I have been kicking these observations around for the past year, and have been unable to find a big fish willing to ‘bite’.  I truly believe that the observations below have the potential to dramatically change the approach to opioid treatment of chronic pain.  Since I have a blog, I have a soapbox– so I’ll share the idea, and welcome comments in return.  I do ask that proper attribution be provided if this article is shared.

Introduction:

Long-term opioid analgesia without tolerance, respiratory depression, or euphoria?  Introducing the Holy Grail for chronic pain treatment!

Premise:

The miracle of opioid pain relief is fatally limited by tolerance, addiction and respiratory depression.  Buprenorphine, when combined with a mu agonist, results in game-changing effects.  Patients experience potent, dose-related analgesia from the agonist, but have NO euphoria.  The therapeutic window is widened.  Patients unable to control their use of a mu agonist alone gain that control when on buprenorphine. And most exciting, buprenorphine indefinitely anchors tolerance, maintaining analgesia WITHOUT DOSE ESCALATION. This finding offers huge implications for pain management.

Discussion:

Use of opioids for chronic pain has severe limitations.  Tolerance removes the benefits of opioid analgesics over time.  Worse, tolerance is associated with dependence and withdrawal.  Many patients use additional doses of their prescription early in the month, then suffer through withdrawal while awaiting refills.  Others find opioids through less-reliable, non-clinical sources.

At the same time, addiction to mu opioids is a nationwide epidemic.  Reformulation Oxycontin has pushed many opioid users toward diacetylmorphine—brand name Heroin.  Some physicians recommend avoiding mu opioids altogether for chronic pain (e.g. Physicians for Responsible Opioid Prescribing), while pain treatment advocates argue to ease narcotic restrictions.

Over the past six years I have treated over 500 patients using buprenorphine, mostly for opioid dependence.  Buprenorphine, a partial mu agonist, is the active ingredient in Suboxone, a medication used for treating opioid dependence. The majority of my patients began their addictions with narcotics prescribed by doctors for back pain, knee pain, shoulder pain, fibromyalgia, chronic headaches, and other conditions.

Many of my patients found their pain reduced or gone after stopping mu agonists and substituting buprenorphine.  Buprenorphine has the mu activity of 40 mg of daily methadone, but this activity is unlikely responsible for significant analgesia, since patients rapidly become tolerant to the agonist actions of buprenorphine. Instead, their pain while on mu agonists was likely maintained by psychological forces.

Patients on buprenorphine occasionally need opioid analgesia, just like other patients.  My patients have had knees replaced, gallbladders removed, hysterectomies and c-sections, rotator cuff repairs, and in two cases, cardiac surgery.  In all cases, sufficient analgesia was provided by maintaining daily buprenorphine at 4-8 mg per day, and using potent mu agonists, usually oxycodone, in doses ranging from 15-45 mg every 4-6 hours as needed.

Several patients have severe chronic pain from avulsion of the brachial plexus, failed spinal fusion, or other conditions, where prior opioid use resulted in rapid tolerance that prevented effective analgesia. These patients are now successfully maintained on combinations of buprenorphine plus mu agonists.

The combination of buprenorphine plus mu agonists has provided perioperative analgesia for patients on buprenorphine.  Patients universally describe adequate pain relief, even after major surgeries.  They also described the absence of euphoria, and to their surprise, the ability to control their use of pain medication—something impossible before taking buprenorphine.

But it is the effects on chronic pain that suggest a ‘game-changer’ for pain treatment.  Even after over a year on combination buprenorphine/oxycodone, my patients 1. have no euphoria;  2. are often able to manage their own narcotic medication; and most important, 3. describe stable analgesia WITHOUT agonist dose escalation.

The ability to treat pain long-term without tolerance or dose-escalation is as exciting a development as was the initial discovery of opioids for pain relief!

Properties of a combination agent

Buprenorphine is administered sublingually, and could be prescribed as a separate medication, and use verified through urine monitoring.   But greater safety benefits would come through regulations requiring buprenorphine (or a similar partial agonist) to be an inseparable part of every opioid prescription.  Such a policy would dramatically lower the addictiveness and reduce the respiratory depression of mu agonists WITHOUT removing efficacy.  The most obvious formulation would be a transdermal system that delivers buprenorphine and fentanyl, since both are already available in separate transdermal systems.

There may be situations, for example hospice care, where euphoria would be a desirable part of opioid treatment.  But for other cases, analgesia without euphoria has obvious benefits.

