Comparison of Aripiprazole and Risperidone for the Treatment of People With First-Episode Psychosis

Official Title: “Preventing Morbidity in First Episode Schizophrenia, Part II”

This 52 week long study evaluates the effectiveness of aripiprazole versus risperidone in treating people with first-episode schizophrenia. Patients who do not improve with these medications receive clozapine as their third medication trial.

Schizophrenia is a severely disabling brain disorder. People with schizophrenia often experience hallucinations, delusions, thought disorders, and movement disorders. Medications are available to alleviate the symptoms of schizophrenia, but many cause undesirable side effects. For example, two early second generation antipsychotics, olanzapine and risperidone, have been shown to be effective in treating schizophrenia symptoms, but cause rapid, substantial weight gain. There is a lower risk of such side effects with newer second generation antipsychotics, such as aripiprazole. Little is known, however, about the effectiveness of these newer medications in treating people with first-episode schizophrenia. This study will evaluate the effectiveness of aripiprazole versus risperidone for the treatment of first-episode schizophrenia.

Participants in this double-blind study will be randomly assigned to receive either aripiprazole or risperidone for 12 weeks. Subjects who do not meet response criteria will be continued on their initial blinded antipsychotic for an additional 4 weeks for a total length of 16 weeks of treatment. Subjects who meet response criteria by week 16 will continue on their successful blinded medication for their remaining time in study. Patients who do not respond will be treated with the other medication (aripiprazole or risperidone) that they did not receive during the first 16 weeks of the study. The second antipsychotic trial will last 16 weeks. Patients who respond during the switch phase will be continued on their successful medication during their remaining time in the study. Patients who do not respond to the second medication trial will then be treated with open-label clozapine for 20 weeks. Safety monitoring for clozapine-treated subjects will follow the established procedures for multi-episode patients (e.g . weekly CBC monitoring). The total length of patient participation is 52 weeks.

During the longitudinal follow-up phase, subjects may be prescribed open-label sodium valproate for manic symptoms and open-label sertraline for symptoms of depression or anxiety empirically responsive to SSRI treatment. Additionally, all participants will take part in a Healthy Lifestyles program aimed at preventing weight gain. The Healthy Lifestyles program will provide psycho-education, supportive psychotherapy, and medication adherence counseling. At each visit, treatment and metabolic outcomes will be assessed. Participants will meet with both a psychiatrist, who will evaluate progress and medication dosage, and a social worker, who will administer the Healthy Lifestyles Program. Upon completion of the study, participants will receive follow-up care from clinical staff members who were not part of the research team.

For information on a related study, please follow this link:

http://clinicaltrials.gov/show/NCT00000374

Intervention(s) in this Clinical Trial

• Drug: Aripiprazole
  • The dosage for aripiprazole will be 5 mg to 30 mg per day in capsule form. The dose of aripiprazole will be based on the participant's clinical improvement and side effects, which will be evaluated weekly for the first 4 weeks and then every 2 weeks until the 12th week and then monthly until study end.
• Drug: Risperidone
  • The dosage for risperidone will be 1 mg to 6 mg per day in capsule form. The dose of risperidone will be based on the participant's clinical improvement and side effects, which will be evaluated weekly for the first 4 weeks, then every 2 weeks until the 12th week, and then monthly until the study end.
• Drug: Clozapine
  • The dosage for clozapine will be 12.5 mg per day on day 1; 25 mg per day on days 2 and 3; 50 mg per day on days 4 and 5; 75 mg per day on days 6 and 7; 100 mg per day on days 8 and 9, and increments of 50 mg per day every 2 days until treatment response, dose-related side effects, or a maximum dose of 600 mg/day. Safety monitoring for clozapine-treated subjects will follow the established procedures for multi-episode patients (e.g. weekly CBC monitoring). Subjects who participate in the clozapine trial will be seen for research assessments weekly for 4 weeks, then every two weeks until study end

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • Participants will take aripiprazole
• Experimental: 2
  • Participants will take risperidone
• Experimental: 3
  • Participants will take Clozapine

Primary Measures

• Treatment response
  • Time Frame: Measured at Weeks 12, 16, 32, 52
    Safety Issue?: No
• Patterns of change in weight and body mass index (BMI)
  • Time Frame: Measured at Weeks 12, 16, 32, 52
    Safety Issue?: No
• Incidence rates of metabolic syndrome and new-onset diabetes
  • Time Frame: Measured at Weeks 12, 16, 32, 52
    Safety Issue?: No

Secondary Measures

• Negative symptoms
  • Time Frame: Measured at Weeks 12, 16, 32, 52
    Safety Issue?: No
• Cognition
  • Time Frame: Measured at Weeks 12, 52
    Safety Issue?: No
• Quality of life
  • Time Frame: Measured at Week 12
    Safety Issue?: No
• Adverse events other than metabolic
  • Time Frame: Measured at Weeks 12, 16, 32, 52
    Safety Issue?: No
• Substance use
  • Time Frame: Measured at Weeks 12, 16, 32, 52
    Safety Issue?: No

Inclusion Criteria:

• Current DSM-IV diagnosis of schizophrenia, schizophreniform disorder, schizoaffective disorder, or similar psychotic disorder not otherwise specified, as assessed using the Structured Clinical Interview for Axis I DSM-IV Disorders (SCID-I/P)
• History of previous antipsychotic medication treatment for a duration of 2 weeks or less
• Current positive symptoms rated 4 (moderate) or more on one or more of the following
• Brief Psychiatric Rating Scale (BPRS-A) items: conceptual disorganization;
• grandiosity; hallucinatory behavior; or unusual thought content
• Agrees to use an effective form of contraception

Exclusion Criteria:

• Any serious neurological or endocrine disorder, or any medical condition or treatment known to affect the brain
• Any current medical condition that requires treatment with a medication with psychotropic effects
• At significant risk for suicidal or homicidal behavior
• Cognitive or language limitations, or any other factor that would interfere with a participant's ability to provide informed consent or safely participate in study procedures
• Diagnosis of diabetes, defined as a fasting plasma glucose level of at least 126 mg/dL, or metabolic syndrome, defined as three or more of the following: high blood pressure (greater than 135/85 mmHg); truncal obesity (having a waist circumference greater than 40 inches for men and greater than 35 inches for women); elevated fasting glucose (greater than 110 mg/dL); low HDL-cholesterol (less than 40 mg/dL for men and less than 50 mg/dL for women); or elevated triglycerides (defined as greater than 150 mg/dL)
• Requires treatment with an antidepressant or mood stabilizing medication
• Meets DSM-IV criteria for a current substance-induced psychotic disorder, a psychotic disorder due to a general medical condition, delusional disorder, brief psychotic disorder, shared psychotic disorder, or a mood disorder (major depression or bipolar) with psychotic features
• Any medical conditions that would make treatment with risperidone or aripiprazole medically inadvisable

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 15 Years

Maximum Age for this Clinical Trial: 40 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: North Shore Long Island Jewish Health System Other

Overall Clinical Trial Officials and Contacts

Delbert Robinson, MD Principal Investigator The North Shore-Long Island Jewish Health System  

Overall Contact: Joanne McCormack, LMSW 718-470-8446 JmcCorma@lij.edu

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00320671

Study ID Number: R01 MH060004-02

ClinicalTrials.gov Identifier: NCT00320671

Health Authority: United States: Federal Government