Addiction Treatment 'Science' and Dead Rats

In my last post I teased that I would write about fake science.  I’ll try to make it interesting.
The internet allows everyone to do research about symptoms and treatments for any condition. If not for need for prescriptions, people could act as their own doctors.  But a huge dose of caution is necessary before anyone takes that path.
Realize first that doctors don’t treat themselves or even their family members.  The saying that ‘a person representing himself in court has a fool for a lawyer’ applies double in healthcare.  Treating someone close to one’s self introduces a bias that is hard to explain, but easy to notice.  As an example, I see a doctor annually to monitor a progressive condition that threatens my vision.  I would like to know the answer to a simple question:  how bad is it?  If I have a patient with that condition I can look at images of his/her retina and have an immediate, rough sense about what the person is facing.  But when I look at my own images and test results I sense nothing beyond fear or relief.  The problems with self-assessment are of course greater in the field of psychiatry and addiction.  After my relapse in 2001 I was told I needed treatment, and my assessment called for a brief refresher course on the twelve steps.  Three months later, still in residential treatment, I recognized how wrong I was.
A larger problem is that research on the internet is nothing like the research used by doctors or scientists.  There are a few sites that offer true research, such as Pub Med, where you can search my name and see the articles from my PhD work in the 1980s.   Doctors at academic hospitals or institutions often have access to an electronic database including thousands of peer-reviewed journals.  In grad school I spent time each morning in the library, reading the Science Citation Index for new stories about vasopressin and then searching the stacks for the article (medical libraries have so many journals that they take up 4 or 5 floors or more of a large building, with narrow halls between floor-to-ceiling shelves).  In the stacks I sometimes realized I was standing amidst the results of the hard work of millions of scientists over the past 50 years.
The information on the internet is useful because it helps patients ask the right questions.  But it is a mistake to consider it as research, or even to assume it is correct.  Doctors and scientists (and any good health practitioners) rely only on peer-reviewed literature.  And even then, a good scientist gathers a sense, over time, of the better peer-reviewed journals vs. the ones with less credence.  What is peer review?  When a scientist submits research for publication, the article is sent to 3 or 4 independent reviewers who work in the same field but have no connection to the author of the study.  I am a peer-reviewer for a couple of journals.  When I receive an invitation to review a study I have to disclose any bias or connection to the study or authors.  If I accept the invitation I have several weeks to carefully review the study, noting if the findings are valuable, whether the groups were sufficiently randomized and blinded, whether the statistics are correct or if a statistician should be involved, and whether the findings support the conclusions.  I then tell the journal editor my opinion, including whether the study should be accepted, rejected, or accepted with certain revisions.  Peer reviewers are not paid;  they provide the service because they recognize that the process is necessary and valuable.
The FDA regulates medications based on the results of research studies.  Some of the studies reviewed by the FDA are already published, and some may never end up in a formal publication.  But their process for evaluating medications is similar to the work of a peer-reviewer in that they determine whether the science is ‘good’ – double blinded, properly randomized, good statistics, etc.  Any claims about a medication MUST be deemed accurate by the FDA.
