Extended-release naltrexone versus buprenorphine-naloxone to treat opioid use disorder among black adults.
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SUBMITTER: Haeny AM
PROVIDER: S-EPMC7433932 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background:Not enough evidence exists to compare buprenorphine-naloxone with extended-release naltrexone for treating opioid use disorder. Objective:To evaluate the cost-effectiveness of buprenorphine-naloxone versus extended-release naltrexone. Design:Cost-effectiveness analysis alongside a previously reported randomized clinical trial of 570 adults in 8 U.S. inpatient or residential treatment programs. Data Sources:Study instruments. Target Population:Adults with opioid use disorder. Time Horizon:24-week intervention with an additional 12 weeks of observation. Perspective:Health care sector and societal. Interventions:Buprenorphine-naloxone and extended-release naltrexone. Outcome Measures:Incremental costs combined with incremental quality-adjusted life-years (QALYs) and incremental time abstinent from opioids. Results of Base-Case Analysis:Use of the health care sector perspective and a willingness-to-pay threshold of $100 000 per QALY showed buprenorphine-naloxone to be preferable to extended-release naltrexone in 97% of bootstrap replications at 24 weeks and in 85% at 36 weeks. Similar results were obtained with incremental time abstinent from opioids as an outcome and with use of the societal perspective. Results of Sensitivity Analysis:The base-case results were sensitive to the cost of the 2 treatments and the success of randomized treatment initiation. Limitation:Relatively short follow-up for a chronic condition, substantial missing data, no information on patient out-of-pocket and social service costs. Conclusion:Buprenorphine-naloxone is preferred to extended-release naltrexone as first-line treatment when both options are clinically appropriate and patients require detoxification before initiating extended-release naltrexone. Primary Funding Source:National Institute on Drug Abuse, National Institutes of Health.
| S-EPMC6581635 | biostudies-literature
Project description:Background: Sublingual buprenorphine-naloxone (BUP-NX), an FDA-approved treatment for opioid use disorder (OUD), combines buprenorphine (a partial mu/kappa agonist) with naloxone (a mu/ kappa antagonist). Extended-release injection naltrexone (XR-NTX; a mu receptor antagonist and kappa receptor partial agonist) is also an FDA-approved treatment for OUD. However, while some patients respond well to these medications, many others leave treatment and relapse. Objectives: Determine whether gene variants in the opioid gene system are associated with better or worse treatment response. Methods: In a 24-week, multisite, randomized, comparative effectiveness trial of daily, sublingual self-administration of BUP-NX versus monthly injection of XR-NTX conducted in the National Drug Abuse Clinical Trials Network, DNA was collected and four opioid gene variants were evaluated: (1) mu opioid receptor 118A>G; (2) 68-bp repeat in prodynorphin; (3) prodynorphin SNP rs910080; and (4) kappa opioid receptor SNP rs6473797. In non-Hispanic Caucasians (N = 334), two outcomes measures were assessed: received first dose (yes/no) and received last dose (yes/no). Separate logistic regressions were used to model each outcome measure as a function of treatment (XR-NTX vs BUP-NX), each gene variant, and their interaction. Results: There were no significant main effects of gene variant on receiving first dose or last dose. There were also no significant gene variant by treatment interactions. Conclusions: The outcome of treatment of OUD with medications is likely a complex function of multiple factors, including environmental, psychosocial, and possibly genetic, such that major effects of genetic variants may be unlikely.
| S-EPMC8376218 | biostudies-literature
Project description:BackgroundCurrent guidelines for opioid dependence recommend daily maintenance of physical dependence with methadone or buprenorphine, and discourage abstinence due to the high risk of relapse and overdose. Extended-release formulations of the opioid antagonist naltrexone (XR-NTX) block heroin and other opioid agonists competitively for around 4 weeks per administration. XR-NTX thus enables opioid users to experience abstinence from opioid agonists with greatly reduced risk of overdose compared to medication-free abstinence. While XR-NTX has shown promise compared to placebo and daily naltrexone tablets, there is limited information on long-term safety and its performance compared to daily maintenance treatment.Methods/designIn this five-hospital RCT with long-term follow-up, we aim to recruit n = 180 patients in treatment for opioid dependence and allocate them in an open, randomized manner (1:1) to receive either 4-week XR-NTX or daily buprenorphine-naloxone (BP-NLX) for the duration of 12 weeks. Allocation is open-label due to the risk of overdose during attempts to self-unmask allocation using heroin. Urine drug tests are scheduled every week with follow-up visits & assessment every 4 weeks. Primary outcomes are abstinence from illicit opioids in urine drug tests and self-report, as well as retention in treatment. Secondary outcomes include other substance use, injecting behavior, drug craving, mental health, quality of life, treatment satisfaction, abstinence motivation, opioid agonist effect rating, insomnia, and pain. Observation is continued for another 36 weeks in order to assess longer-term safety, adherence and effectiveness. The study is an investigator-initiated trial, funded by public grants and approved by an Independent Ethical Committee (the Regional Ethical Committee for Research South-East B # 2011/1320) and the Norwegian Medicines Agency.DiscussionDespite minor implementation problems, the protocol appears sufficiently robust to generate results of high interest to patients, clinicians and policy makers.Trial registrationClinicaltrials.gov # NCT01717963 , first registered: Oct 28, 2012. Protocol version # 3C, June 12th 2012.
