All-Cause Mortality Associated With Atypical and Conventional Antipsychotics Among Nursing Home Residents With Dementia: A Retrospective Cohort Study

Objective: A recent meta-analysis has indicated that, in patients with dementia, the use of atypical antipsychotics is associated with an excess mortality. Later observational studies have suggested that conventional antipsychotics may pose an even greater risk of death. None of these studies could evaluate the risk associated with single antipsychotics nor could they provide any conclusive evidence concerning the risk among nursing home residents. We conducted a retrospective cohort study to compare the risk of death associated with atypical and conventional antipsychotics in a large population of nursing home residents with dementia.

Method: We identified 6,524 new users of atypical antipsychotics and 3,205 new users of conventional antipsychotics living in 1,581 Medicare- or Medicaid-certified nursing homes in 5 US states during the years 1998-2000. The outcome measure was all-cause mortality, which was determined during 6-months of follow-up.

Results: After adjusting for potential confounders relative to users of atypicals, the rate of death was increased for users of conventional antipsychotics (hazard ratio [HR], 1.26; 95% CI, 1.13-1.42). Relative to risperidone, a higher rate of death was documented for haloperidol (HR, 1.31; 95% CI, 1.13-1.53), phenothiazines (HR, 1.17; 95% CI, 1.00-1.38) and other conventional medications (HR, 1.32; 95% CI, 0.99-1.80). No atypical antipsychotic was associated with a differential risk relative to risperidone.

Conclusions: Conventional antipsychotics are associated with a higher risk of all-cause mortality than atypical agents. It seems advisable that they are not used in substitution for atypical antipsychotics among nursing home residents with dementia even when short-term therapy is being prescribed.

Submitted: August 5, 2008; accepted November 24, 2008.

Corresponding author: Rosa Liperoti, MD, MPH, Centro di Medicina dell’ Invecchiamento, Dipartimento di Scienze Gerontologiche, Geriatriche e Fisiatriche, Universití  Cattolica del Sacro Cuore, Largo A. Gemelli, 8 0168 Rome, Italy (rossella_liperoti@rm.unicatt.it).