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Concurrent use of prescription gabapentinoids with opioids and risk for fall-related injury among older US Medicare beneficiaries with chronic noncancer pain: A population-based cohort study

Gabapentinoids are increasingly prescribed to manage chronic noncancer pain (CNCP) in older adults. When used concurrently with opioids, gabapentinoids may potentiate central nervous system (CNS) depression and increase the risks for fall. We aimed to investigate whether concurrent use of gabapentin...

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Published in:PLoS medicine 2022-03, Vol.19 (3), p.e1003921-e1003921
Main Authors: Chen, Cheng, Winterstein, Almut G, Lo-Ciganic, Wei-Hsuan, Tighe, Patrick J, Wei, Yu-Jung Jenny
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Winterstein, Almut G
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description Gabapentinoids are increasingly prescribed to manage chronic noncancer pain (CNCP) in older adults. When used concurrently with opioids, gabapentinoids may potentiate central nervous system (CNS) depression and increase the risks for fall. We aimed to investigate whether concurrent use of gabapentinoids with opioids compared with use of opioids alone is associated with an increased risk of fall-related injury among older adults with CNCP. We conducted a population-based cohort study using a 5% national sample of Medicare beneficiaries in the United States between 2011 and 2018. Study sample consisted of fee-for-service (FFS) beneficiaries aged ≥65 years with CNCP diagnosis who initiated opioids. We identified concurrent users with gabapentinoids and opioids days' supply overlapping for ≥1 day and designated first day of concurrency as the index date. We created 2 cohorts based on whether concurrent users initiated gabapentinoids on the day of opioid initiation (Cohort 1) or after opioid initiation (Cohort 2). Each concurrent user was matched to up to 4 opioid-only users on opioid initiation date and index date using risk set sampling. We followed patients from index date to first fall-related injury event ascertained using a validated claims-based algorithm, treatment discontinuation or switching, death, Medicare disenrollment, hospitalization or nursing home admission, or end of study, whichever occurred first. In each cohort, we used propensity score (PS) weighted Cox models to estimate the adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) of fall-related injury, adjusting for year of the index date, sociodemographics, types of chronic pain, comorbidities, frailty, polypharmacy, healthcare utilization, use of nonopioid medications, and opioid use on and before the index date. We identified 6,733 concurrent users and 27,092 matched opioid-only users in Cohort 1 and 5,709 concurrent users and 22,388 matched opioid-only users in Cohort 2. The incidence rate of fall-related injury was 24.5 per 100 person-years during follow-up (median, 9 days; interquartile range [IQR], 5 to 18 days) in Cohort 1 and was 18.0 per 100 person-years during follow-up (median, 9 days; IQR, 4 to 22 days) in Cohort 2. Concurrent users had similar risk of fall-related injury as opioid-only users in Cohort 1(aHR = 0.97, 95% CI 0.71 to 1.34, p = 0.874), but had higher risk for fall-related injury than opioid-only users in Cohort 2 (aHR = 1.69, 95% CI 1.17 to 2.44, p = 0
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When used concurrently with opioids, gabapentinoids may potentiate central nervous system (CNS) depression and increase the risks for fall. We aimed to investigate whether concurrent use of gabapentinoids with opioids compared with use of opioids alone is associated with an increased risk of fall-related injury among older adults with CNCP. We conducted a population-based cohort study using a 5% national sample of Medicare beneficiaries in the United States between 2011 and 2018. Study sample consisted of fee-for-service (FFS) beneficiaries aged ≥65 years with CNCP diagnosis who initiated opioids. We identified concurrent users with gabapentinoids and opioids days' supply overlapping for ≥1 day and designated first day of concurrency as the index date. We created 2 cohorts based on whether concurrent users initiated gabapentinoids on the day of opioid initiation (Cohort 1) or after opioid initiation (Cohort 2). Each concurrent user was matched to up to 4 opioid-only users on opioid initiation date and index date using risk set sampling. We followed patients from index date to first fall-related injury event ascertained using a validated claims-based algorithm, treatment discontinuation or switching, death, Medicare disenrollment, hospitalization or nursing home admission, or end of study, whichever occurred first. In each cohort, we used propensity score (PS) weighted Cox models to estimate the adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) of fall-related injury, adjusting for year of the index