Buprenorphine Overdose After Naltrexone Treatment

Naltrexone induces mu-receptor hypersensitivity.  Buprenorphine’s protective ‘ceiling effect’ may not prevent overdose in patients with this ‘reverse tolerance’.

A new patient described his recent history of respiratory failure several days into buprenorphine treatment.  He was told by his doctors that he experienced an allergic reaction to Suboxone. The rarity of buprenorphine or naloxone allergy led me to look deeper into his history, and my conclusion differs from what he was told by his last treatment team.

The patient, a man in his mid-50s, has a history of significant opioid use over the past 20 years.  He used a variety of opioid agonists over the past year, mostly prescription opioids, with an average daily dose greater than 200 mg of oxycodone per day.

Three months ago he went through hospitalization and detox, and after a week he was discharged on oral naltrexone.  He sought further treatment at a different institution that offered buprenorphine.  He was told to stop the naltrexone two weeks before induction with buprenorphine.

He avoided all opioids for that two weeks, and then started buprenorphine, 2 mg twice per day as directed by his physician.  The patient became progressively sleepier after each dose of buprenorphine, and after 24 hours could barely maintain wakefulness.  His complaints resulted in his admission to the hospital intensive care unit.

In the ICU he had a rocky course that included several episodes of apnea, hypoxemia and bradycardia.  The patient does not currently have the records from the hospitalization, so the course of events is based only on his recollections from several weeks ago.  He blacked out several times, and was told by doctors and nurses that his ‘heart stopped on the monitor’ during those times.  He says that his oxygen level was very low at those times according to the monitors, and according to what he was told.

After the episodes when he lost consciousness, he was told that since his heart stopped he needed emergency implantation of a pacemaker.  He said that a short time later those concerns were dropped, and no pacemaker was inserted.  He was discharged from the hospital in good condition after several days.  Follow-up with a cardiologist was not deemed necessary. He was told by his hospital physician that the episodes of lost consciousness were caused by an allergic reaction to Suboxone.  He had no rash or pruritus (itching).

I’m writing about this patient’s care in the form of a ‘case report’.  The patient does not have access to his records.  If he did, I would review them and write a formal case report for publication.  Since I’m relying on the patient’s perceptions and memories, I’ll use this blog.  I will say that I have no axe to grind, and my purpose in sharing this case is to help people avoid a similar situation.  And, of course, to keep readers of this blog entertained!

As the patient shared his story, I assumed that he had an opioid tolerance well-below the ceiling actions of buprenorphine.  When I mentioned my hypothesis, the patient smiled, and told me he had been using over 200 mg of oxycodone each day, blowing that theory to pieces.

But I returned to the same theory when he said that he followed the doctor’s orders very closely, including avoiding opioids completely for two weeks before induction.  I wondered, could a 2-week interval of abstinence lower tolerance so dramatically that buprenorphine resulted in overdose? Then the patient mentioned, in an offhanded way, that ‘he even stopped the naltrexone’.

I’ve written about the increased incidence of opioid overdose following treatment with naltrexone, a risk that is unreported and largely unknown beyond brief reports from Australia cited in the linked post.   Opioid antagonists, including naltrexone (the drug that makes up Vivitrol injections), induce ‘reverse tolerance’ in mu opioid receptors to cause a heightened response, and heightened respiratory depression, from subsequent exposure to opioid agonists.  Anyone close to the field of opioid dependence notices the increased frequency of overdose in patients newly released from confinement, whether in jail or in abstinence-based treatment.  The increased risk of death after a period of abstinence is related to the resetting of tolerance during abstinence.  A return to ‘normal’ use creates significant risk of overdose.

That risk is multiplied if the period of abstinence includes treatment with naltrexone.   Imagine a person who is using six ‘30s’ of oxycodone—180 mg—every 24 hours.  If that person waits a week and then goes on naltrexone, tolerance drops to zero and then to negative levels.  After a couple of weeks on naltrexone, a tablet of Vicodin has the potency of a tablet of Percocet.  That 180 mg of oxycodone now has the potency to cause respiratory arrest and death.

Buprenorphine is a partial agonist with a ceiling effect that prevents overdose in almost all patients who have even small degrees of opioid tolerance.   Almost all deaths from buprenorphine occur in people with limited or no tolerance to opioids.  In the presence of inverse or negative tolerance, the ceiling on buprenorphine’s opioid effect has less protective value.  Such was the case in the patient who is the subject of this discussion.

So what would have been a better plan?  Buprenorphine induction is always more dangerous in patients with low opioid tolerance, so careful patient selection will mitigate that risk.  In patients with low tolerance, reducing the starting dose buprenorphine to low-milligram levels does little to reduce the risk of respiratory depression because of the ceiling effect, which reflects the minimal difference in strength between 2 or 16 mg of buprenorphine.   Much lower doses of buprenorphine, on the order of 0.5-1 mg, are required to reduce risk of respiratory depression and overdose in patients with inverse tolerance to mu opioid agonists.

