Psychosocial Therapy and Risperidone Treatment in Work Performance in Recent-Onset Schizophrenia

• Sponsor: University of California, Los Angeles (Other)
• Overall Status: Completed
• CT.gov ID: NCT00333177
• Collaborator: National Institute of Mental Health (NIMH) (NIH), Janssen Scientific Affairs, LLC (Industry)
• Enrollment: 92
• Location: 1
• Arms: 4
• Duration (Months): 82.1
• Patients Per Site Per Month: 1.1

Study Details

Study Description

Brief Summary

This study will determine the effectiveness of various combinations of psychosocial therapy and risperidone treatment in improving work or school performance in people with first-episode schizophrenia.

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia	Behavioral: Cognitive remediation training (CT); Behavioral: Healthy behavior training (HBT); Drug: Risperidone, administered orally (Oral Ris); Drug: Risperidone, administered via injection (RLAI)	Phase 4

Detailed Description

Schizophrenia is a chronic, severe, and disabling brain disorder. People with schizophrenia often experience hallucinations, delusions, thought disorders, and movement disorders. These symptoms make it difficult to maintain a job, participate in school, and keep up self-care. Proper treatment of first-episode schizophrenia may increase the chances of controlling disease progression on a long-term basis. Antipsychotic medications, such as risperidone, and psychosocial treatments, such as cognitive enhancement training and health behavior training, are common, effective treatments for schizophrenia. This study will determine the effectiveness of various combinations of psychosocial therapy and risperidone treatment in improving work or school performance in people with first-episode schizophrenia.

Participants in this open label study will be randomly assigned to receive one of the following four combinations of an antipsychotic medication and a psychosocial treatment: cognitive enhancement training plus oral risperidone; cognitive enhancement training plus long-acting injectable risperidone; health behavior training plus oral risperidone; or health behavior training plus long-acting injectable risperidone. Cognitive enhancement training will entail 2 hours per week of computer-assisted training targeted at improving attention, memory, and problem-solving skills. Additionally, participants will attend a weekly 1-hour group meeting to learn how to apply these skills to work and school situations. Health behavior training will involve 3 hours per week of relaxation training, nutrition education, and physical exercise to enhance wellness. Participants assigned to receive oral risperidone will receive their medication in pill form at the dosage determined to be optimal by the study psychiatrist. Participants assigned to receive injectable risperidone will be given one injection every 2 weeks. Dosages will start at 25 mg per injection and will be adjusted as needed.

Treatment will continue for 1 year following dosage stabilization, which typically occurs 2 to 3 months following study entry. For the first 6 months, participants assigned to receive health behavior training will attend study visits once a week and participants assigned to receive cognitive enhancement training will attend study visits once a week. For the final 6 months, all participants will attend study visits twice weekly. At each visit, participants will receive their assigned psychosocial treatment; attend group therapy; meet with a case manager for counseling and assessment of symptoms, work functioning, and social functioning; and meet with a psychiatrist to monitor medication response. Additional cognitive and health behavior measures will be taken every 6 months to assess treatment effectiveness.

Study Design

• Study Type: Interventional
• Actual Enrollment: 92 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Developmental Processes in Schizophrenic Disorders: Cognitive Remediation, Medication Adherence, and Work Outcome in Recent-Onset Schizophrenia
• Study Start Date: Mar 1, 2006
• Actual Primary Completion Date: Jan 1, 2013
• Actual Study Completion Date: Jan 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cog Remediation, risperidone injection Participants will receive cognitive remediation training plus risperidone, administered via injection.	Behavioral: Cognitive remediation training (CT); Cognitive remediation training includes computerized cognitive training plus learning skills group.; Drug: Risperidone, administered via injection (RLAI); Risperidone in injectable form every 2 weeks, starting with 25 mg and adjusted as needed; Other Names: Risperdal Consta
Active Comparator: Healthy Behavior Training, risperidone injection Participants will receive health behavior training plus risperidone, administered via injection.	Behavioral: Healthy behavior training (HBT); Healthy behavior training includes group skills training in nutrition, exercise, and relaxation.; Drug: Risperidone, administered via injection (RLAI); Risperidone in injectable form every 2 weeks, starting with 25 mg and adjusted as needed; Other Names: Risperdal Consta
Experimental: Cog Remediation, oral risperidone Participants will receive cognitive remediation training plus risperidone administered orally.	Behavioral: Cognitive remediation training (CT); Cognitive remediation training includes computerized cognitive training plus learning skills group.; Drug: Risperidone, administered orally (Oral Ris); Oral risperidone at dosage judged optimal by treating psychiatrist; Other Names: Risperdal
Active Comparator: Healthy Behavior Training, oral risperidone Participants will receive health behavior training plus risperidone administered orally.	Behavioral: Healthy behavior training (HBT); Healthy behavior training includes group skills training in nutrition, exercise, and relaxation.; Drug: Risperidone, administered orally (Oral Ris); Oral risperidone at dosage judged optimal by treating psychiatrist; Other Names: Risperdal

Outcome Measures

Primary Outcome Measures

1. Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) [Measured at baseline and 12 months]

   Values presented here are the changes in MCCB Overall Composite T scores from baseline to 12 months, with higher values representing better outcome. Raw test scores are used to generate T-scores and then the seven MCCB domains are combined to generate an Overall Composite T score. MCCB Overall Composite T scores have a mean in the general population of 50 with a standard deviation of 10. Thus, a positive change of 5 T scores is an improvement of half a standard deviation.

