Quetiapine in the treatment of psychosis in Parkinson's disease.

Psychosis (delusions and/or hallucinations) is a common nonmotor feature of Parkinson's disease (PD). Use of the older 'typical' antipsychotic drugs led to worsening of motor symptoms. The introduction of 'atypical' antipsychotics opened up a range of therapeutic options. These agents include clozapine, risperidone, olanzapine, aripiprazole and quetiapine. All have been used to treat psychosis in PD with varying success. Clozapine is the only drug with proven efficacy. We review the evidence for the efficacy of quetiapine. Eight open-label studies have assessed quetiapine use in 191 patients, with improvement in psychosis recorded in 152 (80%). In addition to the open-label studies, there have been two single-blind, randomized trials comparing quetiapine and clozapine. These studies suggest that quetiapine has similar efficacy to clozapine in controlling psychosis. Following the promising results of the open-label and clozapine comparison studies, five randomized, controlled trials (RCTs) have been performed to further establish the efficacy of quetiapine. Unfortunately, the results have been disappointing. The only positive placebo-controlled study excluded patients with delusions, which seem to be harder to treat than hallucinations. The four negative RCTs discussed seriously undermine the evidence from the open-label studies. The differences in design and interpretation of the RCTs emphasizes the need for further large, well-controlled trials, using strict inclusion criteria, appropriate psychosis rating scales, carer input and clinical significance. Currently, many physicians continue to cautiously offer a trial of low-dose quetiapine empirically. Clozapine should be considered in patients who can tolerate the required blood monitoring.