Addition of Benzodiazepines Increases Risk of Overdose among Opioid Users
Patients treated with opioids for pain who also receive benzodiazepines face an increased risk of death from drug overdose, with higher benzodiazepine dosage raising that risk, a new study co-authored by researchers from the School of Public Health, Brown University, and the Department of Veterans Affairs shows.
While the study could not determine whether benzodiazepines were the direct cause of overdose deaths, it did find that receipt of concurrent benzodiazepines was associated with an increased risk of overdose deaths in a large, national sample of veterans who were taking opioid analgesics. Benzodiazepines—medications commonly used to treat anxiety and insomnia—are often prescribed for patients also receiving high doses of opioid analgesics, used to treat pain.
“Although the design of this study does not allow for the determination of the extent to which benzodiazepines cause deaths from overdose, it does indicate a need for clinicians to be aware of the increased risk among patients currently receiving benzodiazepines and opioids, and that the risk might be higher among those receiving higher doses of either or both drugs,” the study, published in BMJ, says.
The heightened risk “might be due to risks inherent to those (patients) prescribed benzodiazepines, such as the presence of an anxiety condition and/or to the benzodiazepine itself,” the authors said. “Thus, clinicians should be cautious when prescribing benzodiazepines to this group.”
The researchers studied 2,400 US veterans, primarily male, who received Veterans Health Administration (VHA) opioid prescriptions in the years 2004-2009 and who died from a drug overdose. Of that group, 1,185 (49 percent) died during a period in which they had been prescribed concurrent benzodiazepines.
Unadjusted rates of death from overdose were higher during periods when the veterans were receiving benzodiazepines and opioids than if they had stopped receiving benzodiazepines or were only receiving opioids. The rates of death from overdose increased at consecutively higher categories of daily benzodiazepine dose.
Periods during which veterans received lorazepam and temazepam had lower rates of death from overdose than periods involving other benzodiazepine types.
Because benzodiazepines were more likely to be prescribed to those with substance misuse and other psychiatric disorders—conditions that carry their own risk of death from overdose—the researchers said the association between receipt of benzodiazepines and overdose deaths might be partially explained by those underlying conditions.
“Although the risk of death from overdose increased in a benzodiazepine dose-response fashion, this could reflect an effect of greater psychiatric severity, or other differences between patients who did and did not receive benzodiazepines, rather than the benzodiazepine itself,” the authors said.
Because of those considerations, “benzodiazepines might be better conceptualized as a marker of risk, with unknown direct causal links to death from overdose.”
The authors said their findings were largely consistent with studies that have indicated risks associated with concurrent benzodiazepine and opioid use. Previous studies have looked at smaller subgroups of patients taking opioid analgesics. An association between opioid dose and risk of death from overdose has been found in prior studies, a finding replicated in this study.
“The risk of combining benzodiazepines and opioid analgesics was approximately four times higher than in those receiving opioids alone,” said Tae Woo Park, now an assistant professor in medicine and psychiatry at the Warren Alpert Medical School of Brown University, who did the work for his thesis as an MSc student at SPH. “Given that drug overdoses have become a leading cause of injury mortality, more research is needed to help identify which patients receiving benzodiazepines are most at risk of dying and ultimately find ways to reduce that risk.”
The study was funded by a Veteran Affairs Health Services Research and Development Service Career Development Award and by the National Institutes of Health.
Co-authors include Dara Ganoczy, a research health science specialist with the Department of Veterans Affairs; Mark A. Ilgen and Amy S. B. Bohnert, associate professors of psychiatry at the University of Michigan Medical School and researchers with the Department of Veterans Affairs in Ann Arbor; and Richard Saitz, chair of the SPH Department of Community Health Sciences.
Submitted by: Lisa Chedekel