Preventing Relapse in Schizophrenia: Oral Antipsychotics Compared To Injectables: Evaluating Efficacy

As is the case with many chronic illnesses, it can be challenging for people with
schizophrenia to take multiple pills every day on a long-term basis. At the same time,
missing or discontinuing the anti-psychotic medications that treat schizophrenia
substantially increases the risk of relapse and re-hospitalization. This study will determine
how effective long-acting injectable risperidone is compared to oral antipsychotic
medications to help patients who have schizophrenia. Patients who enroll in the study will be
randomly assigned to receive either long-acting injectable risperidone or to receive oral
"atypical" antipsychotic medication. The "atypical" antipsychotics that are included for
patients in the oral group are: aripiprazole, olanzapine, quetiapine, risperidone, and
ziprasidone. Patients in the "oral" group will receive whichever of the five "atypical"
antipsychotic medications they and their study doctor decide is best for them. Patients in
the "oral" group will be allowed to switch to others of the five medications during the study
if they and their doctor think that is best.

Patients in this study will be evaluated at the beginning of the study and then again every
two weeks for up to 30 months (2 1/2 years). Each two-week visit will take about 20 minutes.
At the visit, patients will receive medication and will be examined for side effects of the
medications, their vital signs (heart rate, blood pressure, weight, and waist measurement)
will be measured, and they will be asked a few questions about attendance at visits and
taking medication. The visit that occurs every three months will take about one hour, instead
of 20 minutes, and will include additional questions, an examination for muscle stiffness or
abnormal body movements, and an interview from a member of the research team conducted using
computer technology. In addition, blood and urine samples may be collected about seven times
throughout the 30 months of the study treatment. Patients who enroll in this study after the
halfway point of the study, may not receive a full 30 months of treatment, but it is planned
that all patients will have the opportunity to receive no less than 18 months of treatment.

Inclusion Criteria:

- All schizophrenia and schizoaffective patients whose clinicians are considering
long-term treatment with an "atypical" (second generation) antipsychotic medication

- Worsening of illness (schizophrenia) within 12 months of study entry as defined by:
hospitalization, increased level of clinical care, and/or present clinical Global
Impressions Severity rating of moderate or worse

Exclusion Criteria:

- First episode patients as defined by a patient who: has never received antipsychotic
medication and has never been hospitalized for psychiatric illness; or, is receiving
antipsychotic medication for the first time associated with a first diagnosis of
schizophrenia.

- Pregnant or breastfeeding

- Patients with unstable medical conditions

- Patients with previous history of failure to respond to an adequate trial of clozapine

- Patients with a known allergy to risperidone or a previous history of failure to
respond to an adequate trial of risperidone. However, patients with known allergies or
failure to respond to any of the other medications (aripiprazole, olanzapine,
quetiapine or ziprasidone) will not receive that medication if they are randomized to
the oral medication arm, but are not excluded from the study