A randomized comparison of extended-release naltrexone with or without patient navigation vs enhanced treatment-as-usual for incarcerated adults with opioid use disorder.

The high prevalence of opioid use among justice-involved adults make jails an exceptional setting to initiate opioid use disorder (OUD) treatment, but optimal strategies for delivering these interventions are still not well understood. The objective of this study was to conduct a randomized controlled trial to assess the effectiveness of extended-release naltrexone (XR-NTX, Vivitrol®; Alkermes Inc) alone or in conjunction with patient navigation (XR-NTX + PN) for jail inmates with OUD. We randomized a sample of 135 sentenced jail inmates with moderate to severe OUD to (1) XR-NTX only; (2) XR-NTX + PN; or (3) enhanced treatment-as-usual (ETAU) with drug education, each initiated prior to release from jail. We scheduled follow-up data assessments at 1, 3, 6, and 12 months post-release. Primary outcomes were opioid use (based on Timeline Followback Interview and Addiction Severity Index) and meeting CIDI DSM-5 criteria for OUD 6 months postrelease. We also measured treatment adherence, HIV risk, and recidivism. XR-NTX participants received a mean of 2.26 of 7 possible injections compared to XR-NTX + PN participants, who received a mean of 2.93 injections (Cohen's d = 0.33, 95% CI: -0.09 to 0.74). Thirty-six percent of patients in XR-NTX + PN attended at least one postrelease PN session. We found no significant differences by study condition six months after release from jail for the primary outcomes of any opioid use (ETAU: 17%, XR-NTX: 16%, XR-NTX + PN: 29%) and past 30-day OUD (ETAU: 8%, XR-NTX: 11%, XR-NTX + PN: 10%). Secondary outcomes of rearrest and HIV risk also were similar across groups, with the exception of lower sex-related HIV risk among those in the XR-NTX condition at 12 months. This study did not show superior outcomes of XR-NTX or XR-NTX + PN with regard to opioid use or recidivism outcomes, relative to ETAU. It did, however, highlight the difficulties with adherence to XR-NTX and PN interventions in OUD patients initiating treatment in jail.

Farabee D ，Condon T ，Hallgren KA ，McCrady B ... -  《-》

Injectable pharmacotherapy for opioid use disorders (IPOD).

Despite the growing prevalence of opioid use among offenders, pharmacotherapy remains an underused treatment approach in correctional settings. The aim of this 4-year trial is to assess the clinical utility, effectiveness, and cost implications of extended-release naltrexone (XR-NTX, Vivitrol®; Alkermes Inc.) alone and in conjunction with patient navigation for jail inmates with opioid use disorder (OUD). Opioid-dependent inmates will be randomly assigned to one of three treatment conditions before being released to the community to include: 1) XR-NTX only; 2) XR-NTX plus patient navigation (PN), and 3) enhanced treatment-as-usual (ETAU) with drug education and a community treatment referral. Before release from jail, participants in the XR-NTX and XR-NTX plus PN conditions will receive their first XR-NTX injection. Those in the XR-NTX plus PN condition also will meet with a patient navigator. Participants in both XR-NTX conditions will be scheduled for medical management sessions twice monthly for months 1-3, monthly medical management sessions for months 4-6, with monthly injections for 5months post-release (which, given the pre-release injection, results in a 6-month medication phase). Follow-up data collection will occur at 1, 3, 6, and 12months post release. We discuss the study's rationale, aims, methods, and anticipated findings. The primary outcome is the presence of a DSM 5 OUD diagnosis 1year after randomization (6months after the end of the active treatment phase). We hypothesize that providing XR-NTX prior to release from jail will be particularly beneficial for this extremely high-risk population by reducing opioid use, associated criminal behavior, and injection-related disease risk. ClinicalTrials.Gov: NCT02110264.

Farabee D ，Hillhouse M ，Condon T ，McCrady B ，McCollister K ，Ling W ... -  《-》

Health and economic outcomes of treatment with extended-release naltrexone among pre-release prisoners with opioid use disorder (HOPPER): protocol for an evaluation of two randomized effectiveness trials.

Murphy SM ，Jeng PJ ，Poole SA ，Jalali A ，Vocci FJ ，Gordon MS ，Woody GE ，Polsky D ... -  《-》

Extended-release naltrexone for youth with opioid use disorder.

