Brain Surgery or Suboxone?

Originally posted 12/31/2012
Today I read about the stereotactic brain surgery used to treat opioid dependence in China over the past ten years.   The procedure is relatively straightforward; the patient’s skull is clamped in place while small holes are drilled, guided by computerized, 3-dimensional maps of the brain.  Probes are inserted deeply through brain tissue to the nucleus accumbens, where electric current destroys varying amounts of brain tissue.   Patients are awake and talking during the procedure, so that surgeons know if the probes are too close to brain regions that control speech or other functions.
A large number of ablations for the treatment of addiction were performed in China about ten years ago.  The rapid growth in popularity of the technique, before full knowledge of the risks and long-term effects, led to a ban on the procedures by the Chinese Ministry of Health in 2004.  Still, ablations were performed as part of research studies, with over 1000 people treated by ablation since 2004.
The scientific community outside of China overwhelmingly condemns the technique, and medical journals are pressured to withhold publication of ablation studies.  Human rights advocates claim that such experiments are performed on people who are not fully aware of the risks, or who are pressured to participate in the studies to avoid harsh punishments for drug offenses.  The veracity of the results from ablation studies has also been challenged. Ablation treatment of opioid dependence is in the news lately because of a recent paper describing the five-year follow-up of opioid addicts treated by the procedure.
Neuroscientists distinguish between DBS (deep brain stimulation by electric current) vs. procedures where brain tissue is destroyed.  I’m surprised by the intensity of the distinction, given the similarity of the procedures.  In both cases long probes are passed through brain tissue, risking hemorrhage, stroke, or seizures.  For DBS, wires are left behind and connected to power-packs that release different patterns of electrical current.  In the ablation studies, small areas of tissue at the end of the probes are destroyed, and the probes removed.  If there is a future for addiction treatment using stereotactic brain surgery, DBS is likely to become the procedure of choice, given the preference by the scientific community for non-permanent interventions.
The recent follow-up study found that about half of those treated by ablation of the nucleus accumbens were sober from heroin after five years.  But about a quarter of the patients who had ablation were found to have long-term neuropsychiatric side effects including memory loss, loss of motivation, mood disturbances, and loss of sexual desire.
I found the studies and results interesting in a number of ways.  Throughout the latest paper, the authors point out the severe consequences of opioid dependence and the lack of effective treatment options.  Opioid dependence is noted to be a permanent, progressive, fatal condition, with a prognosis poor enough to warrant drilling holes in the skull and destroying brain tissue.  Even as record numbers of young people die from overdose, I don’t have the sense that US citizens recognize the severity of the problem.
I find it interesting how strongly society’s perceptions influence what are considered appropriate or inappropriate brain procedures. SingularityHub points out the popularity of frontal lobotomies after 1949, when António Egas Moniz won the Nobel Prize for Physiology or Medicine for inventing the procedure.  Over 20,000 lobotomies were performed in the US by 1951, but the procedure was discredited and eventually banned in the US.  Who says the Nobel Prize people always get it right?
The recent study’s introduction points out that the most stringent addiction treatments in China– compulsory detoxification, mandatory labor, education, and skills training for as long as 3 years– have one-year abstinence rate of 44% and 3-year abstinence rates of only 15%.
Drilling holes deep into the brain to destroy the pleasure centers might bring the sobriety rates up to 50%, but at the cost of memory, motivation, and sex drive.
And then there is buprenorphine (brand name Suboxone), a medication that has success rates over 50%, with fewer risks or side effects than drilling holes in the brain– but that remains limited by US law.
Which approach would you prefer for your son or daughter?