This post was inspired by an ad for Declinol, a supplement marketed to ‘treat’ alcoholism.  Supplements are not medications, and not subject to the same rules. Read the FAQ on the Declinol web site and note the answer about FDA approval.  Declinol is not subject to FDA approval because it is a nutrient, not a medication.  The FDA allows greater latitude for promotional claims about nutrients, but even makers of supplements are not allowed to lie.  The acrobatics of marketers of such products are sometimes funny, at least to us nerds, and Declinol is a classic example.  Note that the web page doesn’t say that it treats alcoholism or cravings;  it is a ‘SUPPORT for physical cravings, calmness, and overall well-being’.  What is a ‘support’?  Your guess is as good as mine.
Instead of making claims that can be found to be false, nutrients often show quotes by ‘satisfied customers’.  If the FDA believes that the quotes are misleading, that’s on ‘Bob from California’, not on the marketer of the nutrient.  Instead of describing how the nutrient works, nutrient marketers provide citations about the nutrient that support whatever the marketers want you to think.  So with Declinol we see ingredients like folic acid, with broad generalizations about the value of that substance.  Yes, Folic acid is valuable.  You can’t live without it.  But that’s a far cry from saying that taking extra folic acid has any value, let alone value in reducing alcohol intake.  We give folate to alcoholics in detox because they sometimes have dietary deficiencies caused by consuming nothing but alcoholic beverages.  If you eat meals a couple of times per day you almost surely have plenty of folic acid in your body, and any extra is metabolized and excreted..
Must nutrient ‘treatments’ or supplements contain a blend of vitamins.  It is very easy to write reassuring and positive statements about vitamins because by definition, vitamins (the term comes from ‘vital amines’) are molecules critical to normal function.  But many studies have shown that a typical diet provides adequate amounts of vitamins, even if that diet includes fast food.
Many nutrient ‘treatments’ also contain a couple special ingredients we’ll call ‘secret sauce’.  One secret sauce in Declinol is Kudzu, and support for Kudzu in reducing alcohol consumption can be found on Pub Med.  Like similar products, Declinol’s marketers take a finding about a substance and grossly generalize the findings to create an impression that was never part of the original finding.  According to the study about Kudzu, 20 people in a ‘natural settings laboratory’ (is that an oxymoron?) were given water, juice, and up to six beers, and told to drink at will.  And (wow) when people were given 2 grams of Kudzu first, they drank beer more slowly, and opened fewer bottles.
A couple of problems, though, in concluding relevance to treating alcoholism.  Were the 20 subjects alcoholics? It doesn’t say, but I would guess not because I don’t know if a study giving beer to alcoholics would pass the ethical review board.  Beyond that, WHY did they drink less alcohol?  If I gave you syrup of ipecac, you would probably drink less alcohol.  If I gave you a tablet of oxycodone, you would probably drink less alcohol.  That doesn’t mean that the substances are useful in treating alcoholism or alcohol cravings.  Why did the Kudzu group drink less alcohol? Did it truly reduce interest in alcohol in a study with very few subjects who may or may not have alcohol problems? Or did it leave a nasty taste in their mouths or destroy their taste buds?  Did it cause nausea or dizziness that made alcohol less enticing? Did it reduce vision so they couldn’t find the beer bottles as easily?
As for the title of this post, when I researched vasopressin one hot idea was that vasopressin enhanced learning and memory.  We measured that improvement in studies using ‘passive avoidance.’  We placed rats in a cage that had dark cubbies in one corner, and when rats invariably went into a certain cubby they received an electric shock.  We repeated the task with or without putting vasopressin into the rats’ brains and some rats ‘learned’ to avoid the electric cubby, supposedly by remembering the shock better than other rats.  There is a major flaw in the study that can often be applied to other ‘experiments’, including the one I cited about Kudzu:  the best performer in a passive avoidance task is a dead rat.
I have no idea whether Declinol reduces cravings or generates ‘well being’, whatever that is.   But nothing on their website pushes me toward that conclusion.  I hope readers will keep some of these comments in mind when the next big cure comes along.

