Benzodiazepine Use Linked to Pneumonia

Fran Lowry

December 07, 2012

The use of benzodiazepines is associated with an increased risk of developing and dying of pneumonia, according to a new study.

Benzodiazepines are commonly prescribed for anxiety, epilepsy, muscle spasm, and insomnia. They are also used in palliative care, as a sedative, and to help people who are addicted to alcohol stop drinking.

The authors stressed that although their case-control data show an association between benzodiazepine use and increased risk for the occurrence of and mortality from community-acquired pneumonia, the finding requires confirmation in a prospective study.

In the meantime, "Doctors should reassure their patients that while the study is suggestive of harm, it is not definitive and further information is needed on the safety of benzodiazepine drugs," coauthor Robert Sanders, MD, from the Institute of Cognitive Neuroscience, University College London, United Kingdom (UK) told Medscape Medical News.

"If patients wish to stop their medication they should discuss this with their physician," he added. "I would like this study to stimulate prospective studies, including randomized controlled trials and cohort studies in this area."

Their report is published online December 5 in Thorax.

Susceptibility to Infection

In the UK and the United States, approximately 2% of the population have taken benzodiazepines for at least 12 months, and their use is even more prevalent in the elderly, in whom use has been estimated to be as high as 10%, the study authors, led by Eneanya Obiora, MD, from the University of Nottingham, UK, write.

"Accumulating preclinical and clinical data suggest that benzodiazepines may increase susceptibility to infection, but little is known about the immune effects in humans of subsedative doses of benzodiazepines," Dr. Sanders said.

Dr. Robert Sanders

In the current study, the researchers sought to determine whether these commonly used drugs, specifically diazepam, chlordiazepoxide, lorazepam, and temazepam, were associated with an increased risk for pneumonia.

They analyzed the health records of patients whose data were entered into the Health Improvement Network, a primary care patient database that contains the records of more than 9 million patients from primary care practices across the UK.

They focused on 4964 patients with an incident diagnosis of community-acquired pneumonia between 2001 and 2002 and compared them with 29,697 age- and sex-matched controls.

After adjustment for a variety of confounders (including current smoking, presence of lung disease, diagnosis of depression or psychosis, myocardial infarction, and previous episode of pneumonia), benzodiazepine use was associated with a 54% risk of developing pneumonia (odds ratio, 1.54; 95% confidence interval [CI], 1.42 - 1.67; P < .001).

Use of benzodiazepines was also associated with an increased risk of dying of pneumonia at 30 days, as shown by a hazard ratio (HR) of 1.22 (95% CI, 1.06 - 1.39; P = .004), or within 3 years of diagnosis (HR, 1.32; 95% CI, 1.19 - 1.47; P < .001).

Individually, chlordiazepoxide was not associated with an increased incidence of community-acquired pneumonia, but it was linked to an increased risk of dying of pneumonia.

Dr. Sanders suggested one possible reason for the benzodiazepine-pneumonia link.

"Our working hypothesis is that the immune effects of benzodiazepines are linked to gamma-aminobutyric acid type A, GABA-A, receptors that are expressed on neurons and immune cells," he said.

Benzodiazepine Pneumonia Link Intriguing and Surprising

Medscape Medical News invited immunologist and pulmonologist Gregory E. Holt, MD, PhD, from the University of Miami Miller School of Medicine, Florida, to comment on this study.

Calling the study "intriguing," Dr. Holt confessed that he was "a little surprised" to see that benzodiazepines had an effect on the immune system.

Dr. Gregory E. Holt

"I had never heard of that before, and when I looked it up, the data wasn't as strong as the study authors want to make it sound, that there is something known about benzodiazepines causing specific immune problems," he said.

One strength of the study was its large database. However, a limitation was that the data were based on diagnosis codes as entered by the physician, Dr. Holt noted.

"Everything is coded based on what the physician puts in as a diagnosis code. There's always some problems with getting all of the data from that, but given the limitations of what you can do with such a population study, this was fairly well done," he said.

"The correlation between benzodiazepine use and pneumonia is there. The hazard ratios aren't super high, the study shows that there seems to be something to it, but this is a correlative study, not a causative study."

Also intriguing is the reason for the link between benzodiazepine use and pneumonia that the authors have suggested, Dr. Holt remarked.

"The effect of benzodiazepines acting through the GABA receptor on the immune cells may be one of the things causing this increase in pneumonia. However, another reason may be due to the fact that these medications can decrease patients' sensorium so that they are sedated. In those cases, people do have a harder time protecting their airways, they may aspirate further, and that may be one cause of the increased chance of pneumonia," he said.

Like the study authors, Dr. Holt said a prospective, causative study would be "ideal" to determine causality, but such a study would be very difficult to do.

"In lieu of that, doctors need to be sure they are using these medications wisely. The benzodiazepines are a great class of medications, but unfortunately the better life through chemistry idea of a lot of current medication usage is hurting people, and this may just be one example of it," he said. "If patients need a benzodiazepine, they should use them, but we need to treat the entire patient and consider what we need to do to get this patient off of these drugs," he said.

Dr. Sanders and Dr. Holt have disclosed no relevant financial relationships.

Thorax. Published online December 5, 2012. Abstract