Oral Risperidone Versus Injectable Paliperidone Palmitate for Treating First-Episode Schizophrenia

Schizophrenia is a severely disabling brain disorder. People with schizophrenia often
experience hallucinations, delusions, thought disorders, and movement disorders. Proper
treatment of first-episode schizophrenia may increase the chances of controlling disease
progression on a long-term basis. People experiencing their first episode of schizophrenia
are more responsive to treatment than those with chronic schizophrenia, but are also more
susceptible to adverse treatment side effects. Atypical antipsychotic medications have been
shown to produce fewer extrapyramidal side effects than older "typical" antipsychotics. Oral
risperidone is an atypical antipsychotic medication that is very commonly used to control the
symptoms of schizophrenia. Adherence to prescribed oral medication continues to be a major
clinical issue. This study will determine the effectiveness of oral risperidone versus a
long-acting injectible alternative, paliperidone palmitate, in treating people with
first-episode schizophrenia. Impact on clinical symptoms and cognitive functioning will be
examined.

Participants in this open label study will be randomly assigned to receive either orally
administered risperidone or long-acting paliperidone palmitate administered via injection.
Participants assigned to oral risperidone will receive medication in doses that are
determined to be optimal by the study psychiatrist. Participants assigned to long-acting
risperidone will receive an injection of paliperidone palmitate once every 4 weeks. Dosages
will be adjusted as necessary to achieve the optimal dosage. Following 2 to 3 months to
achieve outpatient oral risperidone dosage stabilization, the randomized medication
conditions will begin and participants will be monitored for 1 year. Study visits will occur
once weekly throughout the study. They will include psychiatrist monitoring of medication
response and side effects; group therapy meetings focused on everyday living skills; family
education about schizophrenia; and individual meetings with a case manager for counseling and
evaluations of schizophrenia symptoms, work recovery, and social functioning.

Inclusion Criteria:

1. A first episode of a psychotic illness is occurring or did occur within the last 2
years;

2. A diagnosis by Diagnostic and Statistical Manual of Mental Disorders, Fourth
Edition(DSM-IV)of schizophrenia, schizoaffective disorder, depressed type, or
schizophreniform disorder; and

3. Between 18 and 45 years of age.

Exclusion Criteria:

1. Neurological disorder (e.g., epilepsy) or significant head injury;

2. Significant alcohol or substance use disorder within the six months prior to the first
episode and evidence that substance abuse triggered the psychotic episode or makes the
schizophrenia diagnosis ambiguous;

3. Mental retardation, i.e. premorbid intelligence quotient (IQ) less than 70;

4. Insufficient acculturation and fluency in the English language to avoid invalidating
research measures of thought, language, and speech disorder or of verbal abilities;

5. Residence likely to be outside of commuting distance of the University of California,
Los Angeles (UCLA) Aftercare Research Program; or

6. Patient has shown an inadequate response to an adequate previous trial of oral or
long-acting injectable risperidone, paliperidone, or paliperidone palmitate.