The Science: Following French Failure, Americans Get a Substitute Addictive Opioid as “Fix” for the Opioid Crisis, Marketed as Reducing Overdose Deaths

Does It?

by Clark Miller

November 27, 2018

In attempts to reclaim appearance of competence, control, and authority in a worsening lethal opioid crisis generated by the unsupportable medicalization of a non-medical problem, healthcare industries responsible have rushed to claim effectiveness for Medication-Assisted Treatment (MAT) with the opioid Suboxone, another medical “fix”, now for the non-medical condition of compulsive substance (opioid) use.

Popular media have followed along with orthodox reinforcement and promotion of medical fixes for the medically-generated opioid crisis, citing reduced opioid-related overdose (OD) deaths as strong evidence and support for MAT and partial agonist assistance with Suboxone (buprenorphine + the antagonist naloxone) as the causal effective factor explaining reduced OD deaths.

shutterstock opioid pills in bottles

But concurrence in time never establishes cause or effectiveness for an intervention, and particularly when there are known confounding factors (as in the studies cited by popularizing writers promoting buprenorphine as a “fix” for the opioid crisis). And especially when a large mounting body of evidence increasingly invalidates that conclusion.

Mounting evidence of another lethal public health failure generated by medical “fixes” for non-medical problems demands a critical look and analysis of the evidence, to protect vulnerable Americans trapped in opioid and substance use epidemics  from increasing harm.

Demands of us a critical discourse.

shutterstock Suboxone

Continued reliance on the medical/pharma industry strategy of widespread distribution of substitute addictive, diverted and abused opioids like buprenorphine for the medically-generated opioid crisis is increasingly invalidated and indicated against by multiple lines of evidence: treatment retention failure; diversion and abuse; focus on perpetuation of the behavioral symptom of compulsive opioid use and away from evidence-based psychosocial treatments for underlying conditions driving compulsive use; failure of the decades-long French experiment with unrestricted buprenorphine substitution to treat problem opioid use; and reinforcement of patient belief in the long-invalidated biomedical (disease) model of addiction, that belief a key predictor of relapse.

Despite those indications and bodies of evidence, including failed outcomes in France, the bupe “fix” is being successfully sold to vulnerable Americans trapped in a worsening opioid epidemic by medical and pharmaceutical industries, government public health entities, mainstream media, and popular writers. Promotional articles for example in The Atlantic, Vox, and other sources have heralded, for example that in France, attributable to buprenorphine prescribing and therapeutic use, “Within four years, overdose deaths had declined by 79 percent”.

That would be significant.

If supported by evidence as likely.

Cause-and-Effect that’s fabricated, not established –

can be lethal

Research reviews and assertions – requiring the capacity for critical analysis of research methods, study design and interpretation – by writers popularizing MAT and bupe substitution citing original research and secondary material have failed to avoid promoting unsupported, optimistic conclusions and have ignored evidence that belies the face-value interpretations and conclusions.

As described and analyzed with links to research, here and here, there is no body of research that supports attributing reduced overdose (OD) deaths in France or elsewhere to opioid substitution (buprenorphine/MAT) programs instead of to the direct, observed results of lethal OD prevention by naloxone made more accessible concurrently with  development of bupe/MAT campaigns.

In the French experience, increasingly widespread use of overdose death-preventing Naloxone kits coincided with the period over which buprenorphine was increasingly prescribed and OD deaths decreased.

More importantly and to the point, in a recent (2014) paper, French addiction professionals describe, in contrast to a country that has “fixed” its heroin problem, “a major public health care problem in France”, after decades of perhaps the world’s least restrictive buprenorphine prescribing policies, with continued serious problems in France with heroin, other opioids, overdose deaths, abuse of buprenorphine with heroin, and additional diversion (misuse) problems with buprenorphine. Heroin- and methadone-related overdose deaths increased over the most recent period reported, 2006 – 2009.

As noted by the authors, “The situation is still particularly worrying due to psychoactive substance use and misuse of opioid substitution treatments. Since 2003, there has been a persistent increase in the number of deaths and comorbidities related to opioid addiction, principally hepatitis C virus infection, which affects up to 40% of intravenous drug users.”

In an analysis of cohort studies cited by writer Maia Szalavitz, neither concurrent problem substance use nor retention rates are reported, the authors noting this as one of several confounding effects.

