Extended-Release Naltrexone Opioid Treatment at Jail Re-Entry

This study is a randomized control trial of XR-NTX (n=85) vs. enhanced TAU (n=85) among opioid dependent adults leaving NYC jails who explicitly reject agonist treatment. Initiating treatment the week prior to release and continuing for 24 weeks post-release, we hypothesize the XR-NTX arm will demonstrate significantly longer time-to-relapse vs. TAU. In parallel, we propose to recruit a matched, quasi-experimental methadone cohort (n=85), which will result in a naturalistic comparison of XR-NTX vs. an established jail-based MTP standard-of-care.

Rationale: Immediate relapse to drug, alcohol, and tobacco use is a nearly universal and expected near-term outcome among adults with addiction disorders leaving U.S. jails. Yet while opioid agonist therapies are proven and effective re-entry interventions, many US correctional facilities, including almost all large U.S. municipal jails, do not offer these treatments. However, in New York City (NYC), jail-to-community methadone treatment is, since 1986, a well-studied standard-of-care, yet many inmates eligible to initiate the methadone treatment program (MTP) while incarcerated do not, possibly due to anti-methadone patient preferences. Rather, the vast majority of these jail detainees undergo a brief 6-day methadone taper following arrest, remain in jail for brief periods out-of-treatment while 'drug free' and undergoing a decline in physiologic opioid tolerance, nearly universally relapse to heroin or other illicit opioid use following release, and are re-arrested in the next 12 months at rates of 50-75%. Extended-release naltrexone (XR-NTX, Vivitrol), now FDA-approved for opioid dependence, produces a 30-day mu opioid receptor antagonist blockade, and offers an potentially promising modality for 'inoculating' persons leaving jails against immediate opioid relapse. Persons injected with 380mg of XR-NTX are unable to effectively experience euphoria or respiratory depression when returning to average doses of illicit opioids for the ensuing 4-5 weeks. An injection prior to release would possibly give the individual a month or so to return home from jail, experience opioid abstinence, and then either continue XR-NTX, initiate agonist or behavioral treatments, or, resume a significantly postponed relapse to illicit use. Our team recently established the feasibility of administering XR-NTX to opioid dependent adults within a week of release in NYC jails. We now propose to conduct a large, definitive randomized controlled trial estimating the effectiveness of XR-NTX as opioid treatment at release from jail vs. a counseling- and referral-enhanced treatment-as-usual (TAU) condition. We also propose to recruit a non-randomized, quasi-experimental cohort of participants in a jail-based methadone maintenance program (MTP), allowing an additional comparison of XR-NTX to a methadone standard-of-care.

Specific Aim 1: Randomized Effectiveness Trial of XR-NTX vs. TAU for Jail-to-Community Re-Entry Opioid Relapse Prevention. Our primary aim is to compare time-to-relapse among participants treated with XR-NTX vs. randomized TAU controls, following release from jail.

Specific Aim 2: Quasi-Experimental Comparison of XR-NTX vs. a Methadone Treatment Program for Re-Entry Opioid Relapse Prevention. To compare time-to-relapse among the XR-NTX RCT arm vs. jail-based MTP participants using a quasi-experimental design.

Specific Aim 3a-e: Related Opioid Treatment Outcomes. To compare re-entry rates of 5 treatment outcomes across all arms: 3a) community treatment initiation and retention, 3b) any opioid and other illicit drug or alcohol use, defined as continuous counts of both days, amount/day, and urine toxicologies, 3c) injection drug use and HIV sexual risk factors, 3d) accidental drug overdose and mortality, and, 3e) rates of re-incarceration and an exploratory analysis of cost-effectiveness.