date, sociodemographics, types of chronic pain, comorbidities, frailty, polypharmacy, healthcare utilization, use of nonopioid medications, and opioid use on and before the index date. We identified 6,733 concurrent users and 27,092 matched opioid-only users in Cohort 1 and 5,709 concurrent users and 22,388 matched opioid-only users in Cohort 2. The incidence rate of fall-related injury was 24.5 per 100 person-years during follow-up (median, 9 days; interquartile range [IQR], 5 to 18 days) in Cohort 1 and was 18.0 per 100 person-years during follow-up (median, 9 days; IQR, 4 to 22 days) in Cohort 2. Concurrent users had similar risk of fall-related injury as opioid-only users in Cohort 1(aHR = 0.97, 95% CI 0.71 to 1.34, p = 0.874), but had higher risk for fall-related injury than opioid-only users in Cohort 2 (aHR = 1.69, 95% CI 1.17 to 2.44, p = 0.005). Limitations of this study included confounding due to unmeasured factors, unavailable information on gabapentinoids' indication, potential misclassification, and limited generalizability beyond older adults insured by Medicare FFS program. In this sample of older Medicare beneficiaries with CNCP, initiating gabapentinoids and opioids simultaneously compared with initiating opioids only was not significantly associated with risk for fall-related injury. However, addition of gabapentinoids to an existing opioid regimen was associated with increased risks for fall. Mechanisms for the observed excess risk, whether pharmacological or because of channeling of combination therapy to high-risk patients, require further investigation. Clinicians should consider the risk-benefit of combination therapy when prescribing gabapentinoids concurrently with opioids.</description><identifier>ISSN: 1549-1676</identifier><identifier>ISSN: 1549-1277</identifier><identifier>EISSN: 1549-1676</identifier><identifier>DOI: 10.1371/journal.pmed.1003921</identifier><identifier>PMID: 35231025</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Accidental Falls ; Aged ; Aged patients ; Analgesics, Opioid - adverse effects ; Beneficiaries ; Central nervous system ; Chronic pain ; Chronic Pain - drug therapy ; Chronic Pain - epidemiology ; Cohort analysis ; Cohort Studies ; Complications and side effects ; Dosage and administration ; Drug therapy ; Drug therapy, Combination ; Falls (Accidents) ; Gabapentin ; Health aspects ; Humans ; Injuries ; Medical diagnosis ; Medicare ; Medicine and Health Sciences ; Narcotics ; Older people ; Opioids ; Pain ; Palliative care ; Patients ; People and Places ; Population ; Population studies ; Population-based studies ; Prescription drugs ; Prescriptions ; Retrospective Studies ; Risk factors ; Risk groups ; Social Sciences ; Sociodemographics ; United States - epidemiology ; Wounds and injuries</subject><ispartof>PLoS medicine, 2022-03, Vol.19 (3), p.e1003921-e1003921</ispartof><rights>COPYRIGHT 2022 Public Library of Science</rights><rights>2022 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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Each concurrent user was matched to up to 4 opioid-only users on opioid initiation date and index date using risk set sampling. We followed patients from index date to first fall-related injury event ascertained using a validated claims-based algorithm, treatment discontinuation or switching, death, Medicare disenrollment, hospitalization or nursing home admission, or end of study, whichever occurred first. In each cohort, we used propensity score (PS) weighted Cox models to estimate the adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) of fall-related injury, adjusting for year of the index date, sociodemographics, types of chronic pain, comorbidities, frailty, polypharmacy, healthcare utilization, use of nonopioid medications, and opioid use on and before the index date. We identified 6,733 concurrent users and 27,092 matched opioid-only users in Cohort 1 and 5,709 concurrent users and 22,388 matched opioid-only users in Cohort 2. The incidence rate of fall-related injury was 24.5 per 100 person-years during follow-up (median, 9 days; interquartile range [IQR], 5 to 18 days) in Cohort 1 and was 18.0 per 100 person-years during follow-up (median, 9 days; IQR, 4 to 22 days) in Cohort 2. Concurrent users had similar risk of fall-related injury as opioid-only users in Cohort 1(aHR = 0.97, 95% CI 0.71 to 1.34, p = 0.874), but had higher risk for fall-related injury than opioid-only users in Cohort 2 (aHR = 1.69, 95% CI 1.17 to 2.44, p = 0.005). Limitations of this study included confounding due to unmeasured factors, unavailable information on gabapentinoids' indication, potential misclassification, and limited generalizability beyond older adults insured by Medicare FFS program. In this sample of older Medicare beneficiaries with CNCP, initiating gabapentinoids and opioids simultaneously compared with initiating opioids only was not significantly associated with risk for fall-related injury. 