A second option would be to continue naltrexone through the induction process, and afterward gradually reduce the dose of naltrexone over a week or two.  As the block from naltrexone decreases, buprenorphine bound to mu receptors would gradually increase, allowing opioid tolerance to grow more slowly.  Precipitated withdrawal would not be a problem, as PW occurs when bound agonist is suddenly displaced by buprenorphine—  not when antagonists are displaced by agonists or partial agonists like buprenorphine.

Thankfully, the patient is now doing well, with no lingering problems caused by his course of treatment.  But the incident also relates to another common problem, i.e. the erroneous blaming of symptoms on medication ‘allergies’.  In an era of electronic medical records, that mistake often removes, permanently, a patient’s access to medication that may someday be helpful—and in the case of buprenorphine, irreplaceable.

This Suboxone Doesn’t Work!

Today on SuboxForum people were writing about their experiences with different buprenorphine formulations.  Doctors occasionally have patients who prefer brand medications over generics, but buprenorphine patients push brand-loyalty to a different level.  The current thread includes references to povidone and crospovidone, compounds included in most medications to improve bioavailability.  Some forum members suggested that their buprenorphine product wasn’t working because of the presence of crospovidone or povidone.  Others shared their experiences with different formulations of buprenorphine and questioned whether buprenorphine products are interchangeable, and  whether buprenorphine was always just buprenorphine, or whether some people respond better to one product or another.

My comments, including my observations about patient tolerance of specific buprenorphine products, are posted below.

Just to get some things straight about povidone and crospovidone (which is just another synthetic formulation of povidone),  both compounds are NEVER absorbed, by anyone.   They are part of a group of compounds called ‘excipients’, and are included in many medications to help with their absorption.  They act as ‘disintegrants’– meaning they allow the medication to ‘unclump’ and dissolve in liquids, such as saliva or intestinal secretions.

Molecules tend to clump together, sometimes into crystals, sometimes into other shapes.  A pile of powdered molecules molded, packed, and dried into pill form wouldn’t dissolve in the GI tract if not for povidone or other disintegrants.  I remember reading somewhere about cheap vitamins that could be found in the stool, looking much the same as they did when they were swallowed.  Not sure who admitted to doing the research for that article..

Buprenorphine IS buprenorphine.  Period.  The absorption isn’t affected much by excipients, because nobody ever complains that their Suboxone or buprenorphine won’t dissolve.  Povidone or crospovidone are also added to increase the volume, because an 8 mg tab of buprenorphine would be the size of 100 or so grains of salt.  Excipients like povidone and crospovidone also help some drugs dissolve, especially drugs that are fatty and don’t usually dissolve well in water-based solutions.   This last purpose does NOT apply to buprenorphine, since buprenorphine is very water-soluble.  Zubsolv is supposedly absorbed more efficiently in part because it dissolves very quickly, and maybe that is due to excipients.

I realize that when I write ‘bupe is bupe’ it sounds like I don’t believe those who complain about their medication.  But honest, I work with people over this issue every day…  I have an equal mix of people who insist Suboxone doesn’t work for them and people who insist ONLY Suboxone works for them.    Today I was reading TIP 43–  a guide about medication-assisted treatment put out by SAMHSA and the Feds that is over 300 pages long, very well-cited– in a section that cited studies about the psychological triggers for withdrawal symptoms.  TIP 43 and other TIPs can be downloaded for free… just Google them.  TIP 43 is primarily about methadone, but some of the information applies to methadone and buprenorphine.  The pertinent section was around page 100, if I remember correctly.

The TIP information mirrored what I see in my practice.  For years, I’ve noticed that patients will complain about withdrawal symptoms even at times when their buprenorphine levels are at their highest.  Patients also report that their withdrawal symptoms go away ‘right away’ after dosing, when in fact buprenorphine levels won’t increase significantly for 45-60 minutes.  People who have been addicted to opioids may remember how even severe withdrawal mysteriously disappeared as soon as oxycodone tabs were sitting on the table in front of them.   The bottom lline– withdrawal experiences are remembered, and those memories are ‘replayed’ in response to triggers or other memories.

In my experience as a prescriber, I’ve come to believe that patients with an open mind will learn to tolerate any type of buprenorphine (the exception being the 1 patient I’ve met who developed hives from meds with naloxone– hives that appeared consistently on three distinct occasions).  But withdrawal symptoms seem to be triggered, in many people, by the expectation of withdrawal symptoms.  So someone convinced he will never tolerate Zubsolv, Bunavail, or Suboxone Film will probably never tolerate those medications.

As for buprenorphine, it IS just buprenorphine.  Molecules with a certain name and structure are always identical to each other.  They are not ‘crafted’ products like bookcases or tables;  some buprenorphine molecules aren’t made with a quality inferior to other buprenorphine molecules.  And once a molecule is in solution, I don’t see much role for excipients.  Of course a tablet or strip could contain too much or too little active drug, but that is an FDA issue, not an excipient issue.

