As I promised several weeks ago, in this blog I’m writing about some of the studies published in the latest issue of the Journal of Addiction Medicine, the journal published by ASAM (American Society of Addiction Medicine). All of the following articles were in the last issue, May/June of 2017.

The opioid situation in the U.S. has temporarily claimed a big chunk of our attention, but elsewhere in the world, amphetamine and methamphetamine use disorders are more common than heroin and cocaine use disorders combined. In fact, amphetamine and methamphetamine are second only to marijuana worldwide as the most commonly used illicit drug.

Many scientists have been working to find a medication that will help in the treatment of patients with this disorder. Thus far, only psychosocial treatments have been helpful, including individual and group therapies using motivational interviewing, cognitive behavioral therapy, 12-step therapy, relapse prevention, and contingency management strategies. These treatments do improve outcomes, but are at best only moderately effective.

In Runarsdottir et al., extended-release injectable naltrexone was studied in 100 subjects with amphetamine use disorder in a randomized, placebo-controlled study done in Iceland.

This authors of this study postulated that the opioid blocker naltrexone could block the opioid receptors and thus the pleasurable effects on any endorphin-mediated dopamine release resulting from methamphetamine use. Preliminary studies in rats, primates, and healthy human volunteers suggested naltrexone could be effective, so this study on human subjects with methamphetamine use disorders was undertaken.

Subjects in one arm of the study were randomized to the usual psychosocial treatments plus placebo injection, and the other arm got the same psychosocial treatments plus active extended-release naltrexone injections.

Unfortunately, in this study, extended-release naltrexone did not show any statistically significant benefit over placebo. Both groups had high rates of drop-out at around 50%, which hampered the study results. However, the study’s authors postulated that their selection criteria for the study may have pre-chosen subjects with more severe use disorders.

This study’s results were disappointing. We would love to have a new and effective was treatment for amphetamine and methamphetamine use disorders, but this study didn’t show benefit from extended-release naltrexone for use in this disorder.


Another article was about a newer product containing buprenorphine: the rapidly-dissolving buprenorphine/naloxone sublingual tablet (brand name Zubsolv). It’s been on the market for a few years, and previous studies showed it works as well as other sublingual buprenorphine products on the market.

This study took patients from the previous studies and extended their treatment with this product for twenty-four more weeks, to evaluate the safety of longer-term treatment. As a secondary goal, study subjects were evaluated for their quality of life, opioid cravings, and their addiction severity.

Of the 665 patients who entered this second-stage study, only 44% completed the 24 week extension study. So that’s not great – we would like to see patients retained in treatment. The authors say patients withdrew due to being lost to follow-up, patient nonadherence to medication, and patient request for discontinuation.

But of the 44% of patients who finished the 24 week extension study, improvements were seen in their addiction severity, in their quality of life, in their employment status, and other measures. This means that the rapidly-dissolving buprenorphine tablet was found to be as safe as other similar products on the market, and the benefits of continued treatment persisted throughout this prolonged study period.

The high rate of discontinuation is concerning, but certainly not unusual. In fact, this drop- out rate was similar to studies done on other sublingual buprenorphine products.

I see this at my work. We use both buprenorphine and methadone at the OTP where I work, and drop-out rates are higher for patients on buprenorphine. They tend to bounce in & out of treatment more often than methadone patients do. I believe, but can’t prove, that the milder withdrawal gives patients less incentive to make sure they dose daily.

Patient drop-out is undesirable for all concerned. When a patient drops out of treatment at an MAT, relapse rates are very high, and risk of death may increase as much as eight-fold.

From that point of view, I might be tempted to regard methadone as a superior treatment. However, I know some of our buprenorphine patients would never consider starting methadone, often citing the difficulty of tapering off methadone as the reason. So offering buprenorphine attracts patients who may not enter treatment otherwise.



Another article in this copy of the journal, titled, “Methadone-Induced Hyperhidrosis Treated with Oxybutynin, by Hong et al., was a case study of a patient with pronounced sweating caused by methadone.

