Benzodiazepines are regularly used to treat anxiety, insomnia, and depression. Guidelines advise only short-term benzodiazepine use for elderly patients, but long-term treatment is still common. According to researchers from the University of Montreal in Canada and the University of Bordeaux in France, long-term dosing can do more harm than good for patients at risk for Alzheimer disease. Previous research has established that long-term benzodiazepine use can have deleterious effects on memory and cognition, say the researchers.
Earlier studies could not prove a connection between the drugs and dementia, because they did not have sufficient power, follow-up was too short, or because of other methodologic limitations. To counter those earlier limitations, the researchers designed their study to assess benzodiazepine treatments initiated > 5 years before the diagnosis of Alzheimer disease or dementia, when prescriptions were less likely to be motivated by prodromes.
The researchers used an administrative claims database with a long follow-up period to look at the potential dose-effect relationship. They defined exposure by 3 criteria: “ever use” (≥ 1 claim for a benzodiazepine from 5 to 10 years before the index date); cumulative dose (≤ 3 months, 3 to 6 months, or > 6 months [long-term use]); and drug elimination half-life (short- [< 20 hours] or long-acting benzodiazepines). The researchers matched 1,796 patients with 7,184 controls and followed them for ≥ 6 years before the index date.
The risk of Alzheimer disease, the study revealed, increased by 43% to 51% among people who had used benzodiazepines in the past: 894 (49.8%) people with Alzheimer disease had used benzodiazepines at some point, compared with 2,873 controls (40%). Short-term use did not differ between the 2 groups. Long-term use was more common among people with Alzheimer disease, the researchers found: 32.9% of those with Alzheimer disease compared with 21.8% of those in the control group.
Risk of Alzheimer disease increased when long-acting benzodiazepines were used. Because there is no prevention or cure for Alzheimer disease, the researchers urge focusing on duration of benzodiazepine use and other modifiable risk factors.
Billioti de Gage S, Moride Y, Ducruet T, et al. BMJ. 2014;349:g5205.