Psychosis in Parkinson’s Disease: Looking Beyond Dopaminergic Treatments

Abstract

Background: Parkinson’s disease (PD) is the second most common neurodegenerative disorder worldwide. The symptoms of PD are characterized not only by motor alterations but also by a spectrum of nonmotor symptoms. Some of these are psychiatric manifestations such as sleep disorders; depression; cognitive difficulties that can evolve into dementia; and symptoms of psychosis, which include hallucinations, illusions, and delusions. Parkinson’s disease psychosis (PDP) occurs in 18%–50% of patients with PD. Treating PDP is challenging because antipsychotic drugs tend to be inefficient or may even worsen the motor symptoms of the disease. Methods: This is a narrative review in which an extensive literature search was performed on the Scopus, EMBASE, PubMed, ISI Web of Science, and Google Scholar databases, from inception to August 2021. The terms “Parkinson’s disease psychosis,” “Parkinson psychosis,” “neurodegenerative psychosis,” and “dopamine psychosis” were among the keywords used in the search. Objective: current understanding of the molecular mechanisms involved in PDP, as well as recent innovative alternatives for its treatment. Results: Recently, views on the etiology of hallucinations and illusions have evolved remarkably. PDP has been cemented as a multifactorial entity that is dependent not only on extrinsic mechanisms but also novel intrinsic mechanisms including genetic factors, neurostructural alterations, functional disruptions, visual processing disturbances, and sleep disorders. Consequently, innovative pharmacological and biological treatments have been proposed. Pimavanserin, a selective 5-HT2A inverse agonist, stands out after its approval for the treatment of PDP-associated hallucinations and illusions. Conclusion: Future results from upcoming clinical trials should further characterize the role of this drug in the management of PDP as well as other treatment options with novel mechanisms of action, such as saracatinib, SEP-363856, cannabidiol, electroconvulsive therapy, and transcranial magnetic stimulation.