Make Sleep Meds Work For You

I’ve been busier than I like, and haven’t had as much time for posting.  But I spend a lot of time answering emails from my patients, and some of my responses may be useful for others.  Below I’ll share my answer to a patient who has been unable to get quality sleep.  Next week I’ll find another answer to share with readers.
This patient asked whether her insurance would cover Lunesta.  She wrote at 2 AM that she is up most of the night tossing and turning. She now takes 10 mg of Ambien, and wrote that it ‘stopped working’.  She doesn’t think 20 mg of Ambien would be covered by insurance (although Ambien is very inexpensive when purchased for cash).  She takes gabapentin for a pain condition and wonders if increasing it would help with sleep.
My response:
Before getting into a discussion about insurance I want to make sure you have a good understanding about the issues you’re facing when you take sleep medications.  Most sleep medications are subject to tolerance, and some share ‘cross tolerance’.  Lunesta (s-zopiclone) and Ambien (zolpidem) act at the same receptor and have the same actions, so if a person is used to one, she is used to the other.  The situation is analogous to opioids, where a person tolerant to a significant dose of oxycodone will find little effect from morphine.
I have taken Lunesta but stopped it for the same reason you are unhappy with Ambien:  it just didn’t do much.  Lunesta also causes a very bitter taste in the mouth, not from the pill touching taste buds, but from the drug circulating in your bloodstream.  The taste is unpleasant but goes away aftef a few weeks in most people.  If you are not responding to Ambien, you won’t likely respond to Lunesta.
Some people change from an ‘ultrashort’ to a benzodiazepine, typically temazepam.  That change will often offer some benefit, but tolerance will eventually match the effects of temazepam just as with the shorter medications.  Patients often ‘chase’ tolerance higher until their doctor refuses to prescribe larger amounts.  The exercise only deepens the plight of the insomniac, making it harder and harder to sleep without medication.
What is your current dose of gabapentin?  Pain docs sometimes taper that drug up to a total of 3 grams per day, and higher doses cause some degree of sedation.  But again, step back and look at the big picture.  With any sedating substance, including gabapentin, you are only  addressing the short-term.  Your body will adjust to any dose of sedative, just as with opioids, and you will eventually need to address the same symptoms on even higher doses of sedatives.
I am willing to look at the gabapentin, but understand what you are up against.   Patients tend to focus on the short-term at 2 AM.  My job is to know that you will be around for years, even decades!  I often see new patients whose doctor prescribed benzodiazepines for years, repeatedly raising the dose.  At some point the patient ran out too early, prompting discharge.  At that point there is little to be done for such patients beyond helping them through several weeks of severe insomnia caused by benzodiasepine withdrawal.  Sometimes questiapine, clonidine, or hydroxyzine will help patients find some restless sleep while lowering their tolerance to benzodiazepines, but that sleep is usually poor in quality and associated with significant daytime sedation.
My best advice:  When taking sleep medications, the most important point is to NEVER ‘double up’.  If you take two tablets instead of one of any medication, you will never get the same benefit from taking one again.  You will only run out early, and the doctor, pharmacist, and state will all prevent early refills  The second point is that newer sleep meds will not just make a person fall asleep.  For the first few nights a new medication might feel more potent, but over time, the best thing a sleep med will do is HELP a person fall asleep.  Patients must do everything else correctly, including sleep hygiene measures such as using a dark, somewhat cool room, using white noise to help the mind avoid focusing on creaking boards or other noises, avoiding significant alcohol use, avoiding caffeine after noon, avoiding eating or smoking right before bed,  calming down at the end of the day (some people can’t  sleep if they exercise late in the day), dimming lights, avoiding watching football right before bedtime, etc.
If you do all those things, a sleep medication will help ease the transition to sleep.   But the shorter meds like Lunesta and Ambien work best when they take effect in people who are in bed already, working on getting to sleep.  People often make the mistake of taking a sleep medication and wating to go to bed until they feel sleepy.  The newer sleep meds don’t cause the sleepiness that came with the older drugs, and they don’t last near as long.  Waiting ‘until they work’ can also cause amnestic behaviors like sleep-eating, sleep-sexting, sleep-driving, and worse.
Give these issues some thought and tell me the amount of gabapentin you take.  Beyond the controlled substances, consider trazodone or clonidine, two medications that work differently than benzodiazepine and Ambien.
The best sleep, of course, is found in the unmedicated condition desiged by evolution.  Evolution is not fast enough to keep up with changes in communication and the social media phenomenon, so it is often useful to think about the sleep environment of our ancestors, 40,000 years ago.  If I knew how to use twitter, I’d hashtag ‘sleep like a caveman.’

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.

