Oral Risperidone Versus Injectable Paliperidone Palmitate for Treating First-Episode Schizophrenia

Clinical and Cognitive Effects of Paliperidone Palmitate vs. Oral Risperidone in First-Episode Schizophrenia

This study will determine the efficacy of oral risperidone (Risperdal) versus long-acting injectable paliperidone palmitate (Invega Sustenna) in treating people with first-episode schizophrenia.

Study Overview

• Status: Completed
• Conditions: Schizophrenia (Recent-onset)
• Intervention / Treatment: Drug: paliperidone palmitate; Drug: risperidone

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 extrapyramidal side effects than older "typical" antipsychotics. Oral risperidone is an atypical antipsychotic medication that is very commonly used to control the symptoms of schizophrenia. Adherence to prescribed oral medication continues to be a major clinical issue. This study will determine the effectiveness of oral risperidone versus a long-acting injectible alternative, paliperidone palmitate, in treating people with first-episode schizophrenia. Impact on clinical symptoms and cognitive functioning will be examined.

Participants in this open label study will be randomly assigned to receive either orally administered risperidone or long-acting paliperidone palmitate 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 paliperidone palmitate once every 4 weeks. Dosages will be adjusted as necessary to achieve the optimal dosage. Following 2 to 3 months to achieve outpatient oral 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 psychiatrist monitoring of medication response and side effects; group therapy meetings focused on everyday living skills; family education about schizophrenia; and individual meetings with a case manager for counseling and evaluations of schizophrenia symptoms, work recovery, and social functioning.

• Study Type: Interventional
• Enrollment (Actual): 146
• Phase: Phase 4

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 43 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. A first episode of a psychotic illness is occurring or did occur within the last 2 years;
2. A diagnosis by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition(DSM-IV)of schizophrenia, schizoaffective disorder, depressed type, or schizophreniform disorder; and
3. Between 18 and 45 years of age.

Exclusion Criteria:

1. Neurological disorder (e.g., epilepsy) or significant head injury;
2. Significant alcohol or substance use disorder within the six months prior to the first episode and evidence that substance abuse triggered the psychotic episode or makes the schizophrenia diagnosis ambiguous;
3. Mental retardation, i.e. premorbid intelligence quotient (IQ) less than 70;
4. Insufficient acculturation and fluency in the English language to avoid invalidating research measures of thought, language, and speech disorder or of verbal abilities;
5. Residence likely to be outside of commuting distance of the University of California, Los Angeles (UCLA) Aftercare Research Program; or
6. Patient has shown an inadequate response to an adequate previous trial of oral or long-acting injectable risperidone, paliperidone, or paliperidone palmitate.

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: paliperidone palmitate (Invega Sustenna); Participants will be provided paliperidone palmitate (Invega Sustenna), administered in injectible long-acting form, plus group skills training and case management	Drug: paliperidone palmitate; long-acting injectable; Other Names: Invega Sustenna
Active Comparator: oral risperidone; Participants will be provided oral risperidone, plus group skills training and case management	Drug: risperidone; oral; Other Names: Risperdal

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exacerbation or relapse of psychotic symptoms	Exacerbation or relapse of psychotic symptoms, as measured by the Brief Psychiatric Rating Scale (BPRS)	Evaluated for 12 months
Cognitive functioning based on Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery	The Overall Composite Score from the MATRICS Consensus Cognitive Battery will be the primary cognitive outcome measure.	Baseline to 12 months
Role Functioning	Role Functioning Scale (RFS; Goodman et al. 1993).	Baseline to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cognitive performance on test battery (MCCB)	The cognitive domain scores from the MATRICS Consensus Cognitive Battery (MCCB) will be used as secondary measures to identify the domains in which treatment effects occurred.	Measured at baseline and 12 months
Insight (Awareness of Mental Disorder)	Awareness of illness, as assessed by the Scale to Assess Unawareness of Mental Disorder, Revised Version (SUMD-R)	Measured at baseline and 12 months
Retention in treatment	Retention in treatment	Measured at 12 months
Social functioning	Social Functioning Scale (Goodman et al., 1993)	Baseline to 12 months
Emotional reactivity on psychophysiological measures	Emotional reactivity on psychophysiological measures	Measured at baseline and 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, Ph.D., University of California, Los Angeles (UCLA) Semel Institute for Neuroscience and Human Behavior

Publications and helpful links

Helpful Links

• UCLA Center for Neurocognition and Emotion in Schizophrenia

Study record dates

Study Major Dates

• Study Start: October 1, 2011
• Primary Completion (Actual): December 1, 2021
• Study Completion (Actual): December 31, 2021

Study Registration Dates

• First Submitted: October 11, 2011
• First Submitted That Met QC Criteria: October 11, 2011
• First Posted (Estimate): October 14, 2011

Study Record Updates

• Last Update Posted (Actual): April 11, 2022
• Last Update Submitted That Met QC Criteria: April 7, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: Schizophreniform Disorder; functional outcome; First-episode Schizophrenia; Schizoaffective Disorder, Depressed Type (recent-onset); oral risperidone; long-acting injectable paliperidone palmitate
• 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 5-HT2 Receptor Antagonists; Serotonin Antagonists; Dopamine D2 Receptor Antagonists; Dopamine Antagonists; Paliperidone Palmitate; Risperidone
• Other Study ID Numbers: P50 MH066286 Phase II; P50MH066286 (U.S. NIH Grant/Contract); R092670SCH4005 (Other Identifier: Ortho-McNeil Janssen Scientific Affairs, LLC.)