• First, Suboxone is better than a placebo medication, but there is room for improvement. For example, Suboxone patients in rigorous studies still produce up to 60% opioid positive urine toxicology screens (“tox” screens), with better outcomes for those who only misuse pharmaceutical opioids.
• Second, like most medications, an individual needs to take buprenorphine on a daily basis – which can be problematic for individuals with substance use disorder given that motivation can be variable especially early in the recovery process.
• Third, some clinicians have concerns about prescribing an opioid agonist like buprenorphine to those who are still drinking alcohol or using benzodiazepines, since they are also central nervous system depressants and, in combination, can have health consequences including overdose.

• One of the main concerns about naltrexone is that because it is an opioid antagonist (i.e., blocker), an individual needs to be abstinent from opioids for at least a few days so that they do not go into immediate withdrawal when administered the medication. For some individuals, this need to not use any opioids before receiving Vivitrol can be very difficult and uncomfortable, and thus can lead to resumption of illicit opioid use making this transition a clinical challenge.

All participants had opioid use disorder according to the diagnostic and statistical manual of mental disorders, 5^th edition (DSM-5) and had used opioids at least one of the past 30 days.

While the sites differed in terms of how they helped individuals medically withdraw from opioids (“detox”), all were short-term (3-7 days) and part of a community program that provided at least weekly therapy sessions (group or individual) on an outpatient basis during the study. The study was conducted as part of the National Institute on Drug Abuse’s Clinical Trials Network, which tests evidence-based treatments for substance use disorder in community settings. Of note, study site and severity in terms of opioid use were taken into account when randomizing patients to receive to Suboxone vs. Vivitrol.

All patients received medical management at each study visit including psychoeducation about opioid use disorder, an adherence plan, advice to abstain from all substance use, monitoring of side effects, and encouraging attendance at therapy and mutual-help groups. The medical management schedule was the same for both Suboxone vs. Vivitrol – weekly for the first month, then every two weeks for the next 3 months, then every month for the final 2 months. Suboxone doses ranged from 8 to 24 mg depending on clinical need – these are typical doses. Vivitrol was administered every 28 days, and before starting the medication, individuals needed to be abstinent from all opioids for at least 3 days, have a toxicology screen negative for opioids, and pass a “naloxone challenge” to be sure they would not withdraw from the Vivitrol.

The primary outcome was “relapse”, measured after the first 3 weeks, and defined as one of the following:

• 4 consecutive weeks of opioid use determined by urine drug test (a missed drug test was counted as “positive” indicating use)
• 4 consecutive weeks of opioid use determined by self-report
• 7 consecutive days of self-reported opioid use

CHARACTERISTICS OF STUDY SAMPLE

Important characteristics of the study sample were that they were 34 years old, on average, 70% male, 75% White and 10% Black and 13-20% Latino. Most (80%) were heroin users, more than 60% were injection drug users, and 35-40% had prior treatment. Other substance use in the past 30 days was common: 47-57% with stimulant use, 25-32% with sedative use, 42-48% with cannabis use, and 25-27% with “heavy” drinking, which was not defined by authors but, according to the Substance Abuse and Mental Health Services Administration (SAMHSA), means 5 or more drinks for men or 4 or more for women on the same occasion at least 5 days in the past month. Nearly 70% reported a lifetime history of another psychiatric disorder, and they had “mild” depressive symptoms, on average, measured by the Hamilton Depression Scale. Individuals were not able to participate in the study if they had “serious medical, psychiatric, or substance use disorder” as determined by the study physician.

In a related study taking place in Norway that also compared Suboxone to Vivitrol, all patients had already detoxified from opioids – essentially removing any influence of needing to establish a period of abstinence to get started on Vivitrol, because it was a constant. Not surprisingly, in that study Vivitrol did as well, or in some cases, better than Suboxone. So, in settings where individuals are safely detoxified and time is not a factor (e.g., in the Veterans Administration), Vivitrol may be an equally effective option at least in the short term. On the other hand, in outpatient settings or when detoxification periods are relatively rigid – more common in addiction treatment settings – Suboxone appears to be the better option.

1. There was no group receiving a placebo medication to which to compare Suboxone and Vivitrol – however, the efficacy of each medication compared to placebo is well established.
2. All individuals were recruited from an inpatient detoxification program while the primary draw of each medication is that they can be initiated and prescribed on an outpatient basis.
3. Individuals with “serious” other psychiatric disorders – – were excluded. This decision on who to exclude was made by a study physician. Also since patients were recruited from an inpatient detoxification program, they may be more motivated for change than your average patient. This introduces two concerns. First, whether the findings from this study can be applied to the population of individuals with opioid use disorder is not clear. Second, those with more psychiatric comorbidities could have greater difficulty with day-to-day tasks, including but not limited to taking a medication. So, daily medication use may be a greater challenge, which might favor Vivitrol which is administered once every 4 weeks. Also, an agonist treatment with some – albeit minimal – potential for misuse may be more of a concern for those with other substance use disorders. Given the study design, it is not possible to answer many of these questions but they are important to applying study results and informing future work.