Literature Review

Benzodiazepines May Not Increase Dementia Risk



Benzodiazepine use by elderly adults is not causally related to an increased risk of dementia and cognitive decline, according to a prospective study published online ahead of print February 2 in BMJ.

The study included 3,434 individuals age 65 or older without dementia. For at least 10 years before enrollment in the study, all participants had been members of Group Health, an integrated health delivery system in the northwestern United States that maintains computerized pharmacy data, including names, drug doses, dates dispensed, and amounts dispensed of drugs used by its members.

Approximately 30% of participants had filled at least one prescription for a benzodiazepine in the 10 years before entering the study, and 3% of participants had used the drug within six months of study entry. The researchers categorized patients based on their level of benzodiazepine use, and patients in the highest-use category took at least 121 total standardized daily doses (TSDDs). The median level of use within that group was 375 TSDDs, equivalent to slightly more than a year of daily use.

In 2004, the study began continuous enrollment to replace participants who developed dementia, died, or dropped out. Participants were assessed for cognitive function at study entry and every two years afterward. All participants were followed until onset of dementia, disenrollment from Group Health, or their last study visit before September 30, 2012.

The researchers found no association between the use of benzodiazepines at the TSDD level defined as highest use and dementia (hazard ratio [HR], 1.07) or Alzheimer’s disease (HR, 0.95), compared with nonuse. “When we split the highest category of benzodiazepine use into two groups, the hazard ratio for dementia was 1.11 (0.78–1.58) for 121–364 TSDDs and 1.03 (0.73–1.44) for greater than or equal to 365 TSDDs. Findings for Alzheimer’s disease were similar,” said Shelly L. Gray, PharmD, Professor of Pharmacy at the University of Washington School of Pharmacy in Seattle, and her colleagues.

The authors found a slightly increased risk of dementia for study participants classified as low users (ie, those who took 1–30 TSDDs) or moderate users (ie, those who took 31–120 TSDDs) of benzodiazepine, when compared with nonusers. Low users of benzodiazepine were also at increased risk for Alzheimer’s disease (HR, 1.27).

“In conclusion, we found a slightly higher risk of dementia in people with the lowest benzodiazepine use, but no increased risk in those with the highest level of exposure. … Overall, our pattern of findings does not support the theory that cumulative benzodiazepine use at the levels observed in our population is causally related to an increased risk for dementia or cognitive decline. … Nonetheless, given the mixed evidence regarding benzodiazepines and risk of dementia and that these drugs are associated with many adverse events, health care providers are still advised to avoid benzodiazepines in older adults to prevent important adverse health outcomes, withdrawal, and dependence,” according to the researchers.

Katie Wagner Lennon

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