I have written to several pharmaceutical companies with this idea, and have heard back that while the idea is interesting and scientifically sound, the generic nature of the component medications reduce the potential for profit that would motivate development.  But given the potential value of this approach for multiple problems– addiction and chronic pain among them—I have to think that there is money to be made—not to mention the advances in treatment that the approach offers.

Reference:

Some supporting background information can be found in:  Alford, D., P Compton, and J Samet, Acute Pain Management for Patients Receiving Maintenance Methadone or Buprenorphine Therapy.  Ann Intern Med. 2006 January 17; 144(2): 127–134.

I also discuss this approach to pain treatment in my ‘Users Guide to Suboxone’, sold on Amazon and at bupeguide.com

Jeffrey T Junig MD PhD

Please do not reproduce without attribution.

I wrote this a couple years ago, and still get questions about the topic today.  Studies show that a small fraction of the amount of buprenorphine in a tablet or film strip actually gets absorbed through mucous membranes;  the rest is swallowed.  The 15%-30% amount of absorption is referred to as the ‘bio-availability’  of the drug.

People who feel like they are not getting enough buprenorphine to remove cravings can review the principles below, to see if there are ways they can easily improve the absorption of buprenorphine.  NOTE:  improving absorption is NOT an ‘addictive’ behavior, for a couple reasons…. first, because of the ceiling effect, increasing the amount absorbed will NOT cause a ‘buzz’ or high, but will only make the medication last the full 24 hours without wearing off.  Second, crushing a tablet will NOT cause a ‘rush’ or ‘high’ for two reasons– first, because of the ceiling effect as I just described, and second, because the rate-limiting step for absorption is the passage through tissue— NOT the dissolution of the tablet.  This is why, by the way, the film does not cause a ‘rush’, even though it dissolves more quickly.

Read on:

I often answer questions about Suboxone that require the qualification ‘if it is being absorbed properly’. If a person asks how long it takes for Suboxone to wear off, or at what dose does the ceiling effect occur, I need to be sure that the person is taking it in a way that maximizes absorption; otherwise all bets are off. If a person simply swallows the tablet, for example, the level of buprenorphine in the bloodstream will be much lower than if it is taken correctly.

The usual instructions for taking Suboxone are to place a tablet under the tongue and let it dissolve.  It is important that Suboxone be taken once per day, in the morning; this instruction is included in the course for physicians but is too often ignored.  I will talk another time about the philosophy for dosing once per day; the basic reason is to extinguish the behavior that has been conditioned as part of the addiction.  But the point of this post is the absorption of buprenorphine from the tablet into the bloodstream, and how to maximize that absorption.  It is important to maximize absorption, particularly if one is trying to save money by reducing the daily dose of Suboxone.

From my experiences as an anesthesiologist, as an addict**, and as a PhD chemist, I recognize that three factors will maximize absorption.  The first is the concentration of buprenorphine in the saliva, as the drug diffuses into tissue down a concentration gradient.  This gradient is maximized by having a small volume of saliva.  I recommend that a person start with a dry mouth, place the tablet in the mouth, and crush the tablet between the teeth until it is dissolved in a small volume of a concentrated solution.

The second factor that affects absorption is the amount of surface area.  Buprenorphine is absorbed through all mucous membranes (the tissue lining the inside of the mouth), passing through the surfaces and entering capillaries, the route into the bloodstream.  So the concentrated solution should be ‘painted’ repeatedly over all of the surfaces inside the oral cavity;  the inside surface of the cheeks, the tongue, the roof of the mouth, under the tongue, the back of the throat…  swished around in the mouth over and over, repeatedly bringing the concentrate into contact with new areas of mucous membranes.

The third factor is time– the longer period of time, the longer for the buprenorphine to make contact with the mucous membranes, attach to the surface, get absorbed into the tissue, and enter the capillaries.  The initial process will be the saturation of the surfaces of the mucous membranes, and the slower process will be the passage into the tissue;  that is why the amount of surface area has such an important effect on absorption.  Fifteen minutes is probablysufficient for most of the absorption to occur;  there may be drug remaining that is attached to the surface but not yet fully absorbed, and so I recommend avoiding eating or drinking within another fifteen minutes or so after swallowing the left-over saliva.

