Insomnia drug class may not affect death and exacerbation risks in patients with COPD

Patients with chronic obstructive pulmonary disease taking newly prescribed non-benzodiazepine benzodiazepine receptor agonists (NBZRAs) such as zolpidem (Ambien, Intermezzo, and other brands), a class of hypnotics prescribed for insomnia, did not have an increased risk of exacerbations requiring hospitalization or death than those who prescribed other types of hypnotics, according to research published at the ATS 2023 International Conference. However, compared to those without hypnotic drugs, the researchers found a greater risk of death or exacerbations.

“Although NBZRAs are commonly used to treat insomnia, they are associated with respiratory depression and even death in patients with COPD,” said lead author Jason Castaneda, MD, resident of internal medicine, University of Washington, Seattle. “While several observational studies have shown this to be the case, these studies lacked an active comparator – another class of drugs to compare with NBZRAs. This may be a confusing factor as insomnia itself is associated with these risks for COPD- patients.”

To tease out the role of NBZRAs, the researchers designed a study that used thousands of Veterans Health Administration medical records to compare the risk of death or inpatient exacerbations for COPD patients who received new prescriptions for NBZRAs with patients who received other medications that were hypnotics, but were not NBZRAs. Among the other hypnotics were melatonin, ramelteon (Rozerem), trazodone (Desyrel, Oleptro), and doxepin (Silenor, SINEquan).

They compared patients who received NBZRAs and other hypnotics on 40 variables, such as demographics, medical and sleep disorders, and the severity of COPD. They also matched patients taking NBZRAs with those not taking sleep aids. Dr. Castaneda and colleagues used a statistical Cox model to compare all-cause death or inpatient COPD exacerbation within one year.

The scientists identified 1,276 COPD patients who received new NBZRA prescriptions in Veterans Health Administration records, and 3,372 who received new prescriptions for other hypnotics. When the NBZRA patients were matched with the same number of patients prescribed other hypnotics, the researchers found no difference in patient mortality or exacerbation risk. When compared to the same number of COPD patients who were not prescribed NBZRAs or other hypnotics, they saw greater risks of both death and worsening of the drugs.

Commenting on the significance of the study’s findings, Dr. Castaneda: “The greater risk of hypnotics may reflect residual, unmeasured confounding related to insomnia. It may also be real side effects of hypnotics breaking hypnotic classes. We need additional research so that we can understand the risks of hypnotics in patients with COPD better understand and then optimize strategies to safely improve symptoms.”

The study was conducted at the VA Puget Sound Health Care System. Several of the researchers, including senior author Lucas Donovan, MD, have dual appointments with the VA health care system and the University of Washington.