Tapering Off Buprenorphine or Suboxone pt. 1

Many patients taking buprenorphine live in fear of a dark world around the corner where they will have to taper off the medication.  They see horror stories on YouTube posted by people who, for some reason, abruptly stopped the medication and kept a video log of their experiences.   My own patients sometimes ask, nervously, if I plan to retire some day.  Some have asked what they should do if I ever, say, drop dead.

It needn’t be all that bad.  Yes, sudden discontinuation of a typical dose of buprenorphine will result in withdrawal symptoms.  But if you taper correctly, your body will slowly reset your tolerance without putting you through the wringer.   In this post I’ll describe my typical approach to helping a person through that process.  But first we should correct some of the misconceptions about buprenorphine and opioid dependence.

It does NOT get harder and harder to stop buprenorphine the longer you take the medication.  I have heard that idea over and over in one form or another, and I presume it comes from the experience people have with active addiction where use tends to grow with time, and other facets of life gradually fade away.   But the opposite occurs in patients treated with maintenance agents like buprenorphine or methadone, where use of the medication does not trigger a reward or relieve the ‘punishment’ of withdrawal.   The conditioning that occurred during active addiction is slowly extinguished, and most people gradually lose the desire to use opioids.   I’ve witnessed this process literally hundreds of times over the past 12 years in patients on buprenorphine or methadone. Patients of successful treatment also develop interests and accomplishments that help them avoid returning to opioids.  And after a few years away from ‘using friends’, people no longer see themselves as part of the using scene.  Patients get to a point where they have too much to lose to get close to that world again.

Opioid withdrawal has physical and psychological dimensions.  During short-term detoxes, minor physical symptoms trigger fears that magnify the perception of those symptoms.  A bead of sweat on the neck signals that hot flashes, diarrhea, and depression are on the way.  Patients who have been away from the cycle of using and withdrawal don’t seem to have as many emotions about their physical symptoms.  I see the change very clearly in methadone-assisted treatment, where the minor withdrawal at the end of the day is a big deal to people starting treatment, but a minor inconvenience in patients tapering off methadone after several years of treatment.

Does buprenorphine ‘get in your bones’?  YES, of course!  Bones are living tissue, so anything in the bloodstream gets in the bones.  Glucose gets in your bones.  Aspirin gets in your bones.  But so what? When you taper off buprenorphine, the buprenorphine in your body will be metabolized and removed.  It does not accumulate or stay in bones or other tissues beyond what occurs with other fat-soluble molecules.

Is buprenorphine or Suboxone ‘the hardest opioid to stop’?  No.  The brain keeps no record of the molecules that pushed opioid tolerance higher.   The challenge during a taper is that opioid receptors have become down-regulated by opioid stimulation, resulting in reduced endorphin tone as the opioid is removed.   Opioids that leave the body quickly tend to have more-intense discontinuation effects than those that leave more slowly because the latter mimics a taper, where opioid activity decreases over time.  The longer half-life of buprenorphine also slightly extends the total period of withdrawal by a few days.

I’ve heard people claim that ‘heroin was much easier to stop’, and rather than tell people what they should think I’ll let them have their opinions on the issue.  But that opinion is not supported by studies comparing withdrawal from different opioids.  Usually the claim is followed by the comment that ‘with heroin I was fine after 4 days’ or something along that line.  But it takes longer for tolerance to reset, after ANY opioid.  I suspect that perception comes from the severity of early heroin withdrawal, making subsequent weeks easier by comparison.  Again, the brain doesn’t care which opioid you used to take;  it only cares that the opioid stimulation that was there is now gone.

In a few days I’ll share the approach I recommend to patients tapering off buprenorphine.