The Opioid Dependence Big Picture

First Posted 1/16/2014
Below, internet colleague Paul Dessauer shares his extensive knowledge of opioids in comments about my naltrexone post. His comments were particularly interesting in that they provide evidence that at least someone is aware of the big picture about addiction to heroin and pain pills.
In my post about naltrexone, I described how some people favored the drug over buprenorphine because of its lack of opioid effects. Unlike buprenorphine, naltrexone is an antagonist that has no abuse potential.  But I wondered… at a time when so many young people are dying, shouldn’t the primary issue be whether naltrexone saves lives?  Sure, it is ‘safe’– but does it work?
Paul provided references to answer my question.  While everyone is focused on the fact that naltrexone can block opioid receptors, Paul’s data shows that when naltrexone is used in the real world, people die.  I’m excited that someone, somewhere, has the courage to investigate the one thing that is never addressed in discussions about addiction, whether related to residential treatment, counseling, or medication: Does it work?
Paul’s comments:
You wrote;
<<< If ‘success’ consists of moving to naltrexone—a medication that many real-world addicts reject– how long is naltrexone continued, and what happens when it is stopped? Do people go back to heroin again? If not, why not? The cycle of ‘use, treat, cease treatment, use, and repeat’ should be a black box warning on naltrexone >>>
The other “black box” issue is dropped tolerance overdose when someone exits naltrexone treatment and relapses to illicit opioid use.
You asked; <<< How many people will die in their quest—or their doctor’s quest—for ‘abstinent recovery’ with or without naltrexone? >>>
This study used Australian coronial records to compare mortality rates amongst patients in methadone treatment, buprenorphine treatment, and naltrexone treatment. The authors make it clear that they believe the mortality rates for naltrexone calculated here are significant underestimates, as coronial data does not record such deaths consistently, and they found the majority of known naltrexone-related deaths did not appear in this data.
<<< When expressed as deaths per number of treatment episodes, it was estimated that naltrexone had a mortality rate of 10.1 per 1000 treatment episodes. If the mean treatment retention in naltrexone treatment was estimated at 3 months (rather than two months, as assumed in the above estimate), the mortality rate for naltrexone treatment increased to 15.2 deaths per 1000 treatment episodes.
Naltrexone was associated with a mortality rate of 22.1 per 100 person years during the period of high risk (2 weeks post-treatment), and 1 per 100 person years during the period of low risk (during treatment)…. >>>
<<< …The estimated mortality rate was 0.02 per 1000 treatment episodes for buprenorphine and 2.7 per 1000 episodes for methadone.
The mortality rate for naltrexone was four times higher than for methadone when calculated as deaths per number of episodes of treatment, and substantially higher than for buprenorphine.
When considering deaths per periods of high and low risk, the mortality related to naltrexone was approximately seven times that of methadone during the period of high risk and three times the rate during the period of low risk. Naltrexone treatment was associated with a mortality rate of 22.1 per 100 person years during the period of high risk (two weeks following treatment cessation) and 1 per 100 person years during the period of low risk (during treatment). Buprenorphine mortality rates were not expressed in terms of periods of high and low risk due to the low number of deaths detected with this search method. >>>
<<< In comparing mortality rates associated with these pharmacotherapies, it is important to draw the reader’s attention to the rates of mortality for active heroin users. It has been estimated that mortality rates for heroin-dependent persons not in treatment are in the vicinity of 0.9 per 100 person years of risk, very similar to the mortality rate of a person in naltrexone treatment (during the period of low risk) calculated in this study. >>>
Actually, this is slightly less than the risk of naltrexone-associated death calculated in the study, which is believed to be an underestimate.
And the risk of naltrexone-related death calculated for the “high risk” period (the two weeks immediately following cessation of naltrexone) is more than TWENTY TWO TIMES higher than the risk of death estimated for someone using street heroin who is not in any form of treatment at all.
<<< While maintained in methadone or buprenorphine treatment after the initial induction stages, opioid-dependent people are at lower risk of dying. Clearly, an important aspect of methadone and buprenorphine treatment for opioid dependence is the improvement of treatment retention rates.
The mortality risks associated with oral naltrexone treatment, particularly following treatment cessation, warrant serious attention. This is especially the case considering that the majority of unselected opioid-dependent persons will return to opioid use soon after leaving naltrexone treatment. It is recommended that future trials of all treatments for opioid dependence include monitoring of post-treatment mortality risk >>>
Gibson, A. and Degenhardt, L. (2005) Mortality related to naltrexone in the treatment of opioid dependence: A comparative analysis, Sydney: National Drug and Alcohol Research Centre

New Bupe News Section

Wanted to take a second or two to point out a new section to the blog, called ‘Bupe News’.  You’ll see the link at the tope of the page, along with an ever-growing list of links.  The point, of course, is to keep y’all reading, since Google knows EVERYTHING, including how many seconds each and every one of you spends on this (and every other) web site.  Understand that I don’t GIVE that information;  that information is simply that is there for the taking on the internet.  Even I can see the average time people spend on the site, the order they went to one page or another, etc.    I do not ‘collect data’ about any reader, meaning that I do not have information about who any individual is or isn’t…   but I DO get reports on my collective audience.
Check the page out, along with the other new section, and of course tell me what you think.  Positive suggestions are ALWAYS welcome!
Thank you for hanging with me,  by the way, for some tough I.T. times.  I’ve got about 3/4 of the ‘lost’ posts back, and then I’ll be back to firing off the NEW things I’m angry about, rather than replaying the things that irritated me a year ago!
J

