This Suboxone Doesn’t Work!

Today on SuboxForum people were writing about their experiences with different buprenorphine formulations.  Doctors occasionally have patients who prefer brand medications over generics, but buprenorphine patients push brand-loyalty to a different level.  The current thread includes references to povidone and crospovidone, compounds included in most medications to improve bioavailability.  Some forum members suggested that their buprenorphine product wasn’t working because of the presence of crospovidone or povidone.  Others shared their experiences with different formulations of buprenorphine and questioned whether buprenorphine products are interchangeable, and  whether buprenorphine was always just buprenorphine, or whether some people respond better to one product or another.
My comments, including my observations about patient tolerance of specific buprenorphine products, are posted below.
Just to get some things straight about povidone and crospovidone (which is just another synthetic formulation of povidone),  both compounds are NEVER absorbed, by anyone.   They are part of a group of compounds called ‘excipients’, and are included in many medications to help with their absorption.  They act as ‘disintegrants’– meaning they allow the medication to ‘unclump’ and dissolve in liquids, such as saliva or intestinal secretions.
Molecules tend to clump together, sometimes into crystals, sometimes into other shapes.  A pile of powdered molecules molded, packed, and dried into pill form wouldn’t dissolve in the GI tract if not for povidone or other disintegrants.  I remember reading somewhere about cheap vitamins that could be found in the stool, looking much the same as they did when they were swallowed.  Not sure who admitted to doing the research for that article..
Buprenorphine IS buprenorphine.  Period.  The absorption isn’t affected much by excipients, because nobody ever complains that their Suboxone or buprenorphine won’t dissolve.  Povidone or crospovidone are also added to increase the volume, because an 8 mg tab of buprenorphine would be the size of 100 or so grains of salt.  Excipients like povidone and crospovidone also help some drugs dissolve, especially drugs that are fatty and don’t usually dissolve well in water-based solutions.   This last purpose does NOT apply to buprenorphine, since buprenorphine is very water-soluble.  Zubsolv is supposedly absorbed more efficiently in part because it dissolves very quickly, and maybe that is due to excipients.
I realize that when I write ‘bupe is bupe’ it sounds like I don’t believe those who complain about their medication.  But honest, I work with people over this issue every day…  I have an equal mix of people who insist Suboxone doesn’t work for them and people who insist ONLY Suboxone works for them.    Today I was reading TIP 43–  a guide about medication-assisted treatment put out by SAMHSA and the Feds that is over 300 pages long, very well-cited– in a section that cited studies about the psychological triggers for withdrawal symptoms.  TIP 43 and other TIPs can be downloaded for free… just Google them.  TIP 43 is primarily about methadone, but some of the information applies to methadone and buprenorphine.  The pertinent section was around page 100, if I remember correctly.
The TIP information mirrored what I see in my practice.  For years, I’ve noticed that patients will complain about withdrawal symptoms even at times when their buprenorphine levels are at their highest.  Patients also report that their withdrawal symptoms go away ‘right away’ after dosing, when in fact buprenorphine levels won’t increase significantly for 45-60 minutes.  People who have been addicted to opioids may remember how even severe withdrawal mysteriously disappeared as soon as oxycodone tabs were sitting on the table in front of them.   The bottom lline– withdrawal experiences are remembered, and those memories are ‘replayed’ in response to triggers or other memories.
In my experience as a prescriber, I’ve come to believe that patients with an open mind will learn to tolerate any type of buprenorphine (the exception being the 1 patient I’ve met who developed hives from meds with naloxone– hives that appeared consistently on three distinct occasions).  But withdrawal symptoms seem to be triggered, in many people, by the expectation of withdrawal symptoms.  So someone convinced he will never tolerate Zubsolv, Bunavail, or Suboxone Film will probably never tolerate those medications.
As for buprenorphine, it IS just buprenorphine.  Molecules with a certain name and structure are always identical to each other.  They are not ‘crafted’ products like bookcases or tables;  some buprenorphine molecules aren’t made with a quality inferior to other buprenorphine molecules.  And once a molecule is in solution, I don’t see much role for excipients.  Of course a tablet or strip could contain too much or too little active drug, but that is an FDA issue, not an excipient issue.