Few published research studies have examined the effectiveness of extended-release naltrexone (XR-NTX) for the treatment of opioid use disorder (OUD) among adolescents and young adults. This two-group randomized controlled trial recruited 288 youth, ages 15-21, with moderate/severe OUD from a residential addiction treatment program in Baltimore, Maryland. The study randomized the youth within the first week of treatment entry to receive either XR-NTX or treatment-as-usual (TAU; either buprenorphine maintenance treatment or treatment without OUD medication following medically managed withdrawal) prior to discharge, with continued treatment in the community for 6 months. However, due to various reasons spanning patients' and caregivers' preferences and constraints, considerable participant nonadherence to randomized condition occurred (i.e., only 30% of the participants randomized to XR-NTX received an initial injection, while 27% of participants randomized to TAU received an XR-NTX injection at treatment discharge, instead of their assigned treatment). The study used generalized linear mixed modeling (GLiMM) to examine self-reported 90-day opioid, cocaine, marijuana, and alcohol use as well as DSM-5 OUD criteria on "intention-to-treat" (as randomized), "as-received" (XR-NTX vs. not XR-NTX), and "as-medicated" (XR-NTX vs. buprenorphine vs. no medication) bases. The condition x time interactions in the intention-to-treat analyses failed to reach significance for past-90-day self-reported use of illicit opioids, cocaine, marijuana, or alcohol, or in meeting DSM-5 OUD criteria at 3 or 6 months [all ps > 0.05]. However, these findings are of limited interpretive value due to participant nonadherence to their randomized condition. When the study analyzed results by the treatment received at discharge, the "as-received" group x time interaction for illicit opioid use was significant [p = .003], with the XR-NTX group reporting less opioid use in the past 90 days at 3 and 6 months. Participants who received their first XR-NTX dose at inpatient discharge (n = 82) received, on average, 1.3 subsequent injections in the community over the 6-month study follow-up period. Only 2 of the 82 study participants received XR-NTX continuously through the 6-month postdischarge follow-up period. Twelve serious adverse events (SAEs) occurred during the study, but the study determined that only 1 was possibly study related (hepatitis C/elevated liver function test results). None of the condition x time interactions in the intention-to-treat analyses reached significance. Participants' nonadherence may have contributed to the failure to reject the null hypothesis. Irrespective of randomized condition, participants who received XR-NTX for OUD demonstrated low retention in treatment, receiving an average of only 1.3 subsequent injections, yet reported less opioid use at follow-up than participants who did not received XR-NTX. Treatment programs should consider XR-NTX as a treatment option for youth motivated to receive it. Future research should focus on building developmentally informed strategies to improve uptake of and adherence to relapse prevention medication in this population.

Mitchell SG ，Monico LB ，Gryczynski J ，Fishman MJ ，O'Grady KE ，Schwartz RP ... -  《-》

Opioid treatment at release from jail using extended-release naltrexone: a pilot proof-of-concept randomized effectiveness trial.

Relapse to addiction following incarceration is common. We estimated the feasibility and effectiveness of extended-release naltrexone (XR-NTX) as relapse prevention among opioid-dependent male adults leaving a large urban jail. Eight-week, proof-of-concept, open-label, non-blinded randomized effectiveness trial. New York City jails and Bellevue Hospital Center Adult Primary Care clinics, USA. From January 2010 to July 2013, 34 opioid-dependent adult males with no stated interest in agonist treatments (methadone, buprenorphine) received a counseling and referral intervention and were randomized to XR-NTX (n = 17) versus no medication (n = 17) within one week prior to jail release. XR-NTX (Vivitrol(®) ; Alkermes Inc.), a long-acting injectable mu opioid receptor antagonist. The primary intent-to-treat outcome was post-release opioid relapse at week 4, defined as ≥10 days of opioid misuse by self-report and urine toxicologies. Secondary outcomes were proportion of urine samples negative for opioids and rates of opioid abstinence, intravenous drug use (IVDU), cocaine use, community treatment participation, re-incarceration and overdose. Acceptance of XR-NTX was high; 15 of 17 initiated treatment. Rates of the primary outcome of week 4 opioid relapse were lower among XR-NTX participants: 38 versus 88% [P<0.004; odds ratio (OR) = 0.08, 95% confidence interval (CI) = 0.01-0.48]; more XR-NTX urine samples were negative for opioids, 59 versus 29% (P<0.009; OR = 3.5, 95% CI = 1.4-8.5). There were no significant differences in the remaining secondary outcomes, including rates of IVDU, cocaine use, re-incarceration and overdose. Extended-release naltrexone is associated with significantly lower rates of opioid relapse among men in the United States following release from jail when compared with a no medication treatment-as-usual condition.

Lee JD ，McDonald R ，Grossman E ，McNeely J ，Laska E ，Rotrosen J ，Gourevitch MN ... -  《-》