If you pay attention to these principles you will maximize absorption of the drug.  The ceiling effect will occur under these conditions at a dose of about 2-4 mg;  the long half-life of the drug will guarantee that if you take over 4 mg or so each morning, you won’t have any significant withdrawal for over 24 hours– allowing once-per-day dosing.  Yes, early in treatment patients will feel as if they need to dose more frequently– but that is not because of too little buprenorphine, but rather because of conditioned behavior.  A person early in Suboxone treatment will have feelings or minor withdrawal in the late afternoon or evening after dosing in the morning;  those minor withdrawal sensations will go away in about 15 minutes if the person takes more Suboxone, and will also go away in 15 minutes if the person doesn’t take Suboxone.  If the person takes more Suboxone, it will reinforce the sensations and the person will get stuck on dosing twice per day.  If, on the other hand, the person uses distraction and avoids dosing, those minor withdrawal sensations will completely disappear in a week or two, as the conditioned behavior is extinguished.

**I mentioned my experience ‘as an addict’;  for a period of time my preferred route of administration of lipid-soluble opioids was ‘trans-mucosal’ or ‘trans-buccal’.  Since the amount of substance available was finite (albeit a fairly large finite amount!) I did all that I could to optimize absorption, including reading about diffusion of lipid-soluble molecules through mucous membranes.

I recently resumed writing for the expert forum on addiction at MedHelp.Org. One result of writing for MedHelp is that I receive a number of e-mails from people with questions about specific issues related to buprenorphine. The most common questions are from people on buprenorphine undergoing surgery, asking about the safety of anesthesia and about postoperative pain control.

There are very significant problems with medical coverage for patients on buprenorphine undergoing surgery. Patients on buprenorphine will occasionally need surgery, and in such cases there are often no doctors willing and/or competent to manage postoperative pain. Psychiatrists, frankly, have little knowledge or experience in this area. Before psychiatry residency, medical school graduates generally complete a medical internship that provides little or no training in critical care or surgery. Making matters even worse, the medical students who go into psychiatry tend to be those who have the least interest in the surgical specialties.

And then there are surgeons. Where psychiatrists lack courage to provide effective pain relief for addicts, surgeons simply lack interest or concern. Surgeons enjoy being in the operating room, cutting things apart and sewing things together. The last thing they want to do is have a heart-to-heart talk about someone’s addiction to pain pills. To a surgeon’s way of thinking, addiction doesn’t even exist. You can’t cut it off or sew it on, so why even talk about it?

Hopefully, those of you who take buprenorphine will slip this article under the door of your psychiatrist to drop a hit about this problem. I cannot provide medical recommendations for people who I do not know, but I will at least provide some general information so that readers of my blog will know when they are being fed a line of nonsense.

Speaking of nonsense, the silliest and most potentially harmful advice that I hear about in e-mails is that buprenorphine will cover a person’s postoperative pain; that the person should simply take his/her normal dose of Suboxone and everything will be fine. Nonsense! People taking buprenorphine quickly become tolerant to the pain-relieving properties of buprenorphine, and therefore will not get adequate pain relief from buprenorphine for anything but the most minor surgical procedures. Buprenorphine has complex actions at opioid receptors, including partial agonism at mu receptors and mixed effects at kappa opioid receptors. The actions at kappa receptors are less subject to tolerance and provide some long-term effects on mood and analgesia, but these effects are not even close to what is required to cover postoperative pain.

There are several articles that have been published that describe various approaches for treating postoperative pain in patients on buprenorphine. I cannot post the articles here because of copyrights, but the general recommendation in the literature for treating post-op pain is to reduce the daily dose of buprenorphine starting several days before the surgery, and to use potent opioid agonists in addition to buprenorphine. Another option is to stop buprenorphine completely before surgery. But buprenorphine has a long half-life, and must be stopped for a week or more in order to significantly lower the level of buprenorphine in the body.
It is important to understand that there are two things that get in the way of pain relief in patients on buprenorphine; the antagonist actions of buprenorphine at the mu receptor, and the patient’s high tolerance to opioid agonists. Even if buprenorphine is stopped a week or two in advance of surgery, the person still has a high tolerance to opioids, and still requires significant doses of opioid agonists for adequate post-operative pain control. And if buprenorphine is stopped completely, the person must go through a period of withdrawal before eventually restarting buprenorphine in order to avoid precipitated withdrawal.

I have found it easiest to keep the person on a small dose of buprenorphine, perhaps 4 mg per day, throughout the entire operative period, until postoperative opioids are no longer needed. I’ve had good success treating post-operative pain with high doses of oxycodone while continuing buprenorphine, even after major surgeries. Interestingly, patients report good pain relief but the complete absence of the euphoria that they used to get from opioids. At the point after surgery when opioid agonists are no longer necessary, patients simply stop the agonists and resume their full dose of buprenorphine.

