Psychosis, agitation, and antipsychotic treatment in dementia.

Uptoone-thi rd of all nursing home residents, primarily patients with dementia, receive antipsychotic medications for the treatment of symptoms of psychosis, agitation, and aggression (1). In patients with dementia, the presence of psychosis or agitation predisposes to worse long-term outcomes, including a higher rate of institutionalization and death (2). Antipsychotic medications that are used to treat these symptoms are associated with a variety of side effects. In particular, a meta-analysis of placebo-controlled trials of antipsychotics in dementia revealed a 60%270% greater risk of mortality, which led to a Food and Drug Administration (FDA) black box warning in 2005 (3). A more recent review found a 54% greater mortality risk for antipsychotics compared with placebo in these patients (4). The study by Lopez et al. (5) in this issue of the Journal examines whether the presence of psychiatric symptoms could account for the negative long-term effects of antipsychotic treatment, particularly institutionalization and death. In a series of 957 outpatients with probable Alzheimer's disease who were followed for an average of 4.3 years during the period from 1983 to 2005, 241 patients received both conventional and atypical antipsy-chotics. The presence of psychosis predicted nursing home admission and time to death, both of which occurred at more than double the rate for patients who received conventional antipsychotics than in those who received atypical antipsychotics. However, this effect of conventional antipsychotics disappeared after several key variables were controlled in the analyses, particularly the co-occurrence of psychiatric symptoms. Critically, in this study the risk of death was not increased in patients exposed to antipsychotics, both conventional and atypical. Worse cognitive performance, extrapyramidal signs, heart disease, agitation , and psychosis were associated with an increased likelihood of admission to a nursing home, while increased age, education level, male gender, worse cognitive performance, extrapyramidal signs, and psychosis were associated with a greater risk of death. Time-dependent statistical models were used, which is the state-of-the-art approach when dealing with longitudinal data that include symptoms and conditions that might appear or disappear at different time points during follow-up. Some surveys conducted in nursing homes also did not find an increase in mortality in patients with dementia who received antipsychotic medications (6, 7). In contrast, a report from a large Medicare and Medicaid database of 75,445 patients (8) demonstrated greater mortality risk associated with the conventional antipsychotic haloperidol compared with the reference antipsychotic, risperidone. Quetiapine was associated with a slight …