Schizophrenia
Conditions
Keywords
Schizoaffective Disorder, Depressed Type, Schizophreniform Disorder, First-episode Schizophrenia, Injectable Risperidone
Brief summary
This study will determine the effectiveness of oral risperidone versus long-acting injectable risperidone in treating people with first-episode schizophrenia.
Detailed description
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.
Interventions
DRUGOral Risperidone
Patients will be treated with oral risperidone daily, with the dosage determined by treating psychiatrist.
DRUGRisperidone in Long-Acting Injectable Form (Consta)
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.
Sponsors
National Institute of Mental Health (NIMH)
Janssen Scientific Affairs, LLC
University of California, Los Angeles
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Global Functioning Scale: Role | Measured at Baseline and Month 12 | 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. |
| Medication Adherence | Measured weekly throughout study participation, averaged over study participation | 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 |
| Number of Participants Who Had an Exacerbation or Relapse of Psychotic Symptoms | Occurrence after randomization and until end of study participation (up to 12 mos.) | 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.). |
| Number of Participants Who Returned to Work or School (SAS Work Section) | Measured from Baseline to Month 12 | 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. |
| Number of Weeks Maintaining Work or School (SAS) | Cumulative total measured from Baseline to Month 12 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Emotional Reactivity on Psychophysiological Measures | Measured from Baseline to Month 12 | 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. |
| Retention in Treatment | From baseline to 12 months | 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. |
| Awareness of Illness, as Assessed by the Scale to Assess Unawareness of Mental Disorder-Revised (SUMD-R) | Baseline to 12 months | 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. |
| MATRICS Consensus Cognitive Battery (MCCB) Overall Composite T Score | Measured at baseline and 12 months | 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. |
Countries
United States
Participant flow
Pre-assignment details
Of the 126 eligible and enrolled participants, 43 dropped out prior to the start of randomized treatment, resulting in 83 randomized.
Participants by arm
| Arm | Count |
|---|---|
| Long-acting Injectable Risperidone Participants taking risperidone, administered in injectable long-acting form (Risperdal Consta), plus group skills training and case management
Group Skills Training and Psychoeducation: Group skills training sessions will be weekly throughout the study. The sessions 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.
Individual Case Management: An individual therapist will provide therapy focused on everyday life skills and aid in interfacing with community agencies, work, and/or school settings.
Risperidone in Long-Acting Injectable Form (Consta): Participants will take a 25 mg dosage of injectable risperidone once every 2 weeks. Dosage will be adjusted if needed. | 40 |
| Oral Risperidone Participants taking daily oral risperidone, plus group skills training and case management
Group Skills Training and Psychoeducation: Group skills training sessions will be weekly throughout the study. The sessions 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.
Individual Case Management: An individual therapist will provide therapy focused on everyday life skills and aid in interfacing with community agencies, work, and/or school settings.
Oral Risperidone: Daily oral risperidone dosage will determined by treating psychiatrist. | 43 |
| Total | 83 |
Baseline characteristics
| Characteristic | Long-acting Injectable Risperidone | Oral Risperidone | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 3 Participants | 9 Participants | 12 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 37 Participants | 34 Participants | 71 Participants |
| Age, Continuous | 21.9 years STANDARD_DEVIATION 3.8 | 21.1 years STANDARD_DEVIATION 3.2 | 21.5 years STANDARD_DEVIATION 3.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 15 Participants | 20 Participants | 35 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 25 Participants | 23 Participants | 48 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 3 Participants | 4 Participants |
| Race (NIH/OMB) Asian | 5 Participants | 4 Participants | 9 Participants |
| Race (NIH/OMB) Black or African American | 14 Participants | 9 Participants | 23 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 3 Participants | 5 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 18 Participants | 23 Participants | 41 Participants |
| Region of Enrollment United States | 40 participants | 43 participants | 83 participants |
| Sex: Female, Male Female | 9 Participants | 9 Participants | 18 Participants |
| Sex: Female, Male Male | 31 Participants | 34 Participants | 65 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 11 / 40 | 19 / 43 |
| serious Total, serious adverse events | 2 / 40 | 8 / 43 |
Outcome results
Primary
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.
