Auvelity as a Potential Treatment for Alzheimer’s Disease

Abstract

Auvelity was approved by the FDA in 2022 for the treatment of Major Depressive Disorder in adults. Auvelity’s relevant mechanisms of action are a combination of NMDA receptor blockade with consequent antagonism of the glutamatergic neurotransmitter pathway, and sigma-1 receptor agonism. Major Depressive Disorder and Alzheimer’s disease share a significant association. Glutamatergic excitotoxicity via NMDA receptors is believed to be a key mechanism underlying neurodegeneration in Alzheimer’s Disease, the most frequent form of dementia in older adults. NMDA antagonists like Memantine appear to inhibit glutamatergic excitotoxicity via blockade of NMDA receptors. As a sigma-1 receptor agonist, Memantine also increases dopaminergic activation. Memantine’s benefit for improving memory, cognition and general functioning in AD patients is generally attributed to the combination of these two mechanisms. Because AD medications like Memantine and Auvelity share the same mechanism of action, it is hypothesized that Auvelity has potential as a medical treatment for reducing the symptoms of Alzheimer’s disease.