Schizophrenia is a devastating brain disorder. Most people with schizophrenia have difficulty filtering out unimportant auditory information. They have an inability to appropriately inhibit, or gate, sensory information that enters the ear. Standard treatments do not address this problem. When the drug ondansetron is taken in addition to typical antipsychotic drugs, P50 auditory gating improves. However, ondansetron has not been used with some of the newer, atypical antipsychotic drugs. This study will evaluate the effect of combining ondansetron with newer, atypical antipsychotic drugs on P50 auditory gating.

Participants in this double-blind study will be randomly assigned to receive either ondansetron or placebo for 3 months. Upon completion of the first 3 months, participants will be crossed over to receive the other treatment for an additional 3 months. All participants will also take an atypical antipsychotic drug, including olanzapine, quietapine, or aripiprazole. Auditory gating will be assessed using computerized cognitive testing and fMRI at baseline and Months 3 and 6. Vital signs and evoked potentials will be assessed at Weeks 1, 3, and 6. Clinical symptoms and cognitive abilities will also be evaluated to determine the effectiveness of ondansetron.

Inclusion Criteria:

• Meets DSM-IV criteria for schizophrenia
• Stable, chronic schizophrenia
• Currently taking atypical medications
• Use of effective form of contraception throughout study

Exclusion Criteria:

• History of any alcohol or drug abuse within 3 months of study start date
• Any other major neurological disorders
• History of or current head trauma
• Any medical conditions affecting the central nervous system
• Current epilepsy, asthma, migraine headache, previous myocardial infarction, stroke, diabetes, hypertension, narrow angle glaucoma, or neuromuscular illnesses
• Pregnant