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Benzodiazepine linked to increased risk of pneumonia

Elaine Soliven
18 Apr 2017

Benzodiazepine use appears to be associated with increased risk of pneumonia among patients with Alzheimer’s disease, according to a recent study.

Researchers analysed data from the MEDALZ* cohort including 49,484 patients (mean age 80 years, 62.7 percent female) diagnosed with Alzheimer’s disease. Of these, 5,232 patients were taking benzodiazepines (ie, alprazolam, chlordiazepoxide, clobazam, diazepam, lorazepam, nitrazepam, oxazepam, and temazepam), while 3,269 patients were taking non-benzodiazepines or Z-drugs (ie, zolpidem and zopiclone), and were matched 1:1 with nonusers. [CMAJ 2017;doi:10.1503/cmaj.160126]

Using propensity score-matched analysis, the rate of pneumonia was higher in both benzodiazepine and Z-drug users compared with nonusers (events per 100 person-years, 8.10, 95 percent confidence interval [CI], 8.03–8.16 vs 6.32, 95 percent CI, 6.28–6.35).

Collectively, benzodiazepine and Z-drug use was associated with an increased risk of pneumonia in patients with Alzheimer’s disease (adjusted hazard ratio [adjHR], 1.22, 95 percent CI, 1.05–1.42).

However, on separate analysis, an increased risk of pneumonia was associated with benzodiazepine use (adjHR, 1.28, 95 percent CI, 1.07–1.54) but not with Z-drug use (adjHR, 1.10, 95 percent CI, 0.84–1.44).

“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,” according to the researchers.

Of note was the higher risk of pneumonia associated with benzodiazepine during the first 30 days of use (hazard ratio, 2.09, 95 percent CI, 1.26–3.48).

“[S]edation is more pronounced at the start of use before tolerance develops,” they said, noting that this could account for the increased risk of pneumonia at the beginning of drug use.

Overall, the findings are consistent with previous studies associating benzodiazepine use with an increased risk of pneumonia as well as respiratory exacerbations and emergency department visits for COPD or pneumonia patients. [Thorax 2013;68:163-170; Eur Respir J 2014;44:332-340]

“[The] benefits and risks of the use of benzodiazepines should be carefully considered for patients with Alzheimer’s disease and include risk of pneumonia,” said the researchers, who called for further investigation to determine other pharmacological mechanisms that could verify the association between respiratory adverse events and use of benzodiazepines and Z-drugs.

*MEDALZ: Medication use and Alzheimer’s disease

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