Atypical antipsychotics for the treatment of behavioral and psychological symptoms in dementia, with a particular focus on longer term outcomes and mortality

Importance of the field: Many people with Alzheimer's disease (AD) and other dementias are prescribed atypical antipsychotics for behavioral and psychiatric symptoms such as aggression and psychosis. Recent evidence has highlighted safety concerns regarding antipsychotics in these individuals. Areas covered in this review: We summarize the evidence pertaining to efficacy and safety from short-term randomized controlled trials (up to 12 weeks), key findings from case-register studies and more detailed discussion of longer term outcome studies, including longer term mortality risk of antipsychotics in AD. What the reader will gain: The review aims to provide a balanced and up to date overview of the efficacy and safety concerns related to atypical antipsychotics in people with AD, in particular providing a detailed overview of mortality risk, and a personal interpretation of the implications and recommendations for the way forward. Take home message: Atypical antipsychotics confer modest benefits for short-term (up to 12 weeks) treatment of aggression and psychosis in AD. These benefits have to be balanced against the risk of serious adverse events including 1.5 - 1.8-fold increased mortality. The benefits are less clear-cut with longer term prescribing, but the mortality risk remains significantly elevated. Pharmacogenetics may provide an opportunity to more effectively focus prescribing in the future.