Time frame: Measured at Baseline and Month 12
Population: All participants with Global Functioning Scale: Role ratings at baseline and 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Long-acting Injectable Risperidone | Change in Global Functioning Scale: Role | 1.5 Changes on a 10-point scale | Standard Deviation 2.7 |
| Oral Risperidone | Change in Global Functioning Scale: Role | 1.2 Changes on a 10-point scale | Standard Deviation 3 |
p-value: 0.71ANOVA
Primary
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
Time frame: Measured weekly throughout study participation, averaged over study participation
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Long-acting Injectable Risperidone | Medication Adherence | 1.1 units on a scale | Standard Deviation 0.5 |
| Oral Risperidone | Medication Adherence | 1.9 units on a scale | Standard Deviation 0.8 |
p-value: =0.0595% CI: [0.483, 1.058]t-test, 2 sided
Primary
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.).
Time frame: Occurrence after randomization and until end of study participation (up to 12 mos.)
Population: All participants randomized to long-acting injectable or oral risperidone
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Long-acting Injectable Risperidone | Number of Participants Who Had an Exacerbation or Relapse of Psychotic Symptoms | 2 Participants |
| Oral Risperidone | Number of Participants Who Had an Exacerbation or Relapse of Psychotic Symptoms | 14 Participants |
p-value: =0.001Chi-squared
Primary
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.
Time frame: Measured from Baseline to Month 12
Population: All participants with data regarding return to work or school
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Long-acting Injectable Risperidone | Number of Participants Who Returned to Work or School (SAS Work Section) | 29 Participants |
| Oral Risperidone | Number of Participants Who Returned to Work or School (SAS Work Section) | 29 Participants |
p-value: =0.83Chi-squared
Primary
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.
Time frame: Cumulative total measured from Baseline to Month 12
Population: All participants with data on duration of work or school
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Long-acting Injectable Risperidone | Number of Weeks Maintaining Work or School (SAS) | 26.7 weeks | Standard Deviation 20.4 |
| Oral Risperidone | Number of Weeks Maintaining Work or School (SAS) | 21.1 weeks | Standard Deviation 18 |
Comparison: A priori hypothesis was that long-acting injectible risperidone would lead to greater duration of work/school attendance than oral risperidone.p-value: =0.2ANOVA
Secondary
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.
Time frame: Baseline to 12 months
Population: All participants with ratings at baseline and 12 months, with 6-month rating carried forward if no 12-month rating was completed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Long-acting Injectable Risperidone | Awareness of Illness, as Assessed by the Scale to Assess Unawareness of Mental Disorder-Revised (SUMD-R) | .07 Change scores on 5-point rating scale | Standard Deviation 1.34 |
| Oral Risperidone | Awareness of Illness, as Assessed by the Scale to Assess Unawareness of Mental Disorder-Revised (SUMD-R) | -.24 Change scores on 5-point rating scale | Standard Deviation 1.56 |
p-value: =0.41ANOVA
Secondary
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.
Time frame: Measured from Baseline to Month 12
Population: No data were available because this part of the initial proposal was not funded.
Secondary
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.
Time frame: Measured at baseline and 12 months
Population: All participants with MCCB Overall Composite scores at baseline and 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Long-acting Injectable Risperidone | MATRICS Consensus Cognitive Battery (MCCB) Overall Composite T Score | 3.5 Change score: change in T scores | Standard Deviation 7.5 |
| Oral Risperidone | MATRICS Consensus Cognitive Battery (MCCB) Overall Composite T Score | 4.4 Change score: change in T scores | Standard Deviation 5 |
p-value: =0.57ANOVA
Secondary
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.
Time frame: From baseline to 12 months
Population: All participants randomized to oral vs. long-acting injectable risperidone
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Long-acting Injectable Risperidone | Retention in Treatment | 307.6 days | Standard Deviation 108.3 |
| Oral Risperidone | Retention in Treatment | 270.7 days | Standard Deviation 126.4 |
p-value: <0.16ANOVA