A closer look at the evidence (Part 3)

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This is the third post in a series taking a look at the evidence provided by advocates of medication-assisted treatment (MAT).

The first section below provides the background. If you’ve already read the first two posts (part 1 and part 2), skip ahead to “A closer look at the evidence (part 3)” below.

This post looks at the last 10 (of the 19) studies from the meta-analysis provided by Newt Gingrich, Patrick Kennedy & Van Jones.

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You may have heard that the unlikely crew of Newt Gingrich, Patrick Kennedy & Van Jones have taken interest in addressing the opioid crisis. More allies is a great thing.

They strongly advocate for medication-assisted treatment as the standard of care:

Medication assisted treatment, or MAT, is the use of FDA-approved medicine in concert with behavioral counseling for opioid addiction that has proven efficacy. Multiple studies have shown that MAT is essential to effective long-term recovery, by reducing cravings and the risk of fatal overdose and increasing abstinence and time in treatment. And we have known this for a long time. In 2003, a multicenter clinical trial published in the New England Journal of Medicine (NEJM) found that buprenorphine reduced the craving to use an opiate by roughly 50 percent and increased the odds of not taking an opiate by about 3.5 times. MAT is the widely accepted and scientifically proven method for successfully treating opioid addiction – and the National Institute on Drug Abuse, the World Health Organization, UNAIDS and many other physician groups all recommend it as the standard of care.

They use the word “recovery” in the title of their article and conflate recovery with access to MAT.

Is that accurate? Fortunately, they provided sources for their statements so we can take a look at their evidence.

But first, consider what you want out of treatment. What would you consider a successful outcome?

Returning to work/school?
Restoration of family life?
Restoration/creation of supportive social networks?
Participation in community life?

Well, they provide 2 studies for their evidence.

The first is a meta-analysis (a study of studies) and the second is a regular old study.

The outcomes these studies measure are: retention in treatment; decrease in illegal opioid use; decrease in mortality; decrease in nonopioid drug use; decrease in criminal activity; decrease in risk behaviors related to HIV and hepatitis C.

These are very important outcomes, especially the ones that could be the difference between life and death. However, I think it’s fair to say that most patients and families would consider these necessary but not sufficient.

A closer look at the evidence (part 3)

Over the course of several posts, I’m going to dig into the findings from these studies.

The meta-analysis provides a review of the 19 studies and a summary of each.

Let’s look at the studies. Some of them consider the effects of various doses and other factors. I’m just going to report on the outcomes above.

Study 10

This study sought to evaluate the efficacy and safety of MMT versus BMT for pregnant, opioid-dependent women.

The study started with 18 subjects and retained 14. There was no information on abstinence among subjects. The information on drug testing among subjects is difficult for me to understand, so I’ve included it below. (I can’t tell whether this is reporting a count of positive drug screens [then, decimals wouldn’t make sense] or a percentage [but, wouldn’t they say?] or something else.)

This table only reports on the subjects retained through the entire study and the paper makes it clear that the dropouts had significant substance use during the study.

fischer-table

A unique feature of this study was that subjects had daily contact with physicians.

Study 11

This study tried to assess the intravenous misuse potential of buprenorphine/naloxone compared with buprenorphine among injection drug users receiving BMT.

This study put subjects on various doses of buprenorphine and buprenorphine/naloxone and used drug-versus-money exercises to assess the abuse potential of buprenorphine and buprenorphine/naloxone.

Their conclusions stated, “although the buprenorphine/naloxone combination has intravenous abuse potential, that potential is lower than it is for buprenorphine alone, particularly when participants received higher maintenance doses.”

Here is a graph they created to illustrate their relative “drug liking” findings.

NIHMS367012.html

Study 12

This study looked at the neurobehavioral effects for neonates exposed to MMT or BMT.

This study only reported on fetal effects. The study does report that it did drug screens throughout the study and provided incentives for negative drug screens, but it provided no information on drug screen results.

Study 13

This study sought to determine the efficacy of buprenorphine implants versus placebo implants.

This was a long study (6 months) and they found that more patients with buprenorphine implants completed the study 65.7% versus 30.9% for the patients with placebo implants.

Strangely, they highlight drug testing results for the first 16 weeks of the study and kind of bury the results for the entire study.

Through the first 16 weeks of the study, 40.4% of the buprenorphine implant group’s drug screens were negative versus 28.3% of the placebo implant group’s.

