Pimavanserin Treatment for Parkinson’s Disease Psychosis in Clinical Practice

Abstract

Background. Parkinson’s disease psychosis (PDP) is a common, nonmotor symptom of Parkinson’s disease (PD), which may affect up to 60% of patients and is associated with impaired quality of life, increased healthcare costs, and nursing home placement, among other adverse outcomes. Characteristic symptoms of PDP include illusions; visual, auditory, tactile, and olfactory hallucinations; and delusions. PDP symptoms typically progress over its course from being mild, infrequent, and often untroubling to complex, sometimes constant, and potentially highly disturbing. PDP has traditionally been treated with atypical antipsychotics (e.g., clozapine and quetiapine) although these are not approved for this indication and clozapine requires frequent white blood cell count monitoring due to the risk of agranulocytosis. Pimavanserin is a newer atypical antipsychotic with highly selective binding to serotonergic receptors, no evidence for worsening motor symptoms in PD, and no need for white blood cell count monitoring. It is currently the only approved medication indicated for PDP treatment. However, because it was approved relatively recently (2016), clinical experience with pimavanserin is limited. Case Presentations. A wide variety of representative clinical scenarios are presented, each with distinct variables and complications. Issues addressed include distinguishing PDP from similar symptoms caused by other disorders such as dementia, coordinating pimavanserin with other PD medications and with deep brain stimulation, adapting pimavanserin dosing for optimal benefit and tolerability, and recognizing variability of PDP symptoms due to patients’ changing life circumstances. Conclusions. These scenarios provide multiple insights regarding PDP management and the role of pimavanserin. Effective treatment of PDP may reduce disturbing symptoms of psychosis, thus improving patient function and quality of life. In addition, effective pharmacotherapy for PDP may also facilitate the use of other medications needed to treat neurological symptoms of PD (e.g., tremor, bradykinesia, and dyskinesia), although they may also have adverse effects that contribute to symptoms of PDP.

Parkinsonism and dementia

“…Pimavanserin, a newer atypical antipsychotic similar to clozapine, and without evidence for worsening of motor symptoms in PD, has been suggested as a plausible safer alternative treatment [9]. Pimavanserin acts as an inverse agonist and antagonist at serotonin 5-HT2A receptors with high binding affinity and at serotonin 5-HT2C receptors with lower binding affinity.…”

“…Behavioral and neuropsychiatric symptoms including apathy, depression and notably psychosis might be a key feature of dementia in PD/DLB and they often have a greater impact than cognitive problems [7]. Symptomatic treatments have been applied for LBDrelated dementia and the concurrent neuropsychiatric problems while quest for novel etiological therapies is ongoing [8,9].…”

Pimavanserin and Parkinson’s Disease Psychosis: A Narrative Review

“…Dashtipour et al reported a case series of PMV treatment for PD psychosis with clinical tips. Table 4 was adapted from the study of Dashtipour et al [ 65 ]. It is worth mentioning that US prescribers of PMV must provide medical documentation of psychosis and the reason for its indication, which can sometimes affect the use of PMV for behavioral management [ 66 ].…”

Emerging role of psychosis in Parkinson's disease: From clinical relevance to molecular mechanisms

“…The therapeutic responsiveness of pimavanserin may be enhanced or facilitated by other PD-related drugs or interventions, such as cholinesterase inhibitors and deep brain stimulation[ 98 ]. Currently, there is limited understanding of the discrepancy between pimavanserin and other antipsychotics with respect to efficacy, safety, and tolerability and further large-scale multicenter studies are required to confirm the clinical utility of pimavanserin in other clinical settings[ 84 ].…”