Counseling Schmounseling

I just noticed a couple of my recent posts….  these people have it wrong, and that person has it wrong.  One of these days I really need to print something positive and uplifting.  But not today.
Excuse the self-flattery, but I like to think of myself as a physician scientist.  That concept motivated my PhD work, and cost me friend after friend in the years that followed!  A physician scientist isn’t all that difficult to be from an educational standpoint, especially in the age of the internet.  The one thing that is necessary is the willingness, or need, to question every assumption by the media, the government, physicians, laypersons, and other scientists.   Ideally, the questions are guided by a knowledge of p-values, the process by which scientific grants are awarded, an understanding of the peer-review process, and the realization that anyone elected to office knows less about science than most other humans on the planet.
Last night I came across an opinion piece– I think in the Bangor Daily News, but I could be wrong about that– that argued that we will never stem the heroin epidemic without use of medications.  The comment section after the article was filled with the usual angry banter over methadone and buprenorphine that now follows every article about medication assisted treatment.  As an aside, why are the abstinence-based treatment people so angry about medication?  There are people out there who choose to treat cancer using crystals, but they don’t spend time bashing monoclonal antibodies!
Here is the part of this post where I start losing friends…  but let me first say that I know some counselors.  I like counselors.  In fact, some of my best friends are counselors.  But in the comments after that article I read the same thing over and over–   that meds aren’t the important thing, and that counseling is what really makes all the difference.  A couple weeks ago  the person sitting to my right said the same thing during a discussion about  medication-assisted treatments.  And that same phrase is repeated ad nauseum in lecture after lecture in ASAM lectures and policy statements related to addiction.  The phrase has even been codified into some state laws.  And why not?  It is something we all ‘know’, after all.
If we are going so far as writing laws requiring that people have counseling in order to obtain medication, shouldn’t we do one thing first?  Shouldn’t we determine if the comment is really true?
A couple years ago two papers came out– someone help me with the reference if you have them– that looked at abstinence rates after a year on buprenorphine in patients with or without counseling.  Guess what?  The counseling group did not do better!  In fact, the counseled patients did worse; not sigificantly so, but enough to clearly show that there was no ‘trend’ toward better performance in the counseled group (which would have been pointed out, were it true.)
I could hypothesize many reasons why the counseled groups would do worse.  Maybe they were angered by the forced counseling and therefore bonded less effectively with their physician.  Maybe they obtained a false sense of expertise in dealing with addiction, making them more likely to relapse, whereas the non-counseled group learned to just do as they were told.  Or maybe the counselors send out signals, consciously or unconsciously, that interfered with medication treatment.
The thing is, we have no idea which of these things, if any, are going on!  There have been no systematic studies or other attempts to understand what happens during the combination of counseling and medication treatments.  We just have a bunch of people saying ‘do them both!  do them both!–  a comment that apparently feels so good to some people that they just cannot consider things any other way.
For the record, I see ALL my patients for at least 30 minutes for every appointment.  As a Board Certified Psychiatrist, I guess that means I’m counseling them.  And from what I can tell, it seems to be working pretty well.  But even in my own case, I would never draw firm conclusions unless someone does a double-blind study and collects the data.
I encourage all physicians, scientists or not, to question some of what we ‘know’ about addiction treatment.  Is it really all about the counseling?  Maybe— but then again, smart people used to ‘know’ the world was flat, and the Earth was the center of the Universe.