Dear CEO

This is a repost of an article from 10/2/2012
I’m going to start by paraphrasing John Le Carre’s comments in his book The Constant Gardener: “Nobody in the letter below is based upon an actual person or outfit in the real world. But I can tell you this; as my knowledge of the pharmaceutical world increases, I come to realize that, by comparison with the reality, my letter is as tame as a holiday postcard.”
Dear Fictional CEO,
I have a question about your company.
Over a decade ago, you took an action unprecedented among cleaning-supply companies by gaining FDA approval to market a combination of two generic compounds. I do not know if you thought that compound N was necessary to gain approval of the medication, or if someone at your company had the prescience to know how things would eventually play out in your marketing department.  Kudos if it was the latter.
You now know, I suspect, that compound N is irrelevant to the use of Product S to treat opioid dependence. You are aware that many people, even prescribers, often confuse the actions of compound B and compound N, mistakenly thinking that compound N does something to reduce cravings or improve the safety of Product S. It isn’t your fault that people get it wrong. True, you spent only fractions of your huge profits on educating psychiatrists, surgeons, ER doctors, and nurses. But just because their ignorance plays into your marketing strategy does not prove that you WANTED them to remain ignorant. Perhaps you figured that education about your product was the responsibility of someone else.
Speaking of education, 12 years ago you fooled the FDA by showing cases of several French people who died from improperly using compound B, and used the cases to justify adding compound N to your product. Never mind that those deaths would not have been prevented by compound N, a low-affinity, short half-life opioid antagonist with little ability to out-compete compound B at the mu receptor— the idea– that the compound N would precipitate withdrawal if Product S is injected, yet do nothing when taken properly, was pretty cool– especially compared to the drudgery of making rat poison!
Maybe the FDA needs more cynics, because they didn’t notice that adding compound N was an effective way to turn a cheap, generic compound– B– into Product S, a cash cow for your company. Even if they had noticed, would anyone really expect you to save opioid addicts WITHOUT the huge profits? I don’t think so!
So I cannot blame you for how things have played out up to now.  Almost all is fair, in the world of business.  And I understand how horrible it must have been over the last five years, as generics threatened to kill off that cash cow.  You needed a strategy to protect Product S.  That unfair Patent Office only gave you a few (well, 8 or 10) years to rake in profits, before going back to the unglamorous, less-profitable world of cleaning supplies.  No limos for those guys!  Time flies when you’re making money… and next thing you know ANYONE can make Product S!  How uncool is that– suddenly you would have to live on only typical profit margins, or even invent a new product like other companies have to do to keep the cash flowing.  Bummer.
I get a bit confused at this point.  Let me get this straight…  after making tons of money off Product S, knowing that someone ELSE is going to make their own cheaper version of Product S, you decide to kill off Product S for EVERYONE?  You make Product S-F, and go back to the FDA (heck, they covered your back once!), and say that the product that made us ALL THAT MONEY is a BAD PRODUCT.   And you just figure this out now, at the same time your patent expired—just when other people are able to make Product S.  Am I getting it right?
Correct me if I’m wrong, but it looks like you somehow got a whole bunch of people—insurance companies, state Medicaid agencies, etc— to require the use of  ONLY Product S-F.  You told everyone that Product S (that you were still selling tons of) wasn’t as ‘safe’ as Product S-F, so they should only use S-F.  It somehow worked; you got close to 70% of those people to require patients to take Product S-F… even though your claims about safety were pretty silly.  Never mind—they actually believed you!
I admit that I do not understand why those insurers and Medicaid agencies were so short-sighted.  Surely they knew what was going on—that you were only trying to destroy Product S for everyone, and take away a market for generic competitors.  Didn’t they recognize that whatever discounts you bribed them with, would be peanuts compared to the savings they would eventually get from generics?  How did you pull it off?
The icing on the cake… I read last week that you are PULLING Product S and ONLY selling Product S-F.  You hired a company (YOU hired THEM!) to show that Product S was unsafe, to justify pulling it.  Again, you did this just as other companies were in a place to make Product S themselves… at a much lower cost than YOUR product.  Your people are saying that 4 kids died from Product-S over the past 5 years.  They didn’t mention that Product-S saved tens of thousands of teenagers over the same time, and they didn’t say that the companies about to make it so much cheaper would save tens of thousands more.  I guess that is a tough calculation— I mean, who is worth more, 4 young kids or 20,000 teenagers?
Most people would be satisfied with the sequence of events and call it a day.  In fact, most people would feel a bit shameful, knowing that they just completed a strategy that 1. Mislead medical science into buying your product for ten years, when plain old compound B would have done the same thing all that time—at a fraction of the cost; 2. Prevented effective education about compound B that could have saved many thousands of those who died from overdose over the past ten years; 3. Bypassed the usual conditions in the world of pharma where a company can make billions of dollars for years, but eventually allows generics to make the product, so that poor people and people without insurance get a chance to save THEIR lives too; and 4. Tricked insurers and agencies into forcing patients to use not the cheaper drug, like they usually do, but your EXPENSIVE drug—causing those same groups to limit life-saving use of the drug to only a year or two, since they can’t afford to cover your expensive one indefinitely.
You’ve accomplished quite a bit.  But I just read that you aren’t resting on wilted laurels.  Even though insurers and agencies are forcing people to buy your expensive product, there are people with no insurance and no Medicaid who have the gall to buy a generic form of compound B.  Sales of the generic are only a fraction of your sales, and some reasonable people would say that even poor people have the right to take life-saving medication, just like the rest of us.   But you are filing a ‘citizens’ petition’ with the FDA to have that medication—the affordable one that is saving all those poor people—taken OFF THE MARKET.
And now my question:
Are you SERIOUS?

How long are you going to take that stuff?

I have produced a few educational items, and I sell themt priced at a small fraction of the street cost of one tablet of oxycodone.  All proceeds go toward the support of this web site, the forum, and other educational efforts.  The most popular item is the e-book called ‘User’s Guide to Buprenorphine.’  You can get a sneak peak at the inside of the book at Amazon.  I receive good feedback about the e-book but the most ‘successful’ recording has been the one entitled ‘How long are you going to take that stuff.’  The recording is designed for parents, spouses, or children of opiate addicts who take buprenorphine;  especialy for those family members who don’t quite ‘get it,’ who ask the title question every week or so.
I have had several patients tell me that their loved ones changed their tone after listening to the recording, in which I explain the basics of opiate dependence and tell the listener why it is often in a person’s best interest to stay on buprenorphine for an extended period of time.  I have also received comments in e-mails from people who had similar success with the recordings.  If you have a close friend or loved one who means well, but who just doesn’t understand the point of buprenorphine, consider turning him/her on to the recording.  Check out the other recordings as well, and thanks in advance for your support.
JJ

Buprenorphine and the Dynamic Nature of Character Defects

What follows is a lightly-edited version of one of my posts from a couple years ago.  I still think that this is a good model for understanding the actions of buprenorphine.

