Relapse to opioid use disorder after inpatient treatment: Protective effect of injection naltrexone

Nunes, Edward V.; Gordon, Michael S.; Friedmann, Peter D.; Fishman, Marc; Lee, Joshua D.; Chen, Donna T.; Hu, Mei Chen; Boney, Tamara Y.; Wilson, Donna; O’Brien, Charles P.

doi:10.1016/j.jsat.2017.04.016

Cited by 91 publications

(60 citation statements)

References 28 publications

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“…A secondary analysis (65) of the pivotal placebo-controlled study (27) showed that none of the 25 baseline factors predicted a positive clinical response to XR-NTX. Two secondary analyses (66, 67) of a large United States study comparing XR-NTX to treatment referral (28) found that XR-NTX induction setting interacted with opioid relapse and that of 36 baseline factors only alcohol use to intoxication moderated the treatment effect. Specifically, because relapse was higher among patients who received XR-NTX during a short-term inpatient stay, its protective effects were greater than those who received XR-NTX during long-term inpatient stays and in outpatient settings.…”

Section: Resultsmentioning

confidence: 99%

“… a Details regarding induction setting reported in (67) b Details regarding induction setting reported in (75) c NTX-assisted detox XR-NTX induction rate significantly higher than buprenorphine-assisted detox d Numbers reported for patients who were recommended for XR-NTX …”

Section: Figurementioning

confidence: 99%

“…Within a sample of opioid users with marijuana use histories, pre-enrollment marijuana use predicted successful induction [39]. Finally, in an out-patient contingency management procedure, participants who had recently completed a long-term detox (≥ 21 days) and who were Details regarding induction setting reported in [66]. b Details regarding induction setting reported in [67].…”

Section: Factors Associated With Inductionmentioning

confidence: 99%

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Extended‐release injectable naltrexone for opioid use disorder: a systematic review

et al. 2018

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Section: Resultsmentioning

confidence: 99%

Section: Figurementioning

confidence: 99%

Section: Factors Associated With Inductionmentioning

confidence: 99%

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Extended‐release injectable naltrexone for opioid use disorder: a systematic review

et al. 2018

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“…The risk of early opioid treatment dropout is likely to be greater among participants actively using heroin and initially admitted to acute detoxification units than opioid patient cohorts initiating outpatient medication treatment. 28 Detoxification admissions typically represent a spectrum of motivation and treatment-seeking; many patients are in crisis and unclear of further treatment options, while other patients are highly motivated to begin a thoughtfully considered new treatment programme. The early randomisation group in this trial, who were more recently admitted and more recently using heroin (or other opioids) than the late randomisation group, had higher overall relapse events in both treatment groups than the late randomisation group.…”

Section: Discussionmentioning

confidence: 99%

Comparative effectiveness of extended-release naltrexone versus buprenorphine-naloxone for opioid relapse prevention (X:BOT): a multicentre, open-label, randomised controlled trial

et al. 2018

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Summary Background Extended-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. Methods We 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. Findings Between 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). Interpretation In 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 wo...

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“…prescription drug monitoring programs and prescriber guidelines) address primary prevention (reducing risk of incidence of OUD) or secondary prevention (early identification) but do not necessarily facilitate progression through the treatment end of the cascade for individuals once identified with OUD (far right of Figure 1). Further, expanding access to shortterm detoxification programs or "detox beds" cannot contribute to successful progression along the cascade unless these facilities are repurposed and entitled "medication initiation units" (40). Detoxification itself is not a treatment for OUD and when used in isolation increases risks of adverse events such as overdose (41).…”

Section: Treatment: Moud Initiation and Retention Beyond 6 Monthsmentioning

confidence: 99%

Development of a Cascade of Care for responding to the opioid epidemic

Williams

Nunes

Bisaga

et al. 2019

The American Journal of Drug and Alcohol Abuse

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Amid worsening opioid overdose death rates, the nation continues to face a persistent addiction treatment gap limiting access to quality care for opioid use disorder (OUD). Three FDAapproved medications (methadone, buprenorphine, and extended-release naltrexone) have high quality evidence demonstrating reductions in drug use and overdose events, but most individuals with OUD do not receive them. The development of a unified public health framework, such as a Cascade of Care, could improve system level practice and treatment outcomes. In response to feedback from many stakeholders over the past year, we have expanded upon the OUD treatment cascade, first published in 2017, with additional attention to prevention stages and both individual-level and population-based services to better inform efforts at the state and federal level. The proposed cascade framework has attracted considerable interest from federal agencies including the Centers for Disease Control and Prevention (CDC) and National Institute on Drug Abuse (NIDA) along with policy-makers nationwide. We have reviewed recent literature and evidence-based interventions related to prevention, identification, and treatment of individuals with OUD and modeled updated figures from the 2016 National Survey on Drug Use and Health. Many currently employed interventions (prescriber guidelines, prescription monitoring programs, naloxone rescue) address prevention of OUD or downstream complications but not treatment of the underlying disorder itself. An OUD Cascade of Care framework could help structure local and national efforts to combat the opioid epidemic by identifying key targets, interventions, and quality indicators across populations and settings to achieve these ends. Improved data collection and reporting methodology will be imperative.

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Relapse to opioid use disorder after inpatient treatment: Protective effect of injection naltrexone

Abstract: Short term inpatient treatment is associated with a high rate of relapse among patients with opioid use disorder. These findings support the recommendation that medically supervised withdrawal from opioids should be followed by medication assisted treatment.

Cited by 91 publications

References 28 publications

Extended‐release injectable naltrexone for opioid use disorder: a systematic review

Extended‐release injectable naltrexone for opioid use disorder: a systematic review

Comparative effectiveness of extended-release naltrexone versus buprenorphine-naloxone for opioid relapse prevention (X:BOT): a multicentre, open-label, randomised controlled trial

Development of a Cascade of Care for responding to the opioid epidemic

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