Grant: Operating Grant

Schizophrenia is a life-long illness requiring daily treatment with antipsychotic medication. Even though older patients are well-known to be very sensitive to medications, we still do not know the lowest effective dose of antipsychotic medication that is necessary in older patients with this condition. This information has traditionally been acquired through large drug studies. Binding of antipsychotics to brain dopamine receptors has previously been used to predict the least effective dose in younger patients using relatively few patients compared to large clinical studies. We therefore seek to study the lowest antipsychotic dose needed to maintain wellness in older patients with early-onset schizophrenia. To do this we plan to conduct a PET study in 40 patients 60 years and older who have had schizophrenia since their young adulthood and have been maintained for > 12 months on risperidone, a very commonly used antipsychotic medication. Participants will undergo a gradual dose reduction up to 40% of their baseline dose to a target dose not lower than the lowest recommended dose 1.25 mg/day. A PET scan will be completed after gradual dose reduction. They will then be followed for 6 months to determine whether they remain well at this low dose. If they experience any new symptoms, they will have their dose increased to treat these symptoms and then undergo a second PET scan. This study will provide new information about the mechanisms involved in antipsychotic drug sensitivity in older patients. This information can be translated to the determination of the lowest effective antipsychotic dose necessary for maintenance of therapeutic effect in older patients with schizophrenia, a clinical question of major public health significance.