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Common sedatives increase pneumonia risk in Alzheimer patients

Commonly used sedatives, benzodiazepines, are associated with an increased risk of pneumonia when used in people with Alzheimer disease, according to a Finnish study.

"An increased risk of pneumonia is an important finding to consider in treatment of patients with Alzheimer disease," writes Dr Heidi Taipale, Kuopio Research Centre of Geriatric Care, University of Eastern Finland, Kuopio, Finland, with co-authors.

"Benzodiazepines and Z-drugs are frequently prescribed for this population, and long-term use is typical. Pneumonia often leads to admission to hospital, and patients with dementia are at increased risk of death related to pneumonia."

Dementia, of which 60%-70% of cases are Alzheimer disease, is a risk factor for pneumonia, and many people with dementia are prescribed benzodiazepines and non- benzodiazepines (called Z-drugs), both of which have sedative effects.

To determine if there is a link between these drugs and pneumonia, Finnish researchers looked at data from national registries on 49 484 adults living in the community diagnosed with Alzheimer disease between 2005 and 2011 in Finland. The mean age of participants was 80 years and almost two-thirds (62.7%) were women. They matched 5232 patients taking benzodiazepines and 3269 patients taking Z-drugs with the remainder not taking either drug.

They found that benzodiazepines were linked to a 30% increased risk of pneumonia in patients with Alzheimer disease, and the risk was highest at the start of treatment (during the first 30 days).

Although the association with Z-drug use and pneumonia was not statistically significant, the authors did not conclude these drugs were safer as the study did not directly compare Z-drugs and benzodiazepines.

The authors suggest that the sedative nature of benzodiazepines may increase the risk of pneumonia by increasing the aspiration of saliva or food into the lungs. The results are consistent with studies that have found an increased risk of pneumonia in patients of all ages taking benzodiazepines.

"Benefits and risks of the use of benzodiazepines should be carefully considered for patients with Alzheimer disease and include risk of pneumonia," the authors conclude.

In a related commentary, Dr Paula Rochon from Women's College Hospital and the University of Toronto, with co-authors, writes this study "is a good reminder to clinicians to 'first do no harm' when prescribing these drugs for frail older women and men with dementia. Non-pharmacologic approaches should be the starting point when managing neuropsychiatric symptoms in this patient population, which should help to limit inappropriate use of these drugs."

Background: Knowledge regarding whether benzodiazepines and similarly acting non-benzodiazepines (Z-drugs) are associated with an increased risk of pneumonia among older adults is lacking. We sought to investigate this association among community-dwelling adults with Alzheimer disease, a condition in which both sedative/hypnotic use and pneumonia are common.
Methods: We obtained data on all community-dwelling adults with a recent diagnosis of Alzheimer disease in Finland (2005–2011) from the Medication use and Alzheimer disease (MEDALZ) cohort, which incorporates national registry data on prescriptions, reimbursement, hospital discharges and causes of death. Incident users of benzodiazepines and Z-drugs were identified using a 1-year washout period and matched with nonusers using propensity scores. The association with hospital admission or death due to pneumonia was analyzed with the Cox proportional hazards model and adjusted for use of other psychotropic drugs in a time-dependent manner.
Results: Among 49 484 eligible participants with Alzheimer disease, 5232 taking benzodiazepines and 3269 taking Z-drugs were matched 1:1 with those not taking these drugs. Collectively, use of benzodiazepines and Z-drugs was associated with an increased risk of pneumonia (adjusted hazard ratio [HR] 1.22, 95% confidence interval [CI] 1.05–1.42). When analyzed separately, benzodiazepine use was significantly associated with an increased risk of pneumonia (adjusted HR 1.28, 95% CI 1.07–1.54), whereas Z-drug use was not (adjusted HR 1.10, 95% CI 0.84–1.44). The risk of pneumonia was greatest within the first 30 days of benzodiazepine use (HR 2.09, 95% CI 1.26–3.48).
Interpretation: Benzodiazepine use was associated with an increased risk of pneumonia among patients with Alzheimer disease. Risk of pneumonia should be considered when weighing the benefits and risks of benzodiazepines in this population.

Heidi Taipale, Anna-Maija Tolppanen, Marjaana Koponen, Antti Tanskanen, Piia Lavikainen, Reijo Sund, Jari Tiihonen, Sirpa Hartikainen

[link url=""]Canadian Medical Association material[/link]
[link url=""]Canadian Medical Association Journal abstract[/link]

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