Missing the Point of Buprenorphine Treatment

A forum reader wrote about concerns over a partner on buprenorphine.  Her concerns pointed out a common misperception about the goals of treatment of opioid use disorder using buprenorphine, or using methadone for that matter.
Her question, amended for privacy:
I married the love of my life.  He is still he love of my life but has been an addict for 15 of them. Our children have been greatly affected by his addiction.  He made promise after promise that he was clean, and I dove back in with complete faith time after time only to get burned.
His addiction started with recreational pills increasing over time, but now he is abusing Suboxone.   He was taking up to 12 mg depending on the day, but no pain pills for the last year. I suggested a Suboxone doctor and a plan to get off, and my husband called one and was able to get right in.
At the visit the doctor did a half ass intake and called in a prescription for an 8 mg tab for induction.   After induction they called in prescription for 20 mg/day.   My husband stayed with 4 mg once a day and was “blah” in the afternoon and irritable but not physically sick.  On his next visit to the doctor he was proud, but when he told the doctor he had only take 4mg in the mornings she got angry. She told him she wouldn’t see him anymore if that’s what he was going to do. He asked how long he would be on it and she wouldn’t give any kind of answer. I asked again before we left and she snapped at me.
I see a profound change in him after each time we see her and she tells him to take more. We walked away last time with another prescription for 16 mg a day which is just about double what he’s been taking for the last year and a half. So my question is, how does it make sense to treat someone taking 8 mg as their addiction with the same medication at double the dosage? Since seeing her he has decided he needs to take it more than once a day as well as up the dosage.  Is this right? Is it right to treat Suboxone addiction with Suboxone? A heroin addict isn’t treated with more heroin and a pill addict isn’t treated with more pills.  While I understand the concept of treating his original pill addiction with Suboxone, I am having a very hard time wrapping my head around what’s happening.
Me again… 
The writer raises interesting questions.  Regarding the ‘drug for a drug’ questions, buprenorphine has significant pharmacologic differences from heroin or pain pills. Those differences, including the long half-life and ceiling on agonist effects, allow the medication to create a level degree of mu-receptor agonism across the dosing interval.  Tolerance to that level mu agonism allows patients on the medication to feel ‘normal’ throughout the day, or at least normal from an opioid standpoint.
But her broader point provides an example of the basic misunderstanding many people have about medication assisted treatment, in focusing on the same short-term goals that their addicted loved ones have focused on: controlling the dose of opioid and tapering off.  That goal is natural, of course;  anyone who loves a person addicted to opioids wishes and hopes that the person will reverse the using behavior and climb down from opioid use.  Those hopes are bolstered by ads for rapid detox, even as studies show that detox is mostly useless.
My response:
I would not be concerned about increasing the dose of buprenorphine, because there is no increase in effect after a dose of about 8 mg per day.  A higher dose might reduce mild withdrawal symptoms at the end of the dosing interval, and sometimes provides a reduction in cravings through a placebo effect.
So why increase? Because the goal with buprenorphine treatment is to put cravings into remission for a considerable length of time. If your husband is still having cravings as he gets by on 8 mg, then his dose is not high enough. Buprenorphine is a safe medication that is used as a tool to extinguish the conditioning that was part of your husband’s addiction.
One of my patients saw a different buprenorphine physician for years, and her dose was constantly lowered over the past year. She would run out of medication after 24 days each month and then go without for 6 days, craving opioids and experiencing wtihdrawal during that time.  In some ways, her entire time in treatment was a waste.  She could boast, I suppose, that she was prescribed less buprenorphine over time. But in most ways she is just as far from stopping opioids as when she entered treatment, still lying to her husband, lying to her doctor, and feeling ashamed of herself.   All of those things  keep her addiction in the dark, where it stays active.
When I started treating her my goal was to promote legitimate behavior. I increased her dose to 12 mg per day, from 8 mg.   After a month she still ran out early, So I raised the dose to 24 mg per day. Now, after 6 months, she has taken the medication as prescribed. Her focus on buprenorphine is going down, as we want it to do. She isn’t lying, and she isn’t craving pain pills or buprenorphine. My goal is for her to take the medication like she would take a vitamin or blood pressure pill, without any special attention or interest.
How long will we do this? I can’t say now. We know from research that the longer a person stays on medication, the less risk of relapse after stopping. I don’t like to push anyone off buprenorphine, because I’ve seen so many people who have relapsed after being pushed off by their former doctors.  I find that many people eventually decide that the time has come to taper off buprenorphine, and those efforts are usually successful.  From my perspective, people forced to taper off buprenorphine do not generally do well.  That perspective is just an opinion, but an opinion based on treating 800 people with buprenorphine over the past 11 years.
Opinions aside, the goal is not about getting off opioids as fast as possible. Your husband can accomplish that in a couple weeks with a remote hotel room and a bottle of clonidine, or a couple weeks in jail. But those experiences rarely lead to prolonged abstinence, and they sometimes precede overdose, when people return to using with a lower tolerance.
I can’t tell whether your husband’s doc is on the right track or not– but she might be. She is a better doctor telling you that she can’t give a time estimate, than a doctor telling you he will be off in 3 months.  Ideally, your husband will be in a state of ‘remission’– on a dose of buprenorphine that virtually eliminates interest in opioids– for a year or more. He can taper for some of that time, but the taper should be slow enough that he doesn’t return to using.  If he returns to active use, he starts over in many ways.
Try to drop the focus on ‘how much’ or ‘how long’. Those things are not important; what is important is to get his interest back on you and the family, not on buprenorphine or other opioids. That will be easier if you let him know that he has your support, even if he takes a medication, and even if he needs that medication for a long time. You would want the same from him if you ever needed a medication for hypertension, diabetes, or anything else.

Raising the Suboxone Patient Cap

HHS Secretary Sylvia Burwell announced yesterday that the cap on buprenorphine patients would be raised in the near future.  Details were not released, but she emphasized that measures would be taken to increase availability of this life-saving treatment, while at the same time taking caution to prevent misuse of the medication.   Anyone who works with buprenorphine understands the importance of her announcement.  I only hope that her actions are swift, and not overloaded with regulations that reduce practical implementation of whatever increases are allowed.
I have been at the cap for years, unable to accept new patients for buprenorphine treatment.  My office receives 3-4 calls each day on average from people addicted to heroin, begging for help.  Patients on buprenorphine (the active substance in Suboxone) are much less likely to die from overdose than are patients not taking buprenorphine– even in the absence of perfect compliance.  Some doctors, in my opinion, over-emphasize the ‘diversion’ of buprenorphine medications.  At least in my part of the country, ‘diversion’ of buprenorphine amounts to heroin addicts trying to stop heroin, taking ‘street buprenorphine’ because of the absence of legitimate treatment spots.    Of the few new patients I’ve been able to take this year, almost all have histories of using buprenorphine products on their own, without prescriptions.  They are very happy to finally have a reliable source of the medication– and to have the medication covered by their health insurance!
Let’s hope the increase in the cap happens sooner rather than later.  After all, lives are literally hanging in the balance.