2. Work/School Functioning (Global Functioning Scale: Role) [Baseline to 6 months]

   Change in role functioning from baseline to the 6 month point (rated on a scale from 1= Extreme Role Dysfunction to 10 = Superior Role Functioning) is presented here.

3. Average Medication Non-adherence [Averaged over study participation (up to 12 months)]

   5-point scale (1 = best adherence, 5= nonadherent) based on pill counts, Medication Event Monitoring System (MEMS) cap readings, plasma assays, and psychiatrist judgements for oral risperidone and timing of injections for long-acting injectable risperidone. Averaged over medication study participation.

4. Work/School Functioning (Global Functioning Scale: Role) [Baseline to 12 months]

   Changes in role functioning from baseline to 12 months. Ratings on a 10-point scale with 10 being best.

Secondary Outcome Measures

1. Work Behavior Inventory (WBI) Quality of Work/School Performance [Baseline to 1 year]

   Change in rating on quality of work/school performance based on patient, employer, and/or teacher reports. The Quality of Work rating at baseline was subtracted from the same rating at 12 mos. Higher scores are better outcome.

2. Maintenance of Work/School Attendance [12 months]

   Modified Work Section of the Social Adjustment Scale (SAS) was used to calculate the total number of weeks in school or competitive work. Range of possible values is 0 to 52, with higher numbers being better outcome.

3. Exacerbation or Relapse of Psychotic Symptoms [Occurence after randomization and until end of study participation (up to 12 mos.)]

   Dichotomous measure: Presence of any of 3 psychotic relapse or exacerbation categories scored from the Brief Psychiatric Rating Scale (BPRS) occurring after randomization and until end of study participation (up to 12 months post baseline). BPRS was administered every two weeks throughout study participation.

4. Retention in Treatment [12 months]

   Days after randomization that a participant continued to receive at least the assigned CT or HBT psychosocial treatment. If a participant needed to end the assigned medication condition (RLAI vs. Oral Ris), they continued in the psychosocial treatment so this outcome focused on the days in the assigned psychosocial treatment. Possible range is 1 to 365, with higher being a better outcome.

5. Awareness of Illness, as Assessed by the Scale to Assess Unawareness of Mental Disorder, Revised Version (SUMD-R) [12 months after randomization]

   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.

6. Change in Motivation for Work/School [Baseline to 12 months]

   The Work Motivation scale is a factor score from the Work Personality Profile. The Work Personality Profile is a set of ratings based on interviewing the participant. Scores at each occasion can range from 8 to 32, with higher indicating better motivation. Scores reported here are changes from baseline to 12 months, which could range from -24 to 24 with higher being better.

7. Change in Coping Strategies [Baseline to 12 months]

   Coping Response Inventory, which rates extent to which active coping strategies were used after a significant stressful life event. Range of possible scores is 1 to 4. Higher scores are better.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 45 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Diagnosis of schizophrenia, schizoaffective disorder (depressed type), or schizophreniform disorder

• First major episode of psychotic symptoms occurred within 2 years prior to study entry

Exclusion Criteria:

• Neurological disorder or injury (e.g., encephalitis, epilepsy, traumatic brain injury)

• Mental retardation (e.g., premorbid intelligence quotient (IQ) less than 70)

• Significant alcohol or substance use during last 6 months

• Unable to complete research measures in English

• Any condition that may make risperidone use medically inadvisable

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Semel Institute for Neuroscience and Human Behavior at UCLA	Los Angeles	California	United States	90095

Sponsors and Collaborators

• University of California, Los Angeles
• National Institute of Mental Health (NIMH)
• Janssen Scientific Affairs, LLC

Investigators

• Principal Investigator: Keith H. Nuechterlein, PhD, University of California, Los Angeles, Department of Psychiatry and Biobehavioral Sciences

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Keith Nuechterlein, Ph.D., Prinicipal Investigator, University of California, Los Angeles
• ClinicalTrials.gov Identifier: NCT00333177
• Other Study ID Numbers: R01MH037705-06; R01MH037705; DAHBR AD-P
• First Posted: Jun 2, 2006
• Last Update Posted: Mar 26, 2020
• Last Verified: Mar 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Keith Nuechterlein, Ph.D., Prinicipal Investigator, University of California, Los Angeles: Schizoaffective Disorder, Depressed Type; Schizophreniform Disorder; First-Episode Schizophrenia; Supported Employment; Cognitive Remediation; Health Behavior Training; Antipsychotic Medication
• Additional relevant MeSH terms: Schizophrenia; Risperidone

Study Results

Participant Flow

Pre-assignment Detail	32 patients who were enrolled in the study dropped out during the initial medication stabilization period prior to the start of randomized treatment resulting in 60 being assigned to the randomized treatments.

