Association of co-prescribing of opioid and benzodiazepine substitutes with incident falls and fractures among older adults: a cohort study

Objective Examine the association between the co-prescribing of opioids, benzodiazepines, gabapentinoids (pregabalin and gabapentin) and selective serotonin reuptake inhibitors/serotonin and norepinephrine reuptake inhibitors (SSRI/SNRIs) in different combinations and the risk of falls and fractures...

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Main Authors: Rahul Shah, Yong-Fang Kuo, Jordan Westra, Mukaila A Raji
Format: Article
Language:English
Published: BMJ Publishing Group 2021-12-01
Series:BMJ Open
Online Access:https://bmjopen.bmj.com/content/11/12/e052057.full
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author Rahul Shah
Yong-Fang Kuo
Jordan Westra
Mukaila A Raji
author_facet Rahul Shah
Yong-Fang Kuo
Jordan Westra
Mukaila A Raji
author_sort Rahul Shah
collection DOAJ
description Objective Examine the association between the co-prescribing of opioids, benzodiazepines, gabapentinoids (pregabalin and gabapentin) and selective serotonin reuptake inhibitors/serotonin and norepinephrine reuptake inhibitors (SSRI/SNRIs) in different combinations and the risk of falls and fractures.Design Retrospective cohort study from 2015 to 2018.Setting Medicare enrolment and claims data.Participants Medicare beneficiaries with both chronic pain and anxiety disorders in 2016 with continuous enrolments in Parts A and B from 2015 to 2016 who were prescribed any combination of opioid, benzodiazepine, gabapentinoid and SSRI/SNRI in 2017 for ≥7 days, as documented in their Medicare Part D coverage.Interventions Any combination of use of seven drug regimens (benzodiazepine +opioid; benzodiazepine +gabapentinoid; benzodiazepine +SSRI/SNRI; opioid +gabapentinoid; opioid +SSRI/SNRI; gabapentinoid +SSRI/SNRI; ≥3 drug classes).Main outcomes First event of fall and the first event of fracture after the index date, which was the first day of combination drug use that lasted ≥7 days in 2017.Results A total of 47 964 patients (mean [SD] age, 75.9 [7.1]; 78.0% woman) with diagnoses of both chronic pain and anxiety were studied. The median (Q1–Q3) duration of drug combination use was 26 (14-30) days. After adjusting for demographic characteristics, chronic conditions and history of hospitalisation and fall or fracture, the co-prescribing of ≥3 drugs (adjusted HR [aHR], 1.38; 95% CI 1.14 to 1.67) and opioid plus gabapentinoid (aHR, 1.18; 95% CI 1.02 to 1.37) were associated with a high fall risk, compared with benzodiazepineplus opioid co-prescribing, findings consistent with the secondary analysis using inverse probability of treatment weighting with propensity scores. The co-prescribing of benzodiazepine plus gabapentinoid (aHR, 0.76; 95% CI 0.59 to 0.98) was associated with lower fracture risk compared with the co-prescribing of benzodiazepine plus opioid, though this finding was not robust.Conclusions Our findings add to comparative toxicity research on different combinations of gabapentinoids and serotonergic agents commonly prescribed with or as substitutes for opioids and benzodiazepines in patients with co-occurring chronic pain and anxiety.
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spelling doaj-art-a7e2755037d24ccd83a16c93040b9a5e2025-08-20T02:48:43ZengBMJ Publishing GroupBMJ Open2044-60552021-12-01111210.1136/bmjopen-2021-052057Association of co-prescribing of opioid and benzodiazepine substitutes with incident falls and fractures among older adults: a cohort studyRahul Shah0Yong-Fang Kuo1Jordan Westra2Mukaila A Raji3Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USASealy Center on Aging, The University of Texas Medical Branch at Galveston, Galveston, Texas, USAOffice of Biostatistics, Department of Preventive Medicine and Population Health, The University of Texas Medical Branch at Galveston, Galveston, Texas, USADivision of Geriatrics and Palliative Medicine, Department of Internal Medicine, The University of Texas Medical Branch at Galveston, Galveston, Texas, USAObjective Examine the association between the co-prescribing of opioids, benzodiazepines, gabapentinoids (pregabalin and gabapentin) and selective serotonin reuptake inhibitors/serotonin and norepinephrine reuptake inhibitors (SSRI/SNRIs) in different combinations and the risk of falls and fractures.Design Retrospective cohort study from 2015 to 2018.Setting Medicare enrolment and claims data.Participants Medicare beneficiaries with both chronic pain and anxiety disorders in 2016 with continuous enrolments in Parts A and B from 2015 to 2016 who were prescribed any combination of opioid, benzodiazepine, gabapentinoid and SSRI/SNRI in 2017 for ≥7 days, as documented in their Medicare Part D coverage.Interventions Any combination of use of seven drug regimens (benzodiazepine +opioid; benzodiazepine +gabapentinoid; benzodiazepine +SSRI/SNRI; opioid +gabapentinoid; opioid +SSRI/SNRI; gabapentinoid +SSRI/SNRI; ≥3 drug classes).Main outcomes First event of fall and the first event of fracture after the index date, which was the first day of combination drug use that lasted ≥7 days in 2017.Results A total of 47 964 patients (mean [SD] age, 75.9 [7.1]; 78.0% woman) with diagnoses of both chronic pain and anxiety were studied. The median (Q1–Q3) duration of drug combination use was 26 (14-30) days. After adjusting for demographic characteristics, chronic conditions and history of hospitalisation and fall or fracture, the co-prescribing of ≥3 drugs (adjusted HR [aHR], 1.38; 95% CI 1.14 to 1.67) and opioid plus gabapentinoid (aHR, 1.18; 95% CI 1.02 to 1.37) were associated with a high fall risk, compared with benzodiazepineplus opioid co-prescribing, findings consistent with the secondary analysis using inverse probability of treatment weighting with propensity scores. The co-prescribing of benzodiazepine plus gabapentinoid (aHR, 0.76; 95% CI 0.59 to 0.98) was associated with lower fracture risk compared with the co-prescribing of benzodiazepine plus opioid, though this finding was not robust.Conclusions Our findings add to comparative toxicity research on different combinations of gabapentinoids and serotonergic agents commonly prescribed with or as substitutes for opioids and benzodiazepines in patients with co-occurring chronic pain and anxiety.https://bmjopen.bmj.com/content/11/12/e052057.full
spellingShingle Rahul Shah
Yong-Fang Kuo
Jordan Westra
Mukaila A Raji
Association of co-prescribing of opioid and benzodiazepine substitutes with incident falls and fractures among older adults: a cohort study
BMJ Open
title Association of co-prescribing of opioid and benzodiazepine substitutes with incident falls and fractures among older adults: a cohort study
title_full Association of co-prescribing of opioid and benzodiazepine substitutes with incident falls and fractures among older adults: a cohort study
title_fullStr Association of co-prescribing of opioid and benzodiazepine substitutes with incident falls and fractures among older adults: a cohort study
title_full_unstemmed Association of co-prescribing of opioid and benzodiazepine substitutes with incident falls and fractures among older adults: a cohort study
title_short Association of co-prescribing of opioid and benzodiazepine substitutes with incident falls and fractures among older adults: a cohort study
title_sort association of co prescribing of opioid and benzodiazepine substitutes with incident falls and fractures among older adults a cohort study
url https://bmjopen.bmj.com/content/11/12/e052057.full
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