All-cause mortality associated with atypical and typical antipsychotics in demented outpatients

Pharmacoepidemiol Drug Saf. 2007 May;16(5):538-44. doi: 10.1002/pds.1334.


Purpose: To estimate the association between use of typical and atypical antipsychotics and all-cause mortality in a population of demented outpatients.

Methods: The study cohort comprised all demented patients older than 65 years and registered in the Integrated Primary Care Information (IPCI) database, during 1996-2004. First, mortality rates were calculated during use of atypical and typical antipsychotics. Second, we assessed the association between use of atypical and typical antipsychotics and all-cause mortality through a nested case-control study in the cohort of demented patients. Each case was matched to all eligible controls at the date of death by age and duration of dementia. Odds ratios were estimated through conditional logistic regression analyses.

Results: The crude mortality rate was 30.1 (95%CI: 18.2-47.1) and 25.2 (21.0-29.8) per 100 person-years (PY) during use of atypical and typical antipsychotics, respectively. No significant difference in risk of death was observed between current users of atypical and typical antipsychotics (OR = 1.3; 95%CI: 0.7-2.4). Both types of antipsychotics were associated with a significantly increased risk of death as compared to non-users (OR = 2.2, 1.2-3.9 for atypical antipsychotics; OR=1.7, 1.3-2.2 for typical antipsychotics).

Conclusions: Conventional antipsychotic drug should be included in the FDA's Public Health advisory, which currently warns only of the increased risk of death with the use of atypical antipsychotics in elderly demented persons.

MeSH terms

  • Age Factors
  • Aged
  • Aged, 80 and over
  • Antipsychotic Agents / adverse effects
  • Antipsychotic Agents / therapeutic use*
  • Benzodiazepines / adverse effects
  • Benzodiazepines / therapeutic use
  • Cardiovascular Diseases / diagnosis
  • Cardiovascular Diseases / mortality
  • Case-Control Studies
  • Cause of Death
  • Dementia / drug therapy*
  • Dementia / mortality
  • Effect Modifier, Epidemiologic
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Netherlands / epidemiology
  • Odds Ratio
  • Olanzapine
  • Outpatients / statistics & numerical data*
  • Sex Factors


  • Antipsychotic Agents
  • Benzodiazepines
  • Olanzapine