The Risk of Head Injuries Associated With Antipsychotic Use Among Persons With Alzheimer's disease

J Am Geriatr Soc. 2020 Mar;68(3):595-602. doi: 10.1111/jgs.16275. Epub 2020 Jan 7.


Background/objectives: Antipsychotic use is associated with risk of falls among older persons, but we are not aware of previous studies investigating risk of head injuries. We studied the association of antipsychotic use and risk of head injuries among community dwellers with Alzheimer's disease (AD).

Design: Nationwide register-based cohort study.

Setting: Medication Use and Alzheimer's Disease (MEDALZ) cohort, Finland.

Participants: The MEDALZ cohort includes Finnish community dwellers who received clinically verified AD diagnosis in 2005 to 2011. Incident antipsychotic users were identified from the Prescription Register and matched with nonusers by age, sex, and time since AD diagnosis (21 795 matched pairs). Persons with prior head injury or history of schizophrenia were excluded.

Measurements: Outcomes were incident head injuries (International Classification of Diseases, Tenth Revision [ICD-10] codes S00-S09) and traumatic brain injuries (TBIs; ICD-10 codes S06.0-S06.9) resulting in a hospital admission (Hospital Discharge Register) or death (Causes of Death Register). Inverse probability of treatment (IPT) weighted Cox proportional hazard models were used to assess relative risks.

Results: Antipsychotic use was associated with an increased risk of head injuries (event rate per 100 person-years = 1.65 [95% confidence interval {CI} = 1.50-1.81] for users and 1.26 [95% CI = 1.16-1.37] for nonusers; IPT-weighted hazard ratio [HR] = 1.29 [95% CI = 1.14-1.47]) and TBIs (event rate per 100 person-years = 0.90 [95% CI = 0.79-1.02] for users and 0.72 [95% CI = 0.65-0.81] for nonusers; IPT-weighted HR = 1.22 [95% CI = 1.03-1.45]). Quetiapine users had higher risk of TBIs (IPT-weighted HR = 1.60 [95% CI = 1.15-2.22]) in comparison to risperidone users.

Conclusions: These findings imply that in addition to previously reported adverse events and effects, antipsychotic use may increase the risk of head injuries and TBIs in persons with AD. Therefore, their use should be restricted to most severe neuropsychiatric symptoms, as recommended by the AGS Beers Criteria®. Additionally, higher relative risk of TBIs in quetiapine users compared to risperidone users should be confirmed in further studies. J Am Geriatr Soc 68:595-602, 2020.

Keywords: Alzheimer's disease; antipsychotics; dementia; risk factors; traumatic brain injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / complications*
  • Antipsychotic Agents / therapeutic use*
  • Cohort Studies
  • Craniocerebral Trauma*
  • Female
  • Finland
  • Hospitalization
  • Humans
  • Independent Living*
  • Male
  • Registries
  • Risk*


  • Antipsychotic Agents