During a 10-week prospective study, overall mortality among elderly patients with Alzheimer disease who were treated with antipsychotic medication did not differ statistically from that in patients who did not receive antipsychotics.
Results of that study were recently reported at the Annual Meeting of the American Association for Geriatric Psychiatry.1
Heii Arai, MD, PhD, of Juntendo University in Tokyo, the study’s lead author, pointed out that the black box label, required by the FDA to warn of heightened mortality risk from use of antipsychotics for behavior disturbances in patients with dementia, is based on an apparent greater risk that “could be generated only when data on randomized clinical trials were combined in a meta-analysis.” He asserted further that “there is no conclusive evidence based on prospective studies about the mortality risk associated with the use of antipsychotics.”1
Arai and co-investigators from Toho University and Kagawa University in Japan, and Otsuka Pharmaceuticals, the study sponsor, conducted a prospective study to contribute additional, and possibly more definitive, data for the risk assessment. Their study cohort comprised 6000 patients at 324 sites throughout Japan. Potential subjects were excluded for having severe, unstable, or uncontrolled medical conditions, as were those deemed unlikely to adhere to the study regimens. Approximately 70% of patients were female; the mean age of the total sample was 81.7 years. Approximately 30% were inpatients and half were receiving antipsychotics on the index date.
The crude 10-week mortality rates were similar: 1.3% of patients who had received antipsychotic treatment, and 1.1% of those who had not. The most common cause of death was pneumonia, which did occur at a higher rate in the antipsychotic-treated group (15 of 34 deaths) than in the group that did not receive antipsychotics (9 of the 28 deaths). After pneumonia, the most common causes of death were cardiovascular, and then cancer-related events.
Co-investigator Hiroyuki Kobayashi, MD, PhD, Otsuka Pharmaceuticals, told Psychiatric Times that further analysis of their data, which is being readied for the Alzheimer’s Association International Conference in July, may ascertain drug effect and, if present, possibly distinguish between agents.
To the question of whether mortality risk would be assessed in relation to duration of treatment, since patients had received antipsychotics for varying durations before the index date, Kobayashi responded, “We needed to evaluate the effect of the 10-week exposure of antipsychotics on elderly persons regardless of earlier exposure. The important thing is, we think, not whether the longer exposure of antipsychotic affects mortality risk, but whether the use of antipsychotics raises the risk.”
Another, smaller prospective study conducted in Hong Kong found no increased mortality in patients who received antipsychotics during an 18-month study period.2 Regarding the similar findings of these two prospective studies from Asia and their apparent contrast with the current FDA label warnings, Kobayashi offered, “I suppose that the medical environment in Asian countries might be more protective for elderly patients than in Western countries.” He elaborated, “Most Asian countries offer patients open access to hospitals so the ratio of the number of deaths at home was very low—just about 10% in Japan.”
1. Arai H, Kobayashi H, Taguchi M, et al. Risk of mortality associated with antipsychotics in patients with dementia: a prospective cohort study. Poster presentation: 2013 Annual Meeting of the American Association for Geriatric Psychiatry; March 14-17, 2013; Los Angeles. Abstract NR 51.
2. Chan TC, Luk JK, Shea YF, et al. Continuous use of antipsychotics and its association with mortality and hospitalization in institutionalized Chinese older adults: an 18-month prospective cohort study. Int Psychogeriatr. 2011;23:1640-1648.