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A closer look at the evidence (Part 4)

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This is the 4th post in a series taking a look at the evidence provided by advocates of medication-assisted treatment (MAT).

If you haven’t seen the other posts in the series, you can find them here. (part 1part 2 and part 3)

This post reviews some of the lessons from a closer look at the 19 studies in the meta-analysis provided by Newt Gingrich, Patrick Kennedy & Van Jones.

What have we learned?

We’ve learned a few things:

  • The subjects in these studies often do not resemble the general population of treatment seekers. They are often pregnant, lower severity or misuse only prescription painkillers.
  • The design of these studies often provide contact with research staff 3 to 5 times per week. Some even used monitored dosing.
  • Even with these non-representative populations, retention ranged from around 30% to 65%, with most of those study periods being 16 weeks or less. There were a few with retention rates as high as 75% over a year. Those studies were in Sweden, with unusually intensive treatment or integrated into essential medical care.
  • There was very little attention to abstinence. In the few studies where abstinence was mentioned, the outcomes were not good–relatively low percentages achieving abstinence for periods of 3 to 12 weeks.
  • Ongoing drug misuse is the norm among the subjects in these studies.
  • If you want to look at apparently effective models of MAT, go to Sweden. (Their studies included very high levels of monitoring, support, contingencies and services to address housing, employment and other needs.)

 

The pitch from Gingrich, Kennedy and Jones sounds very similar to many other advocacy pieces.

I don’t have any problem with advocacy for MAT. It can reduce harms associated with opioid addiction there are problems with access in rural areas. However, I do not understand how people like Gingrich, Kennedy and Jones can reconcile what the research actually find with this statement [emphasis mine]:

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.

These advocates oversell the benefits of MAT and will eventually undermine public confidence in treatment and the belief that opioid addiction is a treatable condition.

If I was a person seeking treatment for opioid addiction, I’d feel misled by the information they provide. For example, their statement “in concert with behavioral counseling” is diametrically opposed to the findings in the paper they share as evidence. Further, the paper does not provide any evidence for MAT as a path to abstinence. In fact, the paper suggests abstinence is rare among MAT research subjects.

Advocating for MAT is fine, but please give an accurate picture of the evidence and, given the limitations of MAT, inform readers about the kind of treatment doctors provide to their peers with opioid addiction.

 

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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.

 

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A closer look at the evidence (Part 2)

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This is the second 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 post, skip ahead part 2.

This post looks at 5 more (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 2)

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 5

This study compared levomethadyl acetate, buprenorphine, and high-dose methadone and low-dose methadone

52% of drug tests from Levomethadyl acetate subjects were positive for opioids, 62% of tests from high-dose methadone and buprenorphine subjects, and 79% of tests from low-dose methadone patients.

The closest they came to reporting on abstinence is as follows, “The percentage of patients with at least 12 consecutive opioid-negative urine specimens differed significantly among groups, ranging from 36 percent in the levomethadyl acetate group to 8 percent in the low-dose methadone group.” (There were 3 drug screens each week.)

The reported also testing for cocaine, but did not provide results.

Regarding retention, they reported that, “Overall, 51 percent of the patients completed the 17-week trial (53 percent of the levomethadyl acetate group, 58 percent of the buprenorphine group, 73 percent of the high-dose methadone group, and 20 percent of the low-dose methadone group).”

It’s worth noting that the buprenorphine dosing was unusual. “Buprenorphine was administered at a dose of 16 to 32 mg on Mondays and Wednesdays (to approximate a dose of methadone of 60 to 100 mg daily)11; the Friday doses were 50 percent higher (24 to 48 mg).”

Study 6

This study compared 4 weeks of office-based treatment with buprenorphine/naloxone vs buprenorphine alone, or placebo

The study reported the following drug testing outcomes, “Opioid negative screens: buprenorphine/naloxone group, 17.8%; buprenorphine group, 20.7%; and placebo group, 5.8%”.

Study 7

The study examined a 12 month buprenorphine program that included monitored dosing and psychotherapy.

This study had outstanding outcomes: “One-year retention was 75% in the buprenorphine group and 0% in the placebo group (p=.001). Roughly 75% of the patients retained in treatment had negative urine screens for illicit opiates, stimulants, cannabinoids, and benzodiazepines.”

Of course, this outlier got me very curious about the details of the study.

It’s worth noting that it was a small study (only 20 receiving buprenorphine) and the inclusion criteria were pretty restrictive. They excluded anyone with 4 or more years of daily heroin use, three or more unsuccessful treatment attempts in abstinence-oriented treatment, and those with a codependence on alcohol, amphetamines, cannabinoids, or benzodiazepines. Other exclusion criteria included any cognitive impairment or psychiatric disorder (unless the patient was stable).

This study was done in Sweden and the treatment was unusually comprehensive.

. . . individual treatment plans were developed in collaboration with social services departments to address issues of housing and occupation (ie, employment, studies, or occupational therapy). Throughout the study period, patients had 45 min individual counselling sessions every week in the treatment unit. We took supervised urine samples thrice weekly under conditions that prevented manipulation of samples. . . .