Blame Suboxone!

First Posted 3/24/2014

I recently came across the blog of a person who has dedicated his life to trashing buprenorphine treatment.  I won’t provide the name or link, as I don’t want to waste my own ‘page rank’ on supporting his misplaced anger.  But I suspect many readers of my blog have stumbled across that one as well, given the similarity of our keywords.    His blog doesn’t contain personal comments, I suppose because there are only so many ways to say ‘darn that Suboxone’.  Instead he auto-posts stories from across the country from newsfeeds, with keyword combinations of ‘Suboxone’ or ‘buprenorphine’ plus ‘robbery’, or ‘death’, or ‘overdose’, or ‘real bad person.’  I made the last one up, but you get the idea.

The person lost his son several years ago, a tragedy that would usually keep me from adding my own commentary.  But in the several years since his son’s death, he has written a number of diatribes on other anti-buprenorphine web sites.  In other words, he has contributed to the deaths of enough young people that by now, counterpoints are long overdue.

In his ‘about me’ section, he writes that his son took Suboxone for about 18 months, and died over two years after stopping buprenorphine/Suboxone.  He explains, in twisted logic, how the death is not the fault of his son’s drug addiction, or the drug dealers, or easy prescribing of prescription opioids or diversion of opioid agonists, or poppy policy in Afghanistan… but because of Suboxone.

He argues that his son’s Suboxone treatment was a ‘waste of time.’  I don’t understand that argument.  Suboxone added 18 months to his son’s life—and if his son had continued taking it, would likely continue to keep his son alive.  Hardly a waste of time.

I’m always impressed by how two people can see the same information and come to opposite conclusions.  He writes that during his son’s time on Suboxone, his son was prescribed over 13,000 pills, including opioid agonists and benzodiazepines.  He doesn’t say who it was who prescribed those 13,000 pills, and doesn’t apparently hold any ill will toward the people who did.  Instead, he blames Suboxone for not keeping his son from doctor shopping, for not keeping doctors from being duped by his son, and for his home state not having the type of database that tells doctors about problem patients.  If a ‘good medication for addiction’ is going to have to do all of those things, I wouldn’t hold out much hope for a new drug approval anytime soon!

The logic he uses on the web site brings to mind a recent encounter with a patient who has successfully stopped opioids, but who is struggling with other addictive substances.  Suboxone (or buprenorphine) is one piece of a person’s recovery, and does that one thing remarkably well.  Suboxone reduces cravings for opioids, making it much more likely that a person willing to do his part of the work will be successful in stopping opioids.   But it doesn’t do everything!  It doesn’t create an interesting life. It doesn’t keep a person from lying.  It doesn’t CURE addiction.  Buprenorphine is a tool that helps people who are ready to help themselves.  Our job as doctors is to try to match the limited treatment slots with the people who are serious about sobriety.  If the doctor treating his son was wrong about anything, it was in that regard—for taking in a patient who was not serious about staying clean.

The other thing that Suboxone or buprenorphine does, remarkably well, screams out from the tragic story.  His son stayed alive while taking buprenorphine, despite taking over 13,000 doses of other dangerous, controlled substances.  Despite the reckless drug use, buprenorphine kept his son alive.  As I’ve written many times, it is very difficult for someone taking buprenorphine or Suboxone to die from overdose.  But when the medication is stopped, that protection goes away.  Should we blame nitroglycerin for NOT stopping heart attacks because a patient chose not to take it?  When a person refuses chemotherapy and then dies from cancer, do we blame the chemotherapy?

The person with the blog writes that he is ‘all about detox and abstinence’.  Who isn’t?!  I’m ‘all about having shorter winters in Wisconsin.’  Should I blame the heating oil companies for the weather we’ve had?   He is angry that doctors who prescribe buprenorphine are not more interested in STOPPING the medication.   He is angry at RB for their lack of interest in detox, and their goal to maintain compliance with their medication.  He wants more people to be in his son’s position—fighting opioid addiction without the benefit of a medication that reduces interest in opioids and prevents overdose!

Those of us who prescribe buprenorphine know the value of the medication for keeping people alive.  I have known a number of family members who bullied patients over their use of buprenorphine.  In at least six cases, those family members won out, and the patients stopped buprenorphine.  In at least six cases, they stayed off buprenorphine, all the way up until their overdose death was announced in the obituary section.  I’m not pointing any fingers…. but I certainly wouldn’t blame the outcome on Suboxone.

