Posts Tagged ‘vivitrol’

Vivitrol Treatment for Opioid-addicted Criminal Justice Offenders

Vivitrol

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.

  1. 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.
  2. 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.
  3. 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.
  4. 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.

  1. 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.
  2. 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.

  1. 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.

 

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Opioid Addicts Have a New “Shot” at Treatment

Several patients last week asked me if I’d heard of the new “shot” for pain pill addiction. It became clear they were talking about Vivitrol, the brand name for the extended-release naltrexone.

This is not a new drug, but a newer formulation of an old drug. Naltrexone is an opioid antagonist that’s been used in tablet form both for alcohol addiction and opioid addiction.  Naltrexone attaches to opioid receptors, but doesn’t activate them, and prevent other opioids from activating the receptors.

It’s used for alcohol addiction because it appears that in some alcoholics, part of the pleasure from drinking is mediated by the opioid receptors. When these alcoholics take naltrexone pills, it doesn’t make them sick, but takes all the fun out of drinking. Alcoholics taking daily oral naltrexone have fewer drinking days, and drink less if they do have a relapse back to drinking. It’s never meant to be used alone, but in combination with some sort of counseling and recovery program.

The problem with the oral form is that the alcoholic has to remember to take it each day, so when Vivitrol released, it meant there was a way to give the medication in shot form to last a month at a time. However, it’s significantly more expensive than oral naltrexone and it’s not a painless injection to receive, according to many patients.

For some reason, the patients I’ve seen lately who asked about the new injection for pain pill addiction seem to believe this injection will prevent opioid withdrawal or prevent cravings. It doesn’t do either. In fact, it can’t be taken until 7 to 10 days after the last opioid, or it will cause opioid withdrawal. Some sources say it can be started sooner, but people who have been on methadone may need to wait even longer.

Naltexone does work for opioid addiction, however. In the initial trials, patient on Vivitrol had significantly more opioid-free urine drug screens that patient receiving placebo injections.

In the past, medical professionals recovering from opioid addiction were often required to take naltrexone as a condition of their return to work. Doctors, pharmacists, and nurses may need to work around opioids, and if they relapse while taking naltrexone, the illicit opioids will have no effect. The antagonist thus serves as extra insurance against a relapse.

Opioid Blockers: Do They Take All the Fun Out of Life?

According to an interesting article in the most recent copy of the American Journal on Addictions, the answer appears to be, “No,” at least for some people. (1)

 This article described a study where researchers asked patients on the extended-release opioid blocker naltrexone to rate the amount of pleasure they obtained from things like eating good food, sex, and exercise. These patients were on naltrexone for the treatment of alcoholism, but of course, the information may be helpful for opioid addicts who are treated with opioid blockers to prevent relapse back to opioid use. The subjects were asked to rate, on a scale of 1 to 5, the amount of pleasure they obtained from activities such as sex, eating good food, exercise, talking with friends, and other usually enjoyable things in life. A score of 1 meant they felt no pleasure at all, and 5 meant they felt much pleasure.

 The good news is that pleasure scores for these patients were relatively high. For example, the average score for pleasure from eating good food was 4.14, out of a possible 5. For listening to music, it was 4.00 out of 5. For sex, it was 3.92. For drinking alcohol, it was only 2.57 out of 5, which supports the use of this medication for alcoholics.

 In summary, the study found that subjects on extended-release naltrexone still experienced a good amount of pleasure from life.

 There were limitations to this study, however. We don’t have a pre-naltrexone baseline for these patients. In other words, we know pleasure ratings were fairly high while on naltrexone, but it’s possible these subjects had even higher pleasure scores before naltrexone. Also, there was no placebo control in the study. Maybe people getting pretend, or sham, treatments would have had higher pleasure scores, but we don’t know. 

In my mind, the biggest weakness was that the study enrolled 187 patients, but only 74 completed the intended survey. That means about 60% of the subjects dropped out of treatment, and the article doesn’t say why they dropped out. Maybe the drop-outs were the ones to feel a lack of pleasure in their lives from being on naltrexone, and the ones who stayed on it didn’t have this same side effect. If so, this would obviously skew the results.

