New trends in pharmacological control of neuropsychiatric symptoms of dementia

Abnormal neuronal and synaptic plasticity occurs in Alzheimer's disease (AD) and depression. The latter, particularly late-life, has been recognized as fundamental in the identification of at-risk prodromal stages of AD. The lack of disease-modifying drugs and the off-label use of antipsychotics and antidepressants for neuropsychiatric symptoms (NPSs) have caused a season of therapeutic inappropriateness. To date, the wealth of clinical trials investigating drugs, diverse for structure and mechanism of action, has failed to provide a cure for all the spectrums of NPSs. Psychedelics in microdosing afford promotion of neurogenesis and synaptic plasticity and, recently, have been considered a revolution for the management of depression endowed with faster action and an improved side effect profile than antidepressants. In the current scenario, therefore, the rapid-acting antidepressant esketamine could represent the first-in-class for treatment of NPSs, and this deserves to be demonstrated with an open-label clinical trial.