Buprenorphine and the Dynamic Nature of Character Defects

‘Suboxone’ and ‘Subutex’ are the trade names for medications that contain buprenorphine, a substance used to treat addiction to pain medications and/or heroin.  Buprenorphine treatment for opiate dependence has been an option in the US since 2003.  Other treatment approaches for opiate dependence have been used for decades but have had limited success.  With a little imagination, treatment approaches can be placed on a continuum depending on the degree to which the treatment demands changes in the personality and behavior of the addict.  Methadone maintenance is often described as a means of ‘harm reduction’ by preventing the behaviors related to the obsession for opiates or by reducing intravenous use of heroin or other substances.  At the other end of the treatment continuum there are the step-based and other Recovery programs.  One limitation of programs that demand personality change is that such change is difficult and rare, and usually only occurs after a significant amount of despair has been experienced by the addict.  Opiate dependence differs from other addictions in the lethality of overdose, and the fatality rate of even early abuse of that class of substances.  Opiate addicts are at significant risk of dying from their addiction before enough desperation has accumulated to motivate personality change.  A second limitation is the high rate of relapse that occurs even after sustained Recovery.  If a ‘changed’ addict stops actively participating in the program that induced the changes, the personality of the addict tends to revert back to the personality that was present during active drug use.
I initially had mixed feelings about buprenorphine treatment of opiate dependence, my opinion likely influenced by my own experiences as an addict in traditional recovery.  But my opinion has changed over the past four years from what I have seen and heard while treating over 400 patients with buprenorphine.  But while buprenorphine has opened a new frontier of treatment for opiate addiction, arguments over the use of buprenorphine often split the recovering and treatment communities along opposing battle lines.  The arguments are fueled by petty notions of ‘whose recovery is more authentic’, and miss the important point that buprenorphine offers huge benefits for the health and lives of opiate addicts.
A unique medication
For clarification, the active ingredient in Suboxone is buprenorphine, a partial agonist at the mu opiate receptor. Suboxone contains naloxone to prevent intravenous use; another form of the medication, Subutex, consists of buprenorphine without naloxone.  The unique effects of buprenorphine can be attributed to the drug’s unique molecular properties.  First, the partial agonist effect at the receptor level results in a ‘ceiling effect’ to dosing after about 4 mg, so that increased dosing does not result in increased opiate effect beyond that dose.  Second, the high binding affinity and partial agonist effect cause the elimination of drug cravings, dispelling the destructive obsession with use that destroys the personality of the user.  Third, the high protein binding and long half-life of buprenorphine allows once per day dosing, allowing the addict to break the conditioned pattern of withdrawal (stimulus)-use (response)- relief (reward) which is the backbone of addictive behavior.  Fourth, the partial agonist effect and long half life cause rapid tolerance to the drug, allowing the patient to feel ‘normal’ within a few days of starting treatment.  Finally, the withdrawal from buprenorphine provides a disincentive to stop taking the drug, and so the drug is always there to assure the person that any attempt to get high would be futile, dispelling any lingering thoughts about using an opiate.
Different treatment approaches
At the present time there are significant differences between the treatment approaches of those who use buprenorphine versus those who use a non-medicated 12-step-based approach.  People who stay sober with the help of AA, NA, or CA, as well as those who treat by this approach tend to look down on patients taking buprenorphine as having an ’inferior’ form of recovery, or no recovery at all.  This leaves buprenorphine patients to go to Narcotics Anonymous and hide their use of buprenorphine.  On one hand, good boundaries include the right to keeping one’s private medical information so one’s self.  But on the other hand, a general recovery principle is that ’secrets keep us sick’, and hiding the use of buprenorphine is a bit at odds with the idea of ’rigorous honesty’. People new to recovery also struggle with low self esteem before they learn to overcome the shame society places on ‘drug addicts’;  they are not in a good position to deal with even more shame coming from other addicts themselves!
An ideal program will combine the benefits of 12-step programs with the benefits of the use of buprenorphine.  The time for such an approach is at hand, as it is likely that more and more medications will be brought forward for treatment of addiction now that Suboxone has proved profitable.  If we already had excellent treatments for opiate addiction there would be less need for the two treatment approaches to learn to live with each other.  But the sad fact is that opiate addiction remains stubbornly difficult to treat by traditional methods.  Success rates for long-term sobriety are lower for opiates than for other substances.  This may be because the ‘high’ from opiate use is different from the effects of other substances—users of cocaine, methamphetamine, and alcohol take the substances to feel up, loose, or energetic—ready to go out and take on the town.  The ‘high’ of opiate use feels content and ‘normal’— users feel at home, as if they are getting back a part of themselves that was always missing. The experience of using rapidly becomes a part of who the person IS, rather than something the patient DOES.  The term ‘denial’ fits nobody better than the active opiate user, particularly when seen as the mnemonic:  Don’t Even Notice I Am Lying.
The challenges for practitioners lie at the juncture between traditional recovery and the use of medication, in finding ways to bring the recovering community together to use all available tools in the struggle against active opiate addiction.
Drug obsession and character defects
Buprenorphine has given us a new paradigm for treatment which I refer to as the ‘remission model’.  This model takes into account that addiction is a dynamic process— far more dynamic than previously assumed.  To explain, the traditional view from recovery circles is that the addict has a number of character defects that were either present before the addiction started, or that grew out of addictive behavior over time.  Opiate addicts have a number of such ‘defects.’  The dishonesty that occurs during active opiate addiction, for example, far surpasses similar defects from other substances, in my opinion.  Other defects are common to all substance users; the addict represses awareness of his/her trapped condition and creates an artificial ‘self’ that comes off as cocky and self-assured, when deep inside the addict is frightened and lonely.  The obsession with using takes more and more energy and time, pushing aside interests in family, self-care, and career.  The addict becomes more and more self-centered, and the opiate addict often becomes very ‘somatic’, convinced that every uncomfortable feeling is an unbearable component of withdrawal.  The opiate addict becomes obsessed with comfort, avoiding activities that cause one to perspire or exert one’s self.  The active addict learns to blame others for his/her own misery, and eventually their irritability results in loss of jobs and relationships.
The traditional view holds that these character defects do not simply go away when the addict stops using.  People in AA know that simply remaining sober will cause a ‘dry drunk’—a nondrinker with all of the alcoholic character defects– when there is no active recovery program in place.  I had such an expectation when I first began treating opiate addicts with buprenorphine—that without involvement in a 12-step group the person would remain just as miserable and dishonest as the active user.  I realize now that I was making the assumption that character defects were relatively static—that they develop slowly over time, and so could only be removed through a great deal of time and hard work.  The most surprising part of my experience in treating people with buprenorphine has been that the defects in fact are not ‘static’, but rather they are quite dynamic.  I have come to believe that the difference between buprenorphine treatment and a patient in a ‘dry drunk’ is that the buprenorphine-treated patient has been freed from the obsession to use.  A patient in a ‘dry drunk’ is not drinking, but in the absence of a recovery program they continue to suffer the conscious and unconscious obsession with drinking.   People in AA will often say that it isn’t the alcohol that is the problem; it is the ‘ism’ that causes the damage.  Such is the case with opiates as well—the opiate is not the issue, but rather it is the obsession with opiates that causes the misery and despair.  With this in mind, I now view character defects as features that develop in response to the obsession to use a substance.  When the obsession is removed the character defects will go way, whether slowly, through working the 12 steps, or rapidly, by the remission of addiction with buprenorphine.
