SEATTLE—Many clinical guidelines specifically recommend against prescribing benzodiazepines to patients with chronic obstructive pulmonary disease and posttraumatic stress disorder.

Yet, a new study revealed that nearly a fourth of veterans with COPD and PTSD use those medications at the VA and, in a result researchers called “concerning,” those patients had a greater risk of suicide.

The study was published online by the Annals of the American Thoracic Society.1

Lucas M. Donovan, MD, and coauthors from the VA Puget Sound Healthcare System conducted a study of 44,555 veterans with COPD and PTSD diagnoses who received medical care between 2010-12. Of those patients, the study team determined that 23.6% percent received benzodiazepines long term, defined as 90 days or longer.

The report noted that benzodiazepines often are prescribed for COPD symptoms, including anxiety, shortness of breath and insomnia, while frequently used to treat the anxiety and insomnia associated with PTSD.

Adverse side effects have made use of the medications controversial, however, especially because of concerns about an increased risk of COPD exacerbations and self-injury. Many guidelines specifically recommend against their use for patients with COPD or PTSD, although the greatest caution has been urged with longer term prescriptions.

“The use of benzodiazepines among patients with high-risk comorbidities is a frequent dilemma for patients and clinicians,” explained Donovan, a pulmonary, critical care and sleep physician and health services researcher who also is also an acting instructor at the University of Washington. “Understanding the risks of benzodiazepines is difficult, because the symptoms that prompt their use, including anxiety and shortness of breath, are themselves linked with poor outcomes.”

According to the 2018 report of the Global Initiative for Chronic Obstructive Lung Disease, COPD patients, even when receiving optimal therapy, continue to experience distressing breathlessness, impaired exercise capacity, fatigue and suffer panic, anxiety and depression. The GOLD guidance pointed out, however, that “there is no evidence for a beneficial effect of benzodiazepines.”

The VA/DoD guideline, “Management of Chronic Obstructive Pulmonary Disease (COPD),” issued in 2014, recommends, “Multiple types of non-pharmacologic therapy, such as cognitive-behavioral programs and pulmonary rehabilitation programs that include psychotherapy, as well as pharmacologic therapy, such as nortriptyline, buspirone, and sertraline, have been shown to reduce anxiety and, in some cases, depression. However, sedatives/anxiolytics, such as non-selective benzodiazepines, may be associated with adverse effects in COPD patients. Therefore, we recommend consultation with a psychiatrist and/or a pulmonologist before deciding on an appropriate course of treatment.”

Mortality Risks

The VA Puget Sound study team sought to assess the mortality risks of long-term benzodiazepine exposure among patients with COPD and comorbid PTSD.

“Benzodiazepines are associated with mortality and poor outcomes among patients with chronic obstructive pulmonary disease (COPD), but use of benzodiazepines for dyspnea among patients with end-stage disease may confound this relationship,” the authors noted.

To do that, all VHA patients with COPD and PTSD between 2010-12 were identified. Researchers calculated propensity scores for benzodiazepine use and compared overall and cause specific mortality of patients with long-term benzodiazepine use to matched patients who had not used the drugs.

Secondary analyses focused on propensity-adjusted survival by characteristics of benzodiazepine exposure.

In the matched sample of 19,552 patients, no mortality difference (HR for long-term use 1.06, 95%CI 0.95-1.18) was observed, but researchers were able to document a greater risk of death by suicide among those with long-term use (HR 2.33, 95%CI 1.14-4.79).

Not only was suicide risk doubled, but the study team found that those patients had higher rates of psychiatric admissions.

Among matched and unmatched patients, meanwhile, short-term benzodiazepine use, although not long-term use, was associated with increased mortality (short-term: HR 1.16, 95% CI 1.05-1.28; long-term: HR 1.03, 95% CI 0.94-1.13).

Donovan cautioned that the finding on mortality did not carry the weight of the other results because researchers did not use the same matching techniques employed in the primary analyses. Study limitations also included the possibility of not being able to fully determine the severity of lung obstruction or PTSD from medical record data.

“Risks for respiratory compromise related to long-term benzodiazepine use in COPD may be less than previously estimated, but short-term use of benzodiazepines could still pose a mortality risk,” study authors concluded. “Suicide associated with benzodiazepine use in this population warrants further investigation.”

Even though more research is needed, Donovan advised that healthcare professionals take into account patients’ suicide risk before prescribing benzodiazepines.

“Although long-term benzodiazepine use among patients with COPD and PTSD is not linked with overall mortality, the association with suicide is concerning,” he advised in an American Thoracic Society press release. “More research will be needed to better understand this link with suicide, but in the meantime we would advise that clinicians reconsider prescribing benzodiazepines to patients who already are at high risk for self-harm.”