Clearbrook President Gets it Wrong

A blurb in the buprenorphine newsfeed (see the bupe news link in the header of this page), has the headline ‘Suboxone challenged by Clearbrook President’.  I followed the link, and after reading the ‘article’ I wanted to comment to that president but the person’s name wasn’t included, let alone an email address or comment section.  So I’ll have to comment here instead.
The article was one of those PR notices that anyone can purchase for about 100 bucks, in this case from ‘PR Newswire’.  It’s a quick and easy way to get a headline into Google News, which pulls headlines for certain keywords like ‘Suboxone’ or ‘addiction’.
The Clearbrook president makes the comment that this 180-degree swing to ‘medication assisted treatment’ is a big mistake.  He says that in his 19 years in the industry he has seen ‘thousands’ of people ‘experience sobriety’.   I’ll cut and paste his conclusion:
There is no coming into treatment and getting cured from the disease of Addiction. There is no pill or remedy that will magically make one better. Those looking for a quick fix to addiction and the treatment modality being used by the vast majority of treatment providers today, will be disappointed with the direction our field is taking when this newest solution doesn’t live up to its claims.
A word to the President of Clearbrook:   I’ve worked in the industry too.  But unlike you, I wasn’t satisfied to see a fraction of the patients who present, desperate for help, ‘experience sobriety’– especially when I read the obituaries of many of those patients months or years later.
The president says that ‘no pill or remedy will magically make one better.’  Addiction, for some reason, has always been considered immune to advances in modern medicine.  We all know that addiction is a disease, just like other psychiatric conditions including depression, bipolar, and schizophrenia.  Why is it that even as medicine makes extraordinary advances in all areas of illness, medications for addiction are considered to be ‘magic’?
Those of us who treat patients with medications, particularly buprenorphine, realize that addiction doesn’t respond to ‘magic’.  But I see a lot more hocus pocus in abstinence-based residential treatment programs than in the medications approved by the FDA for treating addiction.  Residential programs charge tens of thousands of dollars for a variety of treatments–  experiential therapy, art therapy, psychodrama, music therapy, etc.– that have no evidence of efficacy for treating opioid dependence.  Abstinence-based treatments have managed to deflect criticism from their failed treatment models by blaming patients for ‘not wanting recovery enough’.
Buprenorphine finally allows the disease of addiction to be treated like other diseases– by doctors and other health professionals, based on sound scientific and pharmacological principles.   Abstinence-based treatment programs have tried to tarnish medication-assisted treatments, but people are finally recognizing the obvious– that traditional, step-based treatments rarely work.
And that’s just not good enough when dealing with a potentially fatal illness like opioid dependence.

Opioid Analgesia Without Addiction

I don’t have pull with the addiction-related organizations out there. I’m never been a joiner, and I tend to notice the problems caused by medical societies over the good things that they supposedly accomplish. For example PROP, or ‘Physicians for Responsible Opioid Prescribing’, have a specific mission. Once a group has a mission, any considerations about individual patients go out the window. PROP has propagated the message that opioids are NEVER beneficial for patients with chronic pain.

Legislators with no knowledge of clinical medicine hear that message, and respond by passing draconian laws that interfere with any considerations of individual patients. I would guess that the people of PROP pat themselves on the back for encouraging laws that remove physician autonomy. I’m sure they figure that they are smarter than all the family practice docs out there. But in reality, they are only destroying the control of doctors over patient care, and handing that care over to politicians. Way to go, PROP.

In the same way, the societies that hold meetings about meetings, that elect Secretaries who become Vice Presidents who become Presidents, get to publish the articles that describe clinical protocols. The doc who spends every day talking with patients has no access to these sources, and little ability to influence those protocols. Sometimes the societies and organizations get things right… and sometimes they get things wrong. The latter is the case with post-op pain control in patients on buprenorphine products.

I’ve written about this before, as regular readers know. Over the past 8 years I’ve had dozens, if not hundreds, of patients on buprenorphine undergo surgery. The surgeries include coronary bypass, thoracotomy, rotator cuff repair, C-section, nephrectomy, total knee or hip replacement… and a host of minor surgeries with scopes and lasers. I’ve treated these patients in a number of ways, in part because hospitals that provide emergency care have different ways of dealing with post-op analgesia. I rarely have control over what they do acutely– but I almost-always take over pain control when patients are discharged.

In the past few months there have been several ‘articles’ stating that the best way to handle surgery, in people on buprenorphine products, is to stop the buprenorphine before surgery, and treat pain using opioid agonists. This opinion is not supported by any data. It is someone’s opinion– usually someone who has a title, i.e. someone who spends at least some of his/her time in society meetings. That time is removed from the amount of time that could be spent treating and speaking with patients. Frankly, the ‘higher’ a doctor is in society circles, the less time they spend in patient care. That comment will anger the docs who it applies to. I can hear them now– saying I’m only full of ‘sour grapes’. But maybe those same docs should look in the mirror, and wonder how they ended up as ‘President’ of a society.

