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

Developmental Processes in Schizophrenic Disorders: Cognitive Remediation, Medication Adherence, and Work Outcome in Recent-Onset 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.

Study Overview

• Status: Completed
• Conditions: Schizophrenia
• Intervention / Treatment: Behavioral: Cognitive remediation training (CT); Drug: Risperidone, administered via injection (RLAI); Behavioral: Healthy behavior training (HBT); Drug: Risperidone, administered orally (Oral Ris)

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 Type: Interventional
• Enrollment (Actual): 92
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • Semel Institute for Neuroscience and Human Behavior at UCLA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / 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.	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; Behavioral: Healthy behavior training (HBT); Healthy behavior training includes group skills training in nutrition, exercise, and relaxation.
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB)	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.	Measured at baseline and 12 months
Work/School Functioning (Global Functioning Scale: Role)	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.	Baseline to 6 months
Average Medication Non-adherence	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.	Averaged over study participation (up to 12 months)
Work/School Functioning (Global Functioning Scale: Role)	Changes in role functioning from baseline to 12 months. Ratings on a 10-point scale with 10 being best.	Baseline to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Work Behavior Inventory (WBI) Quality of Work/School Performance	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.	Baseline to 1 year
Maintenance of Work/School Attendance	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.	12 months
Exacerbation or Relapse of Psychotic Symptoms	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.	Occurence after randomization and until end of study participation (up to 12 mos.)
Retention in Treatment	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.	12 months
Awareness of Illness, as Assessed by the Scale to Assess Unawareness of Mental Disorder, Revised Version (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.	12 months after randomization
Change in Motivation for Work/School	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.	Baseline to 12 months
Change in Coping Strategies	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.	Baseline to 12 months

Collaborators and Investigators

• Sponsor: University of California, Los Angeles
• Collaborators: 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

Publications and helpful links

General Publications

• Subotnik KL, Casaus LR, Ventura J, Luo JS, Hellemann GS, Gretchen-Doorly D, Marder S, Nuechterlein KH. Long-Acting Injectable Risperidone for Relapse Prevention and Control of Breakthrough Symptoms After a Recent First Episode of Schizophrenia. A Randomized Clinical Trial. JAMA Psychiatry. 2015 Aug;72(8):822-9. doi: 10.1001/jamapsychiatry.2015.0270.
• Nuechterlein KH, Ventura J, Subotnik KL, Gretchen-Doorly D, Turner LR, Casaus LR, Luo J, Boucher ML, Hayata JN, Bell MD, Medalia A. A randomized controlled trial of cognitive remediation and long-acting injectable risperidone after a first episode of schizophrenia: improving cognition and work/school functioning. Psychol Med. 2022 Jun;52(8):1517-1526. doi: 10.1017/S0033291720003335. Epub 2020 Sep 28.

Study record dates

Study Major Dates

• Study Start: March 1, 2006
• Primary Completion (Actual): January 1, 2013
• Study Completion (Actual): January 1, 2013

Study Registration Dates

• First Submitted: June 1, 2006
• First Submitted That Met QC Criteria: June 1, 2006
• First Posted (Estimate): June 2, 2006

Study Record Updates

• Last Update Posted (Actual): March 26, 2020
• Last Update Submitted That Met QC Criteria: March 4, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: Cognitive Remediation; Schizophreniform Disorder; Supported Employment; Schizoaffective Disorder, Depressed Type; First-Episode Schizophrenia; Health Behavior Training; Antipsychotic Medication
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Dopamine Agents; Serotonin Antagonists; Dopamine Antagonists; Risperidone
• Other Study ID Numbers: R01MH037705-06 (U.S. NIH Grant/Contract); R01MH037705 (U.S. NIH Grant/Contract); DAHBR AD-P (WHO ICTRP)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO