Buprenorphine Diversion: Beyond a Superficial Understanding

First Posted 11/19/2013
In ‘Addiction Treatment with a Dark Side’, Deborah Sontag of the New York Times shared her observations of the clinical use of buprenorphine for treating opioid dependence, warts and all.  Readers of the Talk Zone know my bias—that buprenorphine/Suboxone is one of the only effective treatments for opioid dependence, and many patients are best-served by long-term, perhaps life-long treatment with buprenorphine.   But I read the article the article with interest because I know that Ms. Sontag ‘did her homework’, including visiting a number of practices, speaking with a number of patients, and reviewing hundreds of studies about buprenorphine and Suboxone over the course of many months.

From my perspective, the article overstates the diversion problem.  In my last post I asked if the fear of diversion should be a factor in whether buprenorphine-based medications become the leading edge of addiction treatment.    I stated my opinion—that if overdose deaths don’t pull acetaminophen from pharmacy shelves and diversion doesn’t keep hydrocodone off the market, then diversion of buprenorphine deserves little discussion relative to the value of buprenorphine treatment for addiction.

With the wave of stories describing buprenorphine as ‘controversial’, every discussion of the medication seems to revolve around diversion.   Do the numbers support the association? Deaths from Suboxone—deaths where buprenorphine was one of the drugs that caused death—amounted to several hundred over the past ten years, compared to 38,000 drug overdose deaths in 2010 alone.  The magnitude of the difference is so staggering that it deserves repetition; 400 deaths in ten years, vs. 38,000 deaths in one year.  The total number of deaths linked to buprenorphine over the past ten years is about equal to the number of people who die from acetaminophen– EACH year.

Diversion of buprenorphine is a complex issue.   Words like ‘diversion’ and ‘overdose’ are loaded with so much emotion that one word seems to tell the whole story.   A Google search of Suboxone brings up news reports such as ‘Suboxone found at overdose scene’, or ‘man arrested with cocaine, heroin, and three Suboxone tablets.’  The stories create an ugly image, with buprenorphine/naloxone as one more drug of abuse, found at ‘an increasing rate’, according to other headlines. But a superficial look at diversion yields a superficial understanding of the diversion problem.

Take as example a patient has not used illicit substances for 3 years while taking prescribed Suboxone, who relapses to heroin and dies from overdose.  News stories will describe a scene littered with needles, heroin, and Suboxone tablets.  That description creates a misleading impression of the patient’s history, and a misleading impression of buprenorphine.  Even if the story provides more detail, the headline alone will fill the tweet—the ‘news’ of the modern era.

Is the nature of diversion, the reason for diversion, or the consequence of diversion relevant to discussions about the diversion of buprenorphine?  If someone tries to hold life together by purchasing street Suboxone in a geographic region void of certified physicians, should that ‘diversion’ be included in the category as the sale of oxycodone?

What if the powerful mu-receptor blocking effects of buprenorphine have positive effects?  What if studies found a lower rate of overdose deaths in communities with greater diversion of buprenorphine?   Would that be relevant to the diversion discussion?

I do not know of any evidence that diversion of buprenorphine correlates with fewer overdose deaths.  But many public health experts predict that encouraging ‘street use’ of naloxone would reduce overdose deaths, so expecting the same from buprenorphine, a stronger and longer-lasting mu antagonist, is not unreasonable.

Patients on buprenorphine awaiting elective surgery discover that the blocking effects of buprenorphine last for weeks.  The same patients report that even after several weeks off buprenorphine, significant doses of oxycodone will relieve post-op pain, but won’t provide the ‘euphoria’ oxycodone used to provide.  Patients who could never make a week’s script for oxycodone last longer than a day can often control use of opioid agonists after surgery if kept on a small dose of buprenorphine.    Considering these findings, it is not unreasonable to wonder if there is a lower risk of death by overdose in people who ‘divert’ buprenorphine.  Buprenorphine has a much longer half-life than oxycodone or heroin, so diverted buprenorphine intended for use ‘in between’ acts as a blocker during periods of active heroin use.  Is it possible that traces of diverted buprenorphine in the bloodstream saves lives?  If so, is that relevant to discussions about diversion?

The worst diversion scenario is if opioid-naïve people take buprenorphine or Suboxone and becoming addicted to opioids as a result, i.e. diverted buprenorphine serving as a gateway drug to opioid dependence.  Nobody should take that situation lightly.  But stories from the streets bring to mind biological programs where sterile males of an invasive species are released into the wild in effort to eliminate the invasive mosquito, lamprey eel, or fruit fly.  What if the spread of buprenorphine functions as an ‘addiction moderator’ where the more buprenorphine in a community, the lower the rate of overdose deaths?

I realize that I am out on a limb— but as the saying goes, that’s where the fruit is.   If buprenorphine diversion is investigated in a superficial manner, we will collect nothing but superficial results.  The diversion of a medication with the potential to save as many lives as buprenorphine deserves a deeper level of understanding.