Arm/Group Title	CT - RLAI	HBT - RLAI	CT - Oral Ris	HBT - Oral Ris
Arm/Group Description	Participants will receive cognitive remediation training (CT) plus injectable, long-acting risperidone (RLAI). Cognitive remediation: Cognitive remediation training includes computerized cognitive training plus learning skills group. Risperidone, administered via injection: Risperidone in injectable form every 2 weeks, starting with 25 mg and adjusted as needed Individual Placement and Support: Supported education/employment	Participants will receive health behavior training (HBT) plus injectable, long-acting risperidone (RLAI). Health behavior training: Health behavior training includes group skills training in nutrition, exercise, and relaxation. Risperidone, administered via injection: Risperidone in injectable form every 2 weeks, starting with 25 mg and adjusted as needed Individual Placement and Support: Supported education/employment	Participants will receive cognitive remediation training (CT) plus risperidone administered orally (Oral Ris). Cognitive remediation: Cognitive remediation training includes computerized cognitive training plus learning skills group. Risperidone, administered orally: Oral risperidone at dosage judged optimal by treating psychiatrist Individual Placement and Support: Supported education/employment	Participants will receive health behavior training (HBT) plus risperidone administered orally (Oral Ris). Health behavior training: Health behavior training includes group skills training in nutrition, exercise, and relaxation. Risperidone, administered orally: Oral risperidone at dosage judged optimal by treating psychiatrist Individual Placement and Support: Supported education/employment
Period Title: Overall Study
STARTED	12	17	17	14
Received Intervention	12	16	16	12
COMPLETED	12	16	16	12
NOT COMPLETED	0	1	1	2

Baseline Characteristics

Arm/Group Title	CT - RLAI	HBT - RLAI	CT - Oral Ris	HBT - Oral Ris	Total
Arm/Group Description	Participants will receive cognitive remediation training plus injectable, long-acting risperidone. Cognitive remediation: Cognitive remediation training includes computerized cognitive training plus learning skills group. Risperidone, administered via injection: Risperidone in injectable form every 2 weeks, starting with 25 mg and adjusted as needed Individual Placement and Support: Supported education/employment	Participants will receive health behavior training plus injectable, long-acting risperidone. Health behavior training: Health behavior training includes group skills training in nutrition, exercise, and relaxation. Risperidone, administered via injection: Risperidone in injectable form every 2 weeks, starting with 25 mg and adjusted as needed Individual Placement and Support: Supported education/employment	Participants will receive cognitive remediation training plus risperidone administered orally. Cognitive remediation: Cognitive remediation training includes computerized cognitive training plus learning skills group. Risperidone, administered orally: Oral risperidone at dosage judged optimal by treating psychiatrist Individual Placement and Support: Supported education/employment	Participants will receive health behavior training plus risperidone administered orally. Health behavior training: Health behavior training includes group skills training in nutrition, exercise, and relaxation. Risperidone, administered orally: Oral risperidone at dosage judged optimal by treating psychiatrist Individual Placement and Support: Supported education/employment	Total of all reporting groups
Overall Participants	12	17	17	14	60
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	21.7 (2.9)	22.1 (4.6)	21.3 (3.1)	20.8 (3.3)	21.9 (3.9)
Sex: Female, Male (Count of Participants)
Female	2 16.7%	3 17.6%	5 29.4%	4 28.6%	14 23.3%
Male	10 83.3%	14 82.4%	12 70.6%	10 71.4%	46 76.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	4 33.3%	6 35.3%	9 52.9%	6 42.9%	25 41.7%
Not Hispanic or Latino	8 66.7%	11 64.7%	8 47.1%	8 57.1%	35 58.3%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	1 5.9%	0 0%	1 1.7%
Asian	3 25%	2 11.8%	1 5.9%	1 7.1%	7 11.7%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	3 25%	7 41.2%	5 29.4%	2 14.3%	17 28.3%
White	6 50%	8 47.1%	10 58.8%	10 71.4%	34 56.7%
More than one race	0 0%	0 0%	0 0%	1 7.1%	1 1.7%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	12 100%	17 100%	17 100%	14 100%	60 100%

Outcome Measures

1. Primary Outcome

Title	Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB)
Description	Values presented here are the changes in MCCB Overall Composite T scores from baseline to 12 months, with higher values representing better outcome. Raw test scores are used to generate T-scores and then the seven MCCB domains are combined to generate an Overall Composite T score. MCCB Overall Composite T scores have a mean in the general population of 50 with a standard deviation of 10. Thus, a positive change of 5 T scores is an improvement of half a standard deviation.
Time Frame	Measured at baseline and 12 months

Outcome Measure Data

Analysis Population Description

All participants with MCCB outcome data.

