Naltrexone, an oral opioid blocker, is now available as an extended-release monthly injection, under the brand name Vivitrol. Initially marketed for alcohol addiction, it also treats opioid addiction. This medication is an opioid antagonist, which means that though it attaches to opioid receptors, it does not stimulate the receptor. Since naltrexone has a higher affinity for the receptor than opioid agonists (like oxycodone, heroin, and methadone) it can’t be displaced. This means it blocks opioid effects, including euphoria. Vivitrol is used for alcohol addiction because part of the pleasure from alcohol consumption is thought to be mediated through opioid receptors.
Some patients say Vivitrol blocks opioid cravings. From a purely biological view, that would be surprising, since it does not stimulate the opioid receptor. Yet some studies suggest it reduces opioid cravings, and some patients claim it reduces opioid cravings. It’s hard to know if this is due to a physiologic effect, or a mental process. If a patient who has just been given an opioid blocker believes he then is unable to feel any euphoria from opioids, maybe his cravings diminish.
I haven’t used Vivitrol much. I had one patient who came two months in a row for his injection, then was lost to follow up. I’ve had about three prospective Vivitrol patients scheduled to see me in my office and all three were no-shows for their appointments, very irritating.
This medication is expensive, at over a thousand dollars for one monthly injection.
In short, from the studies I’ve read and my own experience, I’m not convinced naltrexone will ever be as effective as methadone or buprenorphine in the treatment of opioid addiction.
When I saw an article in the New England Journal of Medicine, titled “Extended-release Naltrexone to Prevent Opioid Relapse in Criminal Justice Offenders,” I read it with interest. This article was in the March 31, 2016 issue, describing a study of 308 subjects, done by Lee et al., at five sites in the Northeast.
The study subjects were recruited from volunteers with histories of opioid dependence who were involved with the criminal justice system, but not incarcerated. These people agreed to be randomized to the treatment with Vivitrol or treatment as usual. Subjects were excluded if they had elevated liver function tests, were pregnant or trying to become pregnant, or had serious physical or mental health problems. They were also excluded if they had a chronic pain diagnosis for which opioids were prescribed, or if they had been hospitalized with a drug overdose within the past 3 years. They were excluded from the study if they preferred addiction treatment with buprenorphine or methadone medications, since obviously naltrexone can’t be given with those two medications.
The test subjects randomized to the Vivitrol group received injections every 4 weeks with counseling around medication side effects. Beyond that, both the Vivitrol group and the treatment as usual group had similar counseling schedules. People in the treatment as usual group were referred to treatment programs in the community, including providers of methadone and buprenorphine. Test subjects were seen every two weeks for 24 weeks, then at week 27, 52, and 78. Urine toxicology was obtained at each visit, as was self-report of drug use. Researchers also collected subject-reported data about criminal activity, re-arrest and incarceration.
The study examined how long it took subjects in each group to relapse to opioid use. The researchers defined relapse as ten or more days of opioid use out of the preceding four weeks. The rate of opioid-free drug screens was also evaluated for each group.
The treatment lasted 24 weeks. During this time, this study found that subjects randomized to receive naltrexone had significantly longer time until relapse to opioids than the group randomized to treatment as usual: 10 weeks for Vivitrol subjects compared to 5 weeks for treatment as usual group. The naltrexone group had higher rates of opioid-negative drug screens, and lower percentage of self-reported days with opioid use.
The groups didn’t differ significantly on rates of other, non-opioid drug use or the rates of re-incarceration.
This study also examined relapses in both groups after treatment ended, at week 52 and week 78, and found both groups had similar rates of opioid-negative urine samples. Surprisingly, in both groups, about half the subjects had negative drug screens for opioids.
In summary, this study showed that extended-release naltrexone by injection helped people addicted to opioids refrain from using opioids for much longer, and helped them have fewer days of opioid use. However, once the medication was stopped, the rate of drug use for these subjects was the same as treatment as usual group.
I have a few thoughts about the study.
- This data nicely fits with our present disease model of addiction as a chronic illness. Just as with diseases like high blood pressure and diabetes, when the treatment medication stopped, the disease returned.
- Out of the 153 subjects randomized to receive naltrexone, only 91 got all six of the planned injections. Authors state various reasons for the drop-outs, and indicated only five dropped out due to an adverse reaction to Vivitrol.
Really? This interests me. Naltrexone has significant side effects in some people. Since naltrexone is an opioid blocker, it probably blocks the opioids made by the human body, called endorphins. Yet only one patient dropped out due to side effects?
The authors said 39% of the Vivitrol group had adverse events related to the drug, and listed injection site reaction as most common, occurring in nearly a third; next most common were headache, and gastrointestinal upset. Is it possible some subjects in the Vivitrol group dropped out due to side effects but didn’t tell the researchers? I don’t know.
- Compliance was much better in this study of extended-release injection than with daily oral medication. That makes sense. With oral naltrexone, the person with opioid addiction has to decide to take medication every day, as opposed to once a month with Vivitrol.
- None of the naltrexone patients died, either during treatment or after. This is important, since after a period of abstinence from opioids, overdose risk is thought to be increased. But we didn’t see that effect after the medication was stopped. None of the patients died in an attempt to “override” the blockade of Vivitrol either.
Two subjects in the treatment as usual group died. I don’t think those numbers are nearly large enough to draw statistical conclusions, though.
- The authors acknowledge the lack of blinding – with a medication like depot naltrexone, it would be hard to give a sham injection to control subjects. This medication is thick and not an easy shot to give. It would feel much different than a placebo shot of sterile saline, for example. Perhaps the idea of getting an active medication helped subjects in that group believe it was helping, giving better results not due to the actual medication. That’s the problem with no placebo control – there’s no way to know.
- More study subjects in the treatment-as-usual group sought help from opioid-agonist treatments with buprenorphine and methadone than did the naltrexone group, at 37% versus 11%.
Thirty-sever percent?? That’s over a third. That tidbit is thrown in with little explanation, other than they subjects went to MAT “primarily after resumed illicit opioid use and relapse.”
From the article, I can’t tell if these subjects were counted as having relapsed or not. The number of subjects was likely too small to do any meaningful analysis, but I am very curious about their outcome.
- I find the high rate of opioid-negative drug screens in both groups to be surprising. Each had about half the subjects test negative for opioids at one year after treatment and a year and a half after treatment. That’s good…but just a little too good, perhaps.
So, in this study of opioid-addicted people involved with the criminal justice system, extended-release injected naltrexone prolonged the time to first opioid use compared with treatment as usual. Vivitrol also increased the rate of opioid-free days.
Of course, the big question isn’t IF naltrexone works…the question is how well it works, compared with methadone and buprenorphine?
Ongoing studies will hopefully give us that information soon.