Suboxone Side Effects

I’ve received questions over the years from people claiming a range of symptoms from Suboxone or buprenorphine, from back or muscle pain to fatigue, depression, or irritability. I didn’t invent Suboxone, so I don’t take it personally when people blame commonly-occurring symptoms on the drug. But I get bored by the non-scientific thinking behind such claims— that since they started buprenorphine at some point in the past ten years, every symptom or illness that comes along must somehow be related to buprenorphine. No matter, apparently, that people who DIDN’T start buprenorphine often develop the same symptoms. And no matter that they themselves have done a number of things over the past few years BESIDES start buprenorphine. But over and over, people insist that they know, without a doubt, that buprenorphine has to be the problem.

I also get frustrated answering questions about these symptoms when people who complain about them are closed off to other explanations. When I point out that many non-buprenorphine patients have the same complaints, my comments provoke anger. Sometimes I’m accused of having a vested interest to keep people on buprenorphine (I don’t-beyond wanting to provide good medical care).

I have a long waiting list of patients and buprenorphine is only a small part of my practice, so I have no reason to compel use of buprenorphine. But I don’t like the risk that my own patients, or others, might be swayed by faulty logic and fret over problems that have no logical basis.

To the people who have written to ask about feeling depressed, anxious, irritable, numb, sleepy, wakeful, or dulled by buprenorphine, my answer is that in almost all cases, people on buprenorphine feel the same way they would feel if they were not on buprenorphine. People develop full tolerance to the effects of buprenorphine at the mu opioid receptor, so from a scientific standpoint, people on stable doses of buprenorphine should feel ‘normal’. Beyond the science, I can say that after treating over 800 patients with buprenorphine over the past ten years, I have seen no evidence that buprenorphine causes depression, irritability, chronic pain, emotional numbness, lack of interest in things, or personality changes. Honest.

Whenever I answer an email or forum post about buprenorphine I try to think of an explanation for the person’s perception. I try to give the person’s history the benefit of the doubt. I might have a couple of explanations for why someone might feel different on buprenorphine.

One case would be a person who is taking too little buprenorphine to stay above the ceiling threshold. Many doctors, and some patients, apply constant downward pressure to the dose of buprenorphine, I assume because of thinking that less buprenorphine is closer to total abstinence than a full dose of buprenorphine. But the benefits of buprenorphine are lost in doses insufficient to reach the ceiling effect of the medication. People taking too little buprenorphine will experience irritability, fatigue, sweating, and depression when the drug concentration drops below that level. The solution is to increase the dose enough for blood levels to stay above the ceiling threshold.

Another possible cause of irritability requires some speculation on my part. Actively-using addicts have very straightforward problems, which boil down to having enough narcotic to avoid getting sick every few hours. I’ve noticed that my own patients sometimes feel stressed or anxious in early buprenorphine treatment, as they become aware of all of the problems that were less-visible during active addiction. Most of that anxiety is only temporary, resolving as patients catch up with bills, settle legal issues, and feel less shame about behavior during active addiction.

Along the same line, active addiction sometimes allows people to postpone changes that really should be made, but were not possible during active addiction. Bad marriages seem less bad when surrounded by misery and chaos. But when a person finds happiness and moves forward in life, a miserable or abusive partner becomes more noticeable. Or maybe a marriage seemed ‘healthier’ when the partner was making the money necessary to support a drug habit. Effective treatment of opioid dependence empowers patients to make positive changes. But even positive changes come at the cost of emotional pain.

The people who remain convinced that buprenorphine is causing side effects would be best served by an open mind. Most of the complaints that I read about are identical to the complaints of my non-buprenorphine patients, and the most successful interventions include healthy living, stress reduction, and moderate exercise. Stopping buprenorphine is not going to be helpful in the absence of these interventions.

There is also the risk that the symptoms are caused by something other than buprenorphine—something more serious. An extreme example would be blaming buprenorphine for fatigue that in reality is caused by anemia, thyroid dysfunction, or heart disease. That situation is made even worse by the common behavior of doctors, who tend to blame any unexplainable symptom on the medication the patient is taking that the doctor knows the least about. Too often I’ve told patients to go to their GP because of unexplained muscle weakness, numbness, headaches, fatigue, or weight loss, only to have the doctor send them out without any tests or treatments, other than telling them to ‘stop Suboxone!’

Anyone reading this post, who truly suffers from adverse effects from buprenorphine, should report the side effects to the FDA web site so that clusters of symptoms, if present, can be identified.

Hot Flashes from Suboxone and Buprenorphine Treatment

First Posted 1/13/2014

A viewer on YouTube commented on my video about hot flashes  from Suboxone, but I don’t know if that is because the symptoms dissipate, or if people learn to deal with the symptoms.  I suspect that both are true.  But for some people, the sweating and heat are no small matter:

Here is what I wrote back, and a few more thoughts:

There seems to be a form of tolerance that develops more slowly than tolerance to the analgesic and euphoric effects of buprenorphine.  At least in the patients I’ve followed, complaints about constipation and hot flashes only go away over a period of months– after the other subjective effects of buprenorphine are long-gone.

