Dataset Information

Association Between Buprenorphine for Opioid Use Disorder and Mortality Risk.

ABSTRACT:

Introduction

Veterans with opioid use disorder have an increased risk of suicide and overdose compared with the general population. Buprenorphine, a U.S. Food and Drug Administration-approved medication to treat opioid use disorder, has shown benefits, including decreased risk of illicit drug use and overdose. This study assesses the mortality outcomes with buprenorphine pharmacotherapy among Veterans up to 5 years from treatment initiation.

Methods

This was a retrospective cohort study of Veterans receiving buprenorphine (2008-2017) across any Veterans Health Administration facility. Buprenorphine pharmacotherapy was evaluated as a time-varying covariate. The primary outcome was death up to 5 years from treatment initiation by suicide and overdose combined; secondary outcomes included suicide, overdose, opioid-specific overdose, and all-cause death. Secondary analyses included evaluating the risk of mortality in recent discontinuation and effect modification by select characteristics. All analyses were conducted in 2020.

Results

Veterans who were not receiving buprenorphine were 4.33 (adjusted hazard ratio; 95% CI=3.60, 5.21) times more likely to die by suicide/overdose than those receiving buprenorphine pharmacotherapy on any given day, with similar protective associations with treatment across secondary outcomes. The risk of suicide/overdose was highest 8-14 days from treatment discontinuation (adjusted hazard ratio=6.54, 95% CI=4.32, 9.91) than in currently receiving buprenorphine pharmacotherapy. There was no evidence of effect modification by the selected covariates.

Conclusions

Mortality risk was greater among Veterans who were not receiving buprenorphine pharmacotherapy than among those who were. Providers should consider whether buprenorphine pharmacotherapy, either intermittent or continuous, may provide health benefits for their patients and prevent mortality.

SUBMITTER: Vakkalanka P

PROVIDER: S-EPMC8384722 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background and aimsDynamic, adaptive pharmacologic treatment for opioid use disorder (OUD) has been previously recommended over static dosing to prevent relapse, and is aligned with personalized medicine. However, there has been no quantitative evidence demonstrating its advantage. Our objective was to estimate the extent to which a hypothetical intervention that increased buprenorphine dose in response to opioid use would affect risk of relapse over 24 weeks of follow-up.DesignA secondary analysis of the buprenorphine arm of an open-label randomized controlled 24-week comparative effectiveness trial, 2014-17.SettingEight community addiction treatment programs in the United States.ParticipantsEnglish-speaking adults with DSM-5 OUD, recruited during inpatient admission (n = 270). Participants were mainly white (65%) and male (72%).Intervention(s)Participants were treated with daily sublingual buprenorphine-naloxone (BUP-NX), with dose based on clinical indication, determined by the provider. We examined a hypothetical intervention of increasing dose in response to opioid use.MeasurementsOutcome was relapse to regular opioid use during the 24 weeks of outpatient treatment, assessed in a survival framework. We estimated the relapse-free survival curves of participants under a hypothetical (i.e. counterfactual) intervention in which their BUP-NX dosage would be increased following their own subject-specific opioid use during the first 12 weeks of treatment versus a hypothetical intervention in which dose would remain constant.FindingsWe estimated that increasing BUP-NX dose in response to recent opioid use would lower risk of relapse by 19.17 percentage points [95% confidence interval (CI) = -32.17, -6.18) (additive risk)] and 32% (0.68, 95% CI = 0.49, 0.86) (relative risk). The number-needed-to-treat with this intervention to prevent a single relapse is 6.ConclusionsIn people with opioid use disorder, a hypothetical intervention that increases sublingual buprenorphine-naloxone dose in response to opioid use during the first 12 weeks of treatment appears to reduce risk of relapse over 24 weeks, compared with holding the dose constant after week 2.

