Dementia-related psychosis and the potential role for pimavanserin

No pharmacological agents are approved by the U.S. Food and Drug Administration (FDA) to treat dementia-related psychosis (DRP). Pimavanserin, an atypical antipsychotic that acts as a selective serotonin inverse agonist/antagonist at 5-HT_2A receptors (and to a lesser extent, at 5-HT_2c receptors), is the only FDA-approved treatment for hallucinations and delusions associated with Parkinson’s disease (PD) psychosis.^1, Reference Cummings, Isaacson and Mills² A phase 2 study of pimavanserin in Alzheimer’s disease (AD) psychosis met its primary end point at week 6 (mean change in the Neuropsychiatric Inventory-Nursing Home version psychosis score of −3.76 points [SE 0.65] for pimavanserin and −1.93 points [SE 0.63] for placebo; P =0 .045) with an acceptable tolerability profile and no worsening of cognition or motor function.Reference Ballard, Banister and Khan³ Pimavanserin is being investigated (NCT03325556 and 2017-002227-13) for treating hallucinations and delusions associated with DRP across five common neurodegenerative dementias: AD dementia, PD dementia, dementia with Lewy bodies (DLB), frontotemporal dementia (FTD), and vascular dementia (VaD).^4-6 This article discusses the emerging understanding of the neurobiology of psychosis, the current state of knowledge about the neurobiology of psychotic symptoms in dementia syndromes, and the hypothesized role of pimavanserin in treating DRP.