“nothing was quite like Suboxone”

There have been a couple of news stories about buprenorphine over the last couple of days.

The first article looks at the business of pain medication, medications to treat side effects of pain medication and medications to treat addiction to pain medication.

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Opioid prescriptions alone have skyrocketed from 112 million in 1992 to nearly 249 million in 2015, the latest year for which numbers are available, and America’s dependence on the drugs has reached crisis levels. Millions are addicted to or abusing prescription painkillers such as OxyContin, Vicodin and Percocet. Statistics from the Centers for Disease Control and Prevention show that, from 1999 to 2014, more than 165,000 people died in the United States from prescription-opioid overdoses, which have contributed to a startling increase in early mortality among whites, particularly women — a devastating toll that has hit hardest in small towns and rural areas.

The pharmaceutical industry’s response has been more drugs. The opioid market — now worth nearly $10 billion a year in sales in the United States — has expanded to include a growing universe of medications aimed at treating secondary effects rather than controlling pain.

There’s Suboxone, financed and promoted by the U.S. government as a safer alternative to methadone for those trying to break their dependence on opioids. There’s naloxone, the emergency injection and nasal spray carried by first responders to treat overdoses. And now there’s Relistor, the drug based on Moss’s work, and a competitor, Movantik, for constipation.

In colorful charts designed to entice investors, numerous pharmaceutical makers tout the “expansion opportunity” that exists in the “opioid use disorders population.”

Indivior, a specialty pharmaceutical company listed on the London Stock Exchange, sees “around 2.5m potential patients, the majority of whom are addicted to prescription painkillers,” as opposed to illicit drugs such as heroin. Another company, New Jersey-based Braeburn Pharmaceuticals, highlights “growth drivers” for the market, noting that millions of additional Americans not yet identified are also likely to be dependent on opioid painkillers.

Analysts estimate that each of these submarkets — addiction, overdose and side effects — is worth at least $1 billion a year in sales. These economics, experts say, work against efforts to end the epidemic.

If opioid addiction disappeared tomorrow, it would wipe billions of dollars from the drug companies’ bottom lines.

The second story is that 35 states (plus Washington DC) are suing Reckitt Benckiser for engaging in a variety of “deceptive and unconscionable” practices, including using “feared-based messaging” and “sham science” to keep generics out of the market by killing the tablet form of the drug so that they would be the sole purveyor of a patent protected version of the drug.

The plaintiffs in the lawsuit say Reckitt Benckiser took product hopping to a nefarious new level by using “feared-based messaging” and “sham science” to illegally subvert the market for Suboxone tablets while aggressively promoting its new film variation, which was introduced in 2010 and is under patent until 2023.

“The circumstances alleged in this case are particularly egregious in that, in the midst of an epidemic of opioid abuse and addiction… consumers and taxpayers have had to pay more for a drug that may help to mitigate some of the problem,” said George Jepsen, the attorney general of Connecticut, in a statement announcing the suit.

. . .

Patent expiration is a conundrum faced by all drug makers and ordinarily it wouldn’t be a terribly big deal for a global monolith like Reckitt Benckiser—which generated more than $2.5 billion in revenue during the first half of 2016 through its ownership of popular brands like Lysol disinfectant, Mucinex cold medicine, and Durex condoms.

But nothing was quite like Suboxone, a blend of the painkiller buprenorphine and the opiate blocker naloxone.

. . .

By the time it lost its monopoly, Suboxone accounted for 85 percent of all spending on medication-assisted treatment in the U.S.—almost all of it subsidized by taxpayers—and Reckitt Benckiser was sitting on the pharmaceutical equivalent of a goldmine.

That’s when it got creative.

The plaintiffs accuse the company of undermining the market for generics through a “multi-step scheme” that began in 2010 with an aggressive effort to get prescribers to stop dispensing its own Suboxone tablets and replace them with the new film version.

Over the next two years, Reckitt Benckiser allegedly compensated doctors for being advocates of the drug, lobbied legislators on the benefits of Suboxone film, and penalized employees for not meeting sales targets for the new drug. It also raised the price of its tablets, making them more expensive than the newer film version, even though the pills are cheaper to make.

In September 2012, with generics getting closer to approval, Reckitt Benckiser announced its intention to take tablet versions of its drug off the market on the grounds that the pills posed a safety threat to children who might inadvertently eat them. On the same day it filed a “Citizen’s Petition” with the Food and Drug Administration calling on the agency to postpone approval of generics in the interest of public safety.