Project description:ImportanceNonadherence to buprenorphine may increase patient risk of opioid overdose and increase health care spending. Quantifying the impacts of nonadherence can help inform clinician practice and policy.ObjectiveTo estimate the association between buprenorphine treatment gaps, opioid overdose, and health care spending.Design, setting, and participantsThis longitudinal case-control study compared patient opioid overdose and health care spending in buprenorphine-treated months with treatment gap months. Individuals who were US Medicare fee-for-service beneficiaries diagnosed with opioid use disorder who received at least 1 two-week period of continuous buprenorphine treatment between 2010 and 2017 were included. Analysis took place between January 2010 and December 2017.InterventionsA gap in buprenorphine treatment in a month lasting more than 15 consecutive days.Main outcomes and measuresOpioid overdose and total, medical, and drug spending (combined patient out-of-pocket and Medicare spending).ResultsOf 34 505 Medicare beneficiaries (17 927 [520%] male; 16 578 [48.1%] female; mean [SD] age, 49.5 [12.7] years; 168 [0.5%] Asian; 2949 [8.5%] Black; 2089 [6.0%] Hispanic; 266 [0.8%] Native American; 28 525 [82.7%] White; 508 [1.5%] other race), 11 524 beneficiaries (33.4%) experienced 1 or more buprenorphine treatment gaps. Treatment gap beneficiaries, compared with nontreatment gap beneficiaries, were more likely to be younger, be male, have a disability, and be Medicaid dual-eligible while less likely to be White, close to a buprenorphine prescriber, and treated with buprenorphine monotherapy (ie, buprenorphine hydrochloride). Beneficiaries were 2.89 (95% CI, 2.20-3.79) times more likely to experience an opioid overdose during buprenorphine treatment gap months compared with treated months. During treatment gap months, spending was $196.41 (95% CI, $110.53-$282.30) more than in treated months. Patients who continued to take buprenorphine dosages of greater than 8 mg/d and 16 mg/d were 2.61 and 2.84 times more likely to overdose in a treatment gap month, respectively, while patients taking buprenorphine dosages of 8 mg/d or less were 3.62 times more likely to overdose in a treatment gap month (maintenance of >16 mg/d: hazard ratio (HR), 2.64 [95% CI, 1.80-3.87]; maintenance of >8 mg/d: HR, 2.84 [95% CI, 2.13-3.78]; maintenance of ≤8 mg/d: HR, 3.62 [95% CI, 1.54-8.50]). Buprenorphine monotherapy was associated with greater risk of overdose and higher spending during treatment gaps months than buprenorphine/naloxone.Conclusions and relevanceMedicare patients treated with buprenorphine between 2010 and 2017 had a lower associated opioid overdose risk and spending during treatment months than treatment gap months.