Arm/Group Title	CT - RLAI	HBT - RLAI	CT - Oral Ris	HBT - Oral Ris
Arm/Group Description	Participants will receive cognitive remediation training plus injectable, long-acting risperidone. Cognitive remediation: Cognitive remediation training includes computerized cognitive training plus learning skills group. Risperidone, administered via injection: Risperidone in injectable form every 2 weeks, starting with 25 mg and adjusted as needed Individual Placement and Support: Supported education/employment	Participants will receive health behavior training plus injectable, long-acting risperidone. Health behavior training: Health behavior training includes group skills training in nutrition, exercise, and relaxation. Risperidone, administered via injection: Risperidone in injectable form every 2 weeks, starting with 25 mg and adjusted as needed Individual Placement and Support: Supported education/employment	Participants will receive cognitive remediation training plus risperidone administered orally. Cognitive remediation: Cognitive remediation training includes computerized cognitive training plus learning skills group. Risperidone, administered orally: Oral risperidone at dosage judged optimal by treating psychiatrist Individual Placement and Support: Supported education/employment	Participants will receive health behavior training plus risperidone administered orally. Health behavior training: Health behavior training includes group skills training in nutrition, exercise, and relaxation. Risperidone, administered orally: Oral risperidone at dosage judged optimal by treating psychiatrist Individual Placement and Support: Supported education/employment
Measure Participants	12	16	16	12
Mean (Standard Error) [T scores]	6.7 (1.9)	0.9 (1.6)	3.9 (1.6)	5.9 (1.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CT - RLAI, HBT - RLAI, CT - Oral Ris, HBT - Oral Ris
	Comments	A priori hypothesis was that CT would be superior to HBT and that RLAI would enhance this effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.03
	Comments	P value is for CT-HBT X RLAI-Oral Ris interaction
	Method	ANCOVA
	Comments	Covaried baseline value of dependent variable

2. Primary Outcome

Title	Work/School Functioning (Global Functioning Scale: Role)
Description	Change in role functioning from baseline to the 6 month point (rated on a scale from 1= Extreme Role Dysfunction to 10 = Superior Role Functioning) is presented here.
Time Frame	Baseline to 6 months

Outcome Measure Data

Analysis Population Description

Participants who received services from the supported education/employment specialist

Arm/Group Title	CT - RLAI	HBT - RLAI	CT - Oral Ris	HBT - Oral Ris
Arm/Group Description	Participants will receive cognitive remediation training plus injectable, long-acting risperidone. Cognitive remediation: Cognitive remediation training includes computerized cognitive training plus learning skills group. Risperidone, administered via injection: Risperidone in injectable form every 2 weeks, starting with 25 mg and adjusted as needed Individual Placement and Support: Supported education/employment	Participants will receive health behavior training plus injectable, long-acting risperidone. Health behavior training: Health behavior training includes group skills training in nutrition, exercise, and relaxation. Risperidone, administered via injection: Risperidone in injectable form every 2 weeks, starting with 25 mg and adjusted as needed Individual Placement and Support: Supported education/employment	Participants will receive cognitive remediation training plus risperidone administered orally. Cognitive remediation: Cognitive remediation training includes computerized cognitive training plus learning skills group. Risperidone, administered orally: Oral risperidone at dosage judged optimal by treating psychiatrist Individual Placement and Support: Supported education/employment	Participants will receive health behavior training plus risperidone administered orally. Health behavior training: Health behavior training includes group skills training in nutrition, exercise, and relaxation. Risperidone, administered orally: Oral risperidone at dosage judged optimal by treating psychiatrist Individual Placement and Support: Supported education/employment
Measure Participants	10	12	15	11
Mean (Standard Deviation) [Changes on a 10-point scale]	2.90 (2.56)	0.92 (2.75)	1.27 (2.76)	-0.82 (2.93)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CT - RLAI, HBT - RLAI, CT - Oral Ris, HBT - Oral Ris
	Comments	2 X 2 ANOVA was calculated. A priori hypotheses were that LAI would be superior to oral risperidone and that CT would be superior to health behavior training (HBT) based on main effects.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<.02
	Comments	P-value is for each main effect. A priori threshold for statistical significance was p<0.05 for each main effect.
	Method	ANCOVA
	Comments	Baseline value of dependent variable was covaried.

3. Primary Outcome

Title	Average Medication Non-adherence
Description	5-point scale (1 = best adherence, 5= nonadherent) based on pill counts, Medication Event Monitoring System (MEMS) cap readings, plasma assays, and psychiatrist judgements for oral risperidone and timing of injections for long-acting injectable risperidone. Averaged over medication study participation.
Time Frame	Averaged over study participation (up to 12 months)

Outcome Measure Data

Analysis Population Description

A priori hypothesis was that long-acting injectable risperidone would result in better medication adherence than oral risperidone, so CT and HBT groups were merged within each medication administration condition.

