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Factors Associated With Concurrent Benzodiazepine and Opioid Use Following Total Hip and Knee Arthroplasty: A

Manuela Yepes-Calderón^1,2, Rob G H H Nelissen^1,3, Marcel L Bouvy⁴

¹Department of Orthopedics, Leiden University Medical Center, Leiden, the Netherlands.

Pharmacoepidemiology and Drug Safety

|April 10, 2026

Abstract

Purpose:

Concurrent use of benzodiazepines and opioids is discouraged due to synergistic adverse effects. However, patients undergoing total hip or knee arthroplasty (THA/TKA) often receive them, particularly in the first 3 postoperative months. We identified factors associated with new outpatient concurrent benzodiazepine-opioid dispensation following THA/TKA.

Methods:

In this nationwide cohort study, we linked the Dutch Arthroplasty Register with the Dutch Foundation for Pharmaceutical Statistics, which provided medication dispensation data. We included all patients undergoing primary elective THA/TKA (2013-2022) who had no preoperative concurrent use in the 6 months pre-procedure. The primary outcome was ≥ 7 days of a new concurrent benzodiazepine-opioid dispensation within 90-day postoperative. Determinants included patient and implant characteristics, and preoperative medication use. Multivariable logistic regression analyses were performed, adjusted for age, sex, and comorbidity.

Results:

Among 89 139 THA and 76 710 TKA patients, 3756 (4%) and 5571 (7%), respectively, received new postoperative concurrent benzodiazepine-opioid dispensation within 90-days postoperative. The main factor associated with such dispensation was preoperative benzodiazepine use (THA: OR 23.5 [95% CI: 21.8-25.3], TKA: OR 22.8 [95% CI: 21.3-24.3]), followed by preoperative antidepressant/anxiolytic use (THA: OR 2.9 [95% CI: 2.6-3.1], TKA: OR 2.5 [95% CI: 2.3-2.7]). Other factors included female sex, current smoking, and American Society of Anesthesiologists (ASA) scale III-IV. Preoperative pain scores, preoperative opioid use, and implant characteristics showed little to no association with the outcome.

Conclusions:

Preoperative benzodiazepine use was the main factor associated with new outpatient concurrent benzodiazepine-opioid dispensation after THA/TKA, followed by preoperative antidepressant/anxiolytic use. These results highlighted that careful review of the patient's medication history when planning postoperative pain management could help prevent unsafe co-prescription.

Keywords:

arthroplasty benzodiazepines concurrent use opioids pharmacoepidemiology polypharmacy

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