Whether or not buprenorphine is discontinued, high doses of opioid agonists are required to provide adequate pain relief for major surgery. An oxycodone equivalence of about 60 mg per day is required just to ‘break even’ with the tolerance of a typical person on buprenorphine maintenance. You can understand, then, why psychiatrists are wary of treating postoperative pain. Such high doses of oxycodone could easily cause fatal overdose in patients not taking buprenorphine. I am board certified in anesthesiology, but even I get nervous in such situations. But what is the alternative? I have had patients who required coronary bypass, hysterectomy, and total knee replacement, as well as minor surgeries. Dental work in particular is quite common in patients with a history of addiction. Should people on buprenorphine simply go without the necessary procedures that other people are allowed to have?

If psychiatrists or surgeons are unwilling to provide adequate postoperative analgesia for patients to take as outpatients, patients should allowed to stay in the hospital, even the intensive care unit, if that is what it takes for the doctor to feel safe providing adequate analgesia. Surgeons should provide adequate care, even if they have to fill out paperwork and battle insurers to obtain the necessary coverage for hospitalization. They would do the same for patients with brittle diabetes who need close monitoring following surgery. Opioid addicts are people too!

As for general anesthesia, buprenorphine does not pose significant problems, provided that the anesthesiologist is aware that the patient takes buprenorphine and has a high opioid tolerance. Opioids are often used during anesthesia to blunt changes in blood pressure and heart rate, and larger doses of opioids would be required for people taking buprenorphine. The amnesia component of an anesthetic is generally provided by medications not blocked by buprenorphine, such as anesthetic vapors or benzodiazepines.

Another reason that anesthesiologists must be made aware if a patient is taking buprenorphine is so that sufficient opioids are ‘on board’ when the patient awakes. As patients emerge from anesthesia, anesthesiologists often use respiratory rate to gauge whether sufficient doses of narcotics have been provided to cover postoperative pain. Without the knowledge that a patient is on buprenorphine, the anesthesiologist may be confused by the patient’s lack of response to narcotics, causing the anesthesiologist to give too little pain medication—meaning that the patient will awake with considerable pain.

Medications with combined actions (such as tramadol and the newer agent Nucynta) or of little value for post-operative pain control. These medications have actions at mu opioid receptors that are blocked by, and cross-tolerant with, buprenorphine– completely nullifying that component of their action. The other component of their action is through effects on serotonin or norepinephrine pathways, and these actions are insignificant for post-surgical pain. Because of mu receptor tolerance, Nucynta essentially becomes as useful for treating post-op pain as Cymbalta— i.e. worthless!

I must stress that everything I have written here is intended to serve as a basis for discussion between patients and their doctors. Every case has unique variables that must be taken into account, and so my comments must not be taken as medical recommendations or advice. Taking high doses of opioid agonists can be dangerous, particularly in combination with other respiratory depressants.

By the way, I discuss buprenorphine and surgery in greater detail in the e-book that I published a couple years ago.

One final comment… I recently received letters from two different health insurers about ‘buprenorphine policies’ citing situations where Suboxone would not be covered. These situations have included cases where patients are prescribed opioid agonists. I want to point out that there are times when patients on buprenorphine require surgery, and every patient undergoing surgery deserves adequate pain control. There are also patients on buprenorphine maintenance who have chronic pain; pain that in some cases justifies the relief afforded by opioid agonists. I hope that those with the power to influence policy, including Reckitt-Benckiser, the American Society for Addiction Medicine, NIDA, and SAMHSA, will direct attention to this important gap in medical coverage.

While I’m on the subject of rip-offs, I’ll mention an extreme form of ‘detox capitalism’; a process called rapid opioid withdrawal, rapid detox, or ‘the Waismann Method.’

The name of the process supposedly comes from a certain ‘Dr. Waismann’ who helped Israeli soldiers get off opioids after they were treated for various injuries.  It sounds like a pretty exciting history, but to be honest there is nothing in the technique that takes a rocket scientist to figure out.  The basic idea is to precipitate withdrawal using an opioid antagonist— something that is done many times over every day in emergency rooms across the U.S.—but to do it while the person is sedated with non-opioid medications.

Put me out, Doc!

I never expected to admit this back when it occurred, but I had the bright idea of putting myself through ‘rapid opioid detox’ shortly before entering treatment ten years ago, when I was desperately searching for a way to free myself from opioids.

Like any typical addict I wanted to do it entirely by myself, figuring that I knew as much about opioids and medicine as anyone else.  I loaded up on naltrexone (an oral form of naloxone) thinking that the antagonist would block my receptors, lower my tolerance, and prevent me from using for as long as I took the naltrexone.

