Pimavanserin for the treatment of Parkinson's disease psychosis.
BACKGROUND
Parkinson´s disease (PD) is a synucleinopathy that affects millions of people worldwide and leads to progressive disability. Psychosis is highly prevalent in PD patients and is associated with poor prognosis. Until April 2016, there were no licensed drugs available in the United States of America (USA) for the treatment of PD psychosis (PDP). Pimavanserin is the first Food and Drug Administration approved medicine for the treatment of hallucinations and delusions associated with PDP.


METHODS
A MEDLINE literature search, publicly available information provided by ACADIA Pharmaceuticals, and expert opinion were used for this review. A review of PDP, its current treatment and limitations is followed by the rationale for development of pimavanserin. The mechanism of action, preclinical data, pharmacokinetics, pharmacodynamics, and clinical data supporting the efficacy and safety of pimavanserin in PDP are reviewed. We also describe the potential benefits of pimavanserin in other contexts such as schizophrenia and sleep disorders.


CONCLUSIONS
Pimavanserin is an antipsychotic with a unique mechanism of action (5-HT2A receptor inverse agonist) and no measurable dopaminergic activity; it has been demonstrated to be efficacious, well tolerated and safe for the treatment of PDP. The development of pimavanserin as an antipsychotic represents a major breakthrough in the pharmacotherapy of psychotic symptoms associated with PD.
a Psychiatry Department, Department of Neurosciences , Hospital Santa Maria , Lisbon , Portugal.|b Clínica Universitária de Psiquiatria, Faculty of Medicine , University of Lisbon , Lisbon , Portugal.|e CNS-Campus Neurológico Sénior , Torres Vedras , Portugal.
Ines
I
Chendo
c Clinical Pharmacology Unit , Instituto de Medicina Molecular , Lisbon , Portugal.|d Laboratory of Clinical Pharmacology & Therapeutics, Faculty of Medicine , University of Lisbon , Lisbon , Portugal.|e CNS-Campus Neurológico Sénior , Torres Vedras , Portugal.
Joaquim J
JJ
Ferreira
D014150:Antipsychotic Agents / Q000627:therapeutic use; D006801:Humans; D010300:Parkinson Disease / Q000188:drug therapy*; D010880:Piperidines / Q000627:therapeutic use*; D011618:Psychotic Disorders / Q000188:drug therapy*; D012559:Schizophrenia / Q000188:drug therapy; D058826:Serotonin 5-HT2 Receptor Agonists / Q000627:therapeutic use; D014508:Urea / Q000031:analogs & derivatives* / Q000627:therapeutic use
D014150:Antipsychotic Agents; D010880:Piperidines; D058826:Serotonin 5-HT2 Receptor Agonists; D014508:Urea; C510793:pimavanserin
5-HT2A inverse agonist; Parkinson´s disease; delusions; hallucinations; pimavanserin; psychosis