Alzheimer’s psychosis is distinct from the slow progression of Alzheimer’s and indicates a more severe phenotype in which cognitive decline starts even before psychosis onset. It is thought to originate/localized in neocortex rather than medial temporal lobe.
There is currently only one drug that targets Alzheimer’s psychosis. It is called Rexulti (Brexipipazole). It is specifically approved for the agitation that accompanies the early stage of Alzheimer’s dementia. It is a SDAM (serotonin dopamine activity modulator). It targets many receptors: Dopamine D2 receptor, Serotonin 5-HT1A receptor and Serotonin 5-HT2A receptor. There is one another drug called Nuplazid (Pimavanersin) that was approved for Parkinsons psychosis that is used off-label. Surprisingly, FDA declined its approval for Alzheimer’s psychosis in 2022. There is still competition in the market. A drug used to treat schizophrenia in adults – Cobenfy by BMS – is undergoing studies for Alzheimer’s psychosis. Cobenfy targets M1 and M4 in the brain by Xanomeline and is combined with anticholinergic, trospium chloride, to reduce gastrointestinal side effects. Cobenfy was one of the first drugs to treat schizophrenia that did not directly affect dopamine.