Buprenorphine Regulations and Unintended Consequences

First Posted 8/28/2013
I realize that I am halfway through a post called ‘Suboxone Abuse Part I’.  This is poor form, but I am now going to get halfway through a second topic before finishing the first one.  Sorry.
I recently came across a problem relating to the new healthcare law.  I was thinking about writing ‘How the Affordable Care Act Is Killing a Few People’, but I figured that such an inflammatory title would chase away about half of my readership.   So I used the title I liked second-best.
I’ll first write about a couple background issues that are obvious to those of us who work in healthcare but less obvious to others.  These things are important to know, in order to understand the second post.  I won’t try to take one political stand or another, so hopefully the people who reflexively support or bash either side will take a chill pill, tune into the issue, and allow my perspective to filter into their knowledge base.
When I was in med school, I bought a brand new Hyundai for $3900. The car was a ‘loss leader’.  Businesses owners use loss leaders to increase buzz about the business or to get people through the door, hoping to make up the loss by selling more profitable merchandise.
You may have noticed the disappearance of private doctor practices over the past 20 years.  There are many reasons for the loss of private practices, but from the perspective of an owner of such a practice, a primary reason is because individual doctor visits, especially for primary care, have become loss leaders for healthcare systems.  Patients attached to systems through loss leaders– primary care physicians– become sources of profit when they are admitted, have MRI’s or surgeries, or see specialists.
Look at the cost for different types of ‘health care.’  Your insurer pays less than $200 for a doctor to sit with you, 1:1, for 15-30 minutes.  That same amount of time in an MRI costs your insurance ten times more, and an hour in the operating room costs $5,000-$20,000.
Health systems negotiate with insurers with an eye on the big picture.  An orthopedic injury—say a torn ACL—brings an ER visit, X-rays, MRI, surgery, and physical therapy, with revenues well over $20,000. A patient with heart disease brings in $50,000 or more for EKGs, stress tests, cardiac ultrasound, angiogram, angioplasty, and bypass surgery.  Cancer care can top $100,000 when surgeries, radiation therapy, and chemotherapy are included. Even a relatively common injury—lumbar disc herniation– requires MRI, PT, a variety of injections, and laminectomy or spinal fusion, with revenues up to and over $100,000.
While individual doctor visits are more common than heart surgery, the MRI suites and catheterization centers are the profit generators for health systems and the hot topics of insurance negotiations.  To the big systems, whether the family practice doc is reimbursed $120 vs. $160 per visit is a minor consideration—just as we are more careful buying a home than a soda.  But solo-practice docs must carefully consider the payments for office visits, since they are the ONLY revenue.   Independent docs are offered the discounted reimbursements that insurers pay the big healthcare systems, but unlike the systems, small practices have no high-revenue services to subsidize lower-revenue patient visits.  With no high-revenue services to subsidize lower-revenue patient visits, independent physicians must be very careful in providing discounts to be part of insurance panels.  Some types of payments—the $30 for a 20-30 minute office visit paid by Medicaid—won’t keep the lights on after malpractice, office staff, rent, and utilities are paid.
It is hard to run a business selling only loss leaders.  That’s why the Hyundai dealer tried so hard to get me to test drive other cars. It wasn’t until I threatened to make a fuss about ‘bait and switch advertising’ that I was allowed to buy the $3900 car pictured in the newspaper ad.  There was no profit in that sale, but the dealer knew that most people would turn away from the unwashed beater and consider other cars on the lot (he didn’t take into account how broke med students are!).  Without bigger sales, the business can’t survive.
The second issue I need to cover is the shortage of doctors who prescribe buprenorphine, and the reason that buprenorphine prescribers are more likely to be independent or small-practice physicians.
To prescribe buprenorphine, doctors must take a short course and fill out some paperwork—not a big deal.  A bigger deal is that buprenorphine-certified doctors must allow random inspections by the DEA without cause.  Doctors who work for health systems get a paycheck each week, often regardless of the number of patient visits.  For an employed doctor, does it make sense to take an extra course, file extra paperwork, and agree to random inspections, in order to see more people but for the same pay?
Patients in need of buprenorphine treatment have usually lost a great deal due to their addictions, and are not great ‘sources of revenue.’  I suspect that my own enjoyment treating addiction comes in part from my personal experiences ‘in the field’.    Beyond that type of interest, young doctors do not leave residency eager to take on patients who have been dishonest with other doctors, who early in treatment appear a bit ‘rougher’ than their other patients, and who have no disposable income!
The two issues must be understood and combined, in order to understanding the second half of the story (that I will get to eventually…).   In review, the first point is that individual medical practices are disappearing because of a flawed business model.  Fees charged for individual appointments are far lower than revenues from tests, procedures, and surgeries.  Large systems can subsidize doctor visits with revenue from MRIs and surgery centers.  Doctor visits are ‘loss leaders’ for more profitable services.  One cannot make a ‘business’ from loss leaders, without the second half of the equation.
And second, doctors who prescribe buprenorphine are more likely to be independent practitioners with their own businesses.  Another way to say it is that doctors who are employees of health care systems are less likely to obtain certification to prescribe buprenorphine.  The extra patients that comes with buprenorphine certification cause more paperwork and more regulation, without an increase in pay.  Beyond personal motivations, doctors have no incentive to treat addiction; in fact there are significant disincentives to becoming buprenorphine-certified.
Put the two together, and you have more and more communities where several large systems compete for patients, and nobody prescribes buprenorphine except for the one or two independent practices that haven’t closed yet.