The company based its child-safety claims on a single study it had paid for itself.

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Too expensive? (2016)

Discrimination1

I frequently point to health professional recovery programs when discussing the effectiveness of drug-free treatment when it’s delivered in the appropriate dose, frequency and duration. They have stellar outcomes. (More details here.)

The programs were abstinence-based, requiring physicians to abstain from any use of alcohol or other drugs of abuse as assessed by frequent random tests typically lasting for 5 years. Tests rapidly identified any return to substance use, leading to swift and significant consequences. Remarkably, 78% of participants had no positive test for either alcohol or drugs over the 5-year period of intensive monitoring. … The unique PHP care management included close linkages to the 12-step programs of Alcoholics Anonymous and Narcotics Anonymous and the use of residential and outpatient treatment programs that were selected for their excellence.

I generally get three counter-arguments:

  1. That health professionals have more recovery capital and are more likely to recover than other addicts.
  2. That the threat of license suspension/revocation provides a unique combination of carrot and stick. We’ll never get that kind of engagement with regular people.
  3. That treating everyone in this manner would be too expensive—we’ve made a decision, as a culture, that we’re willing to invest this time and capital into addicted doctors but we can’t do it for everyone.

I want to respond to these arguments in this post.

1. “Health professionals have more recovery capital and are more likely to recover than other addicts.”

There may be ways in which health professionals are unique in terms of recovery capital. This may be true. However, they also face a unique set of barriers when initiating recovery. A study of physician recovery programs (this excludes health professionals other than physicians) found high rates of opioid addiction (35%), high rates of combined alcohol and drug problems (31%) and high rates of psychiatric problems (48%). In addition, 74% were not self-referred.

Further, health professionals confront easy access to drugs and with this ease of access to prescription drugs, they often develop tolerance levels that dwarf those of street addicts.

Two pieces of folk wisdom may also be relevant:

  • “Doctors make the worst patients.”
  • “I’ve never met anyone too dumb for recovery, but I’ve met plenty of people who were too smart.”

So…they may have unique advantages, but they also have unique barriers. If there is a difference, is there reason to believe it’s stark enough to it wouldn’t work for other addicts?

2. “Heath professionals are uniquely motivated because of the threat of license suspension/revocation.”

This is probably the strongest counter-argument.

Health professionals place incredibly high value on their profession. They often put enormous time, effort and money into becoming a health professional, but it’s more than that. Their profession often becomes integral to their identity and is a key source of meaning and purpose. In health professional recovery programs, we’ve constructed a system that uses this incredibly powerful element of the addict’s life to initiate and maintain their recovery. And, it’s not just threats. They offer a path to returning to work in a pretty expeditious time-frame, they provide peer support, they develop contracts with employers that provide both support and monitoring.

What would happen if we constructed systems that identified and used (not through coercion or manipulation) elements of the addict’s life that are integral to their identity and are a key sources of meaning and purpose? Debra Jay has developed one model of recovery support that seeks to do exactly this. (Interestingly, she’s had to develop a model that doesn’t require professionally directed services, because it’s not covered by insurance and many families may not be able to afford it.)

What else could be done? We don’t know. Because, as a system, we haven’t tried.

I recently blogged on the issue of coercion and health professional recovery programs and said this:

. . . it is our experience that attracting people to the front door is pretty easy if you have an attractive back door. In our case, this includes:

  • safe, affordable and stable sober housing;
  • opportunities for stable employment with advancement opportunities;
  • a large, welcoming and energetic recovering community (with lots of opioid addicts in long term recovery);
  • two local collegiate recovery programs that support a path to college degrees; and
  • lots of recovery role models providing support and demonstrating that all of this is do-able.

If we can create systems that provide this kind of back door and integrate long term recovery monitoring and support, I think it could go a very long way toward overcoming the long-term-voluntary-engagement-without-coercion issue.

. . .

I’m not suggesting that we’ll have relapse rates as low as 22% over 5 years. I’m also not suggesting that it’d be easy to keep people engaged for 5 years. But, what’s possible? Huge improvements, I’d imagine. But, we don’t know, because we haven’t tried.

Imagine that we tried and engaged in continuous improvement for 10 years. How far could we go?

3. “Treating everyone in this manner would be too expensive.”

So, then, what is provided and what might it cost to replicate it?