| S-EPMC4848871 | biostudies-literature
Project description:BackgroundExtended-release naltrexone (XR-NTX), an opioid antagonist, and sublingual buprenorphine-naloxone (BUP-NX), a partial opioid agonist, are pharmacologically and conceptually distinct interventions to prevent opioid relapse. We aimed to estimate the difference in opioid relapse-free survival between XR-NTX and BUP-NX.MethodsWe initiated this 24 week, open-label, randomised controlled, comparative effectiveness trial at eight US community-based inpatient services and followed up participants as outpatients. Participants were 18 years or older, had Diagnostic and Statistical Manual of Mental Disorders-5 opioid use disorder, and had used non-prescribed opioids in the past 30 days. We stratified participants by treatment site and opioid use severity and used a web-based permuted block design with random equally weighted block sizes of four and six for randomisation (1:1) to receive XR-NTX or BUP-NX. XR-NTX was monthly intramuscular injections (Vivitrol; Alkermes) and BUP-NX was daily self-administered buprenorphine-naloxone sublingual film (Suboxone; Indivior). The primary outcome was opioid relapse-free survival during 24 weeks of outpatient treatment. Relapse was 4 consecutive weeks of any non-study opioid use by urine toxicology or self-report, or 7 consecutive days of self-reported use. This trial is registered with ClinicalTrials.gov, NCT02032433.FindingsBetween Jan 30, 2014, and May 25, 2016, we randomly assigned 570 participants to receive XR-NTX (n=283) or BUP-NX (n=287). The last follow-up visit was Jan 31, 2017. As expected, XR-NTX had a substantial induction hurdle: fewer participants successfully initiated XR-NTX (204 [72%] of 283) than BUP-NX (270 [94%] of 287; p<0·0001). Among all participants who were randomly assigned (intention-to-treat population, n=570) 24 week relapse events were greater for XR-NTX (185 [65%] of 283) than for BUP-NX (163 [57%] of 287; hazard ratio [HR] 1·36, 95% CI 1·10-1·68), most or all of this difference accounted for by early relapse in nearly all (70 [89%] of 79) XR-NTX induction failures. Among participants successfully inducted (per-protocol population, n=474), 24 week relapse events were similar across study groups (p=0·44). Opioid-negative urine samples (p<0·0001) and opioid-abstinent days (p<0·0001) favoured BUP-NX compared with XR-NTX among the intention-to-treat population, but were similar across study groups among the per-protocol population. Self-reported opioid craving was initially less with XR-NTX than with BUP-NX (p=0·0012), then converged by week 24 (p=0·20). With the exception of mild-to-moderate XR-NTX injection site reactions, treatment-emergent adverse events including overdose did not differ between treatment groups. Five fatal overdoses occurred (two in the XR-NTX group and three in the BUP-NX group).InterpretationIn this population it is more difficult to initiate patients to XR-NTX than BUP-NX, and this negatively affected overall relapse. However, once initiated, both medications were equally safe and effective. Future work should focus on facilitating induction to XR-NTX and on improving treatment retention for both medications.FundingNIDA Clinical Trials Network.