I’ve used the approach claimed as best practice in the society journals– i.e stopping buprenorphine before surgery– and the same thing always happens. Tolerance to opioid agonists rises very rapidly in the post-op period. Patients are discharged on huge doses of opioid agonists. And at some point, agonists must be discontinued for 24 hours to allow for re-induction with buprenorphine agents. I’ve had several recent patients go through this exact process– and my frustration motivates this post. One guy shot himself in the femur, and the bullet also passed through his lower leg. He needed fasciotomy to avoid losing the leg. His Suboxone was discontinued at admission, and ten days later he was discharged on 30 mg of oxycodone every 2-3 hours– i.e. over 200 mg per day. The other person was in a serious car accident, and had multiple fractures— femur, pelvis, ribs, wrist– as well as internal injuries. After 3 weeks he was released on over 300 mg of oxycodone per day!

On the other hand, I’ve had many patients go through the surgeries listed earlier while maintained on buprenorphine, 4-8 mg per day. In ALL cases, they had excellent analgesia with lower doses of oxycodone than in the people who stopped buprenorphine. Most patients did well on 15 mg of oxycodone every 3-4 hours– a max of 120 mg of oxycodone per day. In a few cases– i.e. in the most painful operations, in the most sensitive patients– I had to use 30 mg of oxycodone every 4 hours.

The most amazing thing about the combination of buprenorphine and opioid agonists is the absence of tolerance to agonists, when buprenorphine is present. I’ve had patients with recurrent injuries that required repeated surgeries, including a woman who tore her rotator cuff and the surgical repair THREE times over three months. She took the same amount of opioid agonist for three months, with no noticeable decrease in efficacy. After the final operation, after three months on significant amounts of opioid agonist, she simply stopped the agonist and resumed her full dose (16 mg) of buprenorphine. She had no withdrawal, and not other complications. She simply stopped the agonist and resumed buprenorphine treatment.

I’ve come to realize that buprenorphine effectively ‘anchors’ tolerance when patients take opioid agonists, as long as the buprenorphine is continued. Patients always say the same thing: that the pain was reduced by the agonist, but that it didn’t ‘feel’ like the agonist they used to take. In fact, patients who could never control pain pills found that they COULD control agonists if they stayed on buprenorphine.

A couple years ago I presented these findings at an annual meeting of ASAM. The slides can be found here. I believe that some day, combinations of buprenorphine and opioid agonists will be the standard approach to pain treatment. The combination allows for opioid analgesia without tolerance, without euphoria, and with little or no risk of addiction. If THAT doesn’t piqué your interest, you have no business reading about opioid dependence!

I picture combinations of buprenorphine and fentanyl… especially since both are now FDA-approved as transdermal patches. Or perhaps a combination of fentanyl lozenges and sublingual buprenorphine. The possibilities are endless. Throughout history, the miracle of opioid analgesia has been cursed by the attachment to tolerance, dependence, and addiction.

Imagine if that curse was lifted from opioid analgesia. Can you even dare to imagine that world? I’m telling you… it is closer than you think—- and there for the taking.

