Anxiety disorders, benzodiazepine prescription, and incident dementia

Abstract

Background: Prescribing benzodiazepines to older patients is controversial. Anxiety disorders and benzodiazepines have been associated with dementia, but literature is inconsistent. It is unknown if anxiety treated with a benzodiazepine, compared to anxiety disorder alone is associated with dementia risk.

Methods: A retrospective cohort study (n = 72,496) was conducted using electronic health data from 2014 to 2021. Entropy balancing controlled for bias by indication and other confounding factors.

Participants: Eligible patients were ≥65 years old, had clinic encounters before and after index date and were free of dementia for 2 years prior to index date. Of the 72,496 eligible patients, 85.6% were White and 59.9% were female. Mean age was 74.1 (SD ± 7.1) years.

Exposure: Anxiety disorder was a composite of generalized anxiety disorder, anxiety not otherwise specified, panic disorder, and social phobia. Sustained benzodiazepine use was defined as at least two separate prescription orders in any 6-month period.

Main outcome and measures: ICD-9 or ICD-10 dementia diagnoses.

Results: Six percent of eligible patients had an anxiety diagnosis and 3.6% received sustained benzodiazepine prescriptions. There were 6640 (9.2%) incident dementia events. After controlling for confounders, both sustained benzodiazepine use (HR 1.28, 95% CI: 1.11-1.47) and a diagnosis of anxiety (HR 1.19, 95% CI: 1.06-1.33) were associated with incident dementia in patients aged 65-75. Anxiety disorder with sustained benzodiazepine, compared to anxiety disorder alone, was not associated with incident dementia (HR 1.18, 95% CI: 0.92-1.51) after controlling for confounding. Results were not significant when limiting the sample to those ≥75 years of age.

Conclusions: Benzodiazepines and anxiety disorders are associated with increased risk for dementia. In patients with anxiety disorders, benzodiazepines were not associated with additional dementia risk. Further research is warranted to determine if benzodiazepines are associated with a reduced or increased risk for dementia compared to other anxiolytic medications in patients with anxiety disorders.

Keywords: anxiety; benzodiazepine; dementia.