Sensitivity to Antipsychotic Drugs in Older Adults

Antipsychotic medications are widely used to manage psychotic and behavioral disorders in older adults, including primary psychotic disorders such as schizophrenia, and psychosis and behavioral disturbances associated with dementia. These two broad diagnostic indications are associated with contrasting recommended treatment durations, with the former requiring indefinite treatment across the life span. Antipsychotic drug dosing for schizophrenia is based primarily on studies of younger patients and thus may not apply to older adults. It is critically important to address the effects of aging on antipsychotic dosing given the recent emergence of data that suggest a critical role for age-related sensitivity to these drugs. Antipsychotic drugs are not only associated with somatic and neurological adverse effects but also increased all-cause mortality and sudden cardiac death in this vulnerable population. This review focuses on the sensitivity of older adults to adverse effects from antipsychotic medications and the current pharmacokinetic and pharmacodynamic explanatory models of susceptibility. Implications of recent research findings for individualized pharmacotherapy are discussed.