A Shot To Stop From Shooting Up

Monthly injections of an opioid antagonist can help opioid users avoid relapse, decreasing relapse rates by 10 to 20%.  This is especially evident for the high relapse rates seen after short-term hospitalization (detox). Given that these injections last four weeks, this treatment may prevent death by overdose shortly after leaving a short-term hospital program, and helps maintain sobriety for weeks to months.


Given the epidemic of opioid use and the rising mortality from opioid overdose, enhancing the effectiveness of substance use disorder treatment is imperative.  The addition of medications in  treatment has been shown to be effective in reducing opioid-related mortality in those seeking recovery.  However, many suffering from opioid use disorder are opposed to starting long-term treatment with an opioid agonist, such as buprenorphine/naloxone (brand name, “Suboxone”) or methadone (both of which can be and are misused and diverted).

This study examined the effectiveness of using an extended-release injection antagonist, naltrexone (as commonly known by its brand name, Vivitrol )), which rather than maintaining a physiological dependence on opioids, blocks the opioid receptors and may thus be more acceptable to patients desiring complete opioid abstinence.  In addition to not activating the opioid receptors, Vivitrol offers the advantage that it is effective for four weeks after the single injection, thus those leaving short-term hospitalizations after detox would be protected from opioid overdose during the weeks shortly after leaving treatment.

This is a follow-up study of a large randomized-control trial, looking more carefully at the effectiveness of Vivitrol in preventing relapse across three types of treatment settings.   In addition, this study is focused on patients with criminal justice involvement but not currently in prison (they compare effectiveness in outpatient, short-term or long-term inpatient) thus the patient population studied is more apt to represent ‘real-world’ patients with complex psychosocial circumstances.  Though the study did not include those currently in prison, their results do suggest that starting Vivitrol injection treatments while in prison may also be worth studying.


This is a secondary analysis follow-up study of a six-month US-based, multi-site, randomized, controlled effectiveness trial comparing the addition of monthly Vivitrol injections (a long-acting opioid antagonist) to counseling alone without medication-assisted treatment.


The 308 study participants had both a lifetime history of opioid use disorder and recent criminal justice involvement (most commonly on probation or parole) but were not currently in prison.  The three treatment settings compared are outpatient (n=201), short-term inpatient (up to 4 weeks; n=59) and long-term inpatient (up to six months; n=48).  The publication of the primary study results pooled these three treatment venues.  Selected participants desired opioid-free treatment (i.e., those seeking buprenorphine or methadone treatment were excluded), were abstinent at the time of study enrollment, and had urine samples and regular follow-ups with a medical clinician (initially weekly, then biweekly) for six months.  The primary outcome was time to relapse as evidenced by two consecutive opioid-positive urine samples or a self-report of seven consecutive days of opioid use, with data analysis focused on the five-week and six-month time points.

Of note, since active opioid use prior to treatment was not part of the inclusion criteria, only a minority of the participants had any opioid use in the 30 days prior to study enrollment (44% of outpatients, 37% of short-term inpatients, 10% of long-term inpatients).



Across all three treatment settings, the Vivitrol + therapy group had significantly lower relapse rates than those in therapy alone. The effect was greatest in the short-term hospitalization setting where relapse rates at five weeks were 63% for therapy alone compared to 7% for Vivitrol + therapy. Over the course of the full six months of the study, the relapse rates in both treatment groups rose, but a benefit for Vivitrol was still evident (for the same short-term hospitalization groups, the relapse rate at six months as 77% with treatment compared to 59% with Vivitrol). Of those in the Vivitrol group who had relapsed, however, 83% had self-discontinued the Vivitrol injections so the steep rise in relapse rates seen from five weeks to six months for these patients could be attributable to not taking the medication.

The authors did not include detailed medication adherence data by group, so perhaps differing adherence rates may contribute to group differences. Although the majority of study participants had not had any opioid use in the 30 days prior to study enrollment, and then were having visits either weekly or biweekly with the study clinicians, and participating in active treatment, the abstinence rates were below 50% for the three treatment as usual group as well as for the short-term hospitalization + Vivitrol group. They were higher in the remaining two groups (54% in the long-term inpatient group and 62% in the outpatient group receiving Vivitrol) showing a benefit of Vivitrol addition.

