Oral Versus Injectable Risperidone for Treating First-Episode Schizophrenia

• ClinicalTrials.gov Identifier: NCT00330551
• Recruitment Status: Completed
• First Posted: May 29, 2006
• Results First Posted: March 23, 2020
• Last Update Posted: March 23, 2020
• Sponsor: University of California, Los Angeles
• Collaborators: National Institute of Mental Health (NIMH); Janssen Scientific Affairs, LLC
• Information provided by (Responsible Party): Keith Nuechterlein, Ph.D., University of California, Los Angeles

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Schizophrenia	Drug: Oral Risperidone; Drug: Risperidone in Long-Acting Injectable Form (Consta)	Phase 4

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 126 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Effects of Risperdal Consta Versus Oral Antipsychotic Medication on Clinical and Functional Outcome and Neurocognition in First-episode Schizophrenia
• Study Start Date: March 2006
• Actual Primary Completion Date: November 2012
• Actual Study Completion Date: November 2012

Arms and Interventions

Arm	Intervention/treatment
Experimental: Long-acting injectible risperidone; 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); 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.; Other Name: Risperdal Consta
Active Comparator: Oral risperidone; 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; Patients will be treated with oral risperidone daily, with the dosage determined by treating psychiatrist.; Other Name: Risperdal

Outcome Measures

Primary Outcome Measures :

1. Medication Adherence [ Time Frame: Averaged over study participation (up to 12 months) ]
   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
2. Exacerbation or Relapse of Psychotic Symptoms [ Time Frame: 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.).
3. Return to Work or School (SAS Work Section) [ Time Frame: 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.
4. Maintenance of Work/School Attendance (SAS) [ Time Frame: 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.
5. Global Functioning Scale: Role [ Time Frame: Measured from Baseline to Month 12 ]
   Change on a 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.

Secondary Outcome Measures :

1. MATRICS Consensus Cognitive Battery (MCCB) Overall Composite T Score [ Time Frame: 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.
2. Emotional Reactivity on Psychophysiological Measures [ Time Frame: 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.
3. Retention in Treatment [ Time Frame: 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.
4. Awareness of Illness, as Assessed by the Scale to Assess Unawareness of Mental Disorder-Revised (SUMD-R) [ Time Frame: 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.

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, California

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

More Information

Additional Information:

Click here for the UCLA Center for Neurocognition and Emotion in Schizophrenia website 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

Bartzokis G, Lu PH, Amar CP, Raven EP, Detore NR, Altshuler LL, Mintz J, Ventura J, Casaus LR, Luo JS, Subotnik KL, Nuechterlein KH. Long acting injection versus oral risperidone in first-episode schizophrenia: differential impact on white matter myelination trajectory. Schizophr Res. 2011 Oct;132(1):35-41. doi: 10.1016/j.schres.2011.06.029. Epub 2011 Jul 20.

• Responsible Party: Keith Nuechterlein, Ph.D., Professor, University of California, Los Angeles, University of California, Los Angeles
• ClinicalTrials.gov Identifier: NCT00330551
• Other Study ID Numbers: P50MH066286 ( U.S. NIH Grant/Contract ); P50MH066286 ( U.S. NIH Grant/Contract ); DATR A2-AISZ ( Registry Identifier: World Health Organization ICTRP ); Janssen RIS-NAP-4009 ( Other Grant/Funding Number: Janssen Scientific Affairs )
• First Posted: May 29, 2006
• Results First Posted: March 23, 2020
• Last Update Posted: March 23, 2020
• Last Verified: March 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Keith Nuechterlein, Ph.D., University of California, Los Angeles:

Schizoaffective Disorder, Depressed Type; Schizophreniform Disorder; First-episode Schizophrenia; Injectable Risperidone

Additional relevant MeSH terms:

Schizophrenia; Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Risperidone; Serotonin Antagonists; Serotonin Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs; Antipsychotic Agents; Tranquilizing Agents; Central Nervous System Depressants; Psychotropic Drugs; Dopamine Antagonists; Dopamine Agents