Those who struggle with hot flashes may find relief by reducing the daily dose to the lowest amount that keeps blood levels above the ceiling threshold, around 4-8 mg per day. I think that in some case, people make the mistake of blaming withdrawal for the sweats and taking more and more buprenorphine, when the problem is too much opioid effect, not too little.

I recommend that patients carry a damp cloth or folded paper-towel, to use to create a chill when hot flashes start by touch the cloth to the face or neck. Another trick is to find a sink, and run cold water over the backs of the hands.  Anything that creates a chill—a blast of air conditioning to the face in the car, or an ice-cube touching the neck– will turn hot flashes off before they get started.

Nerves release acetylcholine to activate sweat glands in the skin, so medications that block acetylcholine reduce sweating.  But acetylcholine is also the neurotransmitter for salivary glands, so medications that block sweating will cause dryness of the mouth.  Many medications with unrelated primary functions have blocking effects at the acetylcholine receptor, causing ‘anticholinergic side effects.’   Anticholinergic effects are so common that medical students use a mnemonic as a reminder to keep the side effects in mind, when patients present with a certain pattern of symptoms:  dry as a bone, red as a beet, blind as a bat, hot as a hare, and mad as a hatter.  The symptoms are particularly common in the elderly, but can occur in younger patients taking high doses of anticholinergic medications.

The goal is to take an amount of an anticholinergic medication that reduces the worst of the sweating, without causing other anticholinergic effects.  Oxybutynin and glycopyrrolate are two medications used off label to reduce perspiration.  Sweating serves a valuable function by cooling the body, particularly in warm atmospheres.  Anticholinergic medications have the potential to cause hyperthermia, and even death.  Anticholinergic medications can also cause memory problems, particularly in older people.

Most of my patients have found that hot flashes, like constipation, become less severe over time.

Does Suboxone Make You Blind?

Thought I’d share a quickie from a reader, who asked if Suboxone or buprenorphine were affecting his vision.

He asked:

One thing I’ve noticed when I’m not on any drugs is my pupils are fairly large.  For some reason after I stopped the Vicodin, my vision got really blurry.  I’ve worn glasses most of my life, nearsighted but even with the glasses, they were blurry.  Then when I started taking Subutex, things got sharp again.  I didn’t change my prescription or anything.  It’s got to have something to so with opiates or drugs like them.

I answered:

The vision issue is fairly straightforward.  The smaller the pupils (the ‘aperture’), the sharper the vision—a phenomenon that results from basic optics.  All opioids except Demerol (meperidine) cause our pupils to constrict (meperidine has an ‘anticholinergic’ effect that dilates the pupils.  The drug has other anticholinergic effects that doctors often remember using a mnemonic: Dry as a bone, red as a beet, mad as a hatter, and blind as a bat).  But again, the actions of most opioids make pupils smaller, and therefore vision becomes sharper.  The effect is less helpful during low-light conditions thought, when smaller pupils results in less light reaching the retina, which reduces or prevents color vision and makes images harder to define.

Vicodin likely improved your vision by constricting your pupils, as long as you were not in withdrawal, and I’m just assuming you didn’t notice the vision change during withdrawal because of all the other things to worry about!

Why should buprenorphine cause pupillary constriction through an opioid-mediated effect, though, if we accept that people on buprenorphine become fully tolerant to the mu opioid effects of the drug?  There may be some residual opioid effects even during full tolerance, but there is another explanation that I think is more interesting.    When people take a standard tab of film of 8 mg of buprenorphine or Suboxone, respectively, they absorb 25% of the buprenorphine into the bloodstream, and swallow the other 6 mg of drug.  That swallowed buprenorphine is absorbed at the small intestine and converted, at the liver, to norbuprenorphine.  Essentially no buprenorphine makes it past the liver (a phenomenon called the ‘first pass effect’ of buprenorphine), but 6 mg of norbuprenorphine DOES enter the general circulation.

We tend to ignore norbuprenorphine except for forensic or quantitative urine drug testing, because norbuprenorphine does not cross the blood brain barrier in humans.  But norbuprenorphine does have opioid effects elsewhere in the body, including at the pupil and at the intestine.  The effects of norbuprenorphine are NOT subject to a ceiling effect.  It is worth noting that the new buprenorphine drug Bunavail has lower incidence of constipation, possibly because of the reduced exposure to norbuprenorphine (2 mg of buprenorphine is swallowed with a standard dose of Bunavail, compared to 6 mg with Suboxone film).   What else does all that norbuprenorphine do?   Is night vision better with Bunavail than with Suboxone Film?  Where is a good grad student when you need one?

(addendum for the real scientists out there… I realize I’m out on a limb.  But that’s the most enjoyable part about having a blog– I just get to wonder about things!)