An Interview with the ATTC

For those who missed it, I recently provided some opinions about buprenorphine treatment for The Bridge, a journal produced by the Addiction Technology Transfer Center Network.  The discussion was published in The Bridge Volume 4, Issue 3, and is copied below.
Question 1. The introduction to buprenorphine treatment in the U.S. has occurred through a controlled system somewhat parallel to controls on methadone. How would you envision the current buprenorphine treatment scene had these regulations never been imposed, with buprenorphine introduced into medical care with no waivers or patient limitations?
Dr. Junig:  I think it would be different in good and bad ways. Without the regulations, buprenorphine would likely have become prescribed by primary care to a much greater extent, which would have saved the lives of many, many young people. There would be more buprenorphine/Suboxone in the hands of patients and non-patients. The increase in buprenorphine would likely be balanced by reductions in opioid agonists, as primary doctors would have moved chronic pain patients from agonists to buprenorphine. Any reduction in use of opioid agonists would be a good thing, whether through reducing the deaths caused by agonist diversion, or through getting people stuck on the roller-coaster of agonist dependence onto buprenorphine instead. While buprenorphine has similar discontinuation symptoms as agonists, the subjective experience of taking buprenorphine is very different from the experience with agonists—leaving people much better off after the change.
The addiction doctors who seem to see diversion-control as their primary role would see an increase in buprenorphine/Suboxone as a problem. But the dangers of buprenorphine diversion are overblown. Much ‘diversion’ consists of misguided self-treatment by patients who can’t find a prescriber, or by former patients who were not able to maintain sobriety perfectly-enough to avoid discharge from their prescriber. Having more prescribers might have resulted in less non-prescribed use of buprenorphine.
The diversion issue is complicated, even in cases where buprenorphine is used as a bridge between agonists in addicts who do not intend to quit using. Buprenorphine has a strong protective effect against death, whether taken by prescription or through diversion. Specifically, over 35,000 US overdose deaths occur annually in the absence of buprenorphine, compared to about 40 overdose deaths each year when buprenorphine is one of the drugs in the person’s system. If the people most worried about diversion are correct—i.e. if diversion consists less of ‘self-treatment’ than of poly-substance dependence– we would expect many more overdose victims to have buprenorphine in their bloodstream at the time of death. The bottom line: if a person takes buprenorphine for any reason— even just to avoid withdrawal until a better batch of heroin comes to town— that person is less likely to die from overdose.
Question 2.  It is recognized that there are some geographic locations where buprenorphine access is highly limited. Aside from this troubling fact, a devil’s advocate could argue that the numbers of physicians who have been waivered represents a major success. Most of the “folklore” of the field would have suggested that practically no physicians would have wanted to come forward to treat opiate addiction.
Dr. Junig:  The ‘folklore’ is, unfortunately, largely correct. Many waivered physicians never actually prescribe buprenorphine products. Others start treating opioid dependence but then discontinued that aspect of their practice. Last weekend, headlines in Indiana described the arrest of several doctors who prescribed buprenorphine products. News stories demonized aspects of their practice styles, even though they were not at odds with DATA 2000. The articles wrote that (gasp!) they were not doing urine tests at every patient visit, they were asking for cash payments, and they didn’t require counseling for every patient. The lack of ASAM support for these physicians and similar cases will have a chilling effect on physician attitudes toward treating opioid dependence.
Question 3.  Would there be any disadvantages if the current patient limit of 100 was eliminated altogether?
Dr. Junig:  Many lives would be saved. Some doctors picture a sea of buprenorphine abuse, but patients who take the medication know that a ‘buprenorphine habit’ does not yield the experience achieved with heroin or other agonists. The ceiling effect results in constant opioid activity across the dose range, which leads to rapid tolerance— whether the buprenorphine is injected or taken sublingually. For opioid agonist addicts, the primary result from buprenorphine abuse is inadvertent treatment!
Question 4.  From your perspective, how successful have physicians been in linking buprenorphine patients with psychosocial counseling?
Dr. Junig:  Successful enough. Some patients do well on buprenorphine products without counseling. While that statement is almost heresy these days, I encourage addiction doctors to do the specialty the favor of practicing evidence-based medicine, and following the data. Buprenorphine treatment is filled with a range of opinions about best practices. But where are the data?
Question 5.  Simply on the basis of their skills as physicians, and assuming they were willing to spend the time, do you think the majority of physicians could successfully deliver this psychosocial counseling?
