The use of atypical antipsychotics in dementia: rethinking Simpson's paradox.

Higher rates of cerebrovascular adverse events (CVEs) and mortality for dementia patients taking active drugs were reported during industrysponsored clinical trials of atypical antipsychotics for the treatment of behavioral and psychological symptoms of dementia (BPSD). Since then, the use of antipsychotics for BPSD has not been recommended on the basis of advisory warnings issued by regulatory authorities in several countries. Nevertheless, there are currently no demonstrated pharmacologic alternatives. Although early published and unpublished data indicated a risk, few subsequent publications have supported the initial finding. In order to update earlier comments published in International Psychogeriatrics (Shah and Suh, 2005), this editorial briefly introduces subsequent reports, summarizes the discrepant findings of experimental and non-experimental studies, highlights the effect of “Simpson’s paradox”, which causes us to throw doubt on conclusions based on meta-analyses or pooled-analyses, explains this discrepancy in the light of current knowledge, and concludes with practical recommendations regarding the use of atypical antipsychotics in dementia.