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

Taking Buprenorphine, Having Surgery

Originally Posted 8/12/2013

I will get to ‘Part II’, but today I talked with a patient about something that happens too often, that deserves to be pointed out.  The person was in the ER with an injury that resulted in tib/fib francture.  The ER doc provided no analgesia, in the ER or at discharge, telling the patient “you would get sick if I gave you pain medicine because you are on Suboxone.”

I have a few paragraphs typed up that I send to dentists, surgeons, and other physicians when a patient on buprenorphine has a painful procedure.  I am pasting it below so that it can be copied, printed, and given to physicians to encourage them to do a bit of continuing medical education on the topic.  Those of you who are already enlightened, please leave comments if you see something that you would change.   I have literature to back up this type of approach;  send me an email if you’d like the reference.

Painful Procedures and Buprenorphine Patients

Buprenorphine is a partial opioid agonist that is used for several indications.  In low doses—less than 1 mg/day—buprenorphine is used to treat pain (e.g. Butrans transdermal buprenorphine).  In higher doses i.e. 4 – 24 mg per day, buprenorphine is used as a long-term treatment for opioid dependence and less often for pain management.  At those higher doses, Buprenorphine has a unique ‘ceiling effect’ that reduces cravings and prevents dose escalation.  Patients taking higher dose of buprenorphine, trade name Suboxone or Subutex, become tolerant to the effects of opioids, and require special consideration during surgical procedures or when treated for painful medical conditions.

There are two hurdles to providing effective analgesia for patients taking buprenorphine:  1. the high opioid tolerance of these individuals, and 2. the opioid-blocking actions of buprenorphine.  The first can be overcome by using a sufficient dose of opioid agonist, on the order of 60 mg per day of oxycodone-equivalents or more.  The second can be handled by either stopping the buprenorphine a couple weeks before agonists are required—something that most patients on the medication find very difficult or impossible to do—or by reducing the dose of buprenorphine to 4-8 mg per day, starting the day before surgery and continuing through the post-op period.  Given the long half-life of buprenorphine, it is difficult to know exactly how much remains in the body after ‘holding’ the medication.  That fact, along with the difficulty patients have in stopping the medication, leads some physicians (including myself) to use the latter approach- i.e. to continue 4 mg of buprenorphine per day throughout the postoperative period.  People taking 4-8 mg of daily buprenorphine say that opioid agonists relieve pain if taken in sufficient dosage, but the subjective experience is different, in that there is less ‘euphoria.’

Important points:

Patients on daily maintenance doses of buprenorphine do NOT receive surgical analgesia from buprenorphine alone, as they are tolerant to the mu-opioid effects of buprenorphine.

The naloxone in Suboxone does not reach the bloodstream in significant amounts, and has no relevance to the issue of post-operative pain and Suboxone/buprenorphine.

Discontinuation of high dose buprenorphine/Suboxone results in opioid withdrawal symptoms within 24-48 hours, similar to the discontinuation of methadone 40 mg/day.

Normal amounts of opioid pain medication are NOT sufficient for treating pain in people on buprenorphine maintenance.

Opioid agonists will NOT cause withdrawal in people taking buprenorphine.  Initiating buprenorphine WILL precipitate withdrawal in someone tolerant to opioid agonists, unless the person is in opioid withdrawal before initiating buprenorphine.

Non-narcotic pain relievers CAN and should be used for pain whenever possible in people on buprenorphine to reduce need for opioids. Note that Ultram has opioid and non-opioid effects; the opioid effects are blocked by buprenorphine.

I have had success in people taking 4 mg of buprenorphine/day, using oxycodone, 15-30 mg every 4 hours.  Some patients can control their own intake of oxycodone while on buprenorphine, but some patients CAN’T.  Overdose IS possible, if patients take excessive amounts of the opioid agonist. Consider providing multiple prescriptions with ‘fill after’ dates, each for a very short period of time (e.g. 2 days each) to that patients do not have access to large amounts of opioids at one time.

For longer post-operative periods I have used combinations of long and short-duration agonists, e.g. Oxycontin 20 mg BID plus oxycodone, 15 mg q4 hours PRN.

The risk of death is significant for opioid addicts not on buprenorphine.  Buprenorphine/Suboxone has opioid-blocking effects that reduce risk of overdose and death.  Asking a person to stop or ‘hold’ their Suboxone is introducing significant risk of injury.  Opioid addicts are NOT generally able to stop Suboxone without replacing it with illicit opioids.

J Junig MD PhD

The Pain Clinic: Your Money’s Worth?

Originally Posted 7/18/2013

Like most of you, I’m not thrilled with modern healthcare.  I miss how things were twenty years ago, when I had a sense of ‘having a doctor’ who actually knew me, who had my best interests in mind.  I remember my father, a defense attorney in a small town in Wisconsin, telling me about the state’s ban on advertising by lawyers – a once-debated issue that is hard to visualize in the current era.  He believed the ban was a positive thing, helping keep the legal profession honest and avoiding the appearance of impropriety.   I remember comparing the situation to medicine and thinking ‘of course the ban is a good thing; just think of what society would think about DOCTORS, if they hung billboards for their services!

