Pimavanserin: Potential Treatment for Dementia-Related Psychosis

Abstract

Psychosis is common across dementia types with a prevalence of 20% to 70%. Currently, no pharmacologic treatment is approved for dementia-related psychosis. Atypical antipsychotics are frequently used to treat these disorders, despite significant safety concerns. Pimavanserin, a selective 5-HT2A inverse agonist/antagonist, was approved in the U.S. for treating hallucinations and delusions associated with Parkinson’s disease psychosis (PDP). Patients in the pimavanserin group experienced a significant (p=0.001) improvement in Scale for the Assessment of Positive Symptoms – Parkinson’s disease (SAPS-PD) scores vs. placebo. In a subgroup analysis of patients with cognitive impairment (MMSE score ≥21 but ≤24), the observed improvement on the SAPS-PD with pimavanserin (N=50) was also significant (p=0.002) and larger than in the overall study population without an adverse effect on cognition. In a Phase 2 study with pimavanserin in Alzheimer’s disease psychosis, pimavanserin significantly (p=0.045) improved psychosis at Week 6 vs. placebo on the NPI-NH Psychosis Score (PS). In a prespecified subgroup of patients with a baseline NPI-NH PS ≥12, a substantively larger treatment effect (p=0.011) was observed vs. participants with NPI-NH PS

Burden of illness among patients with dementia-related psychosis

“…Depending on dementia type and increasing with disease progression, approximately 20%-70% of patients will experience dementia-related psychosis (DRP), characterized by delusions and hallucinations. 9 This estimate is thought to increase to more than 90% if behavioral symptoms such as dementia-related agitation and aggression are included as indicators of psychosis. 10 In a study by Peters et al (2015), DRP was associated with a more rapid progression to severe dementia (hazard ratio = 2.007; P = 0.028) and earlier death (hazard ratio = 1.537; P = 0.011) among patients with Alzheimer disease.…”

Relevance of 5-HT2A Receptor Modulation of Pyramidal Cell Excitability for Dementia-Related Psychosis: Implications for Pharmacotherapy

“…Pimavanserin effectively reduced hallucinations and delusions associated with DRP in multiple clinical studies, which included patients with the major forms of dementia, and was well tolerated by elderly fragile patients in the studies [33][34][35][36][37]149]. The purpose of this review was to identify mechanisms that explain the role of 5-HT 2A Rs in both the etiology and treatment of DRP.…”

Symptoms and Treatment Needs of People with Dementia-Related Psychosis: A Mixed-Methods Study of the Patient Experience

“…Hallucinations, in particular, are associated with a 1.6-and 1.5-times higher risk of institutionalization and death, respectively (Scarmeas et al, 2005), and with reduced quality of life, subjective wellbeing and life satisfaction (Choi et al, 2021). Furthermore, dementia-related psychosis is associated with a significant increase in care partner burden (Aarsland, Larsen, Karlsen, Lim, & Tandberg, 1999;Cummings et al, 2018;Jeste & Finkel, 2000), and much of the responsibility of caring for individuals with dementia-related psychosis falls on family members. One study found that over 80% of care hours for individuals with probable dementia are provided informally by family care partners (Friedman, Shih, Langa, & Hurd, 2015).…”

“…There are no therapies currently approved by the U.S. Food and Drug Administration (FDA) for treating dementia-related psychosis (Cummings et al, 2018). Persons with dementia are often treated on a short-term basis with existing antipsychotic medications; however, these are associated with known risks and uncertain benefit (Kales, Gitlin, & Lyketsos, 2015;L.…”