| S-EPMC5806119 | biostudies-literature
Project description:ImportanceTo date, extended-release naltrexone hydrochloride has not previously been compared directly with opioid medication treatment (OMT), currently the most commonly prescribed treatment for opioid dependence.ObjectiveTo determine whether treatment with extended-release naltrexone will be as effective as daily buprenorphine hydrochloride with naloxone hydrochloride in maintaining abstinence from heroin and other illicit substances in newly detoxified individuals.Design, setting and participantsA 12-week, multicenter, outpatient, open-label randomized clinical trial was conducted at 5 urban addiction clinics in Norway between November 1, 2012, and December 23, 2015; the last follow-up was performed on October 23, 2015. A total of 232 adult opioid-dependent (per DSM-IV criteria) individuals were recruited from outpatient addiction clinics and detoxification units and assessed for eligibility. Intention-to-treat analyses of efficacy end points were performed with all randomized participants.InterventionsRandomization to either daily oral flexible dose buprenorphine-naloxone, 4 to 24 mg/d, or extended-release naltrexone hydrochloride, 380 mg, administered intramuscularly every fourth week for 12 weeks.Main outcomes and measuresPrimary end points (protocol) were the randomized clinical trial completion rate, the proportion of opioid-negative urine drug tests, and number of days of use of heroin and other illicit opioids. Secondary end points included number of days of use of other illicit substances. Safety was assessed by adverse event reporting.ResultsOf 159 participants, mean (SD) age was 36 (8.6) years and 44 (27.7%) were women. Eighty individuals were randomized to extended-release naltrexone and 79 to buprenorphine-naloxone; 105 (66.0%) completed the trial. Retention in the extended-release naltrexone group was noninferior to the buprenorphine-naloxone group (difference, -0.1; with 95% CI, -0.2 to 0.1; P = .04), with mean (SD) time of 69.3 (25.9) and 63.7 (29.9) days, correspondingly (P = .33, log-rank test). Treatment with extended-release naltrexone showed noninferiority to buprenorphine-naloxone on group proportion of total number of opioid-negative urine drug tests (mean [SD], 0.9 [0.3] and 0.8 [0.4], respectively, difference, 0.1 with 95% CI, -0.04 to 0.2; P < .001) and use of heroin (mean difference, -3.2 with 95% CI, -4.9 to -1.5; P < .001) and other illicit opioids (mean difference, -2.7 with 95% CI, -4.6 to -0.9; P < .001). Superiority analysis showed significantly lower use of heroin and other illicit opioids in the extended-release naltrexone group. No significant differences were found between the treatment groups regarding most other illicit substance use.Conclusions and relevanceExtended-release naltrexone was as effective as buprenorphine-naloxone in maintaining short-term abstinence from heroin and other illicit substances and should be considered as a treatment option for opioid-dependent individuals.Trial registrationclinicaltrials.gov Identifier: NCT01717963.
| S-EPMC6583381 | biostudies-literature
Project description:OBJECTIVES:To advance our understanding of medication treatments for opioid use disorders (OUDs), identification of distinct subgroups and factors associated with differential treatment response is critical. We examined trajectories of opioid use for patients with OUD who were randomized to (but not in all cases inducted onto) buprenorphine-naloxone (BUP-NX) or extended-release naltrexone (XR-NTX), and identified characteristics associated with each trajectory. METHODS:Growth mixture models (GMMs) were run to identify distinct trajectories of days of opioid use among a subsample of 535 individuals with OUD who participated in a 24-week randomized controlled trial (RCT; 2014-2016) of BUP-NX (n?=?281) or XR-NTX (n?=?254). RESULTS:Four distinct opioid use trajectory classes were identified for BUP-NX (near abstinent/no use (59%); low use (13.2%); low use, increasing over time (15%); and moderate use, increasing over time (12.8%)). Three distinct opioid use trajectory classes were found for XR-NTX (near abstinent/no use (59.1%); low use (14.6%); and moderate use, increasing over time (26.4%)). Across both BUP-NX and XR-NTX, the near abstinent/no use class had the highest number of medical management visits. Within BUP-NX, the low use class had a greater proportion of individuals with a previous successful treatment history compared with other classes. Within XR-NTX, the moderate use, increasing over time class had the highest proportion of Hispanic participants compared with other classes. CONCLUSIONS:Findings highlight the significant heterogeneity of opioid use during a RCT of BUP-NX and XR-NTX and factors associated with opioid use patterns including medical management visits and history of treatment success.