First, what is provided:

The first phase of formal addiction treatment for two thirds of these physicians (69%) was residential care often for 90 days. The remaining 31% began treatment in an intensive day treatment setting. The participants at this stage usually received multiple intensive sessions of group, individual, and family counseling as well as an introduction to an abstinence-oriented lifestyle through required attendance at Alcoholics Anonymous (AA), Narcotics Anonymous (NA), and Caduceus meetings (a collegial support association for recovering health professionals) and other mutual-aide community groups. Frequent status reports on treatment progress were required by most PHPs.

Use of pharmacotherapy as a component of treatment for SUDs was rare. Very few of the treatment programs or the medical directors of the PHPs used any of the available maintenance or antagonist medications.

After completion of initial formal addiction treatment, all PHPs developed a continuing care contract with the identified physician consisting of support, counseling, and monitoring for usually 5 years. Most PHPs (95%) also required frequent participation in AA, NA, or other self-help groups and verification of attendance at personal counseling and/or Caduceus meetings.

Physicians were tested randomly throughout the course of their PHP care, typically being subject to testing 5 of 7 days a week.

Physicians were typically tested an average of four times per month in the first year of their contracts for a total of about 48 tests in the year. By the fifth year, the average frequency of testing was about 20 tests per year.

How much would this cost to replicate? The following is based on Dawn Farm’s fees and costs.

  • $16,800 – 120 days of residential treatment plus unlimited aftercare groups
  • $5460 – 364 drug screens over 5 years ($15 per screen. 2x per week for first 2 years, 1x per week for years 3-5.)
  • $10,000 – 100 outpatient group sessions ($25) and 100 outpatient individual sessions ($75)
  • $5000 – 5 years of recovery support and monitoring from a Recovery Support Specialist with a caseload of 40 (A former head of Michigan’s monitoring program reports that their Case Managers have approximately 150 cases each.)
  • Total = $37,260

Now, this does not include one important element—a workplace monitor and a career employer making contract compliance a condition of employment. However, we offer transitional housing to clients for up to two years.

At less than $38,000 for the whole package, in the context of American healthcare spending, this does not seem to be an unsustainable burden and, in fact, is likely to be a very wise investment in pure financial terms. It’s in the same ballpark as inserting a stent–just the procedure, excluding continuing care, medications, etc. We implant 2,000,000 stents per year.

Imagine what would be possible if 2,000,000 addicts were given that opportunity. Imagine what we could learn.

 

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The gold standard and problem of coercion

i_love_evidence_based_medicine_key_chains-r33ff90ead6aa425ea368e31ca9ee70e5_x7j3z_8byvr_512I’ve written a lot on this blog about the gold standard model of treatment for addiction–health professional recovery programs.

Whenever I discuss the model, I get a lot of responses that could be placed into the category of, “Yeah, but they’re different. They’re doctors. And, besides, they’ve got a lot to lose.”

I’ve addressed the first part of that objection here.

Health professionals have more recovery capital and are more likely to recover than other addicts.

There may be ways in which health professionals are unique in terms of recovery capital. This may be true. However, they also face a unique set of barriers when initiating recovery. A study of physician recovery programs(this excludes health professionals other than physicians) found high rates of opioid addiction (35%), high rates of combined alcohol and drug problems (31%) and high rates of psychiatric problems (48%). In addition, 74% were not self-referred.

Further, health professionals confront easy access to drugs and with this ease of access to prescription drugs, they often develop tolerance levels that dwarf those of street addicts.

Two pieces of folk wisdom may also be relevant:

  • “Doctors make the worst patients.”
  • “I’ve never met anyone too dumb for recovery, but I’ve met plenty of people who were too smart.”

So…they may have unique advantages, but they also have unique barriers. If there is a difference, is there reason to believe it’s stark enough to it wouldn’t work for other addicts?

The second set of objections focus on coercion. (We’ll take away your medical license if you don’t do everything we tell you to do.)

Some of these objections argue that coercion is a critical element in the success of the model–that transferring the model to other patients without the element of coercion would not get us similar outcomes because coercion is such an important ingredient.

