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Benzodiazepines rank among the most commonly prescribed psychotropic medications in high income countries and are known for their sedative, hypnotic, and anxiolytic properties.1 These characteristics make benzodiazepine useful among patients undergoing surgery, particularly individuals with cancer.2 However, the stressor characteristics of a cancer diagnosis and treatment can place patients at risk of aversive coping mechanisms.3 Of note, patients with newly prescribed perioperative benzodiazepines can continue to use these drugs for durations longer than initially intended.4 This condition is often referred to as new persistent benzodiazepine use (NPBU).4 Patients with cancer may be at particular risk of NPBU as they often require higher doses to manage conditions such as therapy related nausea or vomiting.2 As such, the current study sought to assess NPBU among patients undergoing a surgical procedure for cancer, and to identify risk factors associated with NPBU.2
Present
Among 34,637 patients who underwent resection of primary cancer of breast, lung, esophagus, stomach, pancreas, liver, gall bladder, colon, rectum, or prostate, almost 8% developed NPBU. Patients with mental health illnesses, such as depression (12.7% versus 7.2%) or anxiety (15.5% versus 7.7%) were more likely to develop NPBU. Similarly, patients who underwent neoadjuvant therapy (chemotherapy: 88.1% versus 61.1%; radiotherapy: 33.8% versus 24.0%) and adjuvant therapy (chemotherapy: 79.4% versus 44.4%; radiotherapy: 17.2% versus 10.5%) more often developed NPBU. Of note, the development of concurrent new persistent use of opioids was associated with 84% higher odds of concomitant NPBU. Interestingly, patients with new perioperative benzodiazepine exposure versus non-exposure had two-fold higher odds of NPBU [odds ratio (OR) 2.00, 95% confidence interval (CI) 1.68–2.38]. This association was consistent across high-versus-low doses of perioperative benzodiazepine (ref. dose of < 10.5 LME; dose of 10.5–19.9 LME: OR 1.71, 95% CI 1.40–2.10; dose of 20.0–32.0 LME: OR 1.88, 95% CI 1.55–2.29; dose of > 32.0 LME: OR 2.42, 95% CI 2.01–2.92).
Future
Surgical patients, particularly individuals with malignancy, can often have multiple co-morbidities and complex care needs.3 There can be a high prevalence of behavioral disorders (e.g., eating or sleeping disorders), as well as mental health problems (e.g., depression or anxiety) among these individuals.3 These morbidities in turn can lead to higher utilization of benzodiazepines following surgery and development of surgical complications, such as NPBU.2 As such, multidisciplinary management of these patients with counseling services can mitigate the risk of such complications.3 Similarly, a vast majority of patients can have leftover pills from prescriptions related to the index surgical admission.5 This reservoir of unneeded medications can act as a major contributor to narcotic diversion among patients.5 NPBU can be addressed through implementation of programs to encourage convenient and safe disposal of leftover medications.2 Furthermore, alternatives to benzodiazepine should be employed whenever possible. When benzodiazepines are unavoidable, these drugs should be used with lower doses and shorter durations.2
References
Peng L, Meeks TW, Blazes CK. Complex persistent benzodiazepine dependence—when benzodiazepine deprescribing goes awry. JAMA Psychiatry. 2022;79(7):639–40. https://doi.org/10.1001/jamapsychiatry.2022.1150.
Rashid Z, Woldesenbet S, Khalil M, et al. Perioperative benzodiazepine exposure impacts risk of new persistent benzodiazepine use among patients with cancer. Ann Surg Oncol. 2024. https://doi.org/10.1245/s10434-024-16788-3.
Katayama ES, Woldesenbet S, Munir MM, et al. effect of behavioral health disorders on surgical outcomes in cancer patients. J Am Coll Surg. 2024;238(4):625–33. https://doi.org/10.1097/XCS.0000000000000954.
Sakamoto MR, Eguchi M, Azelby CM, et al. New persistent opioid and benzodiazepine use after curative-intent treatment in patients with breast cancer. J Natl Compr Canc Netw. 2021;19(1):29–38. https://doi.org/10.6004/jnccn.2020.7612.
Khalil M, Woldesenbet S, Munir MM, et al. Surgical opioid prescription and the risk of opioid initiation among opioid-naive households. Am J Surg. 2025;241:116029. https://doi.org/10.1016/j.amjsurg.2024.116029.
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This article refers to: Rashid Z, Woldesenbet S, Khalil M, et al. Perioperative Benzodiazepine Exposure Impacts Risk of New Persistent Benzodiazepine Use Among Patients with Cancer. Annals Surgical Oncology. (2024). https://doi.org/10.1245/s10434-024-16788-3
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Rashid, Z., Pawlik, T.M. ASO Author Reflections: New Persistent Benzodiazepine Use following Cancer Surgery. Ann Surg Oncol 32, 3441–3442 (2025). https://doi.org/10.1245/s10434-024-16861-x
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DOI: https://doi.org/10.1245/s10434-024-16861-x