Pimavanserin and Parkinson's Disease Psychosis: A Narrative Review

Abstract

Pimavanserin (PMV) is the first approved drug for treating hallucinations and delusions in Parkinson's disease (PD) psychosis. Psychosis is one of the leading causes of nursing home placement in people with PD. Furthermore, hallucinations are a more frequent cause of institutionalization than motor disability or dementia related to PD. The management of PD psychosis involves antipsychotic medications. Most of the drugs in this class directly block dopamine D2 receptors, leading to significantly worsening motor symptoms in patients with PD. The most commonly used medications for managing PD psychosis are quetiapine, clozapine, and PMV. This literature review aims to study pimavanserin's history, mechanism, clinical trials, and post-marketing experience. PMV is a potent 5-HT2A receptor antagonist/inverse agonist. Moreover, this drug can interact with 5-HT2C receptors. We calculated some physicochemical descriptors and pharmacokinetic properties of PMV. Eight clinical trials of PMV and PD psychosis are registered on ClinicalTrials.gov. Only four of them have complete results already published. Meta-analytic results showed that PMV efficacy is inferior to clozapine. However, PMV has a significantly lower number of side-effects for managing psychosis in PD. Medicare database assessment revealed 35% lower mortality with PMV compared to other atypical antipsychotics. Moreover, sensitive statistical analysis demonstrated that PMV is a protective factor for the risk of falls in individuals with PD.

Keywords: ACP-103; Nuplazid; Parkinson’s disease; pimavanserin; psychosis.

Figure 1

Hypothetical mechanism of action of pimavanserin in Parkinson’s disease psychosis.

Figure 2

Physicochemical properties of pimavanserin (ACP-103; BVF-048).

Figure 3

Neuropsychiatric disorders and 5-HT2A receptor. This figure summarizes the conditions studied in the clinical trials with pimavanserin. Abbreviations: IMP: impulsivity; INS: insomnia; DD: depressive disorder; DKN: dyskinesia; SCZ: schizophrenia; TS: Tourette syndrome [37,38,39,40,41,42].