Dementia-related psychosis and the potential role for pimavanserin

Abstract

Dementia-related psychosis (DRP) is prevalent across dementias and typically manifests as delusions and/or hallucinations. The mechanisms underlying psychosis in dementia are unknown; however, neurobiological and pharmacological evidence has implicated multiple signaling pathways and brain regions. Despite differences in dementia pathology, the neurobiology underlying psychosis appears to involve dysregulation of a cortical and limbic pathway involving serotonergic, gamma-aminobutyric acid ergic, glutamatergic, and dopaminergic signaling. Thus, an imbalance in cortical and mesolimbic excitatory tone may drive symptoms of psychosis. Delusions and hallucinations may result from (1) hyperactivation of pyramidal neurons within the visual cortex, causing visual hallucinations and (2) hyperactivation of the mesolimbic pathway, causing both delusions and hallucinations. Modulation of the 5-HT2A receptor may mitigate hyperactivity at both psychosis-associated pathways. Pimavanserin, an atypical antipsychotic, is a selective serotonin inverse agonist/antagonist at 5-HT2A receptors. Pimavanserin may prove beneficial in treating the hallucinations and delusions of DRP without worsening cognitive or motor function.

Fusion assays for screening of fusion inhibitors targeting SARS-CoV-2 entry and syncytia formation

“…Fusion in 293T-ACE2-TMPRSS2 cells was sensitive to inhibition by all non-kite nervous system-acting inhibitors targeting the serotogenic and muscarinic pathways and the cannabinoid CB1 receptor (Hegde, 2006;Oleson et al, 2012;Gillman and Gillman, 2019;Cignarella et al, 2021;Cummings et al, 2022) (Figure 6, Supplementary Figure S12). Fusion in 293T-ACE2 cells was sensitive to select non-kite nervous systemacting inhibitors under different conditions.…”

Evaluating pimavanserin as a treatment for psychiatric disorders: A pharmacological property in search of an indication

“…Pimavanserin may be a treatment for hallucination in dementia because various dementias, especially with Lewy bodies, upregulate the 5-HT 2A receptor [16,17]. In a study of 181 nursing home residents with Alzheimer's disease with associated psychotic symptoms, 90 patients were assigned to pimavanserin and 91 patients to placebo [18].…”

Psychedelic‐inspired approaches for treating neurodegenerative disorders

“…In fact, psychedelic‐assisted psychotherapy is contraindicated for patients suffering from schizophrenia or related psychotic illnesses (Vargas et al, 2021). Moreover, 5‐HT 2A antagonists are commonly prescribed for the treatment of dementia‐related psychosis and the selective 5‐HT 2A antagonist pimavanserin was recently approved by the FDA for Parkinson's disease psychosis (Cummings et al, 2020).…”