In traditional step-based treatment the addict is in a constant battle with the obsession to use. Some addicts will have rapid relief from their obsession when they suddenly experience a ‘shift of thinking’ that allows them to see their powerlessness with their drug of choice.   For other addicts the new thought requires a great deal of addition-induced misery before their mind opens in response to a ‘rock bottom’. But whether fast or slow, the shift of thinking is effective because the new thought approaches addiction where it lives—in the brain’s limbic system.  The ineffectiveness of higher-order thinking has been proven by addicts many times over, as they make promises over pictures of their loved ones or try to summon the will power to stay clean.  While these approaches almost always fail, the addict will find success in surrender and recognition of the futility of the struggle.  The successful addict will view the substance with fear—a primitive emotion from the old brain.  When the substance is viewed as a poison that will always lead to misery and death, the obsession to use will be lifted.  Unfortunately it is man’s nature to strive for power, and over time the recognition of powerlessness will fade.  For that reason, addicts must continue to attend meetings where newcomers arrive with stories of misery and pain, which reinforce and remind addicts of their powerlessness.
The dynamic nature of personality
My experiences with buprenorphine have challenged my old perceptions, and led me to believe that the character defects of addiction are much more dynamic.  Buprenorphine removes the obsession to use almost immediately.  The addict does not then enter into a ‘dry drunk’, but instead the absence of the obsession to use allows the return of positive character traits that had been pushed aside.  The elimination of negative character traits does not always require rigorous step work— in many cases the negative traits simply disappear as the obsession to use is relieved.  I base this opinion on my experiences with scores of buprenorphine patients, and more convincingly with the spouses, parents, and children of buprenorphine patients.  I have seen multiple instances of improved communication and new-found humility.  I have heard families talk about ‘having dad back’, and husbands talk about getting back the women they married.  I sometimes miss my old days as an anesthesiologist placing labor epidurals, as the patients were so grateful—and so I am happy to have found buprenorphine treatment, for it is one of the rare areas in psychiatry where patients quickly get better and express gratitude for their care.
A natural question is why character defects would simply disappear when the obsession to use is lifted?  Why wouldn’t it require a great deal of work?  The answer, I believe, is because the character defects are not the natural personality state of the addict, but rather are traits that are produced by the obsession, and dynamically maintained by the obsession.
Combining buprenorphine treatment and traditional recovery
Once the dynamic relationship between use obsession and character defects is understood, the proper relationship between buprenorphine and traditional recovery becomes clear.  Should people taking buprenorphine attend NA or AA?  Yes, if they want to.  A 12-step program has much to offer an addict, or anyone for that matter.  But I see little use in forced or coerced attendance at meetings.  The recovery message requires a level of acceptance that comes about during desperate times, and people on buprenorphine do not feel desperate.  In fact, people on buprenorphine often report that ‘they feel normal for the first time in their lives’.  A person in this state of mind is not going to do the difficult personal inventories of AA unless otherwise motivated by his/her own internal desire to change.
The role of ‘desperation’ should be addressed at this time:  In traditional treatment desperation is the most important prerequisite to making progress, as it takes the desperation of being at ‘rock bottom’ to open the mind to see one’s  powerlessness. But when recovery from addiction is viewed through the remission model, the lack of desperation is a good thing, as it allows the reinstatement of the addict’s own positive character.  Such a view is consistent with the ‘hierarchy of needs’ put forward by Abraham Maslow in 1943; there can be little interest in higher order traits when one is fighting for one’s life.
Other Questions (and answers):
-Should buprenorphine patients be in a recovery group?
I have reservations about forced attendance, as I question the value of any therapy where the patient is not an eager and voluntary participant.  At the same time, there clearly is much to be gained from the sense of support that a good group can provide.  Groups also ‘show’ the addict that he/she is not as unique as he thought, and that his unhealthy way of visualizing his place in the world is a trait common to other addicts.  Some addicts will learn the patterns of addictive thinking and become better equipped to handle their own addictive thoughts.
-What is the value of the 4th through 6th steps of a 12-step program, where the addict specifically addresses his/her character defects and asks for their removal by a higher power?  Are these steps critical to the resolution of character defects?
These steps are necessary for addicts in ‘sober recovery’, as the obsession to use will come and go to varying degrees over time depending on the individual and his/her stress level.  But for a person taking buprenorphine I see the steps as valuable, but not essential.
-Where does methadone fit in?
Methadone is an opiate agonist that has a long half-life in brain tissue.  This long half-life promotes a relatively constant state of opiate stimulation, reducing opiate cravings between doses.  But while the ceiling effect of the partial agonist buprenorphine results in a stable, unchanging tolerance to the medication, methadone has no such ceiling, and tolerance will always increase with increasing dose of methadone.  This constant increase in tolerance erodes the ability of methadone to satiate cravings for opiates.  A newly-raised dosage will prevent cravings temporarily, but as tolerance inevitably rises, cravings will return.  With cravings comes the obsession to use and the associated character defects.  This explains one difference in the subjective experiences of addicts maintained on buprenorphine versus methadone.  Methadone maintenance is also usually experienced as more sedating than the effects from buprenorphine.  There is a valuable role for methadone to play as we try to prevent deaths from opiate dependence, but I see the mechanisms of action of methadone and buprenorphine to be profoundly different.  Methadone is appropriately described as a ‘maintenance agent,’ but I see a more appropriate term for the actions of buprenorphine, as a ‘remission agent.’  This term accounts for the effects of buprenorphine on the obsession for opiates, and the ability of the medication to allow for dissolution of the character defects caused by active addiction.
The downside of buprenorphine
Practitioners in traditional AODA treatment programs will see buprenorphine as at best a mixed blessing.  Desperation is often required to open the addict’s mind to change, and desperation is harder to achieve when an addict has the option to leave treatment and find a practitioner who will prescribe buprenorphine.  Buprenorphine is sometimes used ‘on the street’ by addicts who want to take time off from addiction without committing to long term sobriety.  Buprenorphine itself can be abused for short periods of time, until tolerance develops to the drug.  Snorting buprenorphine reportedly results in a faster time of onset, without allowing the absorption of the naloxone that prevents intravenous use.  Finally, the remission model of buprenorphine use implies long term use of the drug.  Chronic use of any opiate, including buprenorphine, has the potential for negative effects on testosterone levels and sexual function, and the use of buprenorphine is complicated when surgery is necessary.  Short- or moderate-term use of buprenorphine raises a host of additional questions, including how to convert from drug-induced remission, without desperation, to sober recovery, which often requires desperation.
The beginning of the future
Time will tell whether or not buprenorphine will work with traditional recovery, or whether there will continue to be two distinct options that are in some ways at odds with each other.  The good news is that treatment of opiate addiction has proven to be profitable for at least one pharmaceutical company, and such success will surely invite a great deal of research into addiction treatment.  At one time we had two or three treatment options for hypertension, including a drug called reserpine that would never be used for similar indications today.  Some day we will likely look back on buprenorphine as the beginning of new age of addiction treatment.  But for now, the treatment community would be best served by recognizing each other’s strengths, rather than pointing out each other’s weaknesses.

Does Reckitt-Benckiser have blood on their hands?

Regular readers of this blog know that I am a big fan of buprenorphine treatment of opiate dependence. I used to spend hours arguing with people over whether or not buprenorphine represents “a drug for a drug”, before eventually deciding that those who must be talked into buprenorphine treatment are poor candidates for buprenorphine treatment. I am now less motivated to engage in such discussions, but for those who are interested, my arguments are scattered throughout the archives of the medhelp.org addiction board, the commentary section of my YouTube videos, and in earlier posts to this blog.

The motivation for this current post stems from two recent incidents. The first was the reaction of a group of physicians at a dinner several nights ago, when I was speaking about a different medication.  When I mentioned “Suboxone” I heard hissing and other negative reactions from the assembled group of doctors and nurse prescribers. I am the medical director of a residential AODA treatment center that does not use buprenorphine, so I am familiar with the attitudes of non-prescribing counselors– which tend to run against the use of buprenorphine. But the people at this particular dinner were not addiction counselors, but instead were general practitioners from central Wisconsin.  After hearing the negative reaction to mention of Suboxone, I deviated from the topic of my lecture to address their reaction.  But I soon realized that their opinions were as fixed as those that I ran up against during the arguments described in the first paragraph above. Despite my certainty that buprenorphine has saved thousands of lives, these practitioners see the medication as ‘villain’ rather than ‘hero.’  The assembled physicians see Suboxone as just one more drug of choice for opiate addicts.  More disturbing, they see docs who prescribe Suboxone on a par with physicians who overprescribe opiate agonists.

The second incident that motivated this post was the publication of an excellent group of articles in the Milwaukee Journal Sentinel about the epidemic of opiate dependence in Milwaukee County.  The article included statistics on the number of deaths by overdose, the vast majority consisting of respiratory arrest caused by opiates. The numbers included deaths from Suboxone taken in combination with other respiratory depressants by people who lacked significant tolerance to opiates. One of the most striking images from the series was a graphic with the deaths color-coded by year, by age of the deceased, and by type of drug. I am well aware of the epidemic of heroin and oxycodone addiction in my part of the country, but I was shocked at the sheer number and ubiquitous nature of deaths by overdose over the past six years.

I am grateful for the availability of buprenorphine in the form of Suboxone, but I wonder how different the current situation might be had a different pharmaceutical company been involved in the U.S. introduction of buprenorphine for the treatment of opiate dependence.  Reckitt-Benckiser is a consumer-goods company based in the UK. When Suboxone received FDA approval in 2003, the pharmaceutical wing of the company did not exist in any meaningful form. From the vantage of a Reckitt-Benckiser stockholder, the company did well. They grew their international pharmaceutical division at an amazing pace thanks to the growth of their one product. But when I take a broad look at the current state of affairs, I wonder where we would be if Reckitt-Benckiser had made the decision to team up with one of the bigger players in the pharmaceutical industry. Doing so would have cost them a portion of their profit from Suboxone. But had a company the size of Pfizer, for example, set their sales force on a mission to market Suboxone, I doubt we would have the now-recognized problems with diversion and low physician acceptance.  I am also confident that there would have been far fewer deaths by overdose of opiates over the past six years.

I am old enough to have experienced a number of launches of innovative medications, and I have always been one to quickly adopt the newest approaches and medications.  But my early use of Suboxone for treating opiate addiction was a unique experience in many ways.  I cannot think of any other medication that was (and still is!) as poorly understood by other physicians.  I blame some of the lack of knowledge about Suboxone on the stigma of mental health and addiction, but many psychiatric medications with far more complex mechanisms of action—e.g. atypical antipsychotics—have been introduced without the ignorance that is associated with Suboxone. Even in 2007, four years after the release of Suboxone, the vast majority of physicians had not heard of the medication.  Doctors have the bad habit of blaming unknown medications for unusual symptoms, so patients often called me after visiting ER’s or after doctor’s appointments where they were told that their symptoms were ‘from the Suboxone.’  One patient returned to the ER after I called the staff and persuaded them to take a second look, explaining that Suboxone does not generally cause fever or chest pain.  On his second visit they did a chest x-ray that showed his pneumonia and pleural effusion. I continue to see examples of the same phenomenon today.  The ignorance is not confined to emergency care– I frequently receive e-mails from new mothers with horror stories describing bizarre statements by neonatologists, OB nurses, and obstetricians.

A more common problem is described in the following e-mail:

I need help to figure out what’s wrong with me and what to ask my doctor to do about it.  I’ve just been through knee surgery to replace my ACL. It was pretty painful but the pain is a bit better now.  I’ve been on 16mg Sub for at least five years, although I recently tapered it to 8mgs. This past month I was down to maybe 4mgs/day when I found out my surgery was scheduled. Since I wanted my pain meds to work I immediately cut down even more and called my doc to see if he would give me some pain meds, because the surgeon refused to help me on the grounds that I was on Suboxone and he doesn’t understand it. Unfortunately my doc was out of town. Nobody would help me, everyone said *my* doc was the only one who could, and sorry he’s gone but oh well. This meant i had to get horribly sick the week of my surgery.

I got to see my doc the day before surgery, and he gave me some Norco which helped the w/d symptoms. Then after surgery I had Norco every four hours. Unfortunately after my release the surgeon AGAIN didn’t want anything to do with me. He wrote a script for Norco and told me I’d have to see my own doctor for anything else.  The Norco was barely keeping me out of w/d’s, never mind helping my pain. I was waking up every morning with my nose running, sneezing, and my legs dancing.  I got hold of my doc and he prescribed me Percocet, on the theory that those last longer. I’m permitted 1 or 2 of them every six hours, to a maximum of 6 per day. This seems to be utterly inadequate but I don’t know why my doctor would prescribe me something utterly inadequate unless he doesn’t think it’s inadequate.

Please, I need some solid experienced information so I can talk to my doctor. I am NOT trying to get a buzz here. All I asked of everyone prior to my surgery was “please treat me fairly given my tolerance level”. I wonder if my doc thinks that he is treating me fairly. But I’m clearly not getting sufficient dosage of opiate, and I don’t know how to present my case, especially over the telephone and via an intermediary nurse. (As yet, he won’t talk to me in person.) If I have to re-induct on the Suboxone and just deal with the pain then I’ll need some medicine to keep me asleep and not dancing until I’m sick enough, but I’m running scared asking for anything at all because everyone is treating me like a junkie.

Because of my blog, I receive messages like this one almost every day.  Most doctors have no idea what Suboxone is used for, and how the medication affects the use of other pain medications.  Patients are paying for that lack of knowledge with unnecessary pain and hardship.  Of course, they are just addicts, right?  (Readers should know my sarcasm by now!).

What should have happened?

To describe what could have happened I will use the example of another medication, Vyvanse, which is owned by a different British company called Shire pharmaceuticals. Vyvanse is a clear advance in ADD treatment.  Amphetamine was bound to lysine to create an inactive molecule, and the amphetamine is released at a measured pace after Vyvanse is absorbed into the circulation. Shire is a relatively small company, so they paired with the much larger company, GSK, to get the word out about Vyvanse. The result is that thousands of GSK representatives have provided information about Vyvanse to physicians, pharmacies, and hospitals. Had Reckitt-Benckiser done something similar, doctors everywhere would at minimum know the basics about buprenorphine.  And more, the treatment of addiction may have been brought into the mainstream where it belongs.

Reckitt-Benckiser eventually came out with a program called ‘Here to Help’ in order to provide education and by their description to improve compliance in addicts taking Suboxone. I was disappointed that the program began a number of years after Suboxone was released, not until the eve of the launch of a generic form of the medication. The timing left the impression that the program was more about maintaining brand loyalty than concern for addicts.  The program pales in comparison to the education and outreach provided by major US pharmaceutical companies when they release a new medication.  There are comments about the ‘Here to Help’ program associated with an earlier post on this blog, and I have received a number of similarly negative e-mails, including one just today that included these comments:

This “Here to Help” thing is really not very good. I actually signed up as a patient, and the girl was clueless. Every single issue I wanted to talk about, she told me to “Talk to your physician”.

“I feel scared that when I reduce my dose I’ll go nuts”
Talk to your physician

“I feel like I’ll never, ever feel ok again”
Talk to your physician

“I feel shaky before my morning dose”Talk to you….
You get the point.

When I asked how her course of treatment had gone, she told me that they don’t ever talk about their own personal recovery. Oh, well THAT’S helpful, huh?
There are other complaints about the manufacturer of Suboxone even by addicts who appreciate the medication. They resent the fact that so few non-addiction doctors have any knowledge about the medication. Many have fallen victim to what is described in the first e-mail above, and have suffered painful postoperative recoveries. There are complaints about the cost of the medication, once a pricey four dollars per pill and now up to twice that amount. The patient assistance program offered by Reckitt-Benckiser limits support to only 2-4 patients per practice, a limit that is not present for any other medication that I prescribe for psychiatric patients.

Many addict-patients have experienced poor treatment practices as a result of insufficient education for physician prescribers. Buprenorphine should be taken once per day in a dose range of 8-16 mg, but I have had new patients whose prior doctors prescribed much larger doses at much more frequent intervals. In my experience frequent dosing of buprenorphine is much less effective at extinguishing the psychological component of addiction. Instead of eliminating the relationship between ‘feelings’ and ‘using, such patients remain fixated on how they feel and take small doses of buprenorphine multiple times per day in response to imaginary withdrawal symptoms. Their physicians should have been taught about the value of less-frequent dosing by people who understand addiction. I was, by the way, a Reckitt-Benckiser/Suboxone ‘Treatment Advocate’ for several years. My experiences as an opiate addict for 16 years, my PhD in neurochemistry, my 3+ months of residential treatment and 6 years of formal aftercare, the hundreds of AA and NA meetings I have attended, the eight years I spent working in pain clinics as an anesthesiologist, my psychiatric training, my experience treating over 450 patients using buprenorphine, and four years as medical director of a large residential treatment center have all contributed to some level of insight into addiction and addiction treatment. I called and wrote to R-B multiple times asking that they use me to educate other physicians.  I was called upon to do so three times in four years.  As a comparison, I have been asked to educate groups of prescribers about Vyvanse over ten times in the last month or two alone.  Can you imagine the knowledge-state about buprenorphine had similar efforts been made by Reckitt-Benckiser over the past 6 years?!

