Dangers of Combining Opioids and Benzodiazepines

Opioids are not the only prescription drugs fueling injured worker’s addiction, risk of overdose deaths as well as cost of therapy. Extreme dangers are associated with combined use of benzodiazepines and opioids.

Benzodiazepines (sometimes called “benzos”) work to calm or sedate a person, by raising the level of the inhibitory neurotransmitter GABA in the brain. Common benzodiazepines include diazepam (Valium), alprazolam (Xanax), and clonazepam (Klonopin), among others. Benzodiazepines are habit-forming and are commonly prescribed for chronic pain sufferers, often in dangerous combinations with addictive opioid narcotics. One reason benzodiazepine use is prevalent in workers compensation is they have synergistic impact when combined with opioids, enhancing the drugs’ euphoric qualities. The synergy created when combining benzodiazepines and opioids, however, also boosts the potential for addiction beyond each drug’s individual capacity to become habit forming. Clinically, combining opioids and benzodiazepines sedates users and suppresses breathing—the cause of overdose fatality—in addition to impairing cognitive functions.

Every day, more than 136 Americans die after overdosing on opioids.1 However, between 1996 and 2013, the number of adults who filled a benzodiazepine prescription increased by 67%, from 8.1 million to 13.5 million.[1] The quantity obtained also increased from 1.1 kg to 3.6 kg lorazepam-equivalents per 100,000 adults. 

Multiple studies have highlighted the dangers of co-prescribing opioids and benzodiazepines.

Researchers found that in a cohort of 11,394 lost time claims filed with the Louisiana Workers’ Compensation Corporation from 1999 to 2002, benzodiazepines are almost always prescribed in combination with opioids.[2] The odds ratios of benzodiazepines used alone, with short-acting opioids and with long-acting opioids for claims ≥$100,000, were 2.74, 4.69, and 14.24, respectively. Average benzodiazepine daily dose increased to year 3 postinjury and plateaued thereafter, whereas the average opioid dose escalated each year postinjury. The study concluded that the addition of benzodiazepines to an opioid treatment regimen significantly increases workers’ compensation costs.1

In 2019, 16 percent of overdose deaths involving opioids also involved benzodiazepines.[3]  A cohort study in North Carolina found that the overdose death rate among patients receiving both types of medications, benzos and opioids, was 10 times higher than among those only receiving opioids.[4] In a study of overdose deaths in people prescribed opioids for noncancer pain in Canada, 60 percent also tested positive for benzodiazepines.[5] A study among U.S. veterans with an opioid prescription found that receiving a benzodiazepine prescription was associated with increased risk of drug overdose death in a dose-response fashion.[6]

A U.S. Food and Drug Administration (FDA) review has found that the growing combined use of opioid medicines with benzodiazepines or other drugs that depress the central nervous system (CNS) has resulted in serious side effects, including slowed or difficult breathing and deaths. In an effort to decrease the use of opioids and benzodiazepines, a Boxed Warnings, the strongest warning, was added to the drug labeling of prescription opioids and benzodiazepines.

While dangers of prolonged opioid use have become an accepted concern across the workers compensation landscape, the risk of combining benzodiazepines and opioids has not been as well accepted.  Having conversations with prescribers that highlight those dangers has been one of the main topics of ExamWorks pharmacy reviews. Our clinical services are laser focused on helping delineate and implement safer alternative medications and modalities of therapy, such as cognitive behavioral therapy. Our PharmD’s identify the risk factors that increase the length, dangers and cost of therapy, and offer safer cost-effective alternatives as one of the integral parts of our pharmacy services.

For questions about medications or the ExamWorks Compliance Solutions Pharmacy programs, please contact Yelena (Lena) Berndt, PharmD, MSCC, at 678.256.5023 or yelena.berndt@examworkscompliance.com

[1] Cachhuber MA, Hennessy S, Cunningham CO, Starrels JL. Increasing Benzodiazepine Prescriptions and Overdose Mortality in the United States, 1996-2013. Am J Public Health. 2016;106(4):686-688. doi:10.2105/AJPH.2016.303061

[2] Lavin, R. A., Tao, X., Yuspeh, L., & Bernacki, E. J. (2014). Impact of the combined use of benzodiazepines and opioids on workers’ compensation claim cost. Journal of occupational and environmental medicine, 56(9), 973-978. https://doi.org/10.1097/JOM.0000000000000203 

[3] Centers for Disease Control and Prevention, National Center for Health Statistics. Multiple Cause of Death 1999-2019 on CDC WONDER Online Database, released in 2020. Data are from the Multiple Cause of Death Files, 1999-2019, as compiled from data provided by the 57 vital statistics jurisdictions through the Vital Statistics Cooperative Program.

[4] Dasgupta N, Funk MJ, Proescholdbell S, Hirsch A, Ribisl KM, Marshall S. Cohort Study of the Impact of High-Dose Opioid Analgesics on Overdose Mortality. Pain Med Malden Mass. 2016;17(1):85-98. doi:10.1111/pme.12907.

[5] Gomes T, Mamdani MM, Dhalla IA, Paterson JM, Juurlink DN. Opioid dose and drug-related mortality in patients with nonmalignant pain. Arch Intern Med. 2011;171(7):686-691. doi:10.1001/archinternmed.2011.117.

[6]P ark TW, Saitz R, Ganoczy D, Ilgen MA, Bohnert ASB. Benzodiazepine prescribing patterns and deaths from drug overdose among US veterans receiving opioid analgesics: case-cohort study. BMJ. 2015;350:h2698. doi:10.1136/bmj.h2698.

Yelena Berndt, PharmD, MSCC

Dr. Yelena (Lena) Berndt has 17 years of experience in pharmacy practice. She participated in the pharmacy education programs for the University of New York at Buffalo and she provided management within the retail pharmacy setting. Currently, Dr. Berndt performs prescription analysis to optimize drug therapy using evidence-based guidelines and national guidelines, and participates in physician outreaches to implement the recommendations. Her expertise includes early identification of red flags in prescribing patterns, detecting doctor-shopping behavior, identifying evidence of insurance fraud, and recognizing areas of non-compliance. Dr. Berndt received her Doctorate from the State University of New York-Buffalo.

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