The French Connection

France’s Decades-Long Unrestricted Buprenorphine (Substitute Opioid) Campaign – Promoted as the “Fix” for U.S. Opioid Crisis – is Fueling Widespread Prescribed Opioid Diversion, Trade and Abuse

by Clark Miller

November 20, 2018

While a longstanding body of evidence  – of failed treatment and public health outcomes – continues to mount against prescribed substitute opioids (like Suboxone) for the medically-generated opioid crisis, an alliance of medical and pharmaceutical industries, the Trump administration, and U.S. media continue to promote Suboxone distribution as the “fix” and “gold standard” for the crisis.

 

 

Yet the research evidence for Medication Assisted Treatment (MAT) as implemented – as the evidence was from the start for mass prescription of the opioids that generated the crisis – is invalidating, at best inconclusive, misused, and increasingly points to predictable failure to provide overall benefit.

Early posts here at A Critical Discourse deconstructed arguments and evidence misused to promote a falsely supportive picture of effectiveness of MAT and buprenorphine prescription as a “Fix” for the opioid crisis.

Accumulating new and overlooked results and reports continue to point to lack of support for treatment benefit, instead to buprenorphine program retention failure, diversion, and continued abuse.

The focus – below – of this follow-up/update post: runaway diversion, illicit trade, and abuse of diverted “bupe” on the street in France and exported to outside nations that constitutes – along with additional opioid-related problems – an emerging invalidating body of evidence and picture of continued problem opioid use in France – heralded as the model of buprenorphine success for a U.S. opioid crisis “Fix”.

But First: Are Public Health and other costs from diversion, trafficking, and abuse of medical “fix” substitute opioids outweighed by the benefits ? . . .

there are established benefits . . . right?

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 outlined, 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.

Recent data from a California county hard-hit by opioid abuse and overdose deaths provide preliminary indications that the overdose death-reducing drug naloxone, rather than the opioid substitute Suboxone, most likely accounted for reduced overdose deaths.

 

 

Those results analyzed and discussed in this post.

hospital-ED

Let’s be clear about the nature of required evidence and confounding effects

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.

To attribute prevention of OD deaths to use of buprenorphine in MAT programs requires additional and different evidence. It would require 1) a “naturalistic 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 predicted as 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.

shutterstock Suboxone

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.

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.

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.

 

 

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.

Naloxone

(Below: The French Connection –

Widespread uncontrolled diversion, trafficking, abuse)

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

– described in this upcoming post: additional, mounting evidence against bupe/MAT as the effective factor in decreased OD deaths or as providing treatment or benefit for Americans trapped in opioid and substance use epidemics, like this:

The French Connection

French Medical “Treatment” Model fuels uncontrolled buprenorphine diversion and trafficking

From the start in France, the U.S. and elsewhere the predictable abuse and problem use of buprenorphine (Subutex, Suboxone), a euphoric addictive opioid, quickly became apparent. Congruent evidence of widespread diversion, abuse and trafficking has continued to mount.

France began a campaign in the 1980s of use of the lethal OD reversing drug naloxone, along with essentially unrestricted distribution of buprenorphine (Subutex) by physicians in private practice, without requirements for specialized training or regulatory control.

– French subutex was apparently so easily diverted and plentiful that it fueled a subutex abuse epidemic in Georgia. From the piece by Graeme Wood in The New Republic –

“But starting after 2000, you’d see the line jump dramatically, as if stuck in the ass with a syringe. What drove it up was an opiate called buprenorphine—brand name Subutex, street name “subu”—that effectively did not exist in the country before 2000.

At its peak, one in 20 Georgians was on hard drugs, with Subutex driving the epidemic. “It was like a millennium gift for Georgians who wanted to use drugs,” says George Tsereteli, a physician who is a member of Georgian parliament. . .

And now it’s gone: from zero users to hundreds of thousands and back to zero again, in a decade or less. The journey has been torturous, a case study in grotesque consequences and appalling trade-offs—some former Subutex devotees have taken to injecting pills dissolved in gasoline instead—and it shows that, whatever you think the solution to drug abuse is, you’re probably mistaken.”

– The widespread diversion and illicit use has not been moderated over the decades of use in France – where (from this 2015 piece) “in recent years, dealers have taken hold of it and are supplying international drug rings. . . estimated that one prescription in four is currently being diverted towards small and large-scale trafficking.”

