History, maintenance, overdose and policy

Opioid-prescription-deathsTwo articles came to my attention today.

First, esteemed drug policy historian, David Courtwright, provides a historical perspective on opioid policies and maintenance treatments.

To the extent that Americans remember the Harrison Act, they recall it as a prohibition law rather than a redundant regulatory measure. This impression grew out of two crucial lacunae: the legislation mentioned neither addiction nor the legality of supplying addicts with narcotics for gradual withdrawal or indefinite maintenance of their accustomed use. Treasury Department officials, who administered the law, nevertheless assumed an aggressive antimaintenance stance, which the Supreme Court at first rejected but then narrowly upheld in 1919. Most physicians, including Journal editorialists, had no sympathy for doctors who made a business of supplying addicts. Yet federal harassment and prosecution of physicians deemed too liberal with their prescription pads, together with the shuttering of narcotic clinics (short-lived municipal alternatives to physician maintenance), stimulated the black market and triggered a prolonged debate over the legal and medical propriety of maintenance.

nora-volkow-final-edits-8-728He brings us to the present day with these paragraphs.

The emergence of methadone maintenance in the late 1960s and early 1970s, and its validation by double-blind trials, seemed to resolve the debate in favor of supplying addicts with long-acting opioid agonists. But treatment providers in abstinence-oriented programs and their government allies never accepted indefinite maintenance, and their moral and political reservations kept the issue simmering. It simmers still, despite the 2002 approval by the Food and Drug Administration of new products containing buprenorphine, a partial opioid agonist.

The lack of resolution has hindered another important medical task — tertiary prevention by minimizing harm in cases of firmly established opioid addiction. The key objectives — reducing fatal overdoses, medical and social complications, and injection-drug use and related infections — are difficult to achieve if abstinence-oriented treatment is the only option available. Yet that remains the situation in many places, particularly in rural locales, where officials dismiss methadone and buprenorphine as unacceptable substitute addictions. “IF YOU WANT PROBATION OR DIVERSION AND YOUR ON SUBOXIN,” declared an erratically spelled sign outside a Kentucky courtroom, “YOU MUST BE WEENED OFF BY THE TIME OF YOUR SENTENCING DATE.”5

Such policies defy the logic of longitudinal studies that consistently show recent abstinence to be a major risk factor for fatal opioid overdose. Loss of tolerance and overconfident judgments about dosage often kill relapsing opioid addicts, though not relapsing alcoholics or marijuana users who detoxify in similar fashion. Indifference to this fact has contributed to the rise of fatal prescription opioid and heroin overdoses, which together claimed more than 24,000 lives in the United States in 2013.

I have a few of reactions.

  1. It seems like he could make is point without resorting to an anecdote that reduces people he disagrees with to ignorant yokels.
  2. Earlier in the piece, Courtwright refers to the prescribing of  opioids igniting and sustaining the current epidemic of iatrogenic opioid addiction. However, when discussing the failure of treatment providers and courts to embrace pharmacological interventions, he fails to acknowledge this context as grounds (rightly or wrongly) for skepticism. Further, he does not acknowledge that the prescribing, marketing and systems problems that contributed to this epidemic are not confined to drugs like Vicodin and Oxycontin. These problems are also present in the prescribing, marketing and systems for drugs like buprenorphine.
  3. I don’t doubt there are regions where maintenance treatments may be difficult to access, or that some courts prohibit them. However, to imply that government has never accepted maintenance isn’t entirely accurate. Government funds have provided life support to methadone. For example, in 1994, public funds paid for 80% of all methadone maintenance. Further, there’s a big government push for maintenance treatments—a federal survey finds that opioid replacement treatment admissions accounted for 27.8% of all treatment admissions. (Not 27.8% of opioid addiction admissions. 27.8% of ALL addiction treatment admissions, including alcohol, cocaine, etc.)
  4. While it’s true that “recent abstinence [is] a major risk factor for fatal opioid overdose”, his framing presents abstinence as the problem. Almost as though people die of abstinence (or, reduced tolerance) rather than opioids.
by Fearless Tall Dude Killer
by Fearless Tall Dude Killer

Let’s ignore reactions 1, 2 and 3 for now and just look at the issue of abstinence, tolerance and overdose. In particular, maintaining opioid tolerance with buprenorphine and methadone as a strategy to prevent fatal overdose.

