Increase in mortality rate in patients with dementia treated with atypical antipsychotics: a cohort study in outpatients in Central Italy

Riv Psichiatr. 2014 Jan-Feb;49(1):34-40. doi: 10.1708/1407.15623.


Background: The purpose of this study was to investigate the risk of death among elderly outpatients (>65 years) with a dementia diagnosis treated with atypical antipsychotics.

Methods: We conducted a cohort study of 696 patients who entered the Unit of Alzheimer Evaluation (UVA) of Teramo Hospital in Central Italy, during a 3-year period (January 2007-December 2009). Among these patients, 375 were treated with atypical antipsychotics (quetiapine, risperidone and olanzapine). Data were collected from record files sent to the pharmaceutical service of the hospital.

Results: Patients taking atypical antipsychotic medication were associated with a significantly higher mortality rate than patients not taking antipsychotics. The relative risk of death in patients treated with antipsychotics compared to control patients was 2.354 (95% CI 1.704-3.279). The greatest increases in mortality rate occurred close to the last drug supply, and declined exponentially as time passed from the last drug supply in patients who stopped drug assumption. Quetiapine was the most commonly prescribed drug and higher doses of this drug were associated with higher mortality rates.

Conclusions: These results are in line with the April 2005 warning of the Food and Drug Administration (FDA) that among elderly patients with dementia, the treatment of behavioural disorders with atypical antipsychotics is associated with a higher mortality rate. Given the potential risks of mortality with antipsychotics, and since antipsychotic medications may benefit only a minority of patients, new approaches are clearly needed to manage the neuropsychiatric symptoms of dementia.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / mortality
  • Antipsychotic Agents / adverse effects
  • Antipsychotic Agents / therapeutic use*
  • Benzodiazepines / adverse effects
  • Benzodiazepines / therapeutic use*
  • Causality
  • Cholinesterase Inhibitors / adverse effects
  • Cholinesterase Inhibitors / therapeutic use
  • Dementia / drug therapy*
  • Dementia / mortality
  • Dibenzothiazepines / adverse effects
  • Dibenzothiazepines / therapeutic use*
  • Female
  • Humans
  • Italy / epidemiology
  • Kaplan-Meier Estimate
  • Male
  • Olanzapine
  • Outpatients / statistics & numerical data
  • Quetiapine Fumarate
  • Risk
  • Risperidone / adverse effects
  • Risperidone / therapeutic use*


  • Antipsychotic Agents
  • Cholinesterase Inhibitors
  • Dibenzothiazepines
  • Benzodiazepines
  • Quetiapine Fumarate
  • Risperidone
  • Olanzapine