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

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.

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Journal
Pharmacoepidemiology and Drug Safety
Published
2026-04-01
DOI
https://doi.org/10.1002/pds.70368
Primary Topic
Opioid Use Disorder Treatment
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article
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article

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

Liza N. van Steenbergen, Albert Dahan, Marcel L. Bouvy, Maaike G. J. Gademan et al.
Pharmacoepidemiology and Drug Safety
Opioid Use Disorder Treatment
article

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

Liza N. van Steenbergen, Albert Dahan, Marcel L. Bouvy, Maaike G. J. Gademan, Rob G. H. H. Nelissen, Manuela Yepes‐Calderón, Frits R. Rosendaal
article en

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.

Pharmacoepidemiology and Drug SafetyVol. 35(4)
Leiden University Medical Center (NL), Netherlands Heart Registration (NL), Pharmo Institute (NL)
Good health and well-being
Openalex Percentile: Top 23%
Opioid Use Disorder Treatment
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