Introduction: Psychosis, a frequent complication in Parkinson's disease (PD), contributes significantly to morbidity, mortality, nursing-home placement and quality of life. Medication side effects, issues of trial design and negative outcomes have limited clinical advances of new treatments for PD psychosis. Evidence-based medicine maintains clozapine as the most effective antipsychotic in PD without motor worsening, despite risk of agranulocytosis. Safe, effective treatments that improve psychosis without exacerbating parkinsonism are urgently needed.
Areas covered: This article reviews the: i) phenomenology of PD psychosis, ii) pharmacological rationale for antipsychotics in PD; iii) clinical trials of antipsychotics in PD; iv) novel research strategies such as neuroimaging, genetics and animal models; and v) associated challenges in studying and treating PD psychosis. Preparation of this review included an extensive literature search using PubMed.
Expert opinion: Management of PD psychosis is complex. Challenges pertaining to study design, rating scales, subject recruitment and completion have limited PD psychosis treatment trials. Novel research strategies focus on nondopaminergic systems and incorporate neuroimaging, genetic associations and animal models. These strategies also have challenges but have the potential to enhance our understanding of PD psychosis and advance the development of agents that can ultimately be tested in well-designed, randomized, controlled trials.