Other objections argue that the model is unethical because of the coercion. They point to alleged abuses by monitoring agencies. Many people with these objections seek to discredit the entire model. I’m not going to dive deep into these arguments in this post other than to make 3 statements: 1) It’s possible that monitoring agencies, assessment procedures and inclusion criteria may need to be improved in some states. 2) Where a professional’s impairment creates a public safety issue, it’s seems nearly impossible to avoid the threat of suspending/revoking their license. 3) While the model includes coercion, it also includes a lot of support and benefits–offering a path to returning/continuing to work (often quickly) and establishing support/monitoring systems in the workplace. There’s a stick, but there are also a lot of carrots.

It’s important to note that none of these objections question the actual outcomes of the model.

Is coercion necessary?

I recently had a conversation with a consultant in Washington state. They are shutting down a large facility used for involuntary treatment. (They have some sort of involuntary commitment law.) I think think she said the process was instigated by the expiration of a 99 year property lease agreement rather than some rejection of the model. Nevertheless, they are rethinking the model and wanted to hear about Dawn Farm. She was concerned about the issue of attraction to treatment. Over the course of the conversation, I told her that it is our experience that attracting people to the front door is pretty easy if you have an attractive back door. In our case, this includes:

  • safe, affordable and stable sober housing;
  • opportunities for stable employment with advancement opportunities;
  • a large, welcoming and energetic recovering community (with lots of opioid addicts in long term recovery);
  • two local collegiate recovery programs that support a path to college degrees; and
  • lots of recovery role models providing support and demonstrating that all of this is do-able.

If we can create systems that provide this kind of back door and integrate long term recovery monitoring and support, I think it could go a very long way toward overcoming the long-term-voluntary-engagement-without-coercion issue.

One interesting observation is that many of these “carrots”, like sober housing and employment opportunities, don’t seem to provide as strong a draw for people of higher socio-economic status. They have greater access to housing and employment opportunities. While material capital certainly makes achieving recovery easier in many ways, I wonder if, in this way, those with “lower recovery capital” might be easier to engage in these systems of long term recovery monitoring and support.

I’m not suggesting that we’ll have relapse rates as low as 22% over 5 years. I’m also not suggesting that it’d be easy to keep people engaged for 5 years. But, what’s possible? Huge improvements, I’d imagine. But, we don’t know, because we haven’t tried.

Imagine that we tried and engaged in continuous improvement for 10 years. How far could we go?

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Gold standard addiction treatment

gold standard definition of gold standard by Medical dictionary

(This post was written by djmac and originally posted at Recovery Review. Re-posted with permission.)

ResearchBlogging.orgAddiction to alcohol or other drugs is not easy to recover from. However there are many pathways to recovery, including through treatment. One group of patients does far better than most other groups. In fact their results are so impressive that many commentators have urged us to learn from what’s different about their treatment and follow-up to see if we can transfer learning and experience. This group, claim researchers, sets the standard for addiction treatment. Indeed it represents gold standard addiction treatment. Who are this group? They are doctors.

In 2009, in the Journal of Substance Abuse Treatment, Robert DuPont and colleagues published a study that looked at how addicted doctors were cared for in the treatment system and also what their outcomes following treatment were.

The numbers were large. 906 physicians admitted to 16 different state Physicians’ Health Programmes were followed up for five years or longer.

Treatment

The authors accept that doctors generally come to treatment with more resources than the average patient, but they also point out the hazards that doctors face which potentially increase relapse risk. (Exposure to drugs in the workplace.) What is quite different about doctors in the USA is that they generally have access to specifically designed assessment, treatment and monitoring programmes (Physicians’ Health Programmes). These programmes typically evidence long term abstinence outcomes of between 70 – 96%. Here’s what the researchers say:

For these reasons, the PHPs appeared to represent one of the most sensible and evidence-based approaches to addiction currently available. We reasoned that an examination of this novel care management approach might provide suggestions for optimally organized and delivered addiction treatment — real-world treatment at its best. If there were clear evidence of positive results from this form of care, the findings might provide guidance for improving mainstream treatment efforts.

The features of the Physicians’ Health Programme model

  • Tired young doctorDoctors sign binding contracts
  • Abstinence is the goal
  • Weekly doctor-specific mutual aid groups
  • Attendance at 12-step mutual aid groups (AA, NA, CA etc)
  • The regulatory boards are often avoided if doctors comply
  • Extended care (five years)
  • Recovery often starts with an active/planned intervention
  • This is followed by an intensive residential (or out-patient)
    rehab period, usually three months long
  • Withdrawal from work during treatment
  • Active monitoring and care management
  • Active family engagement
  • Mental & physical health needs assessed
  • Active management of relapse
  • Random drug and alcohol tests over the five years

The study

16 PHPs participated in the national survey which looked at all admissions (intention to treat) over a six year period. The case records and lab results of 904 doctors were studied. Most (86%) were male with an average age of 44. Two thirds were married.

