“Although our findings need further research and confirmation, the increased risk of pneumonia should be considered when benzodiazepines and Z-drugs are prescribed to older adults with Alzheimer disease,” Heidi Tapale, Ph.D., of the University of Eastern Finland and colleagues wrote. Pneumonia is one of the leading causes of death in older adults with Alzheimer’s.
Tapale and colleagues analyzed national registry data on 49,484 community-dwelling adults diagnosed with Alzheimer’s disease between 2005 and 2011.
In this group, there were 5,232 people taking benzodiazepines (diazepam, nitrazepam, chlordiazepoxide, clobazam, oxazepam, alprazolam, lorazepam, and temazepam) and 3,269 taking related Z-drugs (zopiclone and zolpidem). These patients were matched with an equal number of people with Alzheimer’s not taking either medication.
The researchers then evaluated the effect of incident benzodiazepine use on pneumonia risk, both as an overall risk and time-dependent risk based on duration of medication use—30 days or less, 31 to 180 days, 181 to 365 days, 366 to 1,095 days, and more than 1,095 days. As a secondary analysis, they analyzed benzodiazepine use and risks of extended hospital stays (90 days or more) or death due to causes other than pneumonia.
Collectively, patients taking either benzodiazepines or Z-drugs had about a 1.22-fold increased risk of developing pneumonia. When analyzed separately, benzodiazepine use was significantly associated with an increased risk of pneumonia (hazard ratio [HR]=1.28), whereas Z-drug use did not confer any increased risk. Among those who were taking benzodiazepines, the increased risk was only observed during the first 30 days of use (HR=2.09). By comparison, benzodiazepine use increased the risk of hospitalization or non-pneumonia death by 1.13 fold.
“One possible explanation for the increased risk of pneumonia associated with benzodiazepine use may be related to the more pronounced sedative effects of these drugs in this population. Sedation may increase risk of aspiration, which may lead to pneumonia. In addition, sedation is more pronounced at the start of use before tolerance develops,” Tapale and colleagues wrote.
“However,” they cautioned, “the results are not sufficient to support a conclusion that Z-drugs would be safer than benzodiazepines for patients with Alzheimer disease, because our study was not designed for a direct comparison of the these groups. … Accumulating evidence that use of benzodiazepines and Z-drugs is associated with respiratory adverse effects suggests that future studies examine the possible pharmacologic mechanisms.”
For related information, see the Psychiatric News article “Geriatric Psychiatrists List Do’s, Don’ts for Treating Behavioral Disturbances Associated with Dementia.”