Association between Benzodiazepine and Dementia Risk in Treating Depression after Breast Cancer Diagnosis: A Nationwide Population-Based Cohort Study

Yonsei Med J. 2025 Sep;66(9):564-573. doi: 10.3349/ymj.2024.0262.

Abstract

Purpose: This study investigates the risk of developing dementia in breast cancer patients diagnosed with depression within 2 years of their cancer diagnosis, comparing those taking antidepressants alone versus those taking both antidepressants and benzodiazepines.

Materials and methods: Utilizing data from the Korean National Health Insurance claims database collected over 14 years, we included a cohort of 197917 breast cancer patients. Among them, 19170 were diagnosed with depression within 2 years of their cancer diagnosis. After matching for comorbidities and age, we included 1376 patients in each group for 1:1 matching, and 1326 patients taking only antidepressants and 5304 patients taking both antidepressants and benzodiazepines for 1:4 matching.

Results: In the initial 1:1 matched analysis, no significant difference in dementia incidence was observed between the group taking only antidepressants and the group taking both antidepressants and benzodiazepines. However, further detailed analysis revealed that patients taking higher doses or using benzodiazepines for longer durations had an increased risk of dementia. In the 1:4 matched analysis, the group taking both medications exhibited a significantly higher incidence of dementia compared to those taking only antidepressants (hazard ratio, 1.807; 95% confidence interval, 1.263-2.583; p=0.0012).

Conclusion: This study underscores the importance of cautious benzodiazepine use in breast cancer patients diagnosed with depression, given its potential to significantly increase dementia risk.

Keywords: Breast cancer; benzodiazepines; cognitive impairment; dementia; depression.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antidepressive Agents / adverse effects
  • Antidepressive Agents / therapeutic use
  • Benzodiazepines* / adverse effects
  • Benzodiazepines* / therapeutic use
  • Breast Neoplasms* / complications
  • Breast Neoplasms* / diagnosis
  • Breast Neoplasms* / psychology
  • Cohort Studies
  • Dementia* / chemically induced
  • Dementia* / epidemiology
  • Dementia* / etiology
  • Depression* / complications
  • Depression* / drug therapy
  • Depression* / etiology
  • Female
  • Humans
  • Incidence
  • Middle Aged
  • Republic of Korea / epidemiology
  • Risk Factors

Substances

  • Benzodiazepines
  • Antidepressive Agents