Menzies Gets it Wrong

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

Another Suboxone Argument

It has been awhile since I posted a give and take with a misguided reader. I’ve taken that interval as good news that education is winning over misinformation.
But then I read this comment.  I didn’t fix her typos, as I think they provide insight into her opinion:
My daughter was on Suboxone, because she was a heroin addict, when she could not afford this med, the withdrawal lasted for mnths, and was far worse than I have ever seen her go through Heroin withdrawal. These are a Psyhiatrist facts, I absolutely hate Suboxone, YES peple do get high on Suboxone, Yes they absolutely can and do inject this garbage. This medication may have helped people who were not addicts for pain, or addicts who truly took this drug to remain clean, and that’s o.k BUT NO THE DRUG COMPANIES are not going to put the facts out about this dug, and about the deaths caused from overdosing on this drug using it in combination with other drugs. They will not report the abuse of this drug, and the effects of this drug on the bodies organs or how it causes Bone Marrow depression. THE TRUTH WILL COME OUT NO MATTER HOW THE DRUG COMPANIES AND GOOD OLD DOCS, TRY COVER IT UP. Half these Suboxone Dr’s are addicts themselves, I took my daughter to one who’s pupils were so pinned, he was slurring and could hardly stay awake, HMMM Could it be he was abusing the same drug he was supplying. They had a great plan for getting people on it but none what so ever for getting people off of it. The Truth about Suboxone will come out. It should be used only for detox only taken no more than for 10 days. I am a Drug and ETOH detox Nurse, so I have seen not just with my own child, but with clients who, by the way do abuse the drug sell it on the street, so they can buy heroin. IT’S A MONEY MAKER FOR BIG PHARMA, AND THE MAKER OF THIS DRUG PAID DOCTORS THOUSANDS TO BECOME CERTIFIED TO PUSH THIS POISON. I will get the true facts of this drug, but Do NOT JUST PUSH THE PRETTY SIDE TELL THE TRUTH ABUT THE UGLY AND YES SOMETIMES DEADLY SIDE. DR. My daughter committed suicide January 4th 2015 overdose of heroin, among other substances. She went to heroin again because she started going through post SUBOXONE withdrawal. The withdrawal last weeks to months with post withdrawal. So please do make this sound like a miracle drug that saves lives, it also kills and that truth will come out. I am sick of these companies, hiding the facts! Facts to me because I have lived it and have seen personally the effect of this drug.
I responded as follows:
I wish you were at least partially correct, given that you work in the field, and have the potential to spread such inaccurate information.
Deaths…  in the past ten years there were about 35,000 overdose deaths in the US.  None of those people had buprenorphine in their system when they died.  What number of people had measurable amounts of buprenorphine in their bloodstream when they died from overdose?  40 per year.  Most of those 40 people would be alive if there had been more buprenorphine in their bloodstream– the only exception being the few cases each year where a young child ingested the drug.
Note that 400 people die from Tylenol each year in the US– compared to 40 deaths of people who had buprenorphine in the bloodstream.  It is very hard to die from buprenorphine;  those who die must have little or no opioid tolerance, and must also take a second respiratory depressant that they have little tolerance to.
Bone marrow depression?  Really?  Buprenorphine has been in use for almost 40 years.  It has a better safety profile than most meds out there.
‘Plans for getting people off’?  The whole point of buprenorphine is to provide chronic treatment for a chronic illness.   You apparently want something that instantly changes the brain and erases addiction, but that product is not invented yet– and I wouldn’t hold my breath for it.  Your daughter developed a condition that will last the rest of her life.  She will treat it for the rest of her life.  She can take a medication each day, or she can attend meetings several times per week. The latter approach works, mind you, only in the relatively few people who are moved by the 12-step message.  Both approaches must last for years and years, if not a lifetime.  Many people do well on buprenorphine, but some survive without it.  But if she isn’t attending meetings or doing something with similar intensiy, her prognosis off buprenorphine is not good.
The withdrawal from the partial agonist buprenorphine is less severe than from agonists.  ALL opioid withdrawal lasts for 2-3 months, and is followed by post-acute withdrawal.  On buprenorphine, a person’s tolerance is equal to 40 mg methadone per day.  Realize that heroin addicts typically have tolerance that is several times higher.  Your daughter developed a high tolerance to agonists, and then continued to have a high tolerance on buprenorphine.  Any addict, including your daughter, is facing months of detox.  Buprenorphine delayed the detox, giving her the chance to get her act together first.  Many people are successful with that approach, but some blow the chance and keep up the negative behavior.  Buprenorphine relieves cravings;  it doesn’t fix personalities all by itself.
I suspect that the reason you never saw such bad withdrawal in your daughter coming off heroin is because she could never stop heroin long enough to demonstrate 2 months of withdrawal.  Nobody just stops heroin; they stop for a couple weeks and then use again.  On the other hand, many people taper off buprenorphine, and have the chance to experience the full course of opioid withdrawal.
The cost…  The drug companies make much more money from chemotherapy, anti-hypertensives, pain pills, and other meds.  Reckitt Benckiser, the biggest maker of Suboxone products, recently spun off the drug because of the anticipated losses.  Even if buprenorphine was a blockbuster, though, I have nothing against drug companies being rewarded for the risks they take to develop new meds.  There is no doubt that the efforts to market buprenorphine have saved thousands of lives.
If your daughter sold her buprenorphine to buy heroin, that’s her bad.  Most people do not do that, but some probably do.  Understand that heroin is very addictive, and drives all sorts of bad behaviors– theft, prostitution, robberies, etc.  I guarantee you that selling her prescription of buprenorphine alone did not make enough money to pay for a heroin habit.
There are so many things you have wrong…. ‘the drug companies paid doctors to push this drug’… I’m sorry, but you are clearly a zealot, and I can’t even take you seriously with that argument.  If you know of a single doctor paid to prescribe a drug, call the Feds, as that would be a crime.  There are some doctors paid to WORK for pharma— to give lectures about new drugs, for example.  I have done that in the past for drugs I believed in.  Some people seem to hate it when doctors take any money from pharma, but when they do, it is for work–  for travelling to some cheap motel in the middle of nowhere and giving a talk to a group of doctors.  The work is highly regulated, and just like TV commercials, docs are required to stick to a very narrow script that educates, rather than promotes.
‘Detox’ has been marginalized (thankfully) because of recognition that it does nothing to treat addiction.  Likewise, non-medication treatment has very low success rates, especially if you count everyone who enters the door, instead of blaming those who fail for ‘not wanting it bad enough’.
I’m sorry about your daughter.  But one thing many parents eventually realize is that even when a kid is acting irresponsibly, buprenorphine at least keeps them alive.  Buprenorphine allows people to stay alive, even if their recovery is imperfect.  And relieved of most of the cravings to use, many of those patients eventually get it right.
Back to the present…  I’d like to think that I cleared up some misconceptions.  But two days after my comments, I received a very similar set of comments from the same person—except that most of the words were capitalized.  That is the reason I’ve tired of these types of posts….