For the full 24-week treatment period, 36.6% of the buprenorphine implant group’s drug screens were negative versus 22.4% of the placebo implant group’s.

This would suggest that their outcomes were deteriorating in the last 2 months of the study.

Other considerations for this study include the kind of behavioral treatment the patients received. The study reports, “All patients received manual guided individual drug counseling.16 Sessions were held twice a week during the first 12 weeks and then weekly for the subsequent 12 weeks. If a patient missed 6 consecutive counseling sessions, this was judged to be clinically meaningful non-adherence, causing the patient to be withdrawn from the study.”

Further, they did drug screens 3 times per week. So, they had a lot of contact with research staff over this 6 month period.

Study 14

This study compared outcomes for patients that received BMT in an HIV clinic to outcomes for patients that received intensive case management and were referred to an outside specialty opioid clinic using BMT or MMT.

This was a long study (12 months). The retention rates 74% for those getting BMT in their HIV clinic and 41% for those referred out.

Drug testing results indicated that opioid positive urine drug tests were 44% for those getting BMT in their HIV clinic and 65% for those getting intensive case management and referral.

Drug testing results indicated that cocaine positive urine drug tests were 51% for those getting BMT in their HIV clinic and 66% for those getting intensive case management and referral.

They did not appear to measure or report on abstinence.

Study 15

This study wasn’t on treatment at all. It used a survey to understand for use of diverted buprenorphine.

Here’s the summary: “More noninjecting users reported ever using buprenorphine-naloxone to “get high” (69% versus 32%, p,.01). Most participants reporting past use of buprenorphine-naloxone stated that use was to treat withdrawal symptoms (74%) or to stop using other opioids (66%) or because they could not afford drug treatment (64%).”

I wondered how common use of diverted buprenorphine is and went to the original study. Turns out 76% of subjects reported use of diverted buprenorphine.

The researchers also said, “The number of opioid users in our sample who reported having ever used buprenorphine/naloxone to “get high” is surprising, given that buprenorphine/naloxone is a partial opioid agonist that is not expected to produce euphoria in regular users with a tolerance to opioids.”

Study 16

This study looked at brief and extended buprenorphine treatment with various counseling intensities

All urine samples were negative after the first phase for only 6.6% of patients. During extended treatment with buprenorphine-naloxone, 49.2% of patients had successful outcomes (opioid-negative urine samples); this rate fell to 8.6% at 8-week follow-up. Addition of counseling had no effect in either phase

That term “successful outcomes” was not clear to me, so I went to the original study. Here’s what I found:

“In Phase 1, successful outcome was thus defined as completing week 12 with self-reported opioid use on ≤4 days in a month, absence of 2 consecutive opioid-positive urine tests, no additional substance use disorder treatment (other than self-help), and ≤1 missing urine sample during the 12-week period.”

“Phase 2, successful outcome was defined as abstaining from opioids during week 12 (the final week of buprenorphine-naloxone stabilization) and during ≥2 of the previous 3 weeks (weeks 9–11)”

It’s worth noting that the potential subjects were excluded if they used heroin 4 or more days in the past month, met lifetime heroin dependence or ever injected heroin.

Study 17

This study focused on the impact on infant neurobehavior of in-utero exposure to buprenorphine or methadone and found that babies exposed to buprenorphine exhibited less stress.

Study 18

This study investigated the impact of directly observed therapy plus cognitive-behavioral therapy versus usual treatment among patients receiving BMT for 14 weeks.

The summary simply reports, “No difference was found between groups in treatment retention or drug use.”

The study defined retention this way, “Retention was evaluated as the number of weeks participants remained in treatment. Patients who missed three consecutive instances of medication (n = 11) or three consecutive counseling sessions (n = 2) were considered drop outs.”

It was a 12 week study and 68% and 87% were retained for the 2 approaches. 70.4% and 49% drug screens were negative for opioids for the 2 groups.

They also measured the maximum weeks of continuous opioid abstinence for each subject and reported on the mean for both groups. Those were 5.2 weeks and 7 weeks (out of a possible 14). However, there was a very large standard deviation for both, which suggests there was a lot variance in this outcome. The study does not report how many people

Study 19

This study focused on opioid replacement treatment in pregnancy and effect on neonatal outcomes. They did not report on treatment outcomes for the mothers, just the effects on the babies.

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Note: This is not an argument against access to any kind of care. It’s just a push for good informed consent that empowers patients to advocate and choose for themselves.