– Part of the problem is that over the decades of unrestricted distribution of an opioid with abuse potential, French health systems have apparently been unable to regulate doctors and pharmacies either willingly engaging in illicit distribution, or not practicing competently and responsibly in ways to prevent buprenorphine use to become dedicated to abuse rather than therapeutic gains, “How can a doctor provide real patient care when dealing with 300 drug addicts? At this stage, all they are doing is renewing prescriptions.”

This 2015 report on French physician adherence to guidelines aimed at protecting patients and the public from diversion and abuse of a widely-prescribed addictive opioid are troubling and appear explanatory:

“We showed that the physicians we interviewed rarely took into account the guidelines regarding buprenorphine prescription. The actual prescribing of Buprenorphine differed from the guidelines.

Only 42% of independent Family Physicians (FPs), working outside the national health care system, had prescribed buprenorphine as a first-time prescription and 40% of FPs do not follow up patients on buprenorphine.

In terms of compliance with the guidelines, 55% of FPs gave theoretical answers that only partially complied with the guidelines.” [despite that] “physicians declared a high rate of participation in continuous addiction therapy training. 38% of FPs and more than 80% of Network or Hospital physicians reported having attended continuous medical training (CMT) in addiction therapy.”

– These results from 2011, French physician reports, appear to document a remarkably, perhaps predictably, high level of misuse among patients prescribed substitute opioids that cannot be attributed to opioid-dependent patients diverting or receiving diverted buprenorphine for therapeutic purposes, instead for abuse or misuse (measured as “Misuse (Injection, Sniffing, Dose Fractionation, Modification of Prescribed Doses, and Combination With Psychotropic Agents) as Reported by Physician”). From two treatment “arms” or groups:

Group 1 (880 patients) – percentage of patients with no misuse = 15%.

Group 2 (1289 patients) – percentage of patients with no misuse = 16%.

– Excerpts from the Erika Niedowski 2007 Baltimore Sun piece on diversion and abuse of prescribed buprenorphine in France, a decade or so after initiation of the substitute opioid campaign and a decade preceding the current push to implement unrestricted buprenorphine prescribing in the U.S. as the “fix” for the opioid crisis :

Dr. Jean-Pierre Aubert considers himself not only a general practitioner but a dealer of sorts . . .

He is not an addiction expert. He does not screen patients to ensure that they, in fact, are opiate-dependent and need treatment. He concedes that some of them might misuse the medicine, including by injection. And he acknowledges that some of the pills he prescribes might end up the stuff of street sales.
Getting addicts in the door is what matters. Even patients who initially show up seeking the drug to get a fix, he said, might progress into proper treatment.
“I’m a legal dealer,” he said. “But being a legal dealer, I can help them with many, many other health issues.”
Aubert, along with 20,000 other doctors prescribing the medication in France, embodies the revolutionary approach the country adopted 11 years ago in its fight against drug use and the public health problems that accompany it. The French system encourages physicians unfamiliar with addiction to prescribe buprenorphine and trusts patients to use it properly. . .

Schering-Plough, the company that sells it [buprenorphine] in France, terms it a “tremendous success story.”

But the French experience also has a down side, one the United States largely overlooked when it followed a similar path by giving private doctors authority to prescribe buprenorphine to addicts.
Buprenorphine, available in France in a formulation called Subutex, has proved addictive for many and has been widely abused. Pills that addicts legally take home are being sold illegally, just like heroin.
U.S. parallels – Similar problems have begun to emerge in the United States. Street sales are increasing, leading to growing abuse of the drug, a Sun investigation found. American addicts are also injecting buprenorphine, even though U.S. officials took the precaution of approving a form of the drug, Suboxone, with a chemical intended to deter injection. It is the only difference between the two formulations.
With the longest experience in using buprenorphine to treat addiction, France provides the clearest picture of the implications of making such a powerful opiate widely available.
Buprenorphine has become an entry drug for people who haven’t used opiates before, a re-entry drug for former addicts, and a factor in more than 100 deaths since 1996 when taken in combination with other substances, according to researchers and public health authorities.
The drug has created a quandary that no one seemed to anticipate: how to get patients off it. Many stay in treatment for years, including some who want to quit, prompting criticism that substitution therapy doesn’t address the underlying problem of opiate dependence.
Buprenorphine has been widely sold on the streets of France, and well beyond. A report by the French Monitoring Center for Drugs and Drug Addiction found that a fifth to a quarter of all buprenorphine sold was being illegally diverted. Pills originating in France are being smuggled to places as far-flung as the nation of Georgia and the Indian Ocean island of Mauritius.
“It’s overprescribed, and it’s too easily prescribed, without any control,” said Dr. Agnes Lafforgue, who helps recovering addicts at a treatment and assistance center in Toulouse, a university city in southwest France.
She questions treating longtime heroin injectors with Subutex, for fear they will inject it, too, and worries about its addictive qualities. She said she has “practically never” successfully weaned a patient off it, despite having done so many times with methadone.
“It’s a scandal the way Subutex has been introduced in France,” she said. . .