I simplified things a bit by omitting the sedation—a good idea since there was no other doctor monitoring me, but a bad idea because I experienced about a week of withdrawal condensed into several intensely-miserable hours.  I remember being shocked at just how much sweat my body could produce in such a short time, as liquid beaded on my skin as fast as I could wipe it off!

After the real horrible period—the period that I would have slept through had I come up with $15,000 plus airfare—I remained quite ill for a matter of weeks.  And of course that is what happened, since it takes weeks for tolerant mu receptors to be replaced by new, normal mu receptors.  Until the receptors are replaced, the brain’s endorphin pathways remain quiet, causing hypersensitivity to pain—not to mention diarrhea, restless legs, cramping, gooseflesh, and depression.

There are several variations of rapid detox, but the principles are the same for all of them:

-          The addict is given a strong sedating medication or anesthetic

-          While heavily sedated, the addict is given an intravenous infusion of the opioid antagonist naloxone to precipitate withdrawal.

-          After a period of time that varies with the name of the facility, the addict wakes up;  one day of withdrawal gone, and only two more months of withdrawal to go!

-          The process costs from five to ten thousand to tens of thousands of dollars.

-          Different options are tossed in for different programs, everything short of an extended warranty: amino acid cocktails, ‘vital nutrients,’ or long-term sedatives.

-          In some cases a chip of naltrexone is implanted that slowly releases over weeks, supposedly preventing a high from using—provided the addict doesn’t become desperate and use very high doses of heroin, or dig the implant from his/her body using a fork!

Web sites for the procedure point out that opioid dependence is a relapsing illness and that people who use Suboxone relapse when they stop Suboxone (no argument from me), but go on to claim a 70% one-year sobriety rate after their rapid-detox procedure—without any explanation for how they get better numbers than Suboxone patients.  I have never seen peer-reviewed studies showing such success rates.

Speaking of peer-reviewed studies, I have seen a study of rapid detox showing what is intuitively obvious—that since it takes a number of weeks for the body to adjust to the lack of opioids, one day of sedation avoids only a tiny portion of the misery of withdrawal.  Is it worth ten grand to avoid one day of withdrawal, knowing that several more weeks of withdrawal are yet to come?  I suppose it depends on one’s checking account.

But the bigger issue is the poor long-term outcome for these people—a problem similar to what I described in my post about Sneetches.  Early in the spiral of addiction, addicts and their families are under the mistaken belief that the hardest part of ‘kicking opioids’ is to get through physical withdrawal.

They eventually they learn that they are wrong, and that it is much more difficult and rare to STAY clean than it is to GET clean—but ‘rapid detox’ makes money off their ignorance in the meantime.  Quitting opioids by rapid detox, amino acids, magic crystals, hypnosis, or a host of other expensive, highly-promoted methods reminds me of the story about the guy boasting about how easy it was to quit smoking—so easy that he’s done it over 20 times!

Thanks, all of you who wrote comments to my last post.  I remind everyone once again to consider taking your comments here and after writing them, also taking them to SuboxForum.com.  I am going to put up a new category to discuss topics that were initiated here;  it would be great to get a spirited, respectful ‘give and take’ on some of these topics.  As I have mentioned before, the only thing that I will block on that site would be debating whether people on Suboxone are ‘in Recovery’– just because there are plenty of other sites for that, and I want the forum to be for people who have made their decision– and don’t want to be harassed over it.  I will be upgrading that site shortly and changing the hosting account;  hopefully I will pull it off without erasing everything!

OK, tonight’s topic: I am taking my post from a different forum and posting it here also to save wear and tear on my keyboard…  I responded to a person who is taking 32 mg of Suboxone daily and who is concerned that the relatively high dose will raise her tolerance higher than she would like.  She has surgery coming up, and is concerned that the high tolerance will get in the way during or after the surgery.    My reply addresses the level of opiate tolerance in relation to dose of buprenorphine.  Incidentally though I will quickly say that buprenorphine poses little problem during an anesthetic;  it does not interfere to a large degree with general, epidural, or spinal anesthesia.  But buprenorphine DOES interfere with the treatment of post-operative pain.  I will also comment that I consider 32 mg of daily Suboxone to be a waste of money;  my experiences treating people with Suboxone have only reinforced my opinion that there is no benefit, and often considerable harm, in taking more than 16 mg of Suboxone per day,  and in dosing more than once per day.  But that discussion will have to wait.