| S-EPMC6990451 | biostudies-literature
Project description:AIMS:To review systematically the published literature on extended-release naltrexone (XR-NTX, Vivitrol® ), marketed as a once-per-month injection product to treat opioid use disorder. We addressed the following questions: (1) how successful is induction on XR-NTX; (2) what are adherence rates to XR-NTX; and (3) does XR-NTX decrease opioid use? Factors associated with these outcomes as well as overdose rates were examined. METHODS:We searched PubMed and used Google Scholar for forward citation searches of peer-reviewed papers from January 2006 to June 2017. Studies that included individuals seeking treatment for opioid use disorder who were offered XR-NTX were included. RESULTS:We identified and included 34 studies. Pooled estimates showed that XR-NTX induction success was lower in studies that included individuals that required opioid detoxification [62.6%, 95% confidence interval (CI) = 54.5-70.0%] compared with studies that included individuals already detoxified from opioids (85.0%, 95% CI = 78.0-90.1%); 44.2% (95% CI = 33.1-55.9%) of individuals took all scheduled injections of XR-NTX, which were usually six or fewer. Adherence was higher in prospective investigational studies (i.e. studies conducted in a research context according to a study protocol) compared to retrospective studies of medical records taken from routine care (6-month rates: 46.7%, 95% CI = 34.5-59.2% versus 10.5%, 95% CI = 4.6-22.4%, respectively). Compared with referral to treatment, XR-NTX reduced opioid use in adults under criminal justice supervision and when administered to inmates before release. XR-NTX reduced opioid use compared with placebo in Russian adults, but this effect was confounded by differential retention between study groups. XR-NTX showed similar efficacy to buprenorphine when randomization occurred after detoxification, but was inferior to buprenorphine when randomization occurred prior to detoxification. CONCLUSIONS:Many individuals intending to start extended-release naltrexone (XR-NTX) do not and most who do start XR-NTX discontinue treatment prematurely, two factors that limit its clinical utility significantly. XR-NTX appears to decrease opioid use but there are few experimental demonstrations of this effect.
| S-EPMC5993595 | biostudies-literature
Project description:Importance:Extended-release naltrexone (XR-NTX) is a promising alternative treatment of opioid addiction but has never been compared with opioid agonist treatment for effects on symptoms of anxiety, depression, and insomnia. Objective:To investigate whether XR-NTX unmasks or reinforces current comorbid symptoms of anxiety, depression, or insomnia compared with opioid agonist treatment. Design, Setting, and Participants:In this prospective randomized clinical trial, 159 men and women aged 18 to 60 years with opioid dependence were randomized to 12 weeks of treatment with either XR-NTX or combined buprenorphine-naloxone (BP-NLX) followed by a 9-month, open-label treatment study with participant choice of 1 of these 2 drugs. The study was conducted at outpatient addiction clinics in 5 urban hospitals in Norway, with the clinical trial performed from November 1, 2012, to October 23, 2015, and the follow-up study completed on July 23, 2016. All analyses were conducted using an intention-to-treat sample. Interventions:Extended-release naltrexone hydrochloride, 380 mg, administered as an injection every 4 weeks or flexible doses (4-24 mg; target dosage 16 mg/d) of daily oral combined BP-NLX. Main Outcomes and Measures:Every 4 weeks, symptoms of anxiety and depression were assessed using the 25-item Hopkins Symptom Checklist, and symptoms of insomnia were assessed using the Insomnia Severity Index. Results:In total, 159 participants were randomized to treatment with either XR-NTX (n = 80) or BP-NLX (n = 79), and 105 participants (66.0%) completed the trial. The treatment groups showed similar distributions of age (mean [SD], 36.4 [8.8] vs 35.7 [8.5] years), sex (61 [76.3%] women and 54 [68.4%] men), and duration of heroin use (mean [SD], 6.9 [5.8] vs 6.7 [5.2] years). For the clinical trial period, no overall differences were detected between treatment groups for anxiety (effect size [95% CI], -0.14 [-0.47 to 0.19]) or depression (effect size [95% CI], -0.12 [-0.45 to 0.21]) scores, but the insomnia score was significantly lower in the XR-NTX group (effect size [95% CI], -0.32 [-0.61 to -0.02]; P = .008). In the follow-up period, no overall differences could be detected in the effect size [95% CI] of scores for anxiety (0.04 [-0.34 to 0.42]), depression (-0.04 [-0.42 to 0.33]), or insomnia (0.04 [-0.33 to 0.42]) between participants continuing with and participants switching to XR-NTX. No significant sex differences between the 2 treatment groups were detected. Conclusions and Relevance:Comorbid symptoms of anxiety, depression, or insomnia in abstinence-motivated persons with opioid dependence should not prevent switching from treatment with an opioid agonist to treatment with XR-NTX. Trial Registration:ClinicalTrials.gov Identifier: NCT01717963.