The French monitoring center reported in 2004 on Subutex trends. Because of its widespread availability, Subutex was serving as a first opiate for some drug users and a re-entry opiate for some who had previously injected heroin. The report found it to be highly addictive and hard to stop. And it was increasingly being used in dangerous combinations with alcohol, benzodiazepines (such as tranquilizers) and even cocaine. . .

Schering-Plough has aggressively promoted the drug in France, funding the work of harm reduction groups. . .

Lafforgue, the general practitioner from Toulouse, doesn’t see buprenorphine as a solution to opiate addiction.
“We’ve made drug users addicted to Subutex because it calmed them down,” she said. “We’ve cleaned up the country, but we haven’t solved the problem of drug abuse.”

Is it just French-model subutex, (pure opioid buprenorphine) with abuse potential, the naloxone added to buprenorphine in the U.S.-favored Suboxone formulation protective against abuse? Apparently not. Naloxone’s deterrent effect is active only when injected, and predictably work-arounds have emerged for abuse by other routes of administration and with polypharmacy abuse (for example with benzodiazepines) to enhance effects and overcome antagonist effects of naloxone.

And mounting evidence, outlined in upcoming posts, points to increasing abuse and misuse (and treatment outcome ineffectiveness and failures) of the bupe-naloxone formulation Suboxone in the U.S. proposed as the “fix” for the opioid crisis in the U.S. – evidence like the examples linked to above e.g.:

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

Opioid substitution proponents have forwarded the argument that buprenorphine is diverted due to and toward compulsive opioid users motivated and with intention to engage in recovery yet unable to access prescribed bupe and desiring the prescribed drug for self-use to taper off and stop all dependent opioid use, or use buprenorphine without abuse of other substances to reduce risk of harm and return to higher, “normal” levels of functioning in employment, self-sufficiency, family functioning, other measures. But this conjecture 1) is based on direct reports of bupe seekers without verification and 2) more to the point, is belied by multiple lines of invalidating evidence (with links to primary research, other sources, above in this post), for example:

– retention rates in MAT/Suboxone programs trending to zero with concurrent abuse of illicit and licit substances

– use of prescribed opioids concurrently with prescribed buprenorphine

– strong, consistent evidence of high-risk use, instead of recovery-positive use, as evidenced by: bupe-involved ODs, bupe-involved ED visits, etc.

– Direct observations by writers connected to users on the street, as here

– reports of high rates of patient misuse by physicians, versus accounts from substitute opioid seekers, providers having access to drug screen results and prescription use

Bupe: medical industry opioid “fix” for the medically-generated opioid crisis – or fueling the opioid epidemic?

Despite 1) the lack of evidence for benefit to Americans trapped in compulsive use of opioids and other drugs and 2) lack of any research base that would allow attribution of decreased OD deaths to bupe/MAT programs versus concurrent naloxone campaigns, and 3) associated public health and criminal justice problems related to apparently widespread diversion, trafficking, and abuse –

buprenorphine/MAT continues to be branded as a “gold standard” and “fix” for the opioid crisis.

As further described and linked in upcoming posts, consistent evidence points not to protective psychosocial and behavioral benefits from bupe/MAT programs, instead to diversion, abuse, retention rate failure in programs, and misuse by providers. That lack of evidence for gains due to Medication Assisted  “Treatment” (MAT) of the condition of compulsive opioid use has been apparent in France as well, despite unrestricted availability of bupe through primary care doctors resulting in steadily increasing prescriptions over two decades.

Preview of upcoming post: total drug-related overdose deaths (more than half opioid-involved) in France – the country that “fixed” its opioid problem – increased over years  of continued expansion of bupe dispensing (2006 – 2010), and in 2013 returned to near-peak levels for the period 2006 – 2013. In 2015 France remained 5th highest of 20 European nations in prevalence of “high risk opioid use”.

And in the U.S. –