The relatively high relapse rate (cumulative rate of 61% at six months across all three groups) is particularly surprising as most (66%) participants had been opioid-free for 30 days prior to recruitment into this study. Study participants were all using opioids and had criminal justice involvement, which may contribute to lower abstinence rates on average at six months.


This study adds to the growing volume of literature suggesting that medications for opioid use disorder lead to sustained reductions in opioid use and increased abstinence rates.

This was a real-world effectiveness study and highlights the challenges of engaging criminal-justice involved individuals with opioid use disorder in antagonist treatment over time. The more unique contribution of this study is in both its patient population, focused on individuals using opioids with criminal justice involvement, and its comparison of treatment settings.  Given the relatively high rates of relapse after short-term hospitalization, as compared with sustained outpatient or long-term hospitalization, it is here that the addition of Vivitrol injections showed the greatest reductions in opioid relapse at the earlier time point (5 weeks).

This study did not specifically encourage medication or treatment adherence, and the relapse rates at six months were two to four times higher at the six month mark as compared to five weeks. At six months, the addition of Vivitrol had only a modest effect. That may be due to study design (no active enhancement of treatment engagement) and to the population studied (criminal justice involved).

  1. The study excluded those desiring treatment with agonist therapy (e.g., Suboxone). The group studied – those not wanting any physical dependence on opioids in the future -may represent a minority of those individuals using opioids.
  2. Less than 50% of all participants in any of the three treatment groups had any opioid use in the past 30 days prior to beginning the study. Thus, it might be difficult to generalize this study to those with only a week’s abstinence – the group most commonly seen in short-term hospitalizations (and incidentally, the group that benefited the most from the addition of Vivitrol early in treatment).
  3. This study did not include any interventions to increase medication or treatment adherence. In addition, the adherence data was not included in the paper, just the summarized findings of how many of those who relapsed had already discontinued the Vivitrol injections (83%) but given the study design, a high non-completion rate would be expected across all of treatment conditions.
  4. This was a secondary analysis of a previously-published study so participants were not randomized to the five sites, with some sites offering both outpatient and short-term hospitalizations and other sites only offering one of the three treatment modalities (outpatient, short-term or long-term hospitalization).


  • For individuals & families seeking recovery: Vivitrol is an attractive alternative to Suboxone for those not desiring to be maintained on an opioid.  Relapse rates at six months are significant, but are 10-20 percentage points lower with Vivitrol than that seen without medication assisted treatment. In the setting of outpatient care, relapse rates fall to 38% at six months as compared with 61% without the addition of Vivitrol.  Vivitrol is especially appealing for those leaving abstinent settings (prison or detox) as it protects them for four weeks from opioid overdose.
  • For scientists: Given that the relapse and abstinence rates with Vivitrol are comparable to that seen with Suboxone, it is scientifically interesting that similar clinical outcomes are produced by either blocking the opiate receptor or activating it in via an agonist/antagonist mechanism. Head to head trials of Vivitrol vs Suboxone among criminal justice involved individuals with opioid use disorder will give clearer indications of comparative effectiveness.
  • For policy makers: Given the likelihood that chronic and sustained opioid use may lead to involvement with the criminal justice system, starting prisoners with prior opioid use disorders on Vivitrol may remove one of the important barriers to Vivitrol induction (confirmed abstinence for 7-10 days).  By addressing opioid use in the relevant prison population, prison administrators may simultaneously decrease recidivism, relapse and death by overdose.
  • For treatment professionals and treatment systems: For those able to maintain abstinence for a week or longer, Vivitrol may prove to be nearly as effective as Suboxone for enhancing opioid abstinence.  The advantages are that Vivitrol is only administered monthly and does not have any misuse potential as is seen with Suboxone.  Also, this study shows the inferiority of short-term hospitalization as compared with outpatient and long-term hospitalization in term of maintaining abstinence from opioids in this criminal justice-involved population.