Quantitative Urine Drug Testing and Buprenorphine: Tainted Motives?

First Posted 11/23/2013
As fear of buprenorphine diversion sweeps the nation, some states have passed legislation adding more rules for practices that treat addiction using buprenorphine.    Never mind that buprenorphine is linked to about 400 deaths over ten years, one tenth of the number of deaths from acetaminophen during that same time, and 0.1% of the number of overdose deaths overall.

Many parts of the country have seen a reduction in number of buprenorphine-certified physicians over the past few years.  Many rural areas have no buprenorphine prescribers at all.  The lack of prescribers, combined with the limit of 100 patients per prescriber, leaves opioid addicts with one legitimate treatment option— the early morning line for methadone or buprenorphine at methadone clinics.  I’m not against the clinics, but the need to report each morning is a significant barrier to employment in many patients who would do just as well with a prescription for the medication—and a first-shift job. Their other option is to do what all the news stories have been reporting—use buprenorphine without a doctor’s supervision and attempt to stop heroin or pain pills on their own, aka diversion.

One clue about your own state’s buprenorphine policies is whether your doctor is still prescribing buprenorphine products, or has instead moved to an area of medicine where doctors make decisions according to clinical judgment.  As the number of buprenorphine/naloxone prescribers in my part of the country has decreased, the amount of diversion has increased.  I predict that policies that discourage doctors from treating opioid dependence will increase the number of addicted people trying to treat themselves.

Sometimes it is easy to predict unintended consequences.

Regulatory agencies of at least one state prevent insurers from covering specific, FDA-approved medications.  Other states require doctors to follow specific practice patterns instead of their best clinical judgment.  One example of oversight that demonstrates the folly of lawmakers playing doctor is the push to require ‘quantitative urine testing’ in all patients at frequencies determined at the state capital, rather than by the doctors treating the patients.  The expectation is for quantitative testing to reduce diversion.  Note that 30,000 overdose deaths per year from non-buprenorphine products never prompted such oversight, nor did the well-known ‘pill-mill’ pain clinics that have flourished for the past decade.  But an average of 40 deaths per year related to buprenorphine has demanded action by lawmakers!
There are times when quantitative testing is useful, but I suspect that legislators who voted to require such testing heard only the half of the story told by people with vested interests.  After all, quantitative testing is one of the more lucrative areas in all of healthcare.  Even Medicaid agencies that pay pennies on the dollar for office visits pay generously for testing with the right billing codes.  Turn-key testing businesses can be purchased by entrepreneurial doctors to grow revenue at pain clinics, leasing out testing equipment and training techs in return for a piece of the action.

What legislators SHOULD know:

Quantitative urine tests for standard drugs of abuse in just one patient can cost well over $1000.  Costs over $500 per test are the norm.  The costs are paid by insurers, Medicaid, or patients, increasing insurance premiums and taxes and blocking treatment for some patients.

‘Point of care’ test strips that use immunoassay methodology are sensitive and accurate.  A standard test kit shows the presence/absence of trace amounts of specific opioids (methadone, oxycodone, or heroin/morphine derivatives), amphetamine, benzodiazepines, cannabinoids, cocaine, PCP, barbiturates, and buprenorphine.  Typical test kits give all the results for a total price of $5-$10.

