Effectiveness of Tropisetron Plus Risperidone for Improving Cognitive and Perceptual Disturbances in Schizophrenia

Schizophrenia is a chronic and disabling brain disorder. People with schizophrenia may
experience hallucinations, delusions, disordered thinking, movement disorders, social
withdrawal, and cognitive deficits. In considering the high rate of cigarette smoking among
people with schizophrenia, it is also likely that they smoke. People with schizophrenia who
smoke tend to experience improved cognition, and tobacco withdrawal has been associated with
deterioration of cognition. This suggests that nicotine may improve cognitive deficits or
medication side effects in people with schizophrenia.

Auditory sensory gating, a neural mechanism thought to reflect sensory information
processing and affect cognition, is diminished in people with schizophrenia. Auditory
sensory gating has been associated with the 7 nicotinic acetylcholine receptor, a brain
receptor that is important for cognition and can be activated by nicotine. Activation of
this receptor using an agonist medication, such as tropisetron, may produce the same
positive effect that nicotine has on cognition. This study will determine the effectiveness
of using tropisetron as supplemental therapy to the atypical neuroleptic risperidone in
people with schizophrenia.

Participants in this 12-week double blind study will be randomly assigned to receive either
tropisetron or placebo. All participants will also follow a 6-mg risperidone regimen. Study
visits will occur every 2 weeks throughout the study and will include assessments of
cognitive functioning and treatment safety and effectiveness. Participants will also report
the number of cigarettes they smoke per day and provide blood and urine samples to monitor
medication levels and adherence.

Inclusion Criteria:

- Currently resides in Beijing, China

- Diagnosis of schizophrenia or schizophreniform disorder

- Duration of symptoms is no longer than 60 months

- No history of treatment with antipsychotic medication or, if previously treated, a
total lifetime usage of less than 14 days

- Current psychotic symptoms are of moderate severity or greater as measured by one of
the five psychotic items in the Brief Psychiatric Rating Scale (BPRS)

Exclusion Criteria:

- DSM-IV Axis I diagnosis other than schizophrenia or schizophreniform psychosis

- Documented disease of the central nervous system that might interfere with the trial
assessments (e.g., stroke, tumor, Parkinson's disease, Huntington's disease, seizure
disorder, history of brain trauma resulting in significant impairment, chronic
infection)

- Acute, unstable, and/or significant and untreated medical illness (e.g., infection,
unstable diabetes, uncontrolled hypertension)

- A clinically significant echocardiogram (ECG) abnormality in the opinion of the
investigator

- Pregnant or breastfeeding

- Use of prohibited concomitant therapy

- History of severe allergy or hypersensitivity

- Dependence on alcohol or illegal drugs

- Use of any of the following medications during the trial: antipsychotic medications
other than risperidone; psychostimulants; or antidepressants