Drugs of choice

What drugs were problematic?

The primary drugs of choice reported by these physicians were alcohol (50%), opiates (33%), stimulants (8%), or another substance (9%). Fifty percent reported abusing more than one substance, and 14% reported a history of intravenous drug use. Seventeen percent had been arrested for an alcohol or drug-related offense, and 9% had been convicted on those charges.

ORT

And what about our first line treatment for opiate addiction? How many of the hundreds of opiate- addicted doctors ended up on methadone? That would be just one, or to put it another way, 0.001% of the sample.

Work

72% of the doctors got back to work. When they looked at doctors who successfully completed the programme, this rose to 91%.

Overall outcomes

Specifically, of the 904 physicians followed, 72% were still licensed and practicing with no indications of substance abuse or malpractice, 5 to 7 years after signing their contracts. In contrast, the PHP process appears to have moved approximately 18% of these physicians out of the practice of medicine through loss of license or pressure to stop practice.

Of the 904, 180 (19%) had a relapse episode and were reported to their licensing boards. However, only 22% of these had any evidence of a second relapse generally indicating that the intensified treatment and monitoring were successful in maintaining remission.

Nuggets

  • This was the largest sample of doctors ever followed and over the longest period
  • Doctors use in a similar fashion to everyone else
  • 78% of doctors did not have a single positive drug test over the years of monitoriing
  • Outcomes did not differ by drug of choice, opiate addicted docs did as well as alcohol dependent docs
  • IV drug users did as well as everyone else
  • 50% of the doctors were polysubstance abusers
  • This research is in keeping with literature before and since

What does this mean for treatment in general?

If we applied the principles and standard of treatment that doctors get to other patients, would we see improved outcomes overall?

Whatever the differences from other populations experiencing SUDs [substance use disorders], it is likely that the successful treatment of physicians with SUDs has important implications for SUD treatment in general. For example, if physicians were found to have significantly better outcomes than other groups when treated for diabetes or coronary artery disease, this would be of great public health interest.

Raising the bar?

Recognizing that SUDs are biological disorders with major behavioral components (just like diabetes and coronary artery disease), the relatively high level of success exhibited by physicians whose care is managed by PHP is important with respect to the potential for success in addiction treatment generally. Indeed, the observed rate of success among physicians directly contradicts the common misperception that relapse is both inevitable and common, if not universal, among patients recovering from SUDs.

They go on to say:

Indeed, rather than being a defining characteristic of addiction, the inevitable relapse may be a defining characteristic of the acute care model of biopsychosocial stabilization, which offers an opportunity for recovery initiation but lacks the essential ingredients to achieve recovery maintenance.

Making all treatment gold-standard

The paper has some suggestions to transfer learning and improve addiction treatment outcomes:

  1. Adopt the contingency management aspects of PHPs
  2. Offer frequent random drug testing
  3. Create tight linkages with 12-step programmes and abstinence standards
  4. Active management of relapse by intensified treatment and monitoring
  5. Continuing care approach
  6. Focus on lifelong recovery

Reflections

The fact that only one doctor ended up on methadone is a remarkable finding. I’ve written before about the double standards inherent here. Why do doctors so readily turn away from an evidence-based intervention, one they are very happy to prescribe for patients?

The expectation is that doctors will make the journey to abstinent recovery, but there seems to be a much lower expectation of their patients. Some argue this is just realistic, but does such ‘realism’ result in poorer outcomes? We know there is evidence of a mismatchbetween professional expectations and client goals.

I don’t think there’s much doubt that we could get better outcomes for our clients by raising the bar, increasing the intensity and duration of treatment, actively referring to mutual aid and thinking much more about the bridge from treatment to recovery community support, which is the key to lifelong recovery. Should doctors really get better treatment and follow up than the rest of the population? Can we narrow the gap?

DuPont, R., McLellan, A., White, W., Merlo, L., & Gold, M. (2009). Setting the standard for recovery: Physicians’ Health Programs Journal of Substance Abuse Treatment, 36 (2), 159-171 DOI: 10.1016/j.jsat.2008.01.004

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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)

10120260443_560161d92b_b

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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