Arm/Group Title	RLAI	Oral Ris
Arm/Group Description	Participants will receive risperidone, administered via injection: Risperidone in injectable form every 2 weeks, starting with 25 mg and adjusted as needed For this study aim, only the medication comparison is involved, so the cognitive training and Health Behaviors Training groups are combined within this medication condition. Participants will receive either cognitive remediation or healthy behaviors training plus risperidone administered by injection. All participants received individual Placement and Support: Supported education/employment	Risperidone, administered orally: Oral risperidone at dosage judged optimal by treating psychiatrist. For this study aim, only the medication comparison is involved, so the cognitive training and Health Behaviors Training groups are combined within this medication condition. Participants will receive either cognitive remediation or healthy behaviors training plus risperidone administered orally.All participants received individual Placement and Support: Supported education/employment
Measure Participants	28	27
Mean (Standard Deviation) [units on a 5-point scale]	1.0 (0.1)	1.9 (0.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CT - RLAI, HBT - RLAI
	Comments	A priori hypothesis was that RLAI would lead to less medication non-adherence than Oral Ris.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.001
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	.84
	Confidence Interval	(2-Sided) 95%; .57 to 1.10
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Primary Outcome

Title	Work/School Functioning (Global Functioning Scale: Role)
Description	Changes in role functioning from baseline to 12 months. Ratings on a 10-point scale with 10 being best.
Time Frame	Baseline to 12 months

Outcome Measure Data

Analysis Population Description

Participants who received services from the Individual Placement and Support specialist.

Arm/Group Title	CT - RLAI	HBT - RLAI	CT - Oral Ris	HBT - Oral Ris
Arm/Group Description	Participants will receive cognitive remediation training plus injectable, long-acting risperidone. Cognitive remediation: Cognitive remediation training includes computerized cognitive training plus learning skills group. Risperidone, administered via injection: Risperidone in injectable form every 2 weeks, starting with 25 mg and adjusted as needed Individual Placement and Support: Supported education/employment	Participants will receive health behavior training plus injectable, long-acting risperidone. Health behavior training: Health behavior training includes group skills training in nutrition, exercise, and relaxation. Risperidone, administered via injection: Risperidone in injectable form every 2 weeks, starting with 25 mg and adjusted as needed Individual Placement and Support: Supported education/employment	Participants will receive cognitive remediation training plus risperidone administered orally. Cognitive remediation: Cognitive remediation training includes computerized cognitive training plus learning skills group. Risperidone, administered orally: Oral risperidone at dosage judged optimal by treating psychiatrist Individual Placement and Support: Supported education/employment	Participants will receive health behavior training plus risperidone administered orally. Health behavior training: Health behavior training includes group skills training in nutrition, exercise, and relaxation. Risperidone, administered orally: Oral risperidone at dosage judged optimal by treating psychiatrist Individual Placement and Support: Supported education/employment
Measure Participants	10	13	14	11
Mean (Standard Deviation) [Changes on a 10-point scale]	2.70 (2.67)	1.69 (2.66)	2.43 (2.44)	0.18 (3.19)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CT - RLAI, HBT - RLAI, CT - Oral Ris, HBT - Oral Ris
	Comments	2 X 2 ANOVA was calculated. A priori hypotheses were that CT would be superior to HBT and that RLAI would be superior to Oral Ris.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<.05
	Comments	P-value is for CT vs. HBT main effect.
	Method	ANCOVA
	Comments	Baseline value of dependent variable was covaried.

5. Secondary Outcome

Title	Work Behavior Inventory (WBI) Quality of Work/School Performance
Description	Change in rating on quality of work/school performance based on patient, employer, and/or teacher reports. The Quality of Work rating at baseline was subtracted from the same rating at 12 mos. Higher scores are better outcome.
Time Frame	Baseline to 1 year

Outcome Measure Data

Analysis Population Description

This measure could be rated only for individuals who were in school or working at baseline and at 12 months, so it proved not to be useful due to the infrequent return to school or work by baseline.

Arm/Group Title	CT - RLAI	HBT - RLAI	CT - Oral Ris	HBT - Oral Ris
Arm/Group Description	Participants will receive cognitive remediation training plus injectable, long-acting risperidone. Cognitive remediation: Cognitive remediation training includes computerized cognitive training plus learning skills group. Risperidone, administered via injection: Risperidone in injectable form every 2 weeks, starting with 25 mg and adjusted as needed Individual Placement and Support: Supported education/employment	Participants will receive health behavior training plus injectable, long-acting risperidone. Health behavior training: Health behavior training includes group skills training in nutrition, exercise, and relaxation. Risperidone, administered via injection: Risperidone in injectable form every 2 weeks, starting with 25 mg and adjusted as needed Individual Placement and Support: Supported education/employment	Participants will receive cognitive remediation training plus risperidone administered orally. Cognitive remediation: Cognitive remediation training includes computerized cognitive training plus learning skills group. Risperidone, administered orally: Oral risperidone at dosage judged optimal by treating psychiatrist Individual Placement and Support: Supported education/employment	Participants will receive health behavior training plus risperidone administered orally. Health behavior training: Health behavior training includes group skills training in nutrition, exercise, and relaxation. Risperidone, administered orally: Oral risperidone at dosage judged optimal by treating psychiatrist Individual Placement and Support: Supported education/employment
Measure Participants	2	6	8	2
Mean (Standard Deviation) [score on a rating scale]	-6.5 (31.8)	8.8 (34.0)	-3.4 (17.4)	0.0 (33.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CT - RLAI, HBT - RLAI, CT - Oral Ris, HBT - Oral Ris
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.55
	Comments
	Method	ANOVA
	Comments