 But even with these admitted weaknesses, and even though the study was paid for by the company that manufactures the sustained-release naltrexone (Vivitrol), this article gives hope that Vivitrol may work for opioid addiction. It may help prevent relapses, without interfering with life’s pleasures. And we need every tool we can get to fight addiction.

  1. 1.      O’Brien, Charles; Gastfriend, David; Forman, Robert; Schweizer, Edward; Pettinati, Helen, Long-Term Opioid Blockade and Hedonic Response: Preliminary Data from Two Open-Label Extension Studies with Extended-Release Naltrexone, American Journal on Addictions, Vol. 20 (2), March/April 2011, pp106-112.

Medications to treat Opioid Addiction

    This blog entry describes medications (other than methadone and buprenorphine) that treat opioid dependency. None of these medications are opioid stimulating drugs, and therefore have no potential for addiction.

 Clonidine

     Clonidine has been used for decades as a blood pressure medication. It’s cheap and effective, but has some unpleasant side effects: sedation, dry mouth, and constipation. Because newer blood pressure medications have fewer side effects, clonidine is used less today than in the past to treat high blood pressure. However, it’s at least moderately effective at treating many of the symptoms of opioid withdrawal.

     Among many other places in the central nervous system, opioids act on a part of the brain called the locus ceruleus. The locus ceruleus, which in Latin means the “blue place,” is part of the autonomic nervous system. When locus ceruleus neurons are stimulated, norepinephrine is released into the brain, and this causes overall stimulation of the brain. Opioids slow the firing of these neurons in the locus ceruleus, reducing the release of norepinephrine. When the body gets opioids regularly from an outside source, the locus ceruleus makes adjustments, to make up for extra opioids. Then, if the supply of opioids is suddenly stopped, the locus ceruleus becomes unbalanced, and releases an overabundance of norepinephrine. The heart rate and blood pressure increase, along with other symptoms: runny nose, yawning, tearing of the eyes, diarrhea, and nausea.

     Since clonidine works by calming the locus ceruleus, clonidine reduces many of these unpleasant opioid withdrawal symptoms, though it rarely eliminates all withdrawal symptoms. In the past, when it was the only medication available for opioid withdrawal management, patients rarely stayed at a detox facility long enough to complete their withdrawal. It was difficult to retain the addict in treatment. Now, most state-of-the-art detoxification units use Suboxone to ease withdrawal symptoms because it’s more effective, and helps retain patients in detoxification, a necessary step prior to the more intense inpatient rehabilitation.

 Opioid antagonists (blockers)

     Opioid antagonists are drugs that firmly attach to the opioid receptors, but don’t activate these receptors. Antagonists prevent other opioids from reaching and activating the receptors. Antagonists remove opioids from the receptors, so if antagonists are given to an actively using opioid addict, the addict will become sick with withdrawal. This is called “precipitated withdrawal” because it was caused, or precipitated, by a medication.

     Naltrexone is the most commonly used oral opioid blocker. It’s taken orally, in pill form. It’s started after an opioid addict has completed opioid withdrawal. It can be a difficult medication to take, because it may also block endorphins, our own naturally made opioids. Some patients complain of headache, muscle aches, and fatigue while taking naltrexone. Many times these unpleasant symptoms will subside, with more time on the medication. The medication can be started at a half dose for the first week or so, and then increased to the full dose. Most patients tolerate this better.

     Naltrexone has been used in this country mainly for relapse prevention, particularly for addicted professionals. Many professionals, such as doctors and pharmacists, who have been treated for opioid addiction, are started on naltrexone when they return to work. These professionals may need to work around opioids, and if they relapse while taking naltrexone, the opioids will have no effect. The antagonist thus serves as extra insurance against a relapse. Many licensing boards for impaired professionals insist they take naltrexone as a condition of being allowed to return to work in their fields.

     Naltrexone works well, but only if the patient takes it every day.  If the addict “forgets” to take her dose for one or two days, it’s then possible for her to get high from ingested opioids. Because of this, the medication is also available in an implantable form. Pellets containing naltrexone are placed just under the skin and the medication is released into the body over three months. With this method, compliance is obviously higher, since the addict would have to dig the pellets out to be rid of the blocking drug. Not many centers place these pellets, so access to this treatment may involve some travel.