Any benefit in reduced overdose deaths – whether attributable to MAT as a strategy and benefit, or to associated increase in availability of emergency Naloxone kits, not controlled for – would diminish or disappear for individuals leaving the program and engaging in illicit drug use and culture. With retention rates typically low in Suboxone trials (trending toward zero in this naturalistic multisite study) conclusions about significant durable gains are premature.

Additional results for MAT trials are consistent with treatment failure due to retention trending toward zero in the study noted:

Significantly, the 2014 study of MAT trials in natural settings overcomes a number of important design/interpretation problems, with some important results.

 

Take a look here.

What does the Evidence Say?

Prevention of a lethal opioid-related OD resulting from use of naloxone  is directly observable and attributable as such in cases in which naloxone was administered to an opioid user who was evaluated as medically at risk of death.

In contrast, to attribute prevention of OD deaths to use of buprenorphine in MAT programs requires additional and different evidence. It would require 1) a “natural experiment” in which buprenorphine MAT was implemented for a population without the concurrent associated increased availability and successful recorded use of Naloxone, 2) and/or that observed longitudinal decreases in incidence of lethal opioid-related ODs could not be accounted for by naloxone reversals, and 3) that the recorded decreases corresponded to treatment-related psychosocial gains required to explain decreases in high-risk opioid use (e.g. disengagement from drug use culture; decreased use for social and euphoric benefits; gains in treatment and community engagement; evidence of decreased use of bupe to manage withdrawal symptoms when cheaper, more euphoric illicit opioids are unavailable) and/or drug use behavior changes (significant decreases in population illicit “street” opioid use, like heroin and fentanyl) attributable to bupe programs.

More simply: a decrease in opioid-related overdose deaths over time raises the a critically important question for addressing the worsening opioid crisis: what protective, preventative, and/or life-saving factors can be identified as effective? Attributing decrease in lethal ODs to naloxone use is simple and direct – collecting evidence of cases of opioid users at risk of OD death having naloxone successfully administered. Attributing decrease to prescribed Suboxone/buprenorphine requires hypothesis testing, because there is conjecture, not direct observable effect. Attributing a causal relationship to two phenomena simply because they are concurrent is a naïve and primitive error of interpretation, in this case potentially lethal if the error leads to bad public health policy.

Testing the hypothesis that prescribed buprenorphine has prevented and prevents lethal opioid-related ODs requires evaluating evidence that psychosocial benefits of buprenorphine use cause behavioral and other changes that reduce prevalence of high-risk opioid use.

Even more simply:

Opioid deaths decreased over the past four years? Wonderful news. Now, in order to use public health resources effectively to pay for the factor or factors responsible for the decrease, we must evaluate: what concurrent change (intervention) over the period of decrease is supported as the causal factor? Is it the increase in buprenorphine use? The increase in overdose-reversing Naloxone? Other factor?

And:

HIV incidence decreased over the past four years? Wonderful news. Now, in order to use public health resources effectively to pay for the factor or factors responsible for the decrease, we have to evaluate: what concurrent change (intervention) over the period of decrease is supported as the causal factor? Is it the increase in buprenorphine use? The increase in clean needle programs? Public Health education campaign? Other factor?

Etc.

There are no apparent bodies of such evidence that allow attributing decreased OD deaths to bupe MAT programs instead of to reversal of lethal OD with use of naloxone, and/or to other psychosocial supports.

Naloxone

Instead, available evidence points overwhelmingly and increasingly away from OD benefits due to bupe/MAT and instead to associated and concurrent naloxone programs as the protective factor.

That naloxone is being widely used and widely reported as preventing lethal outcomes of opioid overdoses is itself strong evidence of lack of a bupe/MAT effect – because individuals adherent to and successful with bupe use to manage an opioid habit and avoid high-risk opioid use would experience greatly reduced risk of OD, lethal or non-lethal.

hospital-ED

More concretely and definitively, results and information describing naloxone and MAT/bupe campaign development in a California county hard-hit by opioid abuse and overdose deaths – analyzed and discussed here – point to the overdose death-reducing drug naloxone, rather than the opioid substitute Suboxone, as accounting for reduced overdose deaths as described in the piece from the Center for Health Journalism, “How one rural California county went from the state’s highest rate of opioid deaths — to zero”.

As described in that post, observed and documented reversals of potentially lethal opioid-related overdoses accounted for all of the remarkable decrease from prior-years baseline in opioid-related OD deaths in that hard-hit county.

There were simply no unaccounted for OD death preventions left to potentially attribute to use of prescribed buprenorphine.