Chipping Suboxone

First Published 8/31/2013
One reply to my last post said I go ‘on and on’ about things that could be said with fewer words.  I asked the person to send me his/her version, and I hope he does—not to prove anything, but because I appreciate the chance to learn.  He wrote that his problem is the opposite– that he can’t write 90-minute screenplays because he gets to the point too quickly.  Maybe we should be partners!
I suspect that my writing style comes from my days submitting research findings to basic science journals, where each individual comment must be supported by data or by citation.  I’ll try to get to the point more quickly.
In the last post I made two points:  1. Discounts demanded from insurers for front-line services (office visits) create challenges for independent primary care practices that don’t have other sources of revenue, particularly revenue from procedures, and 2. Physicians employed by health systems are less likely to prescribe buprenorphine for treatment of opioid dependence than are small, independent practices.
The result is a shortage of doctors prescribing buprenorphine.  This shortage leads to a number of other problems, the most visible (to those who care to notice) being a large number of heroin-related deaths.  But other consequences are apparent for those who connect the dots.  Wisconsin and other Midwest states contain large, predominately-rural areas where buprenorphine and Suboxone are only available as illicit substances.  People addicted to opioids choose ‘self-treatment’ with Suboxone, purchased from the same person who deals heroin.  The high cost of buprenorphine and Suboxone encourages people to take very small pieces Suboxone tablets or film; just enough to prevent withdrawal.  But the unique pharmacodynamics of buprenorphine that block opioid cravings (the basis for buprenorphine’s efficacy) rely on taking a dosage high enough to maintain blood levels of buprenorphine above the medication’s ‘ceiling effect.’
In other words, small fragments of Suboxone or buprenorphine, taken sublingually, yield the same subjective experience as opioid agonists taken orally.
But this is the tip of a very large iceberg.  In areas where buprenorphine/Suboxone is only available illicitly, the scarcity and cost of the medication leads heroin users to take other steps to reduce the costs of ‘self-treatment’.  Remember that with sublingual dosing only a third of the buprenorphine enters the systemic bloodstream.  Even less reaches the circulation if the drug is swallowed.  But 100% reaches the circulation when heroin addicts use the Suboxone or buprenorphine the way they use heroin—by needle.  The opioid blocker naloxone is added to create Suboxone, but my new patients have reported injecting Suboxone and buprenorphine, and finding no significant difference between the two.
The people who studied in HS Biology realize that the portal vein does not drain the end of the intestinal tract—meaning that drugs or substances entering ‘backwards’ are not subject to ‘first pass effect’ that destroys oral buprenorphine.  This leads to another way to reduce the cost of ‘self-treatment’, referred to as ‘plugging.’  And there’s really nothing more that I want to say about that. Gross.
No matter how clean the marketing, a medication that is injected, ‘plugged’, or sold by heroin dealers will eventually get a black eye.  I’ve written about guilt by association, and how patients doing everything right to end an addiction started by their pain doctor feel denigrated for taking Suboxone or buprenorphine exactly as prescribed.  We’ve heard about part of Eastern Europe where the black eye to buprenorphine treatment led to political blindness, resulting in the replacement of ‘dreaded buprenorphine’ by a yellow chemical nicknamed ‘Krokodil’.  Right now, the primary problem in my region is the potential blurring of lines between treatment and ‘self-treatment’, which is just another form of opioid dependence.  I recently began treating a young woman who had been taking illicit Suboxone/buprenorphine, each day, for over 4 years, without any use of opioid agonists.  She probably would not be driving a couple hours to see me for each appointment, had the withdrawal symptoms of her newborn not prompted the investigation by social services.
To the person who reviewed my last post— my lack of terseness is showing.  I intended to conclude this post today, but when we look more closely, the unintended consequences go on and on.  To summarize so far:  That the shortage of buprenorphine-certified providers makes buprenorphine/Suboxone a scarce commodity.    Buprenorphine has unique effects when taken properly, and the elimination of the obsession to use opioids is a Godsend for many people that cannot be obtained from ANY other substance.  While some politicians and regulators see a world where too many doctors put Suboxone and buprenorphine on the streets, the unintended consequence of having too FEW providers has been to fuel the misuse and diversion of a potentially life-saving medication.
In part one, I promised a bit of drama over the Affordable Care Act.  I’m getting there.  But given that this is a holiday weekend, you will have to wait a few days for part 3!
Addendum:  I’m adding comments from a member of the LinkedIn discussion board, from Shaun Shelly, Addictions Specialist at Hope House in Cape Town, South Africa.  He points out how the blurring lines between abuse and treatment erode confidence in buprenorphine as a treatment strategy:
Great piece, and I look forward to you going “on and on” a bit more! I see the same in the South African setting where we have only one recently started (last week!) trial state funded OMT program. But all our patients know where they can buy scripts from doctors at R50(US$5) a pop. There is no requirement for special buprenorphine training in order to prescribe. Honestly, these doctors are little more than dealers with titles – these are the same guys who are giving long-term repeat scripts for benzos. And the dealers I know also supply bupe.
The real problem is, as you state, that the self-administration is at best sporadic and sub-optimal. This has the effect of many patients saying Bupe doesn’t work, and when we refer them for medically assisted detox they aren’t interested (Bupe is only funded by the state and many medical aids for 7 day detox). Hopefully sanity will prevail and we will get some decent OMT programs in place.
I have the same experience with some injectors – they report a lemon taste in the mouth but little else negative.