Almost all the decisions related to testing rely on the presence or absence of substances—not the number of nanograms of a substance.   The point is whether a patient used heroin or cocaine—not how many milligrams of heroin or cocaine were used.  Test companies claim that measurement of buprenorphine’s first breakdown product, norbuprenorphine, can determine if a patient took buprenorphine only recently to fool the doctor. But I receive dozens of emails each year from patients with nothing to gain by describing their experience in those cases, swearing that they were taking the medication correctly, and asking how they can prove their truthfulness after what is called ‘flipped levels’ in such testing.  Besides, anyone with knowledge of addiction knows how difficult it would be to pull of such a scam. The scammer’s urine would still contain the drug of abuse, unless we suppose the unlikely scenario where scammers successfully stop all opioids for a week each month and experience withdrawal each time, all for the sake of a script for Suboxone.  Beyond the misery, few addicts would be able to control use of narcotics to that extent.  That’s why they are addicted in the first place!

‘Quantitative urine testing’ measures the concentrations of substances in a patient’s urine.   But urine concentrations of substances are not accurate reflections of blood concentrations of the substances.  The first part of kidneys (the glomeruli) act like sieves with very large pores, spilling gallons of dilute liquid that contains drug metabolites and other molecules.  The largest parts of our kidneys consist of tubules that reabsorb water and reabsorb or secrete other molecules and ions.  When that liquid finally reaches the exit from the kidneys at the ureters, the original filtrate has been concentrated by several orders of magnitude, and has had a range of molecules removed from or secreted into it.  Water reabsorption depends on hydration status, circadian rhythms, diuretic and other medications, stress hormones, diet, and other factors.  As a result, concentration of a substance in the urine is not related to concentration in the blood—let alone to the use of the substance.  Blood levels provide far-more-accurate information, but even blood levels vary from differences in metabolism of substances between individuals.
Quantitative testing tries to overcome the gap between blood and urine levels by using levels of other substances, such as creatinine or urea, to estimate the extent of concentration performed by the kidneys.  But there are enough variables to make the results far from reliable.  But frankly, the inaccuracies don’t really matter—since in most cases the presence or absence of a chemical is the issue, not the concentration.

In an era when costs are a concern, why would states become involved in testing processes that force a dramatic increase in treatment costs?   Doctors who know their patients are in better position to decide when such testing is valuable.   In medical school 25 years ago, I learned about the inefficiency of shotgun approaches to lab testing—that instead of ordering routine chemistry panels for every patient, doctors should decide which specific tests are necessary and order accordingly.  To mandate such expensive testing, someone is deciding ‘yes that’s true, but….’.   The annual climb in the cost of healthcare is largely due to those and other ‘buts.’

The only reason the state would think that they know better—from hundreds of miles away, without meeting the patients—is if they assume that doctors treating addiction don’t care what their patients are doing, or are inept.  But if the same inept doctors are the people interpreting the results of mandated quantitative testing, what does the mandate add, exactly?  And why the selective oversight of doctors who treat addiction, when most of the harm from drug diversion comes from opioid agonists prescribed by doctors who don’t work in the addiction field?

Other mandates include the rules found on standard opioid treatment contracts.  The rules themselves are not unreasonable.   But I take issue with the double standard applied to addiction physicians.  Expensive residential treatment programs have abysmal success rates.  Should they be regulated?   People who have too much plastic surgery look ridiculous—should that be regulated?  Everybody talks about the epidemic of opioid overdose deaths— deaths caused 99.9% of the time by something other than buprenorphine, the most effective treatment for opioid dependence.  But it’s buprenorphine that needs regulating?