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When used concurrently with opioids, gabapentinoids may potentiate central nervous system (CNS) depression and increase the risks for fall. We aimed to investigate whether concurrent use of gabapentinoids with opioids compared with use of opioids alone is associated with an increased risk of fall-related injury among older adults with CNCP. We conducted a population-based cohort study using a 5% national sample of Medicare beneficiaries in the United States between 2011 and 2018. Study sample consisted of fee-for-service (FFS) beneficiaries aged ≥65 years with CNCP diagnosis who initiated opioids. We identified concurrent users with gabapentinoids and opioids days' supply overlapping for ≥1 day and designated first day of concurrency as the index date. We created 2 cohorts based on whether concurrent users initiated gabapentinoids on the day of opioid initiation (Cohort 1) or after opioid initiation (Cohort 2). Each concurrent user was matched to up to 4 opioid-only users on opioid initiation date and index date using risk set sampling. We followed patients from index date to first fall-related injury event ascertained using a validated claims-based algorithm, treatment discontinuation or switching, death, Medicare disenrollment, hospitalization or nursing home admission, or end of study, whichever occurred first. In each cohort, we used propensity score (PS) weighted Cox models to estimate the adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) of fall-related injury, adjusting for year of the index date, sociodemographics, types of chronic pain, comorbidities, frailty, polypharmacy, healthcare utilization, use of nonopioid medications, and opioid use on and before the index date. We identified 6,733 concurrent users and 27,092 matched opioid-only users in Cohort 1 and 5,709 concurrent users and 22,388 matched opioid-only users in Cohort 2. The incidence rate of fall-related injury was 24.5 per 100 person-years during follow-up (median, 9 days; interquartile range [IQR], 5 to 18 days) in Cohort 1 and was 18.0 per 100 person-years during follow-up (median, 9 days; IQR, 4 to 22 days) in Cohort 2. Concurrent users had similar risk of fall-related injury as opioid-only users in Cohort 1(aHR = 0.97, 95% CI 0.71 to 1.34, p = 0.874), but had higher risk for fall-related injury than opioid-only users in Cohort 2 (aHR = 1.69, 95% CI 1.17 to 2.44, p = 0.005). Limitations of this study included confounding due to unmeasured factors, unavailable information on gabapentinoids' indication, potential misclassification, and limited generalizability beyond older adults insured by Medicare FFS program. In this sample of older Medicare beneficiaries with CNCP, initiating gabapentinoids and opioids simultaneously compared with initiating opioids only was not significantly associated with risk for fall-related injury. However, addition of gabapentinoids to an existing opioid regimen was associated with increased risks for fall. Mechanisms for the observed excess risk, whether pharmacological or because of channeling of combination therapy to high-risk patients, require further investigation. Clinicians should consider the risk-benefit of combination therapy when prescribing gabapentinoids concurrently with opioids.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>35231025</pmid><doi>10.1371/journal.pmed.1003921</doi><orcidid>https://orcid.org/0000-0002-6518-5961</orcidid><orcidid>https://orcid.org/0000-0002-3240-8153</orcidid><orcidid>https://orcid.org/0000-0001-6590-4770</orcidid><orcidid>https://orcid.org/0000-0001-8861-6907</orcidid><orcidid>https://orcid.org/0000-0002-1881-9941</orcidid><oa>free_for_read</oa></addata></record>
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identifier ISSN: 1549-1676
ispartof PLoS medicine, 2022-03, Vol.19 (3), p.e1003921-e1003921
issn 1549-1676
1549-1277
1549-1676
language eng
recordid cdi_plos_journals_2651153287
source Publicly Available Content Database; PubMed Central(OpenAccess)
subjects Accidental Falls
Aged
Aged patients
Analgesics, Opioid - adverse effects
Beneficiaries
Central nervous system
Chronic pain
Chronic Pain - drug therapy
Chronic Pain - epidemiology
Cohort analysis
Cohort Studies
Complications and side effects
Dosage and administration
Drug therapy
Drug therapy, Combination
Falls (Accidents)
Gabapentin
Health aspects
Humans
Injuries
Medical diagnosis
Medicare
Medicine and Health Sciences
Narcotics
Older people
Opioids
Pain
Palliative care
Patients
People and Places
Population
Population studies
Population-based studies
Prescription drugs
Prescriptions
Retrospective Studies
Risk factors
Risk groups
Social Sciences
Sociodemographics
United States - epidemiology
Wounds and injuries
title Concurrent use of prescription gabapentinoids with opioids and risk for fall-related injury among older US Medicare beneficiaries with chronic noncancer pain: A population-based cohort study
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