My Response:

I will talk about buprenorphine, the active medication in Suboxone, just to simplify things a bit– although Suboxone will have the same effects. First, when talking about the dose, it is important that the method one takes it is identified– as that is what determines how much active drug ends up in the bloodstream. I will assume that the person is taking steps to get maximal absorption of Suboxone; for example keeping it exposed to mucous membranes for a long-enough time, and not rinsing the mouth with liquid for at least 15 minutes after dosing, to avoid rinsing away drug that is attached to the lining of the mouth but not yet absorbed. As an aside, there is a post somewhere on this blog entitled ‘maximizing absorption of Suboxone’ for those who want more info.

When a person takes Suboxone, he is taking a ‘supra-maximal’ dose of buprenorphine. Buprenorphine is used to treat pain in microgram doses; the BuTrans patch is used in the UK to treat pain, and it releases buprenorphine at a rate of 5-20 MICROGRAMS per hour! One tablet of Suboxone containes 8000 micrograms! So whether a person is taking one, two, three, or more tabs of Suboxone per day, he is taking a very large dose of buprenorphine— a dose large enough to ascertain that he is up on the ‘ceiling’ of the dose/response curve. It is important to be on the ceiling, as this is the flat part of the curve (I know– a silly statement) so that as the level of buprenorphine in the bloodstream drops, the opiate potency remains constant, avoiding the sensation of a decreasing effect which would cause cravings.

I have read and heard differing opinions on the dose that gets one to the ‘ceiling’ but from everything I have seen the maximal opiate effect occurs at about 2-4 mg (or 2000-4000 micrograms), assuming good absorption of buprenorphine. I base this on watching many people initiate Suboxone; if a person with a low tolerance to opiates takes 2 mg of buprenorphine, he will have a very severe opiate effect; if he takes that dose for a few days and gets used to it, and then takes a larger dose, there is no significant increase in opiate intoxication– showing that once he is used to 2 mg, he is used to 16 mg— and is ‘on the ceiling’ by definition. I see the same thing in reverse; there is very little withdrawal as a person decreases the dose from 32-24-16-12-8 mg, but once the person gets below 4 mg per day, the real withdrawal starts. This again shows that the response is ‘flat’ at those high doses, and only comes down below about 4 mg of buprenorphine.

The flip side of all of this is that tolerance reaches a maximum at about 4 mg of buprenorphine, and further increase in dose of buprenorphine does not cause substantial increase in tolerance. Tolerance and withdrawal are two sides of the same coin; the lack of withdrawal going from 32 to 8 mg of buprenorphine is consistent with no significant change in tolerance across that range.

So in my opinion, being on 32 vs 4 mg of Suboxone doesn’t raise your tolerance. But in regard to upcoming surgery, there is an additional concern. One issue with surgery on buprenorphine is the high tolerance, but the second issue is blockade of opiate agonists by buprenorphine– and this effect is directly related to the dose of buprenorphine. A person on 32 mg of Suboxone will need much, much higher doses of agonist to get pain relief than will a person on 4 mg of Suboxone– not because of tolerance but because of the blocking effect, which is competitive in nature at the receptor. When people are approaching surgery I recommend that they lower their dose of Suboxone as much as possible– to 4-8 mg if possible. Because of the very long half-life (72 hours), this should be done at least a week before the surgery. Then I have them stop the Suboxone three days before the surgery; it usually takes 2-3 days for significant withdrawal to develop. I say all of this to give a general sense of the issues involved; people should discuss the issue with their physician rather than act on what I am describing here.

Im in a methadone maintenance program and am currently at 130 and I have pre-employment drug screen coming up in about a month. I wanted to see how low I could get off the methandone and switch to suboxone. if it is not detectable in a drug screen. Also, I have a prescription for methadone can they not hire me because a Dr, prescribes methadone.? Any thoughts, ideas?

My thoughts:

There are laws that prevent a person from being fired because of certain illnesses or disabilities, but those laws are complicated. Drug addiction is a ‘protected disability’, so theoretically you cannot be fired for being a RECOVERING drug addict. On the other hand, you can be fired you for any other reason, or for no reason at all! So except for the occasional boss who is a total idiot who says ‘I don’t like recovering addicts so I am firing you’, disability law is not involved.