A contingency management plan was part of the treatment plan, and was thoroughly communicated to the patient during the induction week. If a patient completed a continuous 6-months drug-free (for all drug categories) verified by urine analyses, take-home doses were allowed so that frequency of visits could be reduced to thrice weekly. If relapse occurred—ie, illicit drug intake was reported, or indicated by urine samples positive for drugs, then daily supervised administration was resumed. If a patient did show signs of relapse (such as a positive urine sample, non-attendance at appointments, or both) we offered additional support, including intensified counselling, and ultimately, admission if needed. More than two positive urine samples within 3-months (for any banned substance) would lead to discharge from the study unless the patient agreed to and complied with intensified support efforts as described previously. Other predetermined criteria for involuntary discharge from treatment were failure to attend for more than 7 days, violent behaviour, or dealing in drugs. Discharged patients were all referred to standard clinical treatment at a different site.

So, this treatment approach appears to be unusual in that it was limited to relatively low-severity opioid SUDs and offered some big carrots (housing and employment) and a big stick (termination).

Study 8

This study compared methadone and buprenorphine in pregnant, opioid-dependent women and focused on withdrawal syndromes (NAS) in the babies.

“No significant difference in illicit opioid use between groups. Total of 20.0% and 45.5% of BMT-exposed and MMT-exposed neonates, respectively, were treated for NAS (p=.23). Other primary outcomes were also not significantly different, except that the BMT-exposed neonates had a shorter average hospital stay (p=.021).”

Study 9

This is another Swedish study comparing adaptive, BMT stepped care versus MMT.

No differences between groups were found for retention (76% for both at 6 months) or the proportion of negative screens (80% for both groups).

This one has good outcomes but there’s a lot I don’t understand. This study doesn’t provide the detail the other Swedish study did.

Maybe these Swedish studies are the basis for the insistence that MAT plus behavioral counseling has proven efficacy? However, the meta-analysis itself says, “The addition of structured psychotherapy to standard treatment— which may include peer support services, 12-step programs, and other psychosocial treatment provided at the facility or office—has not been shown to improve outcomes for patients on opioid maintenance therapy.”

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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.

 

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A closer look at the evidence (Part 1)

10120260443_560161d92b_bYou 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

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 1

The summary reports “fewer positive urine drug screens”. I wanted a little more info, so I went to the original study. It doesn’t report exact percentages, but I found this graphic.

study1

So, it looks like approximately 70-75% of male subjects receiving buprenorphine tested positive for opioids and about 90% of female subjects tested positive.

Study 2

This study compared buprenorphine vs high-dose methadone vs low-dose methadone and it was a year long (that’s really good!). Here’s the summary: “At 26 and 52 weeks, the high-dose MMT group had better retention (31% versus 20% at 52 weeks, p=.009) and less opioid use (p=.002) than the low-dose MMT or fixed-dose BMT groups.”

So, high-dose methadone lost 69% of the patients, while buprenorphine and low-dose methadone lost 80% of the patients.

I was curious about “less opioid use” and went to the original study. The researchers did drug screens for opioids and other drugs. “Urine samples were considered to be opioid-free if the test reading was less than 300 mg/mL.” For patients that were retained for all 52 weeks there were 156 drug tests. This outcome was measured by giving 1 point for each opioid-free test. A single patient got 156 points. The median scores were 59 for high-dose methadone, 16 for buprenorphine, and 24 for low-dose methadone.

Study 3

This study compared different doses of buprenorphine. “For retention, 40% in 1-mg group completed treatment, 51% in 4-mg group, 52% in 8-mg group, and 61% in 16-mg group.” 61% retention sounds more encouraging, but over what period of time? Unfortunately, it’s only 16 weeks long.

The summary also reported that the “8-mg group had significantly fewer positive screens than the 1-mg group”. This got me curious about these drug use outcomes.

Here’s what I found:

  • “42% (306/736) failed to contribute a single urine negative for opioids”
  • “36% (68/188) of the 8 mg group” failed to contribute a single urine negative for opioids
  • “Not a single patient contributed the full complement of negative urines”
  • “only 18% (132/736) provided more than 24 negative urines” (i.e. 50% of the maximum possible)

The original study also had the following sentence, “Acceptance of the efficacy of buprenorphine as a maintenance treatment has to be tempered by the reality that the drug use status of many patients will not be altered by buprenorphine.”

Study 4

This study compared buprenorphine maintenance in a primary care setting vs buprenorphine delivered in a methadone clinic. The study is short (12 weeks) and small (23 subjects per treatment condition).

Here’s the summary: “A trend toward higher retention at 12 weeks was noted in the primary care setting (78% versus 52%, p=.06). Patients in that setting had significantly lower rates of illicit opioid use as measured by urine drug tests (63% versus 85%, p,.01) but no difference in rates of cocaine use.”

78% retention is great, but it’s only for 12 weeks.

And, the better outcome for drug use was 63% of drug screens being positive for opioids. (I went to the original paper and found that 30.5-38.5% of tests were positive for cocaine.)

The closest they came to measuring abstinence was this, “The proportion of patients who achieved 3 or more consecutive weeks of abstinence from opioids, as determined by thrice weekly urine toxicology testing, was also higher in the primary care setting (44%, 10 of 23) than in the drug treatment setting (13%).”

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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.

Other posts in this series

 

 

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