| S-EPMC6439739 | biostudies-literature
Project description:Background and objectiveWhen patients seek to discontinue buprenorphine (BUP) treatment, monthly injectable extended-release naltrexone (XR-NTX) may help them avoid relapse. The efficacy of low ascending doses of oral NTX vs placebo for patients transitioning from BUP to XR-NTX is evaluated in this study.MethodsIn a phase 3, hybrid residential/outpatient study, clinically stable participants with opioid use disorder (N = 101), receiving BUP for more than or equal to 3 months and seeking antagonist treatment, were randomized (1:1) to 7 residential days of descending doses of BUP and low ascending doses of oral NTX (NTX/BUP, n = 50) or placebo (PBO-N/BUP, n = 51). Both groups received standing ancillary medications and psychoeducational counseling. Following negative naloxone challenge, participants received XR-NTX (day 8). The primary endpoint was the proportion of participants who received and tolerated XR-NTX.ResultsThere was no statistical difference between groups for participants receiving a first dose of XR-NTX: 68.6% (NTX/BUP) vs 76.0% (PBO-N/BUP; P = .407). The mean number of days with peak Clinical Opiate Withdrawal Scale (COWS) score less than or equal to 12 during the treatment period (days 1-7) was similar for NTX/BUP and PBO-N/BUP groups (5.8 vs 6.3; P = .511). Opioid withdrawal symptoms during XR-NTX induction and post-XR-NTX observation period (days 8-11) were mild and similar between groups (mean peak COWS score: NTX/BUP, 5.1 vs PBO-N/BUP, 5.4; P = .464). Adverse events were mostly mild/moderate.Conclusions and scientific significanceLow ascending doses of oral NTX did not increase induction rates onto XR-NTX compared with placebo. The overall rate of successful induction across treatment groups supports a brief BUP taper with standing ancillary medications as a well-tolerated approach for patients seeking transition from BUP to XR-NTX. (Am J Addict 2020;00:00-00).
| S-EPMC7383475 | biostudies-literature
Project description:ImportanceIn 2017, the US Food and Drug Administration (FDA) approved a monthly injectable form of buprenorphine, extended-release buprenorphine; published data show that extended-release buprenorphine is effective compared with no treatment, but its current cost is higher and current retention is lower than that of transmucosal buprenorphine. Preliminary research suggests that extended-release buprenorphine may be an important addition to treatment options, but the cost-effectiveness of extended-release buprenorphine compared with transmucosal buprenorphine remains unclear.ObjectiveTo evaluate the cost-effectiveness of extended-release buprenorphine compared with transmucosal buprenorphine.Design, setting, and participantsThis economic evaluation used a state transition model starting in 2019 to simulate the lifetime of a closed cohort of individuals with OUD presenting for evaluation for opioid agonist treatment with buprenorphine. The data sources used to estimate model parameters included cohort studies, clinical trials, and administrative data. The model relied on pharmaceutical costs from the Federal Supply Schedule and health care utilization costs from published studies. Data were analyzed from September 2021 to January 2023.InterventionsNo treatment, treatment with transmucosal buprenorphine, or treatment with extended-release buprenorphine.Main outcomes and measuresMean lifetime costs per person, discounted quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs).ResultsThe simulated cohort included 100 000 patients with OUD receiving (61% male; mean [SD] age, 38 [11] years) or not receiving medication treatment (58% male, mean [SD] age, 48 [18] years). Compared with no medication treatment, treatment with transmucosal buprenorphine yielded an ICER of $19 740 per QALY. Compared with treatment with transmucosal buprenorphine, treatment with extended-release buprenorphine yielded lower effectiveness by 0.03 QALYs per person at higher cost, suggesting that treatment with extended-release buprenorphine was dominated and not preferred. In probabilistic sensitivity analyses, treatment with transmucosal buprenorphine was the preferred strategy 60% of the time. Treatment with extended-release buprenorphine was cost-effective compared with treatment with transmucosal buprenorphine at a $100 000 per QALY willingness-to-pay threshold only after substantial changes in key parameters.Conclusions and relevanceIn this economic evaluation of extended-release buprenorphine compared with transmucosal buprenorphine for the treatment of OUD, extended-release buprenorphine was not associated with efficient allocation of limited resources when transmucosal buprenorphine was available. Future initiatives should aim to improve retention rates or decrease costs associated with extended-release buprenorphine.
| S-EPMC10500382 | biostudies-literature