What does Additional, Mounting Evidence Say about the “anti-addiction medicine” buprenorphine “fix” preventing opioid-related overdose deaths?

From a preceding post in this series –

Overwhelmingly, reports, epidemiological trends, research and emerging data point to lack of the type of psychosocial and behavioral gains potentially attributable to buprenorphine prescription (e.g. disengagement from drug use culture; decreased use for social and euphoric benefits; gains in treatment and community engagement; evidence of decreased use of bupe to manage withdrawal symptoms only when cheaper, more euphoric illicit opioids are unavailable; decreases in population illicit “street” opioid use) – those evidenced gains required to attribute reduced OD deaths to buprenorphine programs. Instead accumulating results constitute evidence against those types of benefits:

– increasing involvement of bupe in overdose and OD deaths and in ED visits

longstanding and continuing evidence of diversion, ineffectiveness, and abuse – see here, here, here, and here for example

failed patient retention in bupe programs often trending toward zero

– high rates of abuse of other opioids, other drugs with use of prescribed bupe

– bupe available for decades with prescribed use increasing in the U.S. over past years yet concurrently continually worsening opioid epidemic

– If effective, why must proponents of MAT resort to citing results on only one measure – overdose deaths – unable to provide a body of research pointing to success and benefit by other measures of reduced risks, problems, and harm?

– In New Jersey: Opioid OD deaths up 24% in 2017, “even as the number of prescriptions written for opioids fell”. A treatment directory lists about 500 programs or doctors in New Jersey prescribing suboxone.

criminal distribution by prescribers in the U.S., predicted by widespread criminal diversion in France

So Far:

The evidence overwhelmingly invalidates and points away from presumptions of the types of psychosocial (“recovery”), behavioral, and risk factor gains or benefits required as mechanisms by which prescribed buprenorphine use hypothetically would reduce high-risk opioid use and explain reductions in lethal opioid-related overdoses – the single outcome measure that bupe MAT proponents have been able to assert as support for the publicly-funded substitute opioid campaign.

New Evidence:

Emerging evidence from France and the U.S. adds to the growing body of reports and research that invalidates hypothesized benefit from the MAT buprenorphine campaign to Americans trapped in the opioid epidemic as measured by opioid-related overdose deaths or related gains.

– A systematic review of studies assessing functional benefits potentially attributable to MAT (gains in psychosocial functioning, or “recovery” protective factors including: “cognitive (e.g., memory), physical (e.g., fatigue), occupational (e.g., return to work), social/behavioral (e.g., criminal activity), and neurological (e.g., balance) function”) appeared this year. The review identified 30 randomized controlled trials (RCT) and 10 comparison studies for assessment, at least one of those meeting criteria for “high quality”.

Among the 40 studies aimed at detecting gains in the described outcome measures (above) including employment and criminal justice involvement, only a single outcome and instance was identified as strongly supported: benefit in level of fatigue for buprenorphine patients compared to control opioid users not in a bupe program.

The review included results for both bupe and methadone programs:

“There were few differences among MAT drug types. A pooled analysis of three RCTs found a significantly lower prevalence of fatigue with buprenorphine compared to methadone, while a meta-analysis of the same RCTs found no statistical difference in insomnia prevalence. Three RCTs that focused on cognitive function compared the effects of buprenorphine to methadone; no statistically significant differences in memory, cognitive speed and flexibility, attention, or vision were reported.”

– In the U.S., the most recent evidence is clear. Nationally, per SAMHSA figures, buprenorphine prescribed to opioid users has increased dramatically over this decade:

Over the same time period that the medical/pharmaceutical industry “fix” for the national crisis is increasingly implemented as illustrated above, opioid-related overdose deaths continued to climb, the most recent increase 10% in 2017, up from 2016.

– Trends from Kentucky mirror the national dose-response indicators: as dose of the medical “fix” for the entirely non-medical problem is increased significantly – more and more Americans die by opioid-related overdose:

Note that buprenorphine dispensed medically increased significantly (by about 75%) over the years 2013 – 2016 and over that same period: 1) total opioid related overdose deaths increased notably as well, by about 60 – 70% and 2) overdose deaths appeared to increase or not decrease over the period of expanded bupe provision linked to each of the measured classes of opioids: prescription, synthetic, and heroin.

