Antipsychotic Use Increases Fall Risk for Alzheimer Patients

There are many concerns regarding antipsychotics, especially for Alzheimer disease patients by increasing the risk of falls.

A team based in Finland and Sweden, led by Vesa Tapiainen, MD, School of Pharmacy, University of Eastern Finland, identified the link between antipsychotic use and the risk of head injuries for community dwellers with Alzheimer disease in a nationwide register-based cohort study.

The Medication Use and Alzheimer’s Disease (MEDALZ) cohort included Finnish community dwellers who received a clinically verified Alzheimer disease diagnosis between 2005-2011.

Incident antipsychotic users were identified from the Prescription Register and matched with non-users by age, sex, and time since Alzheimer disease diagnosis.

Overall, the investigators found 21,795 matched pairs.

Antipsychotic use has long been linked to an increased risk of falls for geriatric adults, but previous studies did not look at the risk of head injuries. Patients with a prior history of schizophrenia or a head injury were excluded from the study.

The investigators sought outcomes of incident head injuries based on the International Classification of Diseases, Tenth Revision (ICD‐10) codes S00‐S09 and traumatic brain injuries based on TBIs; ICD‐10 codes S06.0‐S06.9 resulting in a hospital admission or death.

The team assessed the relative risks using inverse probability of treatment (IPT) weighted Cox proportional hazard models.

Antipsychotic use was tied directly to an increased risk of head injuries (event rate per 100 person‐years = 1.65 [95% 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 traumatic brain injuries (TBI) (event rate per 100 person‐years = 0.90 [95% CI, .79‐1.02] for users and .72 [95% CI, .65‐.81] for nonusers; IPT‐weighted HR, 1.22 [95% CI, 1.03‐1.45]).

The risk of traumatic brain injuries was particularly high for quetiapine users (IPT‐weighted HR, 1.60; 95% CI, 1.15‐2.22) in comparison to risperidone users.

“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 [Alzheimer disease},” the authors wrote. “Therefore, their use should be restricted to most severe neuropsychiatric symptoms, as recommended by the AGS Beers Criteria.”

The investigators also suggest investigating the link between quetiapine and traumatic brain injuries further.

In another Finland-based cohort involving 62,250 patients, investigators discovered the link between antipsychotics and schizophrenia.

The investigators identified the use of all antipsychotic drugs, as well as the use of specific antipsychotics. They sought outcomes of somatic and cardiovascular hospitalization and all-cause, cardiovascular, and suicide death.

The adjusted hazard ratios (aHRs) for any somatic hospitalization and cardiovascular hospitalization were 1.00 (95% CI, .98‐1.03) and 1.00 (95% CI, .92‐1.07) during use of any antipsychotic compared to non‐exposure periods within the same individual.

The aHRs were .48 (95% CI, .46‐.51) for all‐cause mortality, .62 (95% CI, .57‐.67) for cardiovascular mortality, and .52 (95% CI, .43‐.62) for suicide mortality during use compared with non‐use of any antipsychotic.

Clozapine was labeled as the drug with the most beneficial mortality outcome in terms of all-cause (aHR, .39; 95% CI, .36‐.43), cardiovascular (aHR, .55; 95% CI, .47‐.64), and suicide mortality (aHR, .21; 95% CI, .15‐.29).

Cumulative mortality rates during maximum follow‐up of 20 years were 46.2% for no antipsychotic use, 25.7% for any antipsychotic use, and 15.6% for clozapine use.

The study, “The Risk of Head Injuries Associated With Antipsychotic Use Among Persons With Alzheimer's disease,” was published online in the Journal of American Geriatrics Society.