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

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

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