperidone will receive an injection of risperidone once every 2 weeks. Dosages will begin at 25 mg and will be adjusted as necessary to achieve the optimal dosage. Following 2 to 3 months to achieve outpatient risperidone dosage stabilization, the randomized medication conditions will begin and participants will be monitored for 1 year. Study visits will occur once weekly throughout the study. They will include group therapy meetings focused on everyday living skills; family education about schizophrenia; assessments of medication response; and individual meetings with a case manager for counseling and evaluations of schizophrenia symptoms.

Official Title
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Effects of Risperdal Consta Versus Oral Antipsychotic Medication on Clinical and Functional Outcome and Neurocognition in First-episode Schizophrenia

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: Oral Risperidone
* Drug: Risperidone in Long-Acting Injectable Form (Consta)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: DSM-IV diagnosis of schizophrenia, schizoaffective disorder (depressed type), or schizophreniform disorder First major episode of psychotic symptoms occurred within 2 years prior to study entry Participant in the UCLA Center for Neurocognition and Emotion in Schizophrenia Exclusion Criteria: Neurological disorder or injury (e.g., encephalitis, epilepsy, traumatic brain injury) Mental retardation (e.g., premorbid IQ less than 70) Significant alcohol or substance abuse within 6 months prior to study entry Inability to complete research measures in English Any condition that may make risperidone use medically inadvisable

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Long-acting injectible risperidone<br>Participants who are randomly assigned to this arm will be administered the long-acting injectible form of risperidone (Risperdal Consta) every two weeks, plus group skills training and case management, for 12 months. | Drug: Risperidone in Long-Acting Injectable Form (Consta)<br>* Participants will take a 25 mg dosage of injectable risperidone (Risperidone in Long-Acting Injectable Form (Consta)) once every 2 weeks. Dosage will be adjusted if needed.<br>* Other names: Risperdal Consta;|
| Active Comparator: Oral risperidone<br>Participants who are randomly assigned to this arm will be treated with the oral version of risperidone (Risperdal) daily, plus group skills training and case management, for 12 months. | Drug: Oral Risperidone<br>* Patients will be treated with oral risperidone daily, with the dosage determined by treating psychiatrist.<br>* Other names: Risperdal;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Medication Adherence | 5-point scale (1 = best adherence, 5= nonadherent) based on pill counts, MEMS cap readings, plasma assays, and psychiatrist judgments for oral risperidone and timing of injections for long-acting injectable risperidone averaged over study participation | Measured weekly throughout study participation, averaged over study participation | 
| Number of Participants Who Had an Exacerbation or Relapse of Psychotic Symptoms | Dichotomous measure: Presence of any of three psychotic relapse or exacerbation categories scored from the Brief Psychiatric Rating Scale (BPRS) occurring any time after randomization and until end of study participation (up to 12 mos.). | Occurrence after randomization and until end of study participation (up to 12 mos.) | 
| Number of Participants Who Returned to Work or School (SAS Work Section) | The Social Adjustment Scale records the return to work or school and the number of weeks in work or school during each 3-month period. For this outcome, outcome as dichotomized as 0 if an individual did not return to work or school and 1 if they did return to competitive work or regular school enrollment. | Measured from Baseline to Month 12 | 
| Number of Weeks Maintaining Work or School (SAS) | Measured as the number of weeks in which a participant has competitive employment or attends regular school courses. Possible range is 0 to 52 weeks. | Cumulative total measured from Baseline to Month 12 | 
| Change in Global Functioning Scale: Role | 10-point scale of work/school functioning. Scale range is from 1 (extreme role dysfunction) to 10 (superior role functioning). Measured by subtracting the baseline rating from the rating at 12 months. | Measured at Baseline and Month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MATRICS Consensus Cognitive Battery (MCCB) Overall Composite T Score | The MCCB Overall Composite T score is computed by the MCCB Computer Scoring Program from the raw scores for 10 individual cognitive tests. The mean for the general population of comparable age and sex is 50 with a standard deviation of 10. Higher scores indicate better cognitive functioning. The outcome measure was the change from baseline to 12 months, calculated as 12-month T score minus baseline T score. Higher values indicate better outcome. | Measured at baseline and 12 months | 
| Emotional Reactivity on Psychophysiological Measures | Electrodermal reactivity to pictures of negative versus neutral stimuli was the initially proposed measure. Larger skin conductance increases in response to negative pictures compared to neutral pictures would indicate stronger emotional reactivity. | Measured from Baseline to Month 12 | 
| Retention in Treatment | Number of days on the randomized medication before being switched to a different antipsychotic medication or dropping out of the medication trial. Possible range is 0 to 365, with higher numbers indicating better retention in treatment. | From baseline to 12 months | 
| Awareness of Illness, as Assessed by the Scale to Assess Unawareness of Mental Disorder-Revised (SUMD-R) | Rating scale based on clinician's interview of patient to determine level of lack of awareness of having a mental disorder. Range is from 1 (Aware) to 5 (Unaware), so lower scores indicate better outcome. | Baseline to 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Schizoaffective Disorder, Depressed Type, Schizophreniform Disorder, First-episode Schizophrenia, Injectable Risperidone