6. Secondary Outcome

Title	Maintenance of Work/School Attendance
Description	Modified Work Section of the Social Adjustment Scale (SAS) was used to calculate the total number of weeks in school or competitive work. Range of possible values is 0 to 52, with higher numbers being better outcome.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

Participants who were served by the Individual Placement and Support specialist

Arm/Group Title	CT - RLAI	HBT - RLAI	CT - Oral Ris	HBT - Oral Ris
Arm/Group Description	Participants will receive cognitive remediation training plus injectable, long-acting risperidone. Cognitive remediation: Cognitive remediation training includes computerized cognitive training plus learning skills group. Risperidone, administered via injection: Risperidone in injectable form every 2 weeks, starting with 25 mg and adjusted as needed Individual Placement and Support: Supported education/employment	Participants will receive health behavior training plus injectable, long-acting risperidone. Health behavior training: Health behavior training includes group skills training in nutrition, exercise, and relaxation. Risperidone, administered via injection: Risperidone in injectable form every 2 weeks, starting with 25 mg and adjusted as needed Individual Placement and Support: Supported education/employment	Participants will receive cognitive remediation training plus risperidone administered orally. Cognitive remediation: Cognitive remediation training includes computerized cognitive training plus learning skills group. Risperidone, administered orally: Oral risperidone at dosage judged optimal by treating psychiatrist Individual Placement and Support: Supported education/employment	Participants will receive health behavior training plus risperidone administered orally. Health behavior training: Health behavior training includes group skills training in nutrition, exercise, and relaxation. Risperidone, administered orally: Oral risperidone at dosage judged optimal by treating psychiatrist Individual Placement and Support: Supported education/employment
Measure Participants	12	16	16	12
Mean (Standard Deviation) [weeks]	35.4 (21.2)	24.4 (19.8)	26.7 (20.0)	12.0 (12.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CT - RLAI, HBT - RLAI, CT - Oral Ris, HBT - Oral Ris
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.02
	Comments	A priori hypotheses were that CT would be superior to HBT and that RLAI would be superior to Oral Ris.
	Method	ANOVA
	Comments	2 X 2 ANOVA was computed.

7. Secondary Outcome

Title	Exacerbation or Relapse of Psychotic Symptoms
Description	Dichotomous measure: Presence of any of 3 psychotic relapse or exacerbation categories scored from the Brief Psychiatric Rating Scale (BPRS) occurring after randomization and until end of study participation (up to 12 months post baseline). BPRS was administered every two weeks throughout study participation.
Time Frame	Occurence after randomization and until end of study participation (up to 12 mos.)

Outcome Measure Data

Analysis Population Description

A priori hypothesis was that RLAI would lead to fewer psychotic exacerbations/relapses than Oral Ris. No effect of CT vs. HBT was hypothesized, so CT and HBT conditions were merged within each medication administration condition.

Arm/Group Title	RLAI	Oral Ris
Arm/Group Description	Participants will receive risperidone, administered via injection: Risperidone in injectable form every 2 weeks, starting with 25 mg and adjusted as needed For this study aim, only the medication comparison is involved, so the cognitive training and Health Behaviors Training groups are combined within this medication condition. Participants will receive either cognitive remediation or healthy behaviors training plus risperidone administered by injection. All participants received individual Placement and Support: Supported education/employment	Risperidone, administered orally: Oral risperidone at dosage judged optimal by treating psychiatrist. For this study aim, only the medication comparison is involved, so the cognitive training and Health Behaviors Training groups are combined within this medication condition. Participants will receive either cognitive remediation or healthy behaviors training plus risperidone administered orally.All participants received individual Placement and Support: Supported education/employment
Measure Participants	28	28
Number [participants]	2 16.7%	10 58.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CT - RLAI, HBT - RLAI
	Comments	Chi-square of frequencies of relapse vs. non-relapse were calculated, with a priori hypothesis that RLAI would be superior to Oral Ris.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.01
	Comments
	Method	Chi-squared
	Comments	df = 1

8. Secondary Outcome

Title	Retention in Treatment
Description	Days after randomization that a participant continued to receive at least the assigned CT or HBT psychosocial treatment. If a participant needed to end the assigned medication condition (RLAI vs. Oral Ris), they continued in the psychosocial treatment so this outcome focused on the days in the assigned psychosocial treatment. Possible range is 1 to 365, with higher being a better outcome.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