I have blogged about my frustration trying to find an application for an educational grant from Reckitt-Benckiser that would allow me to apply for funding to expand my educational efforts on the internet. To compare, a visit to the Mallinckrodt Pharmaceuticals website quickly leads to the application for funding educational programs. There are, in fact, several significant web-based educational programs related to the prevention and treatment of addiction supported by unrestricted educational grants from Mallinckrodt, who manufactures methadone among its products. There is a similar online application for grant support on at least every pharmaceutical company that I visited this evening as I prepared to write this post. I have not found such an application for Reckitt-Benckiser. I even spent four years calling, writing, and e-mailing different branches of the company in search of an application for such support. My hopes were raised on two occasions when I was visited by regional sales directors and promised that information about grants would be provided. But after the visits nothing happened, and when I called in an attempt to follow up, I was back to square one, talking to people who claimed to have never heard about my prior contact with the company.

Does this all sound like ‘sour grapes’ over a snub by Reckitt-Benckiser?  Perhaps it is, to some extent. I am, after all, only human. But I am not only resentful. I spend a great deal of time reading and responding to e-mails from addicts, parents of addicts, spouses of addicts, and friends of addicts, and I am acutely aware of the suffering caused by opiate dependence. I’ve spoken to many people who were close to addicts who lost their lives to opiate dependence, and I have at least some sense of the suffering that they go through. And I have no doubt much of this suffering could—and should– have been avoided.

I fear that the actions of Reckitt-Benckiser, specifically their close-fisted release of a life-saving medication, have permanently endangered the successful use of buprenorphine for the treatment of opiate dependence. Once doctors start hissing, it becomes extremely difficult to create positive impressions of a medication or of a practice technique. I will, for what it is worth, continue with my own small efforts. And I hope that Reckitt-Benckiser will observe one of the principles that we teach addicts in recovery: Ask for help when help is needed.

How ironic if the success of a medication with the potential for a profoundly positive impact on addiction fell victim to addictive thinking by its own manufacturer!?!

Comments?  Write below, or join us at Subox Forum!

Urine drug testing for buprenorphine (in Suboxone)

I will introduce this topic by typing my response to a reader who asked whether buprenorphine, the active ingredient in Suboxone, shows up in urine drug tests.  More specifically he asked whether companies have the ability to test for buprenorphine.  I will end the post with a question… so please stick around to the end!

Suboxone drug test
Typical 10-panel urine dipstick test

There are tests out there—multi-panel dipstick tests– that react ‘positive’ to Suboxone in the opiate panel.  Or at least there used to be;  I used to see that reaction with a brand  of tests I no longer remember, that I used several years ago.  For the past couple years, every dipstick brand that I have purchased has responded ‘negative’ to buprenorphine (or naloxone for that matter) as an ‘opiate,’ and positive in the ‘buprenorphine’ column (i.e. so I know that the urine truly contained buprenorphine).  I pay more for dipstick tests that have a separate panel for buprenorphine, but yes, that test is available if a company wants it.  From what I have heard from owners of companies or from people privy to the inner workings of companies, some businesses will do a dipstick first, and then send only positive samples to a lab for more formal testing in case a firing is challenged in court.  They do the dipstick first because it is MUCH cheaper-  $5 for a dipstick test, and several hundred for a laboratory test for several substances.  It costs more for each test at the lab, so companies will only have the lab test for the substance of concern.
I assume that it comes down to the attitude of the company, but there may be issues that I am not aware of.  I assume that some HR folks know what bupe is, and deliberately choose not to test for it, believing that it is a medication in most cases and not a drug of abuse.  I’m sure there is a company somewhere that tests for bupe to catch any sign of even ‘prior’ addiction, but that has not been the experience of the people who have written to me.  I have not heard from anyone who tested positive for buprenorphine in a random test—but I will put the question on my blog and see what comes up!
So there is my question:  has anyone tested positive for buprenorphine in the workplace?  Has anyone tested negative who takes buprenorphine? Please share your responses in the comment section below, so that I will have more than guesses for people who write.  My attitude, for what it is worth, is that your medication list is your own business, providing that the medication does not influence your ability to perform your job.  But I realize that the answer to the question can be complicated.  For example, I was first treated for opiate dependence in 1993, and was completely ‘clean and sober’ for many years, active in 12-step Recovery and regularly attending meetings.  Every two years I received a re-appointment packet at the hospital where I worked, and one question was ‘Do you have a chronic illness that affects your ability to care for patients?’  I knew what the question was getting at— but to my way of thinking, as a person who had been clean for several years and who was never planning on using again, the correct answer was clearly ‘no, I had no illness that affected my care of patients.’   But when I relapsed in the year 2000 the hospital made much of my answers to that question, reporting to the Board that among my other (much more significant) transgressions, I lied on my re-appointment packets.  I was going to defend myself by saying ‘it depends on what the meaning of ‘is’ is…’  but someone else used that excuse before I could use it!!
The problem people face with workplace drug testing– at least something that would be considered a problem for those sympathetic to people on buprenorphine– is that people are often asked to provide a list of the medications they are taking BEFORE the test.  If not for that question, they could go take the test and explain themselves in the event of a positive result.  But if asked about medications beforehand, the worker must decide whether to disclose a history of addiction to an employer who may be overly judgmental, or keep the medication use private and risk being accused of lying.
To those who are going to write that ‘taking buprenorphine is impairing a person and therefore the person must put the info out there,’ I will say in advance that my patients on buprenorphine, who take the medication properly, are NOT impaired by any definition of the word.  They are completely tolerant to the mu receptor effects and are getting no ‘opiate effect’ from the medication.  I will also point out the double standard applied to addiction.  A person with a history of epilepsy is at risk for losing consciousness while operating a crane from a seizure.  A person with diabetes is at risk for the same from a hypoglycemic reaction.  Someone with heart diseast could drop dead of a lethal arrhythmia while driving a school bus filled with children.  Should opiate addicts who are doing the ‘right thing’ and keeping their addiction in remission be forever identified as ‘addicts’ to employers?
As always, thanks for your comments;  please also be sure to join the forum if you have not already.  You will note that when leaving a comment, it will take a day or so to get read and approved;  I do that because there are people who have nothing better to do, apparently, than respond that I am ‘a little bitch’ or call me some other name– for reasons that are not always entirely clear!   When I read such comments I always get a mental image of Mr T. saying ‘I pity the fool!’  (then I think of the scene in Pee Wee Herman’s Big Adventure where Mr. T. says ‘I pity the fool… who doesn’t eat my cereal!)  I guess you really have to be there.

