Three noteworthy medication assisted treatment (MAT) studies

There have been a few noteworthy medication assisted treatment (MAT) studies published recently.

Two studies evaluated the comparative effectiveness of extended-release naltrexone (Vivitrol) versus buprenorphine-naloxone (Suboxone).

Anticipation of these studies has been heightened by questions about Vivitrol’s effectiveness and marketing.

Study 1

The first of these was published in JAMA in October and summarized their conclusions as follows:

Extended-release naltrexone was as effective as buprenorphine-naloxone in maintaining short-term abstinence from heroin and other illicit substances and should be considered as a treatment option for opioid-dependent individuals.

This study was done in Norway and the only information about other treatments received was this:

Following induction into either medication regimen, participants were asked to attend standard drug counseling, but no behavioral interventions could be initiated.

What that means, I don’t know.

They initiated medication in 143 subjects and had only 1 overdose, which was in the buprenorphine group.

Here is some discussion about this, some subject characteristics, and other findings:

Satisfaction with treatment and willingness to recommend their treatment to others were significantly higher among extended-release naltrexone participants. This finding may be due to the perception of being protected against relapse of opioid use and possible overdose and better opportunities to return to work or educational activities when not having to meet daily or every second day for supervised intake of an opioid agonist. However, the high availability of OMT in Norway34 makes it likely that the majority of participants were mainly motivated to receive the novel extended-release naltrexone treatment and not buprenorphine-naloxone. As treatment preference has been shown to be important for treatment satisfaction and adherence in other settings,35,36 it is difficult to know whether extended-release naltrexone would be equally effective in individuals with lower motivation for opioid abstinence.

There was only 1 reported overdose in the study, which is much lower than most reports on the first 12 weeks after discharge from treatment or prison.9,37,38 This low rate may reflect the high motivation for treatment and good response to regular follow-up by the same study worker in this group of participants.

The rather low reported mean use of opioids the last 30 days before inclusion is probably due to the fact that a number of participants included in the study had already completed detoxification or had sustained abstinence for varying periods of time (prison or inpatient treatment), while others were still actively using opioids at study enrollment.

They report that the medications were equally effective, but I’m not clear exactly what the relapse rates were throughout the study. (I’m not sure I’m reading it right, but did days of heroin and opioid use actually increase in both groups?)

Study 2

The second study comparing the effectiveness of extended-release naltrexone (XR-NTX) versus buprenorphine-naloxone (BUP-NX) was just published by the Lancet and I have been unable to get a full copy.

They summarized their conclusions as follows:

In this population it is more difficult to initiate patients to XR-NTX than BUP-NX, and this negatively affected overall relapse. However, once initiated, both medications were equally safe and effective. Future work should focus on facilitating induction to XR-NTX and on improving treatment retention for both medications.

What did they mean by more difficult to initiated?

As expected, XR-NTX had a substantial induction hurdle: fewer participants successfully initiated XR-NTX (204 [72%] of 283) than BUP-NX (270 [94%] of 287; p<0·0001). Among all participants who were randomly assigned (intention-to-treat population, n=570) 24 week relapse events were greater for XR-NTX (185 [65%] of 283) than for BUP-NX (163 [57%] of 287; hazard ratio [HR] 1·36, 95% CI 1·10–1·68), most or all of this difference accounted for by early relapse in nearly all (70 [89%] of 79) XR-NTX induction failures. Among participants successfully inducted (per-protocol population, n=474), 24 week relapse events were similar across study groups (p=0·44).

This is not surprising, give subjects must be abstinent for 7 to 14 days before beginning extended-release naltrexone. Successful initiation of it is probably going to require a lot of support.

What about overdoses?

Five fatal overdoses occurred (two in the XR-NTX group and three in the BUP-NX group).

I’ve been unable to find much about other treatments involved. The registration reports the following.

The study is conducted in 8 CTN-affiliated CTPs that provide or partner with detoxification services (inpatient/residential) which have the capacity to maintain participants opioid-free for approximately 3-7 days, have the capacity to provide medication-assisted therapy, and can provide a minimum of one group or individual counseling session per week during the 24-week treatment period.

Again, they report that the medications were equally effective, but I’m not clear exactly what the relapse rates were throughout the study.

Study 3

The third study is on neuropsychological function in subjects on buprenorphine-naloxone.

This is important because of questions about cognitive impairment due to maintenance medications.

Their conclusions are as follows:

Among OUD patients, greater adherence to buprenorphine/naloxone is associated with improved neuropsychological functioning over time. In contrast, depressive symptomatology is not associated with neuropsychological functioning over time. Supporting adherence to buprenorphine/naloxone may improve and/or preserve learning and memory functioning in individuals treated for OUD.

I find it hard to know what to make of this study. The following confused me:

  • It had only 20 subjects and put all of the subjects on buprenorphine-naloxone, yet they report “sixteen participants had a current substance use disorder (SUD)”. Why put people without a current SUD on buprenorphine-naloxone.
  • While self-reported substance use declined, positive opioid screens increased from baseline to study completion.

There’s also no mention of other services, like counseling.


Dawn Farm takes informed consent seriously with clients with opioid use disorders. (We do with all clients, but this post is about OUDs and the opioid crisis has made it a very salient issue.) We have developed services to facilitate, support and monitor initiation and ongoing use of extended-release naltrexone. (We also provide screening and referral to other MAT treatment options and provide ongoing outpatient care and recovery support services.) Given our use of extended-release naltrexone and the controversy around the treatment, we’re happy to see evidence to support it.

A lot of attention is given to these studies and others. These studies will be used to write policy and will be referenced by journalists, treatment providers, policy makers, advocates, etc. These studies will determine what all of these people declare the “standard of care”.

Again, the first two studies provide support for a tool we use. (Who doesn’t like validation?)

The questions on my mind have been these: Would I want to be a subject in any of these studies? No. Would I want a loved one to be a subject in any of these studies? No.

These studies looked at the effects of the medications, but they don’t look at the kinds of real world treatments most people get or want. There was little or no counseling. I saw nothing about recovery in any of the studies. I saw nothing about community or family support.

For understandable reasons, they look at easy to measure outcomes like positive drug screens and # of days using. Most people are looking to use fewer days—they are looking for abstinence (from heroin and opioid misuse), recovery,  and a restoration of their quality of life.

So . . . these studies may tell us something. They may tell us some important things. However, what they can tell us is very limited.

It seems hard to draw strong opinions about proper care when I would not want the care provided in the study. (And, when the researchers would never receive similar care.)

These studies provide some data, but they say little about what can be accomplished with treatment of appropriate quality, duration, and intensity, or what it looks like.