All participants who received Individual Placement and Support

Arm/Group Title	CT - RLAI	HBT - RLAI	CT - Oral Ris	HBT - Oral Ris
Arm/Group Description	Participants will receive cognitive remediation training plus injectable, long-acting risperidone. Cognitive remediation: Cognitive remediation training includes computerized cognitive training plus learning skills group. Risperidone, administered via injection: Risperidone in injectable form every 2 weeks, starting with 25 mg and adjusted as needed Individual Placement and Support: Supported education/employment	Participants will receive health behavior training plus injectable, long-acting risperidone. Health behavior training: Health behavior training includes group skills training in nutrition, exercise, and relaxation. Risperidone, administered via injection: Risperidone in injectable form every 2 weeks, starting with 25 mg and adjusted as needed Individual Placement and Support: Supported education/employment	Participants will receive cognitive remediation training plus risperidone administered orally. Cognitive remediation: Cognitive remediation training includes computerized cognitive training plus learning skills group. Risperidone, administered orally: Oral risperidone at dosage judged optimal by treating psychiatrist Individual Placement and Support: Supported education/employment	Participants will receive health behavior training plus risperidone administered orally. Health behavior training: Health behavior training includes group skills training in nutrition, exercise, and relaxation. Risperidone, administered orally: Oral risperidone at dosage judged optimal by treating psychiatrist Individual Placement and Support: Supported education/employment
Measure Participants	12	16	16	12
Mean (Standard Deviation) [days]	359.7 (8.1)	352.2 (26.9)	332.4 (38.8)	348.3 (28.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CT - RLAI, HBT - RLAI, CT - Oral Ris, HBT - Oral Ris
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<.05
	Comments	2 X 2 ANOVA calculated. P-value is for main effect of RLAI vs. Oral Ris.
	Method	ANOVA
	Comments

9. Secondary Outcome

Title	Awareness of Illness, as Assessed by the Scale to Assess Unawareness of Mental Disorder, Revised Version (SUMD-R)
Description	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	12 months after randomization

Outcome Measure Data

Analysis Population Description

All participants with SUMD-R data at 12-month point.

Arm/Group Title	CT - RLAI	HBT - RLAI	CT - Oral Ris	HBT - Oral Ris
Arm/Group Description	Participants will receive cognitive remediation training plus injectable, long-acting risperidone. Cognitive remediation: Cognitive remediation training includes computerized cognitive training plus learning skills group. Risperidone, administered via injection: Risperidone in injectable form every 2 weeks, starting with 25 mg and adjusted as needed Individual Placement and Support: Supported education/employment	Participants will receive health behavior training plus injectable, long-acting risperidone. Health behavior training: Health behavior training includes group skills training in nutrition, exercise, and relaxation. Risperidone, administered via injection: Risperidone in injectable form every 2 weeks, starting with 25 mg and adjusted as needed Individual Placement and Support: Supported education/employment	Participants will receive cognitive remediation training plus risperidone administered orally. Cognitive remediation: Cognitive remediation training includes computerized cognitive training plus learning skills group. Risperidone, administered orally: Oral risperidone at dosage judged optimal by treating psychiatrist Individual Placement and Support: Supported education/employment	Participants will receive health behavior training plus risperidone administered orally. Health behavior training: Health behavior training includes group skills training in nutrition, exercise, and relaxation. Risperidone, administered orally: Oral risperidone at dosage judged optimal by treating psychiatrist Individual Placement and Support: Supported education/employment
Measure Participants	4	7	6	4
Mean (Standard Deviation) [score on a scale]	1.25 (0.50)	3.29 (1.80)	2.00 (1.67)	3.75 (0.96)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CT - RLAI, HBT - RLAI, CT - Oral Ris, HBT - Oral Ris
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<.02
	Comments	2 X 2 ANOVA computed. P-value is for main effect of CT vs. HBT.
	Method	ANOVA
	Comments

10. Secondary Outcome

Title	Change in Motivation for Work/School
Description	The Work Motivation scale is a factor score from the Work Personality Profile. The Work Personality Profile is a set of ratings based on interviewing the participant. Scores at each occasion can range from 8 to 32, with higher indicating better motivation. Scores reported here are changes from baseline to 12 months, which could range from -24 to 24 with higher being better.
Time Frame	Baseline to 12 months

Outcome Measure Data

Analysis Population Description

Participants in school or jobs at baseline and 12 months, which allows change in Work Personality Profile ratings to be assessed.

Arm/Group Title	CT - RLAI	HBT - RLAI	CT - Oral Ris	HBT - Oral Ris
Arm/Group Description	Participants will receive cognitive remediation training plus injectable, long-acting risperidone. Cognitive remediation: Cognitive remediation training includes computerized cognitive training plus learning skills group. Risperidone, administered via injection: Risperidone in injectable form every 2 weeks, starting with 25 mg and adjusted as needed Individual Placement and Support: Supported education/employment	Participants will receive health behavior training plus injectable, long-acting risperidone. Health behavior training: Health behavior training includes group skills training in nutrition, exercise, and relaxation. Risperidone, administered via injection: Risperidone in injectable form every 2 weeks, starting with 25 mg and adjusted as needed Individual Placement and Support: Supported education/employment	Participants will receive cognitive remediation training plus risperidone administered orally. Cognitive remediation: Cognitive remediation training includes computerized cognitive training plus learning skills group. Risperidone, administered orally: Oral risperidone at dosage judged optimal by treating psychiatrist Individual Placement and Support: Supported education/employment	Participants will receive health behavior training plus risperidone administered orally. Health behavior training: Health behavior training includes group skills training in nutrition, exercise, and relaxation. Risperidone, administered orally: Oral risperidone at dosage judged optimal by treating psychiatrist Individual Placement and Support: Supported education/employment
Measure Participants	7	6	9	5
Mean (Standard Deviation) [score on a scale]	3.7 (2.3)	1.2 (4.6)	-2.4 (7.4)	-1.9 (6.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CT - RLAI, HBT - RLAI, CT - Oral Ris, HBT - Oral Ris
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	=.053
	Comments	2 X 2 ANOVA computed. P-value is for RLAI vs. Oral Ris main effect.
	Method	ANOVA
	Comments