How dangerous is opiate dependence?

I frequently point out the lack of outrage over the epidemic of opiate dependence and the consequence of that epidemic.  I live in ‘middle America,’ and sometimes it seems that everyone I know has some connection to opiate dependence– a relative who is an addict, a friend who died, a parent who is in prison.  My perceptions are admittedly distorted by the work that I do, but I don’t know who has the more accurate perceptions; me or the people who seem surprised to hear that most high school kids know where they could get heroin.  Addicts who I treat who come down from the U.P. of Michigan tell me that heroin is very easy to get up there now, even cheaper than oxycodone.  I guess that’s to be expected, given the horrible economic situation up there.  One thing is certain though– SOME people are making money!  In my part of Wisconsin, oxycodone generally sells for 60-80 cents per milligram;  the average user that I see tries to find one or two ’80’s’ per day, ending up with a habit that costs over $100 per day.  Given the number of people actively using, there is a LOT of money going into someone’s pockets!  Of course much of the oxycodone on the street is bought by insurance coverage and then stolen from grandma’s medicine cabinet by her granddaughter, who replaces them with plain tylenol tablets…  but the herion money is probably leaving town, eventually finding its way back to Chicago.  Sorry, Chicago.  We have to blame SOMEBODY.
Many diseases have prominent celebrities who put on pink ribbons and fight for funding.  Not so for opiate dependence, even though the deaths from opiate dependence must rival those from breast cancer.  I’ll have to look at the numbers.  But celebrity opiate addicts tend to end up like Kurt Cobain or Michael Jackson– or slink off to rehab and later proclaim themselves cured.  Anyone who watches knows that there is no cure for opiate dependence, and the celebrity addicts only go back to rehab again as society goes ‘tsk tsk’.  Society doesn’t say ‘tsk tsk’ when someone’s breast cancer comes back.
I found an interesting web site called ‘informationisbeautiful.net’ where information about a variety of topics is presented in visual form.  Below I have a couple images from the site using data from the UK on deaths from overdose of a number of substances.  The images are relevant to the current discussion, as he compares the death rates to the reports about deaths due to the substances in the National media.  At the web site he discusses data collection;  I won’t make conclusions on the data but rather simply let is provide ‘food for thought.’  After viewing the first image be sure to contine to the next image down.
Opiates have the highest death rate of a range of substances.
In the next image he manipulates the data slightly to add a denominator to the information– he provides the number of deaths per user of the substance.  Again, I will let people truly interested in his findings visit his web site to look into whatever assumptions were made and which data sources were used.  I would like to again leave the data without much comment, in part because I don’t really know how to explain the high rate of fatalities among methadone users.  I will point out that use of methadone in the UK may be quite different than in the US, because in the US the medication is prescribed in two ways– as a cheap opiate for chronic pain management, and as a maintenance agent for opiate dependence.  In the latter case, prescriptions for the medication are regulated very closely (actually ‘prescription’ is not even the right word, as addicts must personally pick up their dose of methadone each morning for at least the early part of their management by a particular clinic).  I should also point out that Heroin is a pain medication in the UK that is prescribed by physicians (as well as a ‘black market’ substance), whereas in the US all Heroin is illegal and cannot be prescribed for ANY indication.  Finally, paracetamol is the Brit’s term for acetominophen, or Tylenol.  The graphic:
Methadone deaths per user lead the pack for deaths from substances in the UK.
I do have a couple final comments.  On other blogs or in response to my videos I sometimes come across remarks by people who are ‘anti-suboxone’ that ‘the problem with treating addicts with buprenorphine is that you then can’t get them off buprenorphine, and you have another problem to deal with’– that the addicts are ‘addicted to buprenorphine.’   I find that argument to be faulty for a couple reasons.  First, ‘addiction’ is not so much about the taking of the substance as it is about the obsession with the substance.  An addict who is properly treated with buprenorphine loses the obsession for opiates– something that is amazing to witness at the first follow-up appointment, when the addict sometimes cries over how wonderful it is to be freed from the obsession to use.  So I don’t see buprenorphine as a ‘replacement’, and I don’t see the physical dependence on buprenorphine as ‘addiction’ any more than people taking effexor or propranolol are ‘addicted’ to those medications (which also have withdrawal symtoms of stopped abruptly).   But even beyond that consideration, given the high mortality rate for opiate dependence, when people complain about taking buprenorphine I am always tempted to say ‘compared to what?’   People are DYING from this disease– frankly I don’t CARE if they get dependent on buprenorphine.  I am on the record here over and over with my opinion– that buprenorphine should be a long-term medication.  Use it to keep a person alive during his or her 20’s, and then worry about tapering off– and if the person cannot taper off, so be it!  It beats death.   And any parent of an addict in his or her 20’s knows that a string of ‘sober’ treatment centers and repeated relapses is NOT a great life… assuming the person even manages to stay alive.  We are left with comparing the two options of taking buprenorphine and living or avoiding it– and likely dying.   A pretty easy choice to make in my opinion.    I have to wonder what the people making arguments about ‘the problem with buprenorphine’ think about all of the problems with chemotherapy…   if a person’s child develops leukemia, if you treat him with chemotherapy he may end up sterile, and with an increased risk of a different cancer years later.   Would you recommend avoiding using chemotherapy to save his life now?  What’s the difference?
As always I am interested in your comments here and over on the forum.  We’ll talk again in 2010!
JJ
http://suboxonetalkzone.com