This is where the second article comes in.

It compares buprenorphine maintenance and methadone maintenance, and describes itself this way.

This study, the first to follow opioid dependent individuals randomized to two opioid maintenance treatments prospectively over 5 or more years, is instructive about longer term outcomes and poses a challenge to the field to enhance retention in opioid maintenance treatment.

Here’s a little more info on the timeframe of the study.

A follow-up study of all randomized study participants was conducted during 2011- 2014, approximately 2 to 8 years (a mean of 4.5 years) post randomization.

What did they find in terms of mortality?

There were 23 deaths in the BUP group (n=630, or 3.6%) and 26 deaths in the MET group (n=450, or 5.8%);

If I’m reading the CDC rates correctly, the annual mortality rate for people 35-44 years old (the study had an average age of 37) is 0.184%. If we multiply this by 4.5 (the average follow-up time), we get 0.828%.  The study had an overall mortality rate of 4.5%, which is 5.4 times higher than what the CDC says you might expect for the average age of the subjects.

What about retention? Patients aren’t protected if they’re not still using the maintenance drug, right? There’s no info about the number who were continuously engaged in maintenance.

  • 87.7% of the buprenorphine subjects were not in buprenorphine treatment at follow-up.
  • The buprenorphine subjects were in buprenorphine treatment for 19.8% of the months during the trial and the follow-up period.
  • 51.8% of the methadone subjects were not in methadone treatment at follow-up.
  • The methadone subjects were in methadone treatment for 53.3% of the months during the trial and the follow-up period.

A presentation on the same federal study reported the following retention data:

A disproportionately larger number of the Suboxone group, compared to the methadone group, discontinued study participation prematurely, with many dropping out shortly after enrollment (57% Suboxone vs. 27% methadone).

What about drug use? The article offers no info on abstinence from other opioids or other drugs. It reports drug outcomes in terms of reductions in the number of days using opioids per month.

Participation in MET or BUP treatment, relative to no MET or BUP treatment, was associated with reduced opioid use. The estimated reduction on days of opioid use was 8.5 days for MET and 7.8 days for BUP treatment, respectively . . .

It also offers a comparison to no treatment.

Compared to being in no treatment, MET treatment was associated with a reduction of opioid use by 9.8 days per month for white participants and by 7.1 days for non-white participants. BUP treatment, compared to being in no treatment, was associated with a reduction of opioid use by 7.6 days for white participants and by 8.0 days for non-white participants.

I don’t doubt that opioid maintenance reduces fatal overdose, and I have no interest in interfering with any addict’s access to these treatments. However, upon learning the details of these studies, I think most addicts and their families would feel misled by reporters who describe these treatments as “highly effective“, when effectiveness is defined as fewer days per month using and mortality rates that may be lower than no treatment, but are still more than 5 times higher than their peers in the general population.

This isn’t to suggest that they shouldn’t be offered or that addicts shouldn’t be able to choose them. But, I am suggesting that those who imply that maintenance treatments are going to get us out of the opioid addition and overdose crises need to look beyond press releases and abstracts, and look at the actual results in these studies.

Clearly, we need to keep looking for and trying better ways to keep opioid addicts engaged in treatment and get them into stable recovery. And, where we’re not able to do this, we need to keep looking for ways to keep them alive.

It’s worth mentioning that there is a highly effective treatment model that doesn’t have to be too expensive and might be adapted to other populations. Unfortunately, it does not fit the current narrative and does not get any attention in the press coverage.