Suboxone Abuse Pt I

First Posted 8/11/2013
We’ve all read articles about the epidemic of opioid dependence during the past ten years.  We’ve heard the concern over pain medications being overly-prescribed by some physicians.  Some of us older docs even remember the claims, by the Joint Commission on Hospital Accreditation and other medical watchdogs, that physicians were undertreating pain and were in need of education to increase their responsiveness to suffering patients.
We witnessed the increased use of potent opioids, a trend favored by regulators and fueled by the growth of ‘health systems’, large hospital and provider businesses that added the concept of efficiency to the doctor/patient relationship.  Along with insurance networks, the systems eliminated many traditional aspects of healthcare in the US, leaving behind a system where one doctor is easily replaced by a different doctor, and doctors who take too great an interest in their patients’ welfare are seen as paternalistic.
We remember the controversy over Oxycontin, a delayed-release preparation of oxycodone that was claimed to have less addictive potential.  Purdue eventually paid $600 million over claims that their sales force misrepresented the risk of diversion and overdose of Oxycontin.  Never mind that the product truly was less addictive than the immediate-release drug that it was intended to replace.  Purdue did not foresee that they would be held responsible when the pill was crushed, snorted, and injected, and the drug was a handy scapegoat.  But more about scapegoats later.
In the late 1990’s the combination of two old drugs created ‘Suboxone’, which hit the US market in 2003.  The epidemic of opioid dependence continued to grow, and overdose became the leading cause of death for young adults in many parts of the country.  Suboxone and buprenorphine have prevented thousands of deaths during that time, but now are considered contributors to the problem.  Even as hundreds of thousands of patients benefit from proper use of buprenorphine, the deaths related to buprenorphine and Suboxone, measured in dozens, capture headlines.
Opioid dependence has long been known as a permanent, lifelong illness that requires long-term treatment.  But the long-term nature of the illness is lost on some people who have come to see effective long-term treatment— a concept not even considered a couple decades ago— as a problem rather than a solution.  The features of buprenorphine treatment that increase compliance and effectiveness, such as discontinuation effects (a.k.a. withdrawal), are viewed as drawbacks.  Many people eventually ‘freed’ from Suboxone die within a year of stopping the medication, and countless others return to desperate lives of active addiction.  Yet more and more, the lifelong addiction faced by opioid users is blamed not on the long-term nature of the illness, but on the presence of life-preserving treatment.
Physicians who treat patients with opioid dependence using buprenorphine are not the best positioned to defend the treatment.  One of the most common arguments against treating people with buprenorphine is that doctors want to keep people on the medication ‘for the money.’   How do I argue that I’m NOT in it for the money?
I read a blog post today that used what the writer considered ‘conservative estimates’ to conclude that doctors prescribing Suboxone could make as much as $150,000 per year.  The estimates require that the doctor’s buprenorphine practice is completely full—not a horrible assumption given the number of people in need these days, but the reason practices are full is because few doctors want to take on the difficult aspects of treating patients with addictions, such as the high rate of no-shows that leave doctors with hours of unused time.  The writer assumed that every one of the 100 patients is seen monthly, apparently for however long they take the medication—something at odds with most physician practices. The writer assumes no overhead, leaving out the cost of rent, malpractice insurance, furniture, office staff….   Do you know what an ad in the yellow pages costs?!
But even if I used his numbers, does it matter that doctors who prescribe buprenorphine have the same education (and education debt) as other physicians—i.e. at least 4 years of college, 4 years of med school, and then internship, residency, and annual CME?   Medical students (including future buprenorphine prescribers) where I lecture graduate with debt literally in the hundreds of thousands of dollars.  The future anesthesiologists, surgeons, radiation oncologists, dermatologists, and radiologists will average salaries 2-4 times greater than their classmates who decide to treat addiction using buprenorphine.
Does it matter that the people arguing against long term treatment with buprenorphine are generally in favor of using buprenorphine SHORT term—which is exactly the way to make money off buprenorphine?  Does it matter that the doctors who make a lot of money are the same doctors whose patients do the worst—the doctors who market buprenorphine detox?
I suspect that the answer is ‘no.’ I’ve debated this issue on my forum, with visitors who stop in to argue against the use of buprenorphine.  I suspect that just mentioning the word ‘money’ makes it easier for such people to see me as greedy.  Envy wins over logic, at least when it comes to headlines.