In general you cannot be fired for having an illness… unless the illness interferes with your job. A surgeon can be fired for being HIV positive, as there are just some risks of transmitting the virus during surgery that cannot be TOTALLY avoided– an accidental needle stick during a frenzied attempt to get a suture around the splenic artery, for example.  I used to be an anesthesiologist and miss those days– in the situation I’m referring to, a person came in with a ruptured spleen from a car accident. The blood pressure was stable, but in such a case the intra-abdominal pressure is often holding the spleen together, and as soon as the belly is opened the spleen will pour blood into the belly and the patient will crash…  so the anesthesiologist gets several large-bore lines in the patient, hangs fluids and blood through blood-warmers, maybe even get an infusion of a pressor set up and at the ready to maintain the pressure as best one can when there is a large hole in the spleen…    I loved that work but like the HIV-positive surgeon, it just was not the place for me anymore.  How could I keep all of my attention on the patients under my care, when there were buckets of opiates right next to me under my control?  I think that on Suboxone I would be OK– I think the cravings would be treated so that they would not be a distraction– but I understand, and accept, that I would never be able to convince an employer of that fact.   Alas…. I miss that job, but I am surprised by how I enjoy being a psychiatrist in a different way, and the enjoyment grows as each year passes and I get to know my patients more and more.    OK, enough about me– back to the letter:  A person on methadone can be fired, regardless of getting it legally for pain or from an addiction program, if the job requires operating heavy machinery– because taking methadone, other opiates, sedatives, etc are simply not compatible with operating machinery. Yes, you might feel fine, and even be fine– but it would be so easy for an injured party to file a lawsuit and win by saying that ‘the company had a person taking these drugs, and it says right here on the bottle not to operate machinery!!’ So you will never win the ‘right’ to work while taking impairing medication.

As for drug tests, first realize that methadone shows up in tests for a LONG time– for weeks in some cases. Whether Suboxone will show up is hard to predict; it sometimes shows up and sometimes doesn’t, depending on the manufacturer of the test. I have many patients who have undergone drug testing, and none have come up as positive, but I have purchased test kits that have shown buprenorphine as positive for ‘opiates’. The problem is that you have to list your meds at the start of the test, and if you hide it and then it does happen to show, you are in trouble.  One solution to that problem is to say you take Suboxone for chronic pain; that you use it because it causes less CNS effects (sedation, etc) and you want to be ‘super sharp for your job!!’. Of course you would need your doctor to verify that when he is called by your company.

If you are switching to Suboxone, do it sooner rather than later– get the methadone out of you as quick as you can. And in MOST cases, the Suboxone that you would take would not show up in any test. It isn’t the number of panels on the testing kit– it is the manufacturer of the kit, and there are many manufacturers. I have kits with many different panel set-ups– the companies will make whatever collection of tests that I ask for. I have kits that detect buprenorphine (suboxone), or OC, or methadone, or whatever. If a company wants to test for buprenorphine they could get a buprenorphine test strip for about 3 bucks. But the companies know that they would be challenged for ‘snooping’ into your personal medical history, rather than searching for active drug abuse– that is the only reason they don’t test for buprenorphine.

Wouldn’t it be nice if addiction was treated like any other illness, and you could explain to your employer that you ‘caught’ opiate dependence when your doctor prescribed high-potency narcotics for your back pain, and that now you are under treatment…  and for that, you weren’t fired?  Maybe some day.

This gentleman answered my post about the limits of will power. I feel for him– I moved his post up here because it describes what happens when one partner falls in love with narcotics. As I read the post, about his wife slowly checking out with opiates and then with benzos… addiction makes a person fade away, lost in hazy fog… I had this image of his wife cheating on him, telling him lies about it being over…but going back again to the other man without even having the decency to go to a motel.

Will Power. I’m a person with strong will power, but my wife is not. My will has no power to get her help. Twenty years after 3 spinal fusions, she is now a daily methadone user (which I just found out 8 months ago?) for the past six years, to get off Oxycontin for chronic back pain. Since I confronted her about it she has repeatedly said she was getting weaned off of Methadone, and only had to go to the clinic twice a month now. Eight months later, nothing has changed, only getting worse. She is losing her mind, nodding out on her feet sometimes (“Oh, I was just thinking!” she’ll say) forgetting the most simple things and saying the craziest things. I have found Xanax, and Ambien in her purse and flushed them. Apparently local doctors (the ones she hasn’t been to before) have given them to her for depression. These combined with the Methadone makes for a person I can’t stand. Disgusting. Like someone who has been drinking scotch all night.

This is a nightmare, and my 31yr. marriage is about to end unless I have an intervention or something. She says she will do “whatever it takes,” but she’s dosed-up when she says it. She says her life sucks, and she knows Methadone is a wedge that is driven between us, but she is powerless to do the right thing.