11. Secondary Outcome

Title	Change in Coping Strategies
Description	Coping Response Inventory, which rates extent to which active coping strategies were used after a significant stressful life event. Range of possible scores is 1 to 4. Higher scores are better.
Time Frame	Baseline to 12 months

Outcome Measure Data

Analysis Population Description

Participants with Coping Response Inventories completed for a comparable stressful life event at baseline and 12 months. This was so rare in practice that this outcome was not feasible to evaluate.

Arm/Group Title	CT - RLAI	HBT - RLAI	CT - Oral Ris	HBT - Oral Ris
Arm/Group Description	Participants will receive cognitive remediation training plus injectable, long-acting risperidone. Cognitive remediation: Cognitive remediation training includes computerized cognitive training plus learning skills group. Risperidone, administered via injection: Risperidone in injectable form every 2 weeks, starting with 25 mg and adjusted as needed Individual Placement and Support: Supported education/employment	Participants will receive health behavior training plus injectable, long-acting risperidone. Health behavior training: Health behavior training includes group skills training in nutrition, exercise, and relaxation. Risperidone, administered via injection: Risperidone in injectable form every 2 weeks, starting with 25 mg and adjusted as needed Individual Placement and Support: Supported education/employment	Participants will receive cognitive remediation training plus risperidone administered orally. Cognitive remediation: Cognitive remediation training includes computerized cognitive training plus learning skills group. Risperidone, administered orally: Oral risperidone at dosage judged optimal by treating psychiatrist Individual Placement and Support: Supported education/employment	Participants will receive health behavior training plus risperidone administered orally. Health behavior training: Health behavior training includes group skills training in nutrition, exercise, and relaxation. Risperidone, administered orally: Oral risperidone at dosage judged optimal by treating psychiatrist Individual Placement and Support: Supported education/employment
Measure Participants	0	0	0	0

Adverse Events

Time Frame	12 months
Arm/Group Title	CT - RLAI		HBT - RLAI		CT - Oral Ris		HBT - Oral Ris
Arm/Group Description	Participants will receive cognitive remediation training plus injectable, long-acting risperidone. Cognitive remediation: Cognitive remediation training includes computerized cognitive training plus learning skills group. Risperidone, administered via injection: Risperidone in injectable form every 2 weeks, starting with 25 mg and adjusted as needed Individual Placement and Support: Supported education/employment		Participants will receive health behavior training plus injectable, long-acting risperidone. Health behavior training: Health behavior training includes group skills training in nutrition, exercise, and relaxation. Risperidone, administered via injection: Risperidone in injectable form every 2 weeks, starting with 25 mg and adjusted as needed Individual Placement and Support: Supported education/employment		Participants will receive cognitive remediation training plus risperidone administered orally. Cognitive remediation: Cognitive remediation training includes computerized cognitive training plus learning skills group. Risperidone, administered orally: Oral risperidone at dosage judged optimal by treating psychiatrist Individual Placement and Support: Supported education/employment		Participants will receive health behavior training plus risperidone administered orally. Health behavior training: Health behavior training includes group skills training in nutrition, exercise, and relaxation. Risperidone, administered orally: Oral risperidone at dosage judged optimal by treating psychiatrist Individual Placement and Support: Supported education/employment
All Cause Mortality
	CT - RLAI		HBT - RLAI		CT - Oral Ris		HBT - Oral Ris
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	CT - RLAI		HBT - RLAI		CT - Oral Ris		HBT - Oral Ris
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/12 (8.3%)		0/16 (0%)		3/16 (18.8%)		1/12 (8.3%)
Psychiatric disorders
psychiatric hospitalization	1/12 (8.3%)	1	0/16 (0%)	0	3/16 (18.8%)	3	1/12 (8.3%)	1
Other (Not Including Serious) Adverse Events
	CT - RLAI		HBT - RLAI		CT - Oral Ris		HBT - Oral Ris
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/12 (41.7%)		5/16 (31.3%)		11/16 (68.8%)		6/12 (50%)
Cardiac disorders
LDL or Triglyceride increase	1/12 (8.3%)	1	1/16 (6.3%)	1	4/16 (25%)	4	5/12 (41.7%)	5
Endocrine disorders
Prolactin related symptom	2/12 (16.7%)	2	1/16 (6.3%)	1	2/16 (12.5%)	2	2/12 (16.7%)	2
Metabolism and nutrition disorders
BMI increase normal/overweight to Obese	3/12 (25%)	3	2/16 (12.5%)	2	5/16 (31.3%)	5	0/12 (0%)	0
Nervous system disorders
TD early signs	1/12 (8.3%)	1	1/16 (6.3%)	1	1/16 (6.3%)	1	0/12 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.