Addicted to Suboxone

First Published 7/23/2013
I hear from the anti-buprenorphine people now and then, less than I used to.  I also hear from fans of this blog’s early days, when I routinely lost my temper in response to those people.  Their general line was that things on heroin weren’t all that bad, but now, on buprenorphine, things are miserable.  Starting buprenorphine somehow removed an opportunity to be clean that they used to have, that they would have used if not for buprenorphine.
They somehow miss the obvious—that they could ALWAYS go back to the heroin addiction that worked so well for them.  They’ll say they could stop heroin any time they wanted (you know the joke—‘It is so easy to quit that I quit a hundred times!’), but act as if someone is forcing them to take buprenorphine.
If it is so easy to stop heroin, why not go back to heroin and stop?
For the record, I don’t advise people on buprenorphine to change to heroin.  It is difficult to wean off any opioid, including buprenorphine.  But I do have patients who have tapered off buprenorphine; something I’ve never witnessed with agonists like oxycodone or heroin (i.e. tapering outside of a controlled environment).    Most people who read my blog know that I don’t recommend tapering off buprenorphine for most people, an opinion I’ve come to after seeing many people relapse, and some people die, after stopping buprenorphine.
I received a typical anti-bupe message yesterday; the message and my response are below.  There are a few typos that I can’t decipher….
Errors of logic, anyone?
Subutex was the worst mistake I ever made. I was an off and on heroin user for 5 years. I was clean for over a year and relapsed that when I survived Subutex first I was getting it off the streets then my wife ego had the insurance got a script. She was pregnant so the doctor prescribed Subutex. She told her that her brain would never be the same from her opiate use and would need Subutex most likely for the rest of her life. We both were quickly using it IV IT killed our sex life. It made me feel like a woman or something I have no libido at all. I quit using it IV for 9 months then started again which caused me to have a full blown relapse I’m in 12 step recovery. I lost our home shortly after our new born son was born forcing her to move in with her parents and I moved into an sober living house. We are now both trying to taper off this drug that it’s overly prescribed. The doctor put her on 26mg a day mind you we shared but the doctor doesn’t know that. I do believe in short term low dose setting this drug has a therapeutic value. But I believe it’s been designed to get money lost to drug dealers into the pockets of our government. I kicked Heroin and Oxycontin more then once. Getting off Subutex has been the toughest one yet the physical and mental withdraws are horrible. The best bet for addiction treatment is 12 step meetings. All Subutex or Suboxone does is give you a crutch and prolongs actual recovery from the disease of addiction. They don’t tell you about all the terrible side effects behind this medication its marketed as a miracle drug. A wise man once said if it sounds too good to be true then it’s probably not. Rant done hopefully this helps someone. The answer to recovery is the 12 and staying sober 1 day at a time, most important a relationship with a higher power.
My Response:
An interesting comment… You’ve taken heroin for over five years as an ‘off and on user’.  You then illegally obtained buprenorphine, and injected it (!)… illegally shared what a physician prescribed for your wife… but it’s all buprenorphine’s fault that you are experiencing problems?  Part of the 12 steps that you favor includes taking responsibility for what happens in one’s life, yet I don’t hear a lot of that in your narrative.
I don’t know about ‘miracle drug’, although it probably has saved the lives of both you and your wife, since IV heroin addicts don’t tend to do well beyond 5 years.  There is nothing in your history to suggest that your ‘on and off use of heroin’ would have somehow come to an end, had you not changed your drug of choice to buprenorphine.  But one aspect of buprenorphine is the ‘ceiling effect’, which makes overdose much less likely.
Likewise, I don’t see a government conspiracy, and I disagree with your comment about ‘low dose use’.  Buprenorphine HAS been used in low dosage for treating pain for the past 30 years, but everything about buprenorphine that makes it a good addiction treatment relies on the person taking a dose that assures a high blood level, i.e. above the ceiling level for the drug’s effects.  In low doses, buprenorphine acts like any other agonist– i.e. causes the same up/down mood, cravings, and obsessive use pattern.
Your problem is that you became addicted to opioids, and your opioid addiction has cost you a great deal.  You misused buprenorphine by injecting it, but luckily for you the drug has certain safety features that helped keep you from overdosing– something heroin doesn’t have.    But now you blame buprenorphine for all your problems.
I certainly do not suggest that you do this, but for the sake of making a point—-  you could easily go right back to where you were, before you met buprenorphine, if you returned to your addiction to IV heroin.    If you started heroin tomorrow, the buprenorphine would be out of your system in a week or so, and… voila….. you would be ‘cured’ from this horrible affliction that you claim to have, i.e. an addiction to buprenorphine.  Or are you going to suggest that taking sublingual buprenorphine was somehow WORSE for you than doing what you were doing before finding a doctor, when you were injecting foul solutions of heroin into your veins?!  You were FINE with the heroin, but BUPRENORPHINE has ruined your life?
Sorry– I don’t buy it.  Most people who stop ANY opioid– buprenorphine, oxycodone, or heroin— end up using again.  Buprenorphine, as a partial agonist, relieves cravings in a way that opioid agonists can’t.  And taking buprenorphine certainly doesn’t make anything ‘worse’;  a person addicted to heroin, who doesn’t like taking buprenorphine, can always go back to heroin!  I don’t recommend it, as the overdose risk is very high with heroin, and people on heroin suffer from constant obsessions to take more and more– a life far worse than the person properly taking buprenorphine.
This is where I come in… THESE are the patients I see on a regular basis.  The doctors who used to call them ‘good patients’ now call the same people ‘drug addicts.’  And the pain doctors—the ones who create so many addicts—give lectures on ‘how to prescribe opioids.’   I can spare you the need to attend the lecture— the main message is that after you make the patient an addict, you must do everything that you can to separate yourself from the patient before the consequences of that addiction become apparent—so that your hands appear sparkly-clean!

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.

