New York, NY—Benzodiazepines heighten opioid-induced respiratory depression—the cause of opioid overdose. Coadministration of the two drug classes is strongly discouraged because concurrent receipt of prescribed opioids and benzodiazepines is associated with adverse patient outcomes.

A recent study in Journal of the American Medical Association Health Forum pointed out that one-third to one-half of prescription opioid overdose deaths involve a benzodiazepine. Yet, researchers from Columbia University Mailman School of Public Health in New York and colleagues noted that in 2017, more than one in five patients prescribed an opioid also received a benzodiazepine. The rate has declined recently, they added, but 3 million adults still receive coprescriptions.

That is despite recommendations against coprescribing in guidelines from the CDC, the joint Department of Veterans Affairs, a Department of Defense document, Choosing Wisely guidance from the American Society of Anesthesiologists, and the Beers Criteria from the American Geriatrics Society. The FDA also requires black box warnings about overdose on all opioid and benzodiazepine product labeling.

One possible solution is for pharmacists to send email alerts to practitioners to reduce the concurrent prescribing of opioids and benzodiazepines. The authors said past “nudge-like interventions” had been effective in reducing benzodiazepine prescribing. In addition, they added “nonrandomized studies of engaging pharmacists to deliver interventions to the rest of the care team have reported the interventions as effective strategies.”

That led to the randomized clinical trial intervention, conducted in 2019-2021, involving 2,237 patients coprescribed opioids and benzodiazepines and 789 practitioners who treated them.

Yet, the study found that email alerts failed to significantly reduce concurrent prescribing of opioids and benzodiazepines. “These findings suggest that alternative strategies may be more fruitful targets for efforts to make opioid prescribing safer and demonstrate that pairing randomization with quality improvement activities can generate evidence for stakeholders,” the authors wrote.

The trial involved patients, healthcare prescribers, and primary care managers in the National Capital Region of the Military Health System. The study randomized patients to either email alerts to their practitioners or as-usual care.

Standardized messages were sent by clinical pharmacists. The report stated they were “designed to facilitate coordination between practitioners, increase awareness of guidelines, and provide action steps and resources.”

The primary outcomes were defined as the patients’ days receiving opioids, benzodiazepines, and concurrent opioids and benzodiazepines during the 90 days following enrollment. The secondary outcomes were total prescribing of opioids and benzodiazepines by patients’ practitioners, including to patients outside of the study (the researchers were seeking to gauge broader outcomes on their prescribing).

The patients (57% women) were assigned either to treatment (1,187) or to control (1,050). Before enrollment, they received a mean (SD) of 31 (44) days of opioids and 33 (34) days of benzodiazepines in the 90 days before enrollment.

Results indicate no detected differences in the primary end points between treatment and control. That included patients’ receipt of:

• Opioids (adjusted difference, 1.1 days; 95% CI, –∞ to 3.0; P = .81)
• Benzodiazepines (adjusted difference, –0.6 days; 95% CI, –∞ to 1.4; P = .30)
• Opioids and benzodiazepines together (adjusted difference, –0.1 days; 95% CI, –∞ to 0.7; P = .41).

“In this randomized clinical trial of pharmacist emails to practitioners, email alerts failed to detectably reduce coprescribing, highlighting the value of alternative approaches,” the authors concluded. “Combining randomization with quality improvement activities may help stakeholders seeking evidence-based interventions to encourage guideline-concordant care.”

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