Dr. Junig:  Many different interventions fall under the label of ‘counseling’. If a counselor spends each session trying to convince a patient to ‘get off buprenorphine’, is that effective counseling? Any physician who knows his/her patient, and cares enough to counsel, educate, and refer appropriately, should be allowed to decide what is best for the patient. Surgeons are given the responsibility to decide, all by themselves, which organ to remove—but addiction doctors aren’t trusted to make decisions about counseling? No other medical specialty assumes such a high level of ignorance in their doctors!
Question 6.  From your perspective, how successful have physicians been in delivering other needed medical services (services they likely would not otherwise receive) to the patients to whom they prescribe buprenorphine?
Dr. Junig:  Practices vary. I have great respect for primary care physicians who manage opioid dependence, and at the same time manage other forms of illness in the same patient. In other areas, addiction doctors have become ‘super-specialists’ who only provide buprenorphine treatment. I know that in my own practice, patients who initially present for buprenorphine treatment end up with much better psychiatric care than they otherwise would have received.
Question 7.  Has your buprenorphine practice added significant numbers of new primary care patients to your overall practice?
Dr. Junig:  I am a psychiatrist, and buprenorphine has added new psychiatric patients. I also evaluate rashes, infections, aneurysms and pseudo-aneurysms, GI issues, and many other conditions outside of psychiatry that have some connection to the patients’ buprenorphine treatment.
Question 8.  On the basis of your own experience and the experience of your colleagues, has the presence of patient addicts in your practice caused difficulties with other patients or with your colleagues/staff?
Dr. Junig:  I suspect some non-addiction patients have been uncomfortable in the presence of patients with addictions who are new to treatment, who sometimes appear a bit rough. I encourage patients to talk about their concerns, and I do not believe I’ve lost patients over that issue.
Question 9.  What key indicators should determine when tapering off buprenorphine should begin?
Dr. Junig:  Given the high rate of relapse, I believe patients have a right to ongoing buprenorphine treatment without time limitation. I advise patients about the risk of relapse. We need more data, but I suspect that age, occupational status, and personality factors play a role in risk of relapse, and should therefore be factored into decisions about discontinuation of buprenorphine.
Question 10.  What are the prospects for insurance coverage for indefinite/as needed maintenance on buprenorphine?
Dr. Junig:  I believe prospects will be good, IF our professional advocate agencies step up to the plate and educate insurers—and legislators. We should demand access to lifelong medication for our patients with lifelong illnesses!
Question 11.  For currently active buprenorphine-waivered physicians, what should they be considering in terms of the use of injectable naltrexone for their opiate addicted patients?
Dr. Junig:  Naltrexone looks good on the surface, but too few people consider the long-term outcomes. We seem to have a fantasy that if we block a person from using for a year, counsel the heck out of the person, and then remove the block, that the patient will live happily ever after. But Australian studies show high death rates in patients who were maintained on naltrexone in the year after naltrexone was discontinued. Since we have no data showing that counseling is effective in maintaining abstinence from opioids, I am not convinced that it is a good idea to keep someone from his drug of choice with monthly injections, and then stop those injections—particularly when the injections create hypersensitivity to opioids and respiratory depression from opioids. Patients stop Vivitrol knowing that IF they relapse, they will get the biggest ‘high’ they’ve ever had… which is not a good situation for addicts! Will there be a high death rate in people who were placed on naltrexone, when the drug is discontinued? I suspect the answer will be ‘yes’—but in either case, I hope that physicians pay attention to that data.
Question 12.  If you found yourself appointed Czar of All Drug Treatment in the U.S., what steps would you take to improve the delivery of buprenorphine to opiate-addicted patients?
 Dr. Junig:  I would ask physicians to practice medicine first, and to follow the science. We have a role in preventing diversion, but that is not our primary role as physicians. Physicians should point out, and resist, any regulation or policy that increases the number of deaths from opioid dependence. Who will carry that message if not physicians?
When physicians become obsessed with out-regulating each other, the result has been policies based on opinions or business models, not on science. Some of the policies being advocated– for example quantitative testing or counseling for all patients— have large profit incentives for doctors and health systems, but stand in the way of care for uninsured or underinsured patients.
I would want to see opioid dependence treated as the disease that it is. With any new regulation, we should ask ourselves: would we do the same for asthma or hypertension? Do we require nutrition counseling, for example, in order to receive insulin? I would also assume that doctors treating addiction have the same intelligence, competence, and compassion to stay current with the standard of care for treating addiction, as any other physicians. We shouldn’t add regulations that would not be tolerated by any other medical specialty.

