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

• ClinicalTrials.gov Identifier: NCT00320671
• Recruitment Status: Completed
• First Posted: May 3, 2006
• Results First Posted: August 31, 2016
• Last Update Posted: September 8, 2016
• Sponsor: Northwell Health
• Collaborator: National Institute of Mental Health (NIMH)
• Information provided by (Responsible Party): Delbert Robinson, Northwell Health

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Schizophrenia	Drug: Aripiprazole; Drug: Risperidone	Phase 4

Detailed Description:

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 complete blood count (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 (Selective serotonin reuptake inhibitor)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

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 198 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Preventing Morbidity in First Episode Schizophrenia, Part II
• Study Start Date: December 2005
• Actual Primary Completion Date: December 2014
• Actual Study Completion Date: December 2015

Arms and Interventions

Arm	Intervention/treatment
Experimental: Participants will take aripiprazole; Participants will take aripiprazole	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.; Other Name: Abilify
Experimental: Participants will take risperidone; Participants will take risperidone	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.; Other Name: Risperdal

Outcome Measures

Primary Outcome Measures :

1. Percentage of Participants That Responded to Treatment [ Time Frame: this outcome was assessed throughout the study. ]
   Brief Psychiatric Rating Scale-Anchored (BPRS-A) 4 items on this scale were examined to determine subjects responder status: Items 4. Conceptual Disorganization 8. Grandiosity 12. Hallucinations and 15. Unusual Thought Content. Scores range from-7 (not assessed) to 7 (very severe) Subjects with scores of 3 or less on all 4 items for 2 consecutive visits are deemed responders, subjects with 4 or greater and any of the aforementioned items for 2 consecutive study visits are non responders. Additionally, the subjects response on the Clinical Global Impressions Scale. A Clinical Global Improvement CGI) rating of much or very much improved on 2 consecutive ratings were deemed a responder. Percentages and confidence intervals were used to report response outcome. Response status was assessed throughout the duration of the study; a participant can be deemed a responder any time between weeks 1-week 12. The possible range for this outcome is a score of 4 to 28

Eligibility Criteria

• Ages Eligible for Study: 15 Years to 40 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Current Diagnostic and Statistical Manual of Mental Disorders (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

Contacts and Locations

Locations

United States, New York

The Zucker Hillside Hospital

Glen Oaks, New York, United States, 11004

Sponsors and Collaborators

Northwell Health

National Institute of Mental Health (NIMH)

Investigators

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

More Information

Additional Information:

Aripiprazole and Risperidone for the Acute Treatment of First-Episode Schizophrenia 

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

Robinson DG, Gallego JA, John M, Petrides G, Hassoun Y, Zhang JP, Lopez L, Braga RJ, Sevy SM, Addington J, Kellner CH, Tohen M, Naraine M, Bennett N, Greenberg J, Lencz T, Correll CU, Kane JM, Malhotra AK. A Randomized Comparison of Aripiprazole and Risperidone for the Acute Treatment of First-Episode Schizophrenia and Related Disorders: 3-Month Outcomes. Schizophr Bull. 2015 Nov;41(6):1227-36. doi: 10.1093/schbul/sbv125. Epub 2015 Sep 3.

• Responsible Party: Delbert Robinson, Professor of Psychiatry and Molecular Medicine, Northwell Health
• ClinicalTrials.gov Identifier: NCT00320671
• Other Study ID Numbers: R01MH060004-02 ( U.S. NIH Grant/Contract ); R01MH060004-02 ( U.S. NIH Grant/Contract )
• First Posted: May 3, 2006
• Results First Posted: August 31, 2016
• Last Update Posted: September 8, 2016
• Last Verified: September 2016

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes

Keywords provided by Delbert Robinson, Northwell Health:

First-episode; Schizoaffective Disorder; Schizophreniform Disorder; Psychotic Disorder Not Otherwise Specified NOS; Aripiprazole; Clozapine; Risperidone

Additional relevant MeSH terms:

Schizophrenia; Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Risperidone; Aripiprazole; 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; Antidepressive Agents; Dopamine Agonists; Serotonin 5-HT1 Receptor Agonists; Serotonin Receptor Agonists; Serotonin 5-HT2 Receptor Antagonists; Dopamine D2 Receptor Antagonists