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Project description:ImportanceAgonist medications for opioid use disorder (MOUD), buprenorphine and methadone, in carceral settings might reduce the risk of postrelease opioid overdose but are uncommonly offered. In April 2019, the Massachusetts Department of Correction (MADOC), the state prison system, provided buprenorphine for incarcerated individuals in addition to previously offered injectable naltrexone.ObjectiveTo evaluate postrelease outcomes after buprenorphine implementation.Design, setting, and participantsThis cohort study with interrupted time-series analysis used linked data across multiple statewide data sets in the Massachusetts Public Health Data Warehouse stratified by sex due to differences in carceral systems. Eligible participants were individuals sentenced and released from a MADOC facility to the community. The study period for the male sample was January 2014 to November 2020; for the female sample, January 2015 to October 2019. Data were analyzed between February 2022 and January 2024.ExposureApril 2019 implementation of buprenorphine during incarceration.Main outcomes and measuresReceipt of MOUD within 4 weeks after release, opioid overdose, and all-cause mortality within 8 weeks after release, each measured as a percentage of monthly releases who experienced the outcome. Segmented linear regression analyzed changes in outcome rates after implementation.ResultsA total of 15 225 individuals were included. In the male sample there were 14 582 releases among 12 688 individuals (mean [SD] age, 35.0 [10.8] years; 133 Asian and Pacific Islander [0.9%], 4079 Black [28.0%], 4208 Hispanic [28.9%], 6117 White [41.9%]), a rate of 175.7 releases per month; the female sample included 3269 releases among 2537 individuals (mean [SD] age, 34.9 [9.8] years; 328 Black [10.0%], 225 Hispanic [6.9%], 2545 White [77.9%]), a rate of 56.4 releases per month. Among male participants at 20 months postimplementation, the monthly rate of postrelease buprenorphine receipt was higher than would have been expected under baseline trends (21.2% vs 10.6% of monthly releases; 18.6 additional releases per month). Naltrexone receipt was lower than expected (1.0% vs 6.0%; 8.8 fewer releases per month). Monthly rates of methadone receipt (1.4%) and opioid overdose (1.8%) were not significantly different than expected. All-cause mortality was lower than expected (1.9% vs 2.8%; 1.5 fewer deaths per month). Among female participants at 7 months postimplementation, buprenorphine receipt was higher than expected (31.6% vs 9.5%; 12.4 additional releases per month). Naltrexone receipt was lower than expected (3.4% vs 7.2%) but not statistically significantly different. Monthly rates of methadone receipt (1.1%), opioid overdose (4.8%), and all-cause mortality (1.6%) were not significantly different than expected.Conclusions and relevanceIn this cohort study of state prison releases, postrelease buprenorphine receipt increased and naltrexone receipt decreased after buprenorphine became available during incarceration.

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Project description:ImportanceEmergency department (ED)-based initiation of buprenorphine has been shown to increase engagement in outpatient treatment and reduce the risk of subsequent opioid overdose; however, rates of buprenorphine treatment in the ED and follow-up care for opioid use disorder (OUD) remain low in the US. The Opioid Hospital Quality Improvement Program (O-HQIP), a statewide financial incentive program designed to increase engagement in OUD treatment for Medicaid-enrolled patients who have ED encounters, has the potential to increase ED-initiated buprenorphine treatment.ObjectiveTo evaluate the association between hospitals attesting to an ED buprenorphine treatment O-HQIP pathway and patients' subsequent initiation of buprenorphine treatment.Design, setting, and participantsThis cohort study included Pennsylvania patients aged 18 to 64 years with continuous Medicaid enrollment 6 months before their OUD ED encounter and at least 30 days after discharge between January 1, 2016, and December 31, 2020. Patients with a claim for medication for OUD 6 months before their index encounter were excluded.ExposuresHospital implementation of an ED buprenorphine treatment O-HQIP pathway.Main outcomes and measuresThe main outcome was patients' receipt of buprenorphine within 30 days of their index OUD ED visit. Between August 2021 and January 2023, data were analyzed using a difference-in-differences method to evaluate the association between hospitals' O-HQIP attestation status and patients' treatment with buprenorphine after ED discharge.ResultsThe analysis included 17 428 Medicaid-enrolled patients (female, 43.4%; male, 56.6%; mean [SD] age, 37.4 [10.8] years; Black, 17.5%; Hispanic, 7.9%; White, 71.6%; other race or ethnicity, 3.0%) with OUD seen at O-HQIP-attesting or non-O-HQIP-attesting hospital EDs. The rate of prescription fills for buprenorphine within 30 days of an OUD ED discharge in the O-HQIP attestation hospitals before the O-HQIP intervention was 5%. The O-HQIP attestation was associated with a statistically significant increase (2.6 percentage points) in prescription fills for buprenorphine within 30 days of an OUD ED discharge (β, 0.026; 95% CI, 0.005-0.047).Conclusions and relevanceIn this cohort study, the O-HQIP was associated with an increased initiation of buprenorphine in patients with OUD presenting to the ED. These findings suggest that statewide incentive programs may effectively improve outcomes for patients with OUD.