Patients on hemodialysis (HD) prescribed an opioid concurrently with a short-acting benzodiazepine have greater risks of dying than patients not taking these drugs, according to new study findings published in the Clinical Journal of the American Society of Nephrology.

Patients on HD suffer from a high burden of physical and psychiatric conditions often treated with benzodiazepines and are 3 times more likely to be prescribed opioids for pain than the general population, Mara McAdams-DeMarco, PhD, of Johns Hopkins Bloomberg School of Public Health in Baltimore, and colleagues noted.

Of 69,368 patients new to HD (median age 67 years; 68% white; 46% female) in the United States Renal Data System (USRDS), 10,854 patients (16%) were dispensed a short-acting (ie, half-life of 24 hours or less) and 3262 patients (5%) were dispensed a long-acting benzodiazepine within 12 months. Co-dispensing of opioids (eg, hydrocodone, oxycodone, and tramadol) and short-acting benzodiazepines on the same day occurred among 3819 patients and long-acting benzodiazepines among 1238 patients. Opioid users were 66% more likely to be prescribed a short-acting benzodiazepine, such as alprazolam, lorazepam, and temazepam, and 11% more likely to be prescribed a long-acting benzodiazepine such as clonazepam or diazepam than opioid nonusers.

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Patients dispensed a short-acting benzodiazepine were a significant 45% more likely to die early than patients not dispensed the sedative. Among users of short-acting benzodiazepines, a concurrent opioid prescription was significantly associated with a 90% increased mortality risk, Dr McAdams-DeMarco’s team reported. In contrast, users of long-acting benzodiazepine had lower death risks than nonusers.

“Our findings of a synergistic impact of short-acting benzodiazepines and opioids are of great concern in light of the opioid epidemic,” Dr McAdams-DeMarco and colleagues wrote. Benzodiazepines interact with opioids and enhance the respiratory depressant effects of opioids, the authors explained.

Older white females were more likely than others to be prescribed a short-acting benzodiazepine. These particular drugs have a rapid onset and are linked with physical dependence, symptomatic withdrawal, misuse, and addiction.

Prior to prescribing a short-acting benzodiazepine, clinicians should check their state’s prescription drug monitoring programs to determine whether a patient has been dispensed opioids, they stated.

“The potential risks associated with short-acting benzodiazepines should always be weighed against their therapeutic benefit and patients undergoing hemodialysis who are currently undergoing treatment with short-acting benzodiazepines should consider other treatments when clinically appropriate,” Dr McAdams-DeMarco’s team wrote.


Muzaale AD, Daubresse M, Bae S, et al. Benzodiazepines, co-dispensed opioids, and mortality among patients initiating long-term in-center hemodialysis. Clin J Am Soc Nephrol.

Sedative drug in combination with opioids may be especially dangerous [news release]. American Society of Nephrology; May 26, 2020.

Thomas C. A patient’s perspective on benzodiazepines, co-dispensed opioids, and mortality among patients initiating long-term in-center hemodialysis. Clin J Am Soc Nephrol.