Menzies Gets it Wrong

In Opioid Addiction Treatment Should Not Last a Lifetime, Percy Menzies resurrects old theories  to tarnish buprenorphine-based addiction treatment.  Methadone maintenance withstood similar attacks over the decades, and remains the gold standard for the most important aspect of treating opioid dependence:  preventing death.
Menzies begins by claiming that a number of ideas that never had the support of modern medicine are somehow similar to buprenorphine treatment.  Replacing beer with benzodiazepines?  Replacing morphine with alcohol?  Replacing opioids with cocaine?  Where, exactly, did these programs exist, that Menzies claims were precursors for methadone maintenance?
Buprenorphine has unique properties as a partial agonist that allows for effects far beyond ‘replacement’.  The ceiling effect of the drug effectively eliminates the desire to use opioids.  Seeing buprenorphine only as ‘replacement therapy’ misses the point, and ignores the unique pharmacology of the medication.
Highly-regulated clinics dispense methadone for addiction treatment., and other physicians prescribe methadone for chronic pain.  Menzies claims ‘it is an axiom of medicine that drugs with an addiction potential are inappropriate for the treatment of chronic conditions.’  For that reason, he claims, methadone treatment is ‘out of the ambit of mainstream medicine.’ The 250,000-plus US patients who benefit from methadone treatment would be amused by his reasoning.    I suspect that the thousands of patients who experience a lifetime of chronic pain—including veterans with crushed spines and traumatic amputations—would likely NOT be amused by his suggestion that ‘opioids… were never intended to be prescribed forever.’   Those of us who treat chronic pain take our patients as they come—often with addictions and other psychiatric baggage.  Pain doesn’t stop from the presence of addiction, neither does the right for some measure of relief from that pain.
Menzies cites the old stories about Vietnam veterans who returned to the US and gave up heroin, as evidence that prolonged treatment for opioid dependence is unnecessary for current addicts.   But there is no similarity between the two samples in his comparison!  US Servicemen forced into a jungle to engage in lethal combat use heroin for different reasons than do teenagers attending high school.   Beyond the different reasons for using, after returning home, soldiers associated heroin with danger and death!  Of course they were able to stop using!  And that has to do with current addicts… how?
Teens in the US have no mainland to take them back.  Their addiction began in their parents’ basement, and without valid treatment, too often ends in the same place.
Menzies refers to buprenorphine treatment as ‘a conundrum’ that has not had any effect on deaths from opioid dependence—a claim impossible to support without an alternative universe and a time machine.  He claims that buprenorphine treatment is unsafe and plagued by diversion.  In reality, most ‘diversion’ consists of self-treatment by addicts who are unable to find a physician able to take new patients under the Federal cap.  In the worst cases, some addicts keep a tablet of buprenorphine in their pockets to prevent the worst of the withdrawal symptoms if heroin is not available.  But even in these cases, buprenorphine inadvertently treats addicts who take the medication, preventing euphoria from heroin for up to several days and more importantly, preventing death from overdose.
Just look at the numbers.  In the past ten years, about 35,000 people have died from overdose each year in the US with no buprenorphine in their bloodstream.  How many people died WITH buprenorphine in their bloodstream?  About 40.  Even in those cases, buprenorphine was almost never the cause of death.  In fact, in many of those 40 cases, the person’s life would have been saved if MORE buprenorphine had been in the bloodstream because buprenorphine blocks the respiratory depression caused by opioid agonists.
Naltrexone is a pure opioid blocker that some favor for addiction treatment because it has no abuse potential.  Naltrexone compliance is very low when the medication is not injected, and naltrexone injections cost well over $1000 per month.   Naltrexone may have some utility in the case of drug courts, where monthly injections are a required condition of probation.  But even in those circumstances, the success of naltrexone likely benefits the most from another fact about the drug, i.e. that the deaths from naltrexone treatment are hidden on the back end.  Fans of naltrexone focus, optimistically, on its ability to block heroin up to a certain dose, up to a certain length of time after taking the medication.  But Australian studies of naltrexone show death rates ten times higher than with methadone when the drug is discontinued, when patients have been discharged from treatment, and short-term treatment professionals have shifted their attention to the next group of desperate but misguided patients.
The physicians who treat addiction with buprenorphine, on the other hand, follow their patients long term because they see, first-hand, the long-term nature of addiction.  Menzies’ claim that ‘the longer you take it, the harder it is to stop’ has no basis in the science of buprenorphine, or in clinical practice.  Patients often get to a point—after several years—when they are ready to discontinue buprenorphine.  And while buprenorphine has discontinuation symptoms, the severity of those symptoms is less than stopping agonists—and unrelated to the duration of taking buprenorphine.   Until that point in time, buprenorphine effectively interrupts the natural progression of the addiction to misery and death.
The physicians who prescribe buprenorphine and the practitioners at methadone clinics are the only addiction professionals who witness the true, long-term nature of opioid dependence. In contrast, too many addiction practitioners see only the front end of addiction, discharging patients after weeks or months, considering them ‘cured’…  and somehow missing the familiar names in the obituary columns months or years later.