     A long-acting, monthly injection of this drug has just been approved for the treatment of opioid addiction. It’s marketed under the brand name Vivitrol, and it’s also used for alcohol addiction.

     Obviously, compliance with naltrexone will be much better with this method, because after it’s injected, there’s no turning back. Studies are ongoing to see what the success rate will be with this easier option.

Unfortunately, the injection is quite a bit more expensive than the daily pills. Another concern with the opioid antagonists described above is pain control. What if the patient is in a bad accident, and needs opioid pain medications, or needs surgery? Most patients will have to be admitted to the hospital, with close monitoring, because it takes large doses of opioids to override the effect of these opioid blockers. Pain control is obviously more complicated in such a situation.

     Naloxone is the intravenous form of an opioid antagonist, better known by its brand name Narcan. It’s injected to rapidly reverse the effects of opioids. Emergency workers often carry Narcan with them to use if they encounter a person who has overdosed with opioids. This medication can be life-saving, but it also puts the opioid addict into immediate withdrawal. 

Detoxification under anesthesia

     Because of the fear that many opioid addicts have of opioid withdrawal symptoms, some treatment programs have used a method of inducing physical withdrawal while the patient is under anesthesia.

     With rapid or ultra-rapid detoxification, the patient is first given some type of general anesthesia, and then given doses of an intravenous opioid antagonist like naloxone. The naloxone puts the patient’s body into withdrawal, but since he’s unconscious, he won’t be aware of it. Hours later, the patient is brought out of anesthesia. Proponents of this method of detoxification say that the patient has no further withdrawal once he is out of anesthesia. However, several studies show significant post-procedure symptoms, with nausea, vomiting, and insomnia. These symptoms can continue for days after the procedure. (1)

      This method appeals to many addicts because it’s advertised to be quick and painless. However, most evidence shows patient outcomes using rapid or ultra-rapid detoxification have the same results as techniques using buprenorphine to transition off of opioids and onto naltrexone. (2) Plus, ultrarapid detox costs much more. In many places, the procedure costs tens of thousands of dollars. This method also has the added risks of general anesthesia.

     Treatment centers that perform rapid detox advertise claims of “100%” success, speaking of numbers of patients that complete treatment.  But if the patient is under anesthesia, of course 100% will complete the treatment. They aren’t going anywhere, since they are unconscious. Many proponents of rapid detox exaggerate and inflate success rates in this way. However, most studies show that at one year, success rates with rapid detox under anesthesia, compared to detox with a short course of buprenorphine are equal. They’re equally dismal, with only twenty percent of the addicts still abstinent from all opioids.

     Most reputable treatment centers no longer use this expensive, and relatively riskier, method of detoxification under general anesthesia. Since the studies don’t show greater abstinence rates with this method, it’s difficult to justify its expense and risk. (2)

     However, there may be some patients for whom this is an acceptable treatment. Perhaps if ultra-rapid detox is the only treatment option that an addict is willing to try, the potential benefits may outweigh risks, since we know continued active addiction is very risky. This method of detox may be most successful with a very motivated addict who, for whatever reason, has a deadline they want to meet for detoxification. Even though there’s less than a twenty percent chance that he will be off opioids at one year after the procedure, that addict  will still be introduced to the idea of  addiction treatment

 End notes:

  1. Singh j, Ultra-rapid opioid detoxification: Current status and controversies, Journal of Postgraduate Medicine 2004; 50:227-232.
  2. Collins ED, Kleber HD, Whittington RA, Heitler NE, Anesthesia-assisted vs buprenorphine- or clonidine-assisted heroin detoxification and naltrexone induction: A randomized trial, Journal of the American Medical Association, 2005; 294 (8) 903-913.
  3. Cucchia AT, Monnat M, et.al; Ultra-rapid opiate detoxification using deep sedation with oral midazolam: short and long-term results. The authors conclude that patients still had withdrawal symptoms after the detoxification procedure, and withy percent had relapsed back to opioid use at the six month follow up. Drug and Alcohol Dependence, 1998; 52(3) 243-250.