Clinical trial NCT00320671: Comparison of Aripiprazole and Risperidone for the Treatment of People With First-Episode Psychosis
Official title: Preventing Morbidity in First Episode Schizophrenia, Part II
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Schizophrenia
Keywords: First-episode
Schizoaffective Disorder
Schizophreniform Disorder
Psychotic Disorder Not Otherwise Specified NOS
Aripiprazole
Clozapine
Risperidone
Lead sponsor: Northwell Health
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
First posted: 2006-05-03
Enrollment: 198
Sex: ALL
Minimum age (years): 15
Maximum age (years): 40
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Eligibility 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

Primary outcomes:
measure: Percentage of Participants That Responded to Treatment
timeFrame: this outcome was assessed throughout the study.
Secondary outcomes:
Other outcomes:
Locations:
city: Glen Oaks
country: United States
facility: The Zucker Hillside Hospital
state: New York
Study officials:
affiliation: The North Shore-Long Island Jewish Health System
name: Delbert Robinson, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.