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?

Suboxone and Tooth Decay

Originally posted 10/21/2012
I have received a several emails over the past few years from people who experienced deteriorating dental health while taking buprenorphine or Suboxone.  I also have patients in my practice who have had extensive dental work, and wonder if Suboxone is to blame for their cavities or other problems.
I wrote about this issue several years ago.  At that time I wrote that there was no evidence that sublingual buprenorphine or Suboxone cause or accelerate tooth decay.  After writing the article I received a number of angry emails from people who insisted that I was wrong.
Let’s step back for a moment to highlight the difference between thinking something vs. proving something.  Some people misunderstood my comments about tooth decay and Suboxone, thinking that I was arguing that Suboxone does not harm teeth.  That was not what I wrote.  My point was that as of that time, there was no evidence that Suboxone or buprenorphine caused tooth decay.  When I write about the science of buprenorphine, I try my best to distinguish between what I think is true vs. what was established through scientific study.
I recently met with a patient who has had extensive dental work over the past few years, the same time that she was taking sublingual buprenorphine.  She asked if I thought that the two were related.   I made a few comments (that I’ll be getting to), but also promised her that I would do a literature search, to see whether any connection has since been established.  Ironically, a case report of a woman on Suboxone who required extensive dental work was just published yesterday.  The case report is in the latest issue of The American Journal on Addictions, and the same case is cited in the October 20, 2012 edition of Reactions Weekly.
The world of science is not efficient.  Knowledge moves forward slowly, based on findings amassed from many studies, often repeated multiple times.  Case reports are not intended to prove something.  In fact, case reports are often unusual clinical examples that defy the norm.  They are often published to point out an area that deserves more study.
I cannot copy the case report here because of copyright laws.  But the case described a 35-y-o woman who used oxycodone for about a year at doses up to 160 mg per day, and then went on buprenorphine/naloxone.  After 18 months, her dentist told her that she had extensive decay of 4 molars requiring root canal.  She reportedly had minimal history of dental problems before starting opioids or buprenorphine.
The author of the case report hypothesized that if there is a connection between Suboxone and tooth decay, one reason could be xerostomia, i.e. dry mouth, caused by buprenorphine.  The lack of saliva was my thought, too, as a mediator of any possible effects of buprenorphine on teeth.  Saliva serves an important role in dental health, including rinsing away food particles and acting as a buffer.  The patient in the case report did not report a dry mouth, so the author pointed out that all opioids have some ability to suppress the immune response, and perhaps buprenorphine and/or naloxone reduce the immune response, allowing for greater destruction of teeth by bacteria.
The case report, surprisingly, did not say which buprenorphine product(s) the patient had used, e.g. tablets, film, or generic buprenorphine.
What needs to happen next is for someone to do a case-control study of patients on buprenorphine, to see if they are more or less likely to have tooth decay.  The most valuable study is usually a prospective, randomized clinical trial;  that would not be proper here, since it would not be appropriate to randomize subjects to buprenorphine vs. no buprenorphine.  But a close second would be a case controlled study, where patients on buprenorphine are matched to ‘controls’ with similar characteristics— age, sex, eating habits, income level, education, etc.– and the dental outcomes are followed forward over a number of years.  A less-costly, less-reliable study is one that looks backward, comparing patients on buprenorphine with those not on buprenorphine to see which group has a higher incidence of dental caries.
We are not much better off at this point in our knowledge of whether Suboxone or buprenorphine predispose toward tooth decay.  The case report only mirrors what I see in my practice.  But as I often tell patients, I have other patients who are not on buprenorphine or Suboxone, who have tooth problems.  I also have patients on Suboxone with great teeth.  Hopefully some ambitious PhD candidate will sort through the issue soon.

$uboxone Clinically Identical to Buprenorphine??

As I give my last post more thought….  I wonder if there is ANY clinical difference between $uboxone at $7 per dose, vs. generic buprenorphine at $2.33 per dose?  Researchers out there– can anyone send me a reference?
Read my last post for details– but the essence is that naloxone is destroyed when Suboxone is taken properly (orally, sublingually), and has no action whatsoever– on that issue there is scientifc agreement (although there is a great deal of ignorance among prescribers about this fact).  The ONLY think naloxone does, is to supposedly serve as a deterrent to IV injection of buprenorphine.
Sounds good, but…  we know that people divert Suboxone intravenously, naloxone and all.  Buprenorphine binds opioid receptors very tightly- so tightly that the naloxone doesn’t effectively compete with buprenorphine.
The State of WI requires Medicaid patients to take expensive Suboxone Film, whereas in other cases they require prescribing the generic.  What is the argument for requiring the film?  RB would argue (now that the tablet has lost the luster of being on-patent) that the film is harder to ‘divert’– i.e. to inject.  But frankly, the intravenous diversion of buprenorphine is a tiny issue compared to things like heroin addiction and a budget crisis.  Most of the diversion of buprenorphine, either Suboxone or generic, is not injected, but rather taken orally to ward off withdrawal– and the film makes no difference in that case.
Insurers, likewise, are wasting millions of dollars (literally) by paying for Suboxone— sometimes exclusively(!)  Have the bean counters fallen asleep on this issue?
I have nothing personal against Reckitt-Benckiser, beyond the fact that they refuse to engage in conversation with me.  If the good Brits at RB have discovered a way to suck millions of dollars from the weakest members of society, more power to them.  But I am a big fan of intellectual honesty, particularly in regard to the science behind medical practice.  So if someone has evidence that $uboxone is clinically different than generic buprenorphine, whether used properly or injected, please send it my way.