In a California county hard-hit by opioid abuse, reduced death rate points to OD reversal drug naloxone, not opioid substitute Suboxone

by Clark Miller

July 27, 2018

As described here, healthcare industries responsible for the opioid crisis have rushed to claim effectiveness for Medication-Assisted Treatment (MAT) with the substitute opioid Suboxone, a medical fix for a lethal epidemic caused by the unsupportable medicalization of a non-medical problem, popular media tagging along without critical examination of claims and evidence that, on examination, does not support MAT as an effective response to the opioid crisis.

Popular media have followed along with orthodox reinforcement and promotion of medical fixes for the medically-generated opioid crisis, citing reduced overdose deaths due to opioid misuse as strong evidence and support for effectiveness of Medication-Assisted Treatment (MAT) and partial agonist assistance with Suboxone (buprenorphine + the antagonist naloxone) to address problem opioid use and the opioid epidemic.

Numerous print and online news sources are running feature articles and series on the crisis, like at Vox where the appearance of reduced heroin overdose deaths with increased use of “anti-addiction” opioids like subutex in France in the 1980s and 1990s is asserted as establishing buprenorphine-based MAT as both effective and a form of “treatment”, the “gold standard” and fix for the opioid problem. As portrayed by popular addiction writer German Lopez at Vox: “France had a big heroin epidemic in the 1980s and ’90s. Here’s how the country fixed it.

Similarly, addiction writer Maia Szalavitz recently cited a 2017 retrospective cohort study of patients provided methadone or buprenorphine for problem opioid use, interpreting and concluding that significant increases in overdose deaths for patients no longer retained in treatment determine that MAT is a first line or sole treatment approach to problem opioid use and the opioid epidemic, advocating for prescription of the opioids to patients for extended or life-long use.

These lines of evidence and research and the confident conclusions drawn from them about effective treatment for a public health crisis are important to examine, analyze, and understand, because they are not supported by the research.

A more general, less research-based look at the problem and how popular media is helping drive it is in this week’s less research-focused companion post – The False Promise of Medication-Assisted Treatment (MAT) for the Opioid Crisis.

At Vox, journalist German Lopez writes:

Lopez notes that “other policies at the time” may also have accounted for the drop, that is – it is unclear to what extent the increased dispensing of buprenorphine accounted for the decrease in deaths. He does not address the most likely confounding factor: Naloxone, the opioid overdose emergency antidote that became available in France in 1977. French addiction researchers place the reduction of opioid overdose deaths across a slightly different time frame, 1994 to 2002, during a period when Naloxone emergency use in communities in Europe was being promoted and injectable Naloxone was increasingly available to emergency medical personnel in France.

Those factors confuse and confound things, preventing confident interpretation of results –

Do overdose deaths decrease because buprenorphine use has therapeutic factors, changing users’ lives in lasting, positive and protective ways that decrease risk of drug abuse and overdose?

Or are users, while in buprenorphine programs, more connected to healthy, functional social environments, and socially isolating less – as opposed to “street”, or drug culture life – so that overdoses are more likely to be responded to effectively, preventing death?

Those same confounding factors prevent confident interpretation of possible benefit from use of substitute opioid harm-reducing drugs in the study cited by addiction writer Maia Szalavitz. In that study neither problems with drug use by participants while in the methadone/suboxone programs, nor retention rates (how many subjects actually stayed in the program?) are reported, the study authors noting this as one of several confounding effects limiting confident conclusions.

Clearly, any benefit in reduced overdose deaths – whether due to MAT as a strategy and benefit, or to associated increase in availability of emergency Naloxone kits – would disappear or likely diminish for individuals leaving the programs and becoming enmeshed in illegal drug use and culture. With retention rates typically low to very low in Suboxone trials (trending toward zero in this study,) conclusions about significant lasting benefits from Suboxone and MAT are premature.

A New Look at the Evidence

(Below: Plumas County, CA – A Case Study)

While the results and influential media interpretations of research results helping fuel the rush to identify opioid substitution as the medical fix for the medically-generated opioid crisis are at best inconclusive, we can look at available evidence in other ways to evaluate those claims.

The presumed psychosocial mechanisms for reduced overdose deaths attributable to hypothesized benefits of partial agonist (Suboxone) use by subjects would seem necessarily to include: relief from intrapsychic (emotional, mental) stressors driving compulsive opioid use for euphoric relief; strengthened, protective psychosocial integration in a rewarding recovery ecology; intrinsic motivation for and engagement in appropriate services and supports.

Accordingly, reduced overdose deaths attributable to hypothesized benefits of partial agonist (Suboxone) use by subjects motivated for relief from correlates of problem opioid use would predict:

  • high retention rates in MAT programs
  • reduced concurrent use of drugs of abuse by subjects in MAT
  • reduced overdoses/emergency medical contacts in addition to reduced overdose deaths
  • reduced measures of psychosocial correlates of problem use of substances

In contrast, if MAT is not providing significant benefit for problem opioid use and diminishing compulsive drive for euphoric use of opioids and supporting engagement in associated treatments (behavioral and psychotherapy treatment component of MAT), providing gains in emotional and mental health, as well as improved functioning – then predictions would be distinctly different:

  • low retention rates in MAT programs
  • continued concurrent use of drugs of abuse by subjects in MAT
  • continued risk of overdoses/emergency medical contacts apart from overdose deaths
  • lack of significant change in psychosocial correlates of problem use of substances

These considerations set out a research agenda and need for additional research and interpretation before beneficial effects due to MAT and Suboxone can be asserted.

How do the evidence and research results fit with these predictions based on benefit versus no benefit from substitute opioid use (MAT)?

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 the 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 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.