Those debates must appear bizarre to young people now, who can’t drive a mile without hearing or seeing ads urging people to sue over work grievances, accidental injuries, discrimination, medication side effects, malpractice… while hospitals and doctors compete for space for their own ads for pain clinics, wellness centers, hip and knee replacements, or robotic surgery.

Billboards announce the next great thing that one hospital has that others don’t, one medical gimmick replacing another.  ‘Pain treatment’ is one of the biggest healthcare scams of the past 20 years, with ads promising treatment for chronic pain in an ‘advanced’ or ‘collaborative’ manner.   The scam is easy to see if one drops all positive assumptions about medicine—and health insurance– and observes what happens to patients who use pain clinics.  Follow two hypothetical patients, one with insurance and another with no money or insurance, with the exact same injury—let’s say back pain from lifting crates in a factory every night for several years. Their experiences will demonstrate why being insured is not always in one’s best interest.

Epidural injection
Are epidurals worth the money for chronic pain treatment?

Our uninsured man develops pain in his lower back that does not extend into his legs, without leg weakness or incontinence.  He goes to urgent care and pays cash for the visit, and tells the doctor that he can’t afford to be referred anywhere.  The doc tells him to avoid heavy lifting for a week, and when he returns to work, to lift with his legs and knees instead of bending his back.  He is told to stretch at least 30 minutes every morning and evening and to exercise each day.  Back pain usually comes from a combination of ‘pain generators’ in muscle, bones, tendons, ligaments, and nerves in the lower back.   But the body has amazing recuperative powers, and if our hypothetical patient stretches, exercises, and avoids repeat injury, he will get better over several weeks.  Not a bad outcome for $150!

The guy with insurance goes to his doctor, who prescribes 90 tablets of Percocet and schedules an MRI.  This doctor doesn’t explain the need for stretching, assuming that the patient will hear all that from the next doc he is referring to… or maybe he recommends stretching and exercise, but the Percocet helps the patient feel less restless while sitting in front of the TV, reducing the stretching or exercising that would have helped him feel better.  When the MRI shows ‘degenerative disk disease’ (as it always does in people over 40), the doc refers him to a neurologist for EMGs.  The patient meanwhile sees his chiropractor for 5 ‘adjustments’ per week.  The neurologist refers him to a physical medicine and rehab doc, who orders physical therapy.  All of these steps in the process extract their pound of flesh, paid by either the patient or society (through higher insurance rates).

The people who are getting rich in medicine know that it’s all about PROCEDURES.   Our insured patient already paid over $1000 for his share of the costs for a lumbar spine MRI (not to mention the plain films and a CT scan done first, just in case they might be helpful).  He or his insurer paid another grand for the EMG.  The chiropractor cost another 1-4 grand, depending on the patient’s zip code.

The money really starts to flow when the rehab doc sends him to a pain clinic.  The pain clinic starts with more x-rays, CT, and MRIs, claiming that THEIR techniques will give a better look at things that the others may have missed.   For the most common diagnoses—degenerative disc disease, lumbar strain, or facet arthropathy– treatment choices include lumbar epidural steroid injections, selective nerve root injections, and local anesthetic ‘trigger point’ injections to relax tightened muscles.  The doctor’s charge to do an epidural or nerve root injection?  About $500-$1200, for a procedure that takes about 15 minutes.  An efficient doc could easily do 10-12 injections per day.  If the doc attended one of those meetings that teach ‘maximizing reimbursement’—meetings often held on cruises or tropical islands—the doc calls his office an ‘ambulatory care center’ so that he can bill ‘facility fees’, turning a $700 epidural into a $5000 ‘short stay.’

I hear what you’re thinking—that relief from back pain is WORTH the $5,000-$10,000 cost for this patient.  What if the procedure provides only partial relief—the typical result?  Or What if the epidural steroid injection only MIGHT provide pain relief— but probably WON’T?  Is it still worth as much?  What if the pain relief won’t start for a few weeks and only lasts a month or two, and then the shot must be repeated?  What if the injection can be done only 3-4 times per year, and the patient has less than a month of relief each time.  Is 3 months of moderate reduction in pain worth $15,000?

The scam is aided by a simple fact that patients often forget: most minor injuries will heal on their own without medical intervention, as long as re-injury is avoided.   It is no coincidence that many medical procedures or treatments take ‘a few weeks’ to work, the amount of time most often associated with natural healing.  You’ve heard the joke….  With treatment, you’ll improve in 14 days; otherwise a couple weeks!  Present-day back injuries last about as long as they did 50 years ago—even though we now spend tens of thousands of dollars per injury, rather than a few weeks of ‘taking it easy.’

