Most symptoms appear to be due to disease pathology with exacerbation caused by dopaminergic treatment. More than 50% of patients with PD develop psychosis at some point throughout their disease course. Clinicians need to routinely assess patients with PD for psychotic symptoms, particularly hallucinations. Treatment of psychotic symptoms in PD is an unmet need as there are currently no US Food and Drug Administration (FDA) approved medications specifically for PD psychosis (PDP).
Current treatments for PDP have been adapted from dopamine antagonists used to treat psychosis in other conditions, such as schizophrenia. Typical antipsychotics, as well as some atypical antipsychotics, worsen PD motor symptoms due to blockade of dopamine D2 receptors. Quetiapine and clozapine have been studied in PDP and are the most commonly used treatments for PDP.
Clozapine has been shown to be effective; however, regular bloodwork is required, while data for quetiapine are inconsistent. Pimavanserin, a highly selective serotonin (5HT2A subtype) receptor inverse agonist, is not associated with motor worsening in PDP patients due to the absence of dopamine blockade. In a double-blind, placebo-controlled study, pimavanserin showed significant improvement in moderate to severe psychosis compared to placebo, with good tolerability and without worsening of PD motor symptoms. These data suggest that pimavanserin is a safe and efficacious treatment for PDP psychosis and could be a potential new treatment option for PDP.