Benzodiazepine Use and Risk of Community-Acquired Pneumonia in a Population-Based Cohort Study From North-Eastern Spain

Abstract

Background: Benzodiazepine (Bz) exposure has been identified as a risk factor of community-acquired pneumonia (CAP) in some observational studies, but this remains controversial. This study was designed to quantify the risk of CAP associated with treatment with Bz. Methods: All individuals ⩾14 years of age registered in any of 3 primary health care providers in our area between January 2011 and May 2013 were included in the study. This resulted in a population of 51 912 individuals who contributed to a total of 1 496 680 person-months of observation. Previously anonymized data for each participant were obtained from their personal health records and the official prescription database. The primary outcome measures were the incidence of CAP during the study period and the relative risk (RR) that could be attributed to Bz exposure. Results: A total of 696 CAP cases were diagnosed. Incidence density was 12.4 cases per 1000 person-years in individuals exposed to Bz and 4.51 cases per 1000 person-years in those who were not. Benzodiazepine exposure increased the risk of CAP in the whole population (RR: 2.76, 95% confidence interval: 2.35-3.25) and in all the evaluated subgroups. Stratified analysis showed an interaction only with age (RR: 2.99 in patients under 65 years and 1.78 in those aged 65 or older). Benzodiazepine exposure was associated with an excess 0.79 cases of CAP per 100 person-years. Conclusions: Benzodiazepine exposure increases the risk of CAP. Given the clinical relevance of CAP, prescribers should be aware of this potentially preventable risk and consider it while newly prescribing Bz.

Benzodiazepines or related drugs and risk of pneumonia: A systematic review and meta‐analysis

“…Two case‐control studies used the National Health Insurance Research Database of Taiwan; however, we include both two studies in the meta‐analysis because they were conducted by different investigators, and a study conducted by Chen et al provided additional data for individual BZRD drug analysis. Altogether, the meta‐analysis included 12 citations of 10 studies, which involved over 120,000 pneumonia cases from six case‐control studies and four cohort studies . The study selection process is presented in Figure .…”

“…The earliest study was published in 1999 and the most recent in 2018. All included studies were population‐based and were conducted in the USA (n = 2), Europe (n = 7), and Asia (n = 1) . Nine studies identified patients through administrative databases, whereas only one used medical records.…”

“…Nine studies identified patients through administrative databases, whereas only one used medical records. Four studies focused on only elderly subjects (older than 65 years); six studies included both adult and elderly participants, and four of these six studies grouped participants into two age groups. The outcome of interest was defined as influenza‐like illness‐related pneumonia in one study, community‐acquired pneumonia(CAP) in four studies, and pneumonia with no further specification in the other studies.…”

“…The mean NOS score of the nine studies included in the analysis was 7.4. Eight studies were of high quality (NOS ≥ 7), and two studies were of low quality (NOS < 7) (Supporting Information Tables S3 and S4).…”

“…However, whether BZRD therapy is associated with an increased risk of pneumonia is still much debated. A number of epidemiological studies have investigated this possible association, and some studies reported an increased risk of pneumonia in BZRD users, whereas others did not. Given the widespread use of BZRDs, it is important to determine whether there is a relationship between BZRD use and risk of pneumonia.…”