Urine Drug Testing on Suboxone

First Posted 2/15/2013
A recent exchange with a reader:
I have been on buprenorphine for 5 yrs.  Recently my doctor stated that my u/a t looked like I have been ‘loading my meds.’  He said my levels where ‘backwards’ and that would happen if I took just a few doses just before my appt.   My doc had me come back in two weeks to go over my next u/a, and again it came back funky.  So my doc starts having me take my meds in front of the nurses on a daily basis.  Two weeks later with supervised u/a’s, my urine comes back the same.  My doc looked perplexed but kind of ignored the results like I was still doing something to mess with the results.  I had to come in again for another urine test and it finally came back normal.  My numbers were fine after that, and all was good until last week.
I went to my normal monthly check up and the u/a showed NO buprenorphine in my system.  My doc looked at me like I am the biggest liar.  I am perplexed.  I am taking my meds daily.  I don’t know what is going on and I need to figure it out soon before my doc kicks me out of the program. What could be wrong with the test, that is says that I have no buprenorphine in my body?
My response:
There are several directions we could go with this issue.  One aspect is whether it is always fair to believe the results of drug tests over the word of our patients.  I understand the reasons for testing, but I think that doctors sometimes lose the forest (the patient’s addiction problem) on account of the trees (quantitative testing).  This patient has been on buprenorphine for five years; I would hope to have sufficient trust established with patients after that period of time, such that the lab results wouldn’t be seen as the only answer.  There can be problems with any laboratory test.  Drug tests are one tool– not the ultimate arbiter of truth.
Most people metabolize buprenorphine a certain way, leading to the build-up of a chemical called norbuprenorphine.   I assume that by ‘backwards’ the doctor is saying that the buprenorphine level is higher than the norbuprenorphine level, whereas with daily use of buprenorphine the opposite would be true. As your doctor said, if a person takes one dose of buprenorphine and is tested an hour later, buprenorphine would be present, with only small amounts of the metabolite norbuprenorphine.
Urine tests for any substance are affected by many variables, including the actions that different parts of the kidney have on certain substances.  Some substances are concentrated at the kidneys, making urine testing more sensitive than blood testing.  But other substances might be re-absorbed by the kidneys to a varying degree, depending on hydration status, nutritional and dietary factors, hormonal factors, and personal genetics.  Because of concentration and reabsorption effects, the drug levels from urine tests are not accurate indicators of drug levels in the bloodstream.
In addition, the metabolic pathways for certain substances might be changed by the presence of other substances.   For example, if the enzyme that turns buprenorphine into norbuprenorphine is blocked or occupied by other substances, the pathway may change such that metabolites other than norbuprenorphine are formed—- including metabolites that won’t show up unless they are specifically tested for.
I asked the patient:
Are you taking any other medications?  Are you able to get the actual lab results showing the details of the test?
She replied:
I thank you for responding to me.  I am on many medications because I have fibromyalgia among many other things.  My list of meds:
Prozac 20 mg; Provigil 200 mg; Clonidine 0.1 mg 4x’s a day; Amlodipine 5mg once a day; Nabumetone 500mg 2x’s a day; omeprazole 20mg once a day; Ambien 10mg per day; Relpax when I have a migraine; Buspirone 10mg about 2x’s a day; Subutex 16 mgs per day. I also take diphenhydramine 50 mgs at bedtime when needed to help sleep, and Vitamin D3-1000 iu once per day.  I take this because my blood tests showed it was low.
I asked to see my results and my doctor told me that I didn’t need to see them; that he had told me what it said and that it should be enough for me to know.
The receptionist in the office is getting the number to the lab for me.  Do you have any questions that I should ask?  What should I know?  I am going to ask for a copy of my labs at my next visit.  I am nervous that my doc will just stop prescribing.  This medication has saved my life and I don’t know where I would be without it.  Please help me make my doctor believe in me again.  I know that is a lot to ask but I’m in trouble.  Where can I turn?  There aren’t any Suboxone docs in my area taking new patients.
(A couple thoughts)
Over my 20 years as a physician, I’ve come across times when tests were mistakenly trusted over the word of patients.  At a maximum security prison for women where I worked as a psychiatrist, for example, many women were disciplined for diverting clonazepam, until a call to the lab revealed that testing wasn’t reliable for that medication.
Over time, we learn more and more about how the metabolism of one medication impacts other medications.  One such interaction was apparent in this person’s case.
My comments:
The most obvious interaction from your list is that Provigil is an ‘inducer’ of cytochrome 3A4, the enzyme that breaks down buprenorphine.  A person taking Provigil develops greater amounts of that enzyme in the liver, which results in faster metabolism of buprenorphine.  The first step in metabolism of buprenorphine is conversion to norbuprenorphine, so levels of buprenorphine and norbuprenorphine would be affected by Provigil, in unpredictable ways.
From the program that I use to search for interactions: buprenorphine ↔ modafinil
Coadministration with modafinil (the racemate) may decrease the plasma concentrations of drugs that are substrates of the CYP450 3A4 isoenzyme. Modafinil and armodafinil are modest inducers of CYP450 3A4, and pharmacokinetic studies suggest that their effects may be primarily intestinal rather than hepatic. Thus, clinically significant interactions would most likely be expected with drugs that have low oral bioavailability due to significant intestinal CYP450 3A4-mediated first-pass metabolism (e.g., buspirone, cyclosporine, lovastatin, midazolam, saquinavir, simvastatin, sirolimus, tacrolimus, triazolam, calcium channel blockers). However, the potential for interaction should be considered with any drug metabolized by CYP450 3A4, especially given the high degree of interpatient variability with respect to CYP450-mediated metabolism. Pharmacologic response to these drugs may be altered and should be monitored more closely whenever modafinil or armodafinil is added to or withdrawn from therapy. Dosage adjustments may be required if an interaction is suspected.
That is just one of many possible interactions. When a person takes multiple medications, there are often other, less predictable interactions.  Some medications also interfere with the testing of other medications.  You may know that there are chemicals available on the internet to block the testing for certain compounds;  some medications do the same thing.
She answered:
I can’t thank you enough for even responding to me……  You are a very kind man!  I hope this helps me.  I am very scared my doctor will take me off my meds.
But then she wrote again:
I wanted to send you an update.  My doctor wouldn’t even look at the conversation we had.  I guess for whatever reason, he refuses to look deeper into the issue.  It is sad when a doctor has had a patient for over 5 yrs and he won’t look into this further.  I don’t ever have dirty u/a’s.  I don’t drink, I don’t smoke marijuana, I only take what he prescribes to me.  He refuses to look further into the matter so much that it is clouding his judgment.  He won’t even test me another way.  He states urine test are the most accurate but there is something wrong because I know that I take my meds.  He refuses to do another supervised dosage week because he doesn’t have the manpower.  
I know in his eyes that all I am is a drug addict but I deserve respect. Why would a man who believes in science have such a closed-minded view?  I would think he would at least want to discover what is happening.  There has to be more patients like me that are being thrown away because we don’t fit a certain mold.  When he throws me out of treatment on Monday, I have nowhere to go.  There are large waiting lists to see a doctor in my area. I can’t go back on the streets for medication.  I don’t have any of those friends left in my life.  I am in so much trouble.
I don’t know why I felt the need to vent to you but my hope was to find one person that believes me in hopes that this problem could be addressed someday, somehow.  Thank you for listening.  I do appreciate it.