Risperidone Treatment in Schizophrenia Patients Who Are Currently Taking Clozapine

Clozapine Treatment of Schizophrenic Patients

This study will determine whether adding the drug risperidone (Risperdal®) is more effective than placebo in treating schizophrenic patients who are taking the drug clozapine.

Study Overview

• Status: Completed
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: Risperdal; Drug: Placebo

Detailed Description

Clozapine is the only antipsychotic drug that has been approved for treatment resistant patients with schizophrenia. However, up to 50% of patients treated with clozapine fail to respond and continue to exhibit clinically significant residual positive and negative symptoms and cognitive impairments. An emerging trend in treatment is the addition of a second antipsychotic drug. This study will determine if risperidone when given as adjunctive treatment is more effective than placebo in treating schizophrenic patients failing clozapine therapy.

Participants are randomly assigned to add either adjunctive risperidone or placebo to their current clozapine treatment in a single, daily dose for 16 weeks. Positive and negative symptoms, cognitive impairments, side effects of the treatment, anxiety, depression, hostility symptoms, and quality of life are assessed. Neurological tests, self administered questionnaires, and interviews are used to assess patients.

• Study Type: Interventional
• Enrollment (Actual): 65
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Catonsville, Maryland, United States, 21228
      • Maryland Psychiatric Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• DSM-IV criteria for schizophrenia or schizoaffective disorder
• Current clozapine treatment
• Moderate illness severity and inadequate positive symptom response to clozapine treatment
• 6 month period of clozapine treatment with documented clozapine blood level greater than or equal to 350 ng/ml or clozapine and norclozapine blood level greater than or equal to 450 ng/ml

Exclusion Criteria:

• Organic brain disorder
• Mental retardation
• Medical condition whose pathology or treatment could alter the presentation or treatment of schizophrenia or significantly increase the risk associated with the proposed treatment protocol
• Pregnancy
• DSM-IV criteria for current alcohol or substance dependence within the last 6 months or DSM-IV criteria for alcohol or substance abuse within the last month
• Previously received adjunctive risperidone (at doses greater than or equal to 8 mg/day) with their clozapine treatment for greater than or equal to 6 weeks

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Active; Participants assigned to risperidone	Drug: Risperdal; Risperdal 4 mg per day for 16 weeks; Other Names: Risperidone
PLACEBO_COMPARATOR: Placebo; Participants assigned to placebo	Drug: Placebo; Placebo capsule daily for 16 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Positive Symptom Item Scores by Week and Treatment Group	The Brief Psychiatric Rating Scale (BPRS) positive symptom items are: conceptual disorganization, hallucinatory behavior, unusual thought content, and suspiciousness. The total score is calculated by adding the scores for each item. Each scale ranges from "1=Not Present" to "7=Very Severe". The minimum score is 4 and the maximum score is 28. A higher score indicates a more severe positive symptom rating. A mixed model for unbalanced repeated measures analysis of covariance (ANCOVA), in which follow-up symptom score = baseline symptom score + treatment + week + treatment x week, and week is treated as a categorical, rather than a continuous measure. The treatment term estimates the average across weeks of the week-specific group differences, and is used as the main test for treatment effects on symptom change.	Baseline and every two weeks for 16 weeks.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neuropsychological Testing - Overall Composite Z-score	The neuropsychological testing measured attention, executive function/problem solving, motor speed, processing speed/response generation, and verbal, visual, and working memory. The individual test raw scores were converted to z-scores and an overall composite z-score was computed from the average of the individual test z-scores. Z-scores range from -3 standard deviations up to +3 standard deviations. Higher scores indicate better test performance.	Baseline and Week 16
Negative Symptom Total Score by Week and Treatment Group	The Scale for the Assessment of Negative Symptoms (SANS) total score, minus the global items, inappropriate affect, poverty of content of speech, and attention items, used to measure negative symptoms. SANS total score range = 0-85. Higher scores indicate more severe negative symptoms. A mixed model for unbalanced repeated measures analysis of covariance (ANCOVA), in which follow-up symptom score = baseline symptom score + treatment + week + treatment x week, and week is treated as a categorical, rather than a continuous measure. The treatment term estimates the average across weeks of the week-specific group differences, and is used as the main test for treatment effects on symptom change.	Baseline and every two weeks for 16 weeks.

Collaborators and Investigators

• Sponsor: University of Maryland, Baltimore
• Collaborators: National Institute of Mental Health (NIMH); Ortho-McNeil Janssen Scientific Affairs, LLC

Publications and helpful links

General Publications

• Weiner E, Conley RR, Ball MP, Feldman S, Gold JM, Kelly DL, Wonodi I, McMahon RP, Buchanan RW. Adjunctive risperidone for partially responsive people with schizophrenia treated with clozapine. Neuropsychopharmacology. 2010 Oct;35(11):2274-83. doi: 10.1038/npp.2010.101. Epub 2010 Jul 21.

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 1, 2001
• Primary Completion (ACTUAL): December 1, 2007
• Study Completion (ACTUAL): December 1, 2007

Study Registration Dates

• First Submitted: March 14, 2003
• First Submitted That Met QC Criteria: March 14, 2003
• First Posted (ESTIMATE): March 17, 2003

Study Record Updates

• Last Update Posted (ACTUAL): October 1, 2019
• Last Update Submitted That Met QC Criteria: September 23, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• 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: R01 MH045074 H-21270; DSIR 83-ATAP (NIMH/DSIR); R01MH045074 (NIH)