I’m taking care to present examples that give medicine the benefit of the doubt.  I’m not mentioning the many injections done on people despite clear evidence, on exam or MRI, that the injection will do nothing for their pain.  I’m not talking about trigger injections (done thousands of times each day throughout the US) that hurt like blazes during the shot, giving the illusion of pain relief (and nothing else) when the needle is removed.  I’m not talking about the many MRI’s, ultrasounds, CTs, and EMGs that could be replaced by a smart doctor with basic physical examination skills.

And I’m not talking (until now) about the people who suffer from iatrogenic addiction—- those who go to pain clinics for aches and pains that will either gradually go away or won’t ever go away, that in either case have a trajectory of recovery that can’t be altered by the pain clinic.  The patients are prescribed opioids, and asked to return for one procedure after another.  The patients notice that the procedures are doing nothing for the pain, but they return over and over for refills on the pain pills that they now physically depend on.

The insurer eventually balks at paying for more procedures… and at this same point the pain clinic docs decide that further attempts at pain relief would be pointless.  The doc tells the patient that since he is doing nothing but prescribing pain pills, the patient should go back to his primary care doctor and never return to the pain clinic (unless a new, reimbursable injury comes along).  The referring doctor is not comfortable prescribing the same large dose of narcotics, and tells the patient to ‘taper off the pain pills’—- something that most people just can’t do.  The patient inevitably violates the opioid treatment contract by asking for early refills, smoking marijuana, missing an appointment, running out of money to pay for visits, seeing another doctor, using the wrong pharmacy, etc…. allowing the doctor to blame the patient for breaking the rules, requiring discharge.

Suboxone Makes Me Fat and Boring and Stupid

Originally posted 3/6/2013

A late post tonight, since my new exercise program has pushed my blogging back by an hour or so each night.  My suspicions about exercise were correct, by the way; it is much easier to suggest exercise to other people than it is to actually exercise.  I’ve been at it since the beginning of the year, and I at least feel a bit less hypocritical.

While I’m on the topic…  I’ve received many comments over the years from people complaining that they’ve been taking Suboxone or buprenorphine for X many years, and they have no energy, they feel stressed, they have gained weight, they don’t sleep well or they sleep TOO well… and concluding that all of the problems are from Suboxone.

Suboxone causes… everything!

They aren’t (from Suboxone).   Not at all.  But I wonder, at this point, if regular readers of my blog know EXACTLY what I’m going to say.  I’m tempted to stop typing and ask people answer so I get a sense of how predictable I’ve become.    But then I’d have to wait and then come back, read, and assess the situation….  I really can’t imagine much positive to come out of THAT experience, so I’ll just finish my thoughts, about the problems that people often blame on Suboxone.

The problems are the result of other things, including things that tend to occur naturally as our lives become less chaotic and more outwardly-secure.  The problems I mentioned above, for example, come from inactivity.  They come from thinking that we’ve ‘paid our dues’ at the age of 30, and it’s time to coast in life.  They come from failing to seek out challenges, and from failing to do our best to tackle those challenges.  They come from letting out minds be idle, smoking pot or watching American Idol  instead of responding to the naggings sense of boredom that ideally pushes people to join basketball, tennis, or bowling leagues.

Our minds and bodies are capable of SO much.  I (honestly) am not a network TV viewer, but I love the contrast of ‘before and after’ scenes on ‘Biggest Loser.’  People magazine (it sits in my waiting room) had a section a while back about people who lost half their body size, by exercise and dieting.  The part I found most interesting was the deeply personal answer that each person had to the question, ‘what was your turning point?’  Each cited an episode of humiliation or shame that lifted the veil of denial, and helped them do what they knew, all along, needed to be done.

We are not all capable of ‘Biggest Loser’ comebacks. But it is important for people to understand that feeling good, physically or mentally, takes work.   That incredible feeling of a ‘sense of accomplishment’ only comes when we accomplish something.  We don’t need to eliminate global hunger or cure cancer; sometimes we just need to shovel the driveway, mow the lawn, or do a crossword puzzle.  I’ve learned, as a psychiatrist, that the people who walk around with smiles on their faces usually did something that made the smile happen.  I’ve learned that ‘feeling happy’ does not just happen for most people.  And I don’t think I’ve ever met a person who answered, when asked about stress, ‘no—I don’t have anxiety.’

Once someone blames Suboxone for their problems, it becomes less likely that the real causes of those problems will become apparent. For example, If I think that my glasses are giving me headaches, I’m less likely to make changes in my diet that might make the headaches better.  Once we have something to blame, our problems become more and more engrained, and the real solutions become less and less evident.

I’m truly sorry if I am coming across as ‘preachy’; understand that I’m just trying to make my way through life like everyone else.  But I now take note of all those people power-walking at 6 AM, and I understand why they do it.  Some of them might be on Suboxone.  Some of them might not be.  But I respect all of them for opening their minds, and for their willingness to do the hard work that brings happiness—or at least points in that general direction.