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

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 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.

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).

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.