– In France recent trends are somewhat less confidently interpreted. Over the period 2006 – 2015 patients enrolled in opioid substitution treatment (OST) in France increased by about 35%. Graphically represented, over that same period total drug-related overdose deaths increased over the period 2006 – 2010, then in 2013 returned to a level at the higher end of levels for that period. OD deaths attributable to opioids were estimated at 48% in 2013, and “Toxicological data available from the Special Mortality Register indicate that OST [buprenorphine and methadone] medications were involved in about 55 % of deaths recorded in 2014”. In a 2014 review and report, French addiction specialists noted that the national increase in drug overdose deaths over the period 2006 – 2009 was “partly due to the increased presence of heroin and to methadone overdose”.

French OD death trends 2006-2013

Based on the reports, it does seem possible to confidently conclude that in the country that “fixed” its opioid problem opioid-related overdose deaths increased over the period 2006 – 2009, and there is no evidence to support that opioid-related OD deaths decreased over 2006 to 2013, a period over which the national “dose” of buprenorphine increased substantially.

– Despite France’s unmatched national campaign to dispense buprenorphine, nearly unrestricted, by primary care doctors over past decades – evidenced by continuing trend through 2015 of increase in patients enrolled in OST – France remains 5th highest among 20 European countries in prevalence of “high-risk” opioid use.

Evidence of reduction of “high-risk” opioid use, as the hypothesized mechanism for beneficial effects from OST (MAT), would be required to support claims that bupe MAT provides benefit for the opioid crisis and has reduced overdose deaths.

A worsening public health, institutional and social crisis

There has never existed evidence to credibly attribute decreases in opioid-related overdose deaths or other gains for individuals trapped in the opioid crisis to buprenorphine MAT interventions, versus other plausible explanations. Available evidence that is varied and congruent overwhelmingly points to lack of effects constituting psychosocial, functional, behavioral, or recovery benefits required as mechanisms to support conclusions that buprenorphine provision provides benefit in reduced OD deaths or other measures.

Instead, evidence consistently points to prescribed buprenorphine as generating and increasingly involved in harms including: continued opioid dependence; diversion; abuse; child exposure; involvement in overdose and overdose deaths; involvement in emergency medical visits; involvement in criminal drug trafficking.

In the face of those bodies of research U.S. healthcare institutions, medical and pharmaceutical industries, and popular media have rushed to endorse the medical “fix” of a substitute addictive and commonly diverted and abused opioid for a non-medical problem – compulsive substance use – and for the medically-generated public health crisis which is itself the outcome of unwarranted runaway use of addictive drugs for a non-medical problem – centralized chronic pain.

The enthusiastic assertions – by popular writers without training or competence in research or its analysis – heralding Subutex as not just an “anti-addiction medication” but the “fix” for the U.S. medically-generated opioid crisis – constituted a naïve, basic and dangerous error of interpretation: asserting causality with no evidence or analysis to rule out competing explanations for differences observed, in this case highly plausible competing explanations.

Just as decades earlier, abdication of research-based evaluation, journalistic examination, critical thought and ethical reasoning allowed the runaway prescription of addictive opioids generating the crisis – against all relevant, longstanding lines of evidence predicting the crisis.

Based on status of current evidence, the provision of prescribed buprenorphine in MAT programs as currently implemented predicts harm, is medically inappropriate, and as such appears to constitute billing fraud, that is, Medicaid abuse.

TAKEAWAYS

  • There has never been research evidence to attribute reduced opioid-related overdose deaths confidently to substitute opioid (buprenorphine) campaigns instead of other plausible causes.
  • Instead, direct evidence points to population effects of the OD death reversing drug naloxone – increasing in availability and use concurrently with bupe MAT programs – as accounting for decreases in OD deaths.
  • In contrast to the direct, observable outcomes from naloxone use, attributing lethal OD protection to buprenorphine prescription requires evidence of a psychosocial (treatment, or “recovery”) mechanism – bupe in MAT programs reducing high-risk opioid use.
  • There is no evidence for that mechanism, and consistent and mounting research and epidemiological evidence instead invalidates such protective effects presumed to link bupe campaigns to decreased OD deaths or other gains.
  • Instead, consistent and mounting evidence establishes worsening, predictable harms attributable to the MAT bupe medical approach to the non-medial problem of compulsive opioid use including: continued opioid dependence; diversion; abuse; child exposure; involvement in overdose and overdose deaths; involvement in emergency medical visits; involvement in criminal drug trafficking.
  • As currently designed and implemented buprenorphine MAT campaigns and practices are established by mounting bodies of evidence to predict harms, not benefits, and as such appear to constitute malfeasance, public health threat, misuse of public healthcare resources, and billing fraud.