Opioid dependence is a chronic relapsing disease often associated with an increased frequency of criminal behavior resulting in severe legal consequences, including incarceration. Cyclic patterns of relapse, criminal behavior, and re-incarceration are common.(1
) In addition to legal problems, the opioid-dependent individual suffers many adverse health and social consequences of addiction, including HIV and hepatitis C infection, as well as unemployment and family problems.(2
Despite the well-established link between opioid addiction and crime, relatively few addiction pharmacotherapy studies have been conducted within the criminal justice setting, particularly in the United States.(3
) Concerns stemming from prior past abuses of prisoners, including failure to obtain informed consent, sensitivity, and ethical concerns, have constrained medication research with this vulnerable population.
Treatments such as methadone(4
) and buprenorphine(6
) are efficacious for opioid dependence in terms of maintaining patients in treatment and reducing heroin use and criminal activity, primarily in the community and, more recently, in criminal justice settings.(3
) However, these opioid receptor agonist medications have limitations. For example, there is evidence that some patients continue to use illicit drugs (mainly cocaine) while receiving these treatments.(2
) In addition, patients cite barriers to methadone maintenance treatment (MMT) such as the daily dosing regimens that often hamper employment efforts,(13
) the fear of prolonged withdrawal if they are detoxified from the medication,(14
) especially in jail, and negative attitudes and myths surrounding methadone treatment.(15
) Moreover, since these agonist treatments produce opioid effects similar to heroin and can be abused and diverted, they have not been universally accepted by the criminal justice system.(16
Maintenance therapy with naltrexone, an opioid receptor antagonist medication, is an underutilized alternative for opioid-dependent persons. Unlike methadone or buprenorphine, naltrexone blocks the intoxicating and reinforcing effects of opioids and has virtually no psychotropic or euphoric effects. Naltrexone does not induce physical dependence, and there is therefore no withdrawal when it is stopped. However, many who provide treatment to offenders are not aware of the medication or may erroneously believe it to be similar to the agonist treatments.
Our work with naltrexone has involved both the oral and the extended-release formulations that include Vivitrol® and Depotrex®. The frequent dosing required for oral naltrexone (daily or multiple times per week) results in lack of patient adherence to the medication. Technology has been developed that enables naltrexone to be prepared in an extended-release injectable formulation (XR-NTX). This extended-release formulation removes barriers to medication compliance since it can provide effective blood levels for 30 days or more following a single injection. Vivitrol® which is manufactured by Alkermes is administered as an intramuscular injection, whereas Depotrex® which was manufactured by Biotek is administered as a subcutaneous injection. Only Vivitrol® is currently available in the United States and Europe and has recently received FDA approval for opioid addiction. The safety of XR-NTX has been demonstrated in alcoholic patients indicating that it is well tolerated(20
) with no evidence of hepatotoxicity.(21
Our prior work with oral naltrexone in the United States Federal Probation Offices demonstrated that 34 probationers who received oral naltrexone significantly reduced their use of opiates over the course of six months of treatment compared to 17 probationers who did not receive oral naltrexone (8% versus 30%)(23
) Of those receiving oral naltrexone, 26% had their probation revoked compared to 56% of the control group.
Based upon the promising findings from these pilot results, a larger study was conducted comparing the outcomes of 111 subjects who were randomized to six months of either 300 mg per week of oral naltrexone (150 mg twice a week) plus psychosocial treatment as usual (n=56) or standard psychosocial treatment as usual (TAU) without naltrexone (n=55). Whereas the study conducted by the Federal Probation Offices included only federal probationers, the more recent study(24
) involved participants from city and federal programs. The results of this larger, more mixed group failed to show a significant advantage for the patients randomized to oral naltrexone in terms of retention, crime, and urine tests negative for opiates.(24
) While naltrexone subjects retained in treatment used less opiates than the TAU subjects who were also retained in treatment, both groups experienced substantial dropout, an outcome that made it difficult to separate group differences from the selective effects of drop out. The major difference in the two studies was that supervision was more closely monitored in the federal probation system than in the more diverse setting of city and federal programs. Based on the findings from the second study, we believe that the success of oral naltrexone would require much more supervision than is typically provided by the criminal justice system. It is anticipated that XR-NTX could be substantially more effective than oral naltrexone despite variation in levels of supervision. Its long duration of action has the potential to improve retention and reduce the likelihood of relapse.
Extended-release naltrexone was tested in a collaborative study between Columbia University and the University of Pennsylvania(25
) with 60 heroin-dependent non-offenders who were treated for two months. The study used Depotrex®, the Biotek version of extended-release naltrexone, and demonstrated that, over the two-month treatment period, injectable long-acting naltrexone was well tolerated and produced a significant dose-related increase in treatment retention compared to placebo.
More recently, preliminary findings from a double-blind, randomized multi-site trial of 250 opioid-dependent patients in Russia found that patients treated with Vivitrol® brand XR-NTX had significantly fewer opioid positive urines, better treatment retention, and reduced cravings for opioids compared to patients who received a placebo.(26
Since opioid-addicted individuals under criminal justice supervision are considered a vulnerable population there has been limited research, making it important to study medication treatments in this group. It is also important to understand the generalizability of the treatment across a range of real world treatment settings. Therefore, in order to obtain a sufficient generalizable sample, a multi-site feasibility study was conducted to assess our ability to recruit, treat, and retain opioid-dependent offenders in this pilot study of Depotrex® brand XR-NTX. The five sites included: 1) University of Pennsylvania, (Penn; coordinating site), 2) New York University/Bellevue (NYU), 3) Rhode Island Hospital, 4) Columbia University, and 5) Friends Research Institute in Baltimore. The primary study outcomes were retention in the six month treatment program, opioid use, and incarcerations. It was anticipated that participants who received all six monthly injections of XR-NTX would have fewer opioid positive urines and experience less recidivism that those who did not complete the treatment protocol.