The limited, inconclusive nature of evaluation of effectiveness based on overdose rates (attributable to MAT success in treating problem opioid use, or to associated increased training and distribution of naloxone overdose kits?), along with MAT trials that result in treatment failure (e.g. less than 5% treatment retention/success rate; with MAT for prescription opioid abuse, 91% failure over a 12-week trial – links above) point to the status of MAT as currently being an unvalidated approach for problem opioid use and to address the opioid crisis.

Preliminary results from a case study –

Plumas County, California

Recent reports 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.

To review: If reduced opioid deaths are attributable to use of Suboxone, predicted outcomes include measurable gains in functioning and wellness, in addition to reduced deaths, including psychosocial functioning and reduced need for emergency medical services, because the therapeutic mechanisms are indirect: reduced distress and impulses to abuse substances, improved functioning in life.

In contrast, if reduced overdose deaths are largely or primary due to reversal of overdose with naloxone, predicted outcomes include reduced number of OD deaths, not other measures.

James Wilson, featured in the Center for Health Journalism piece on the remarkable reversal of opioid overdose deaths, in Plumas County, is that county’s health education coordinator with California’s Northern Sierra Opioid Safety Coalition. Wilson explained (personal communication via email) that some of the data available for Suboxone use in the county is misleading: buprenorphine (Suboxone) was prescribed prior to late 2016, but for pain, not as partial agonist therapy for problem opioid use in a MAT program. That did not begin in Plumas County until November of 2016, then rose dramatically over the next year or so.

Preliminary results from Plumas County, California:

A Naloxone campaign that included widespread distribution and education began in September of 2016 and was immediately followed by a drop in opioid-related OD deaths to zero over 2016, from 3 or 4 in 2014 and 5 or 6 in 2015.

Since the start of that campaign, there has been just one confirmed OD death.

Suboxone use in a MAT program began two months later, with enrollment of a single patient in November of 2016, a factor unable to account for the decline in OD deaths to zero in 2016.

Naloxone, by contrast, prevents OD deaths directly and immediately as soon as it is available to trained individuals, and the campaign begun on a large scale in September of 2016 would reasonably account for the drop in OD deaths to zero.

Since the start of that campaign in September 2016, Plumas County recorded reports by patients of 14 potential OD death reversals, almost certainly an under-report according to Wilson, because these were voluntary reports, not based on surveys.

With an average of around 4 – 5 OD deaths in the preceding years of 2014 and 2015, the use of Naloxone would directly account for the entire drop in OD deaths.

Despite the dramatic rise in Suboxone prescribing in a MAT program beginning November of 2016, opioid-related Emergency Department visits remained high, with relatively slight decline over a period of a 200% increase in Suboxone use.

From these preliminary results, it appears that the Naloxone campaign, including intensive distribution and education efforts, almost certainly accounted for the drop in OD deaths, with any significant role for Suboxone in a MAT program open to question.

But perhaps the most direct and powerful evaluation –

of the potential effectiveness and benefit from Suboxone for the opioid crisis – buprenorphine and MAT now having been in use worldwide for more than three decades – would be simply to pose the questions:

1) If effective, why has problem use of illicit and prescription opioids worsened, instead of been moderated, over those decades?

2) If effective, why must proponents of MAT resort to citing what appear to be positive 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?

These results and critical discourse raise a critically important question: if at best Suboxone or other substitute opioids can provide a window of improved functioning and potential benefit from the actual Treatment part of Medication-Assisted Treatment for compulsive substance use, what is the status of provision of those effective, evidence-based treatments for substance use as incorporated into MAT programs?

Using hard-hit rural Oregon as an example, described and discussed here, under the clinical and medical direction provided by managed healthcare organizations in Oregon the regional “best practice” response to the opioid crisis, including a model MAT program “center of excellence” in fact reflects a profound ignorance of and profound disregard for current research outcomes and evidence-based treatment of substance use disorders, predicting no benefit or harm to individuals trapped in the crisis and seeking competent care.

As designed and implemented by professionals at two clinics examined and professionals employed by the insurance companies – professionals who are out of scope of competence for evaluation of relevant research and for program development for use of evidence based practice (EBP) MH and SU practices for substance use disorders – neither program is providing any services constituting EBP for substance use disorders or opioid use disorder, instead treatment as usual (TAU), TAU established as predicting no benefit or harm by decades of established research and as by academic, journalistic and documentary exposure:

In Summary

Evidence for the universally accepted medical fix for the medically-generated opioid crisis, Medication-Assisted Treatment, is at best inconclusive, with multiple studies pointing to treatment failure and MAT as a currently unvalidated approach. More fundamentally problematic, the over-focus on medically managed programs prescribing substitute opioids for the crisis appears to have resulted in the actual treatment part of MAT regressing to traditional “addiction treatment”, or treatment as usual (TAU), approaches that have never been evidenced as effective.

Current research does not support confidence in benefit attributable directly to use of prescribed Suboxone or other substitute opioids. Instead, it points strongly to the conclusion that whatever factors are responsible for decreases in lethal overdoses (distinguished from overdoses), Suboxone and MAT are not providing outcomes predicted if those approaches had been over past decades providing significant therapeutic/behavioral/psychosocial benefit to problem opioid users.

Critically, the at best mixed and inconclusive research base for benefit from Suboxone and other MAT, with short windows of opportunity for treatment engagement, points to the necessary and crucial role of the actual treatment component of MAT to provide benefit and begin to address the opioid crisis. As evidenced and referenced in a series of Upcoming Posts, therapies supported as effective are psychotherapies in individual, not group modality, (behavioral health therapies delivered by qualified mental health professionals with background in substance use treatment) for substance use, a set of practices that are distinct from those historically and currently provided almost universally in programs and settings providing treatment as usual (TAU) for substance use.