Pronounced sweating from any cause is termed “hyperhidrosis.” All opioids can cause this, including methadone. As the author points out, we think this may be caused by muscarinic receptor activity in the part of the brain that controls body temperature.

This case study is of a patient who stabilized on methadone 100mg for the treatment of his opioid use disorder, but had severe sweating, to the point he had to change clothes multiple times per day. This patient went to his internist, who prescribed oxybutynin, a medication also known under the brand name Ditropan. It’s used for overactive bladder disorders, and works through its anti-muscarinic activity.

The patient had resolution of his excessive sweating within two days, so the treatment was a success in this case.

I think I will start recommending to my patients with excessive sweating see their primary care providers for a trial of oxybutynin.

There are some pitfalls…it can lead to urinary retention, of course, and that’s always vexing when we ask patients to give urine drug screens.



3 responses to this post.

  1. Posted by Andrew angelos on July 16, 2017 at 8:18 pm

    Great blog this week. I feel your not seeing some things just for what they are. I’ve been on methadone and bupe. The withdrawal is worse for methadone for sure at least the first few days. The withdrawals dosent really start on either for about 36 to 60 hours though. I feel the reason you have the drop out rate is because the methadone give the addict the high that there used to. As far as meth addicts getting bupe for treatment is weird. In my experience the clinics that treat opioid addiction already have these people in them to the tune of about 25 percent. Mostly because of the courts mandating drug treatment. Maybe in the questionare At meant all health they said they used opioids. I’ve done meth a lot years ago. I’ve known math addicts. That addiction is a very different beast. At least in my opinion. I’ve been addicted to everything at one point or another. Out of all opioids were the only thing I could not stop using. Still to this day I take bupe. I feel putting people addicted to meth on bupe or worse yet methadone is doing a disservice to them. Meth is a 1 week detox of mostly sleep. Go to any jail in this country and you could probably see this in action. After about 2 weeks of being sober most are fine. That’s verses a one month to 3 month steady detox from methadone or bupe. I’d also almost be willing to put money on the fact that most meth use is from undiagnosed add and self medication. I would urge doctors not to put meth addicts on bupe unless they have an opioid addiction as well. If it’s just meth unfortunately good old abstenence and therapy is the best action at present in my opinion.


    • No, the study looked at extended-release naltrexone, NOT buprenorphine.


    • Posted by Jwalk on July 19, 2017 at 3:23 am

      I have been on methadone treatment for many years. I feel no “high” associated with this medication. I feal no different when I take it. I continue to stay in treatment because I fear if I leave i will return to a life of being homeless and prostituting myself for drugs.
      Since starting MMT I am raising my children and have kept custody of them, I have gainful employment, I have my own home, a car, I am a active member of society, I haven’t relapsed once. I have a good relationship with my family. I haven’t been charged or arrested for any crimes.
      These are all things I couldn’t have said before MMT.
      People stay on MMT because you have to make a real change in order to do well on methadone treatment. You have to earn your take homes, you have to stop using and most people are scared to death to leave because their life was so chaotic before and after starting this treatment life got better. Why would you leave stable ground to get on a sinking ship. Most of us fear the “old me” is just waiting on you to leave treatment.
      The reason bupe doesn’t work for many is because they don’t have to make any real changes in order to get their prescription. Many I know get suboxone to sell so they can buy heroin. Many people do good on suboxone but many don’t.
      Alot of us need to be monitored for awhile to make sure we r taking our medication right. When u have to earn your take homes you respect having them and don’t want to do anything to screw it up. I used to sleep all day and stay up all night. After having to go daily to dose for so long it taught me to get up in the morning and participate in the world around me.
      Also most stay on MMT so long because we didn’t become hard core addicts over night. I was homeless and prostituting for 12 yrs. I started this at 16 yrs old. It takes time to learn to change this behavior. In my case it takes time to learn to become a adult even though I am a grown woman.
      Im not sure if it would help people on meth but Im not a Dr. Maybe it would work great.


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