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. 2025 May;32(5):3416-3428.
doi: 10.1245/s10434-024-16788-3. Epub 2024 Dec 28.

Perioperative Benzodiazepine Exposure Impacts Risk of New Persistent Benzodiazepine Use Among Patients with Cancer

Zayed Rashid  1 , Selamawit Woldesenbet  1 , Mujtaba Khalil  1 , Abdullah Altaf  1 , Shreya Shaw  1 , Amanda B Macedo  2 , Shahzaib Zindani  1 , Giovanni Catalano  1 , Timothy M Pawlik  3
Affiliations

Perioperative Benzodiazepine Exposure Impacts Risk of New Persistent Benzodiazepine Use Among Patients with Cancer

Zayed Rashid et al. Ann Surg Oncol. 2025 May.

Abstract

Background: Benzodiazepines are the third most misused medication, with many patients having their first exposure during a surgical episode. We sought to characterize factors associated with new persistent benzodiazepine use (NPBU) among patients undergoing cancer surgery.

Patients and methods: Patients who underwent cancer surgery between 2013 and 2021 were identified using the IBM-MarketScan database. NPBU was defined as one prescription filled during the 90-180 days period after surgery by patients who were previously benzodiazepine naïve. The association of variables with perioperative benzodiazepine use and NPBU was assessed using multivariable regression.

Results: Among 34,637 patients with cancer (breast: n = 5460, 15.8%; lung: n = 3479, 10.0%; esophagus: n = 384, 1.1%; gastric: n = 852, 2.5%; liver: n =502, 1.4%; biliary: n = 268, 0.8%; pancreas: n = 1290, 3.7%; colon: n = 10,838, 31.3%; rectum: n = 2566, 7.4%; prostate: n = 8998, 26.0%), most were male (n = 19,687, 56.8%) with a median age of 57 years (IQR 51-61 years). Overall, 8.8% of patients had perioperative benzodiazepine use and 7.5% of patients developed NPBU following surgery. On multivariable analyses, perioperative benzodiazepine exposure (ref. no perioperative exposure: OR 2.00, 95% CI 1.68-2.38) and higher perioperative dose of > 32.0 lorazepam milligram equivalents (LME) (ref. < 10 LME: OR 2.42, 95% CI 2.01-2.92) were independently associated with higher odds of NPBU. Notably, male patients had lower odds of NPBU versus female patients (OR 0.80, 95% CI 0.68-0.94).

Conclusions: Roughly 1 in 13 commercially insured patients developed NPBU following surgery for cancer. Judicious use of benzodiazepines among patients with high risk of misuse can mitigate NPBU to help avoid benzodiazepine-related complications such as overdose or accidental deaths.

Keywords: Chemoradiotherapy; Lorazepam milligram equivalents; Misuse; Prescription drugs; Temporal trends.

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Conflict of interest statement

Disclosures: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. The authors declare no funding or financial support. The authors declare no conflict of interest.

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