I can’t afford Narcanon(?) and really don’t understand all this “agonist” stuff to well. I quit doing drugs at least twenty years ago and don’t even take an aspirin anymore, so I’m a little apprehensive about taking another drug (Suboxone) to get off another one (Methadone). The money she must have spent all this time on something that has convinced her brain she will die without it, she could have had two laser spine corrective surgeries by now. This is absolutely crazy. What’s to prevent a Suboxone user to not also include their Methadone dose as well? Chasing the dragon.

Is Suboxone a way to get off of Methadone?

Man I hope somebody reads this.

A couple thoughts.

Yes, Suboxone can be a way off methadone.  You will find some disagreement on the web, but since this is my site I can share my observations and opinions.   I have helped a number of people  change from methadone to Suboxone; most of the time those people were happy with the change.  But I don’t get the impression that this gentleman’s wife would be happy.

Methadone is an opiate agonist, and buprenorphine is a partial agonist.  The ceiling effect of buprenorphine allows one to take a sufficient dose to bind up all of the opiate receptors, which results in the loss of cravings for opiates.  To my way of thinking, buprenorphine, by eliminating the obsession to use, treats the heart of addiction itself.  That’s a good thing most of the time;  the person describes feeling much less ‘busy’– suddenly the person has tons of time and empty space in his/her mind to think about other things, such as wondering how one’s partner is doing, wondering about the meaning of life… whatever.

But I don’t get the impression that this gentleman’s wife is into all of that.  Were she to change to Suboxone, she would have time to feel ashamed of herself for what her life has become.  She would have to acknowledge her husband’s anger.  She would have to return to the living. s That would be a dramatic change from her self-obsessed fog.

For the writer, it is obvious that your wife has checked out of the relationship.  Is she still inside that doped up person?  I don’t know.  If you give her an ultimatum– come back to planet earth, or you are out of there– which will she choose?

A question about Suboxone and Surgery:

Hi-this is in reply to your message back to me. I am the girl who is soon to have surgery. You said that 3 days would be good to be off the suboxone, but you said the worst withdrawal takes about 3 days to hit, so it’s a bit of a compromise. But, won’t the withdrawal be halted once the pain medication gets into my body? Are you just saying that I will have to deal with some detox discomfort during the 3 day period? I, unlike many people, know quite a bit about suboxone (it is so surprising how many people are clueless), but the one thing I am not clear on is how long it would take to “feel” opiates after stopping suboxone (thank God I am ignorrant in this area!). On one of your blogs you said that opiates would work as short as a day afterwards, but that you would have to have quite a bit to get past the buprenorphine. I just dont think I can go off of them for 3 days prior to surgery. I am on 16 mg 2x a day.

My Response:

You are on a pretty large dose of Suboxone.  Everything is relative, but about 4 months ago the manufacturer of Suboxone sent a notice to doctors and pharmacists saying that because of the ceiling effect of buprenorphine, and because of the diversion of the drug, the maximum dose should be no more than 16 mg per day. The notice went on to state that a rare patient may require doses of up to 24 mg for a very short period of time, but that higher doses were never indicated.

In my local area, one clinic uses a max dose of 4 mg per day, a dose that I consider to be too low, but in my own practice I almost never use doses about 16 mg per day.  Overall, 30% of my patients take 8-12 mg per day, 60% take 12-16 mg per day, 3% take 16-24 mg per day, and the remaining 7% (7 patients) take less than 8 mg per day.

If the dose is taken correctly so that maximum uptake occurs, there is no subjective difference between 8 and 16 mg per day.  I have taken a number of people down in dose from 16 to 8 mg, and there is never any significant withdrawal;  there is, though, the ‘imaginary withdrawal’ that happens so much with early use of Suboxone. What is the difference?  Real withdrawal lasts until the person takes another dose;  the ‘imaginary withdrawal’ comes in waves, and then disappears as soon as the person is distracted a little bit.

Grrl, I strongly recommend that you get your dose down to 8 mg or so per day before surgery.  The blockade of the receptor is competitive;  it will be almost impossible to get enough agonist to overcome the blockade of 32 mg of daily buprenorphine.  Yes, 1000 mg of oxycodone might do it, but you will never get anyone to give you that amount in a hospital.  Even the less-ridiculous doses are hard to get, as every person in the chain gets in the way.  The surgeon doesn’t want to write for such high doses, as he doesn’t want to take the time to explain why he is doing so to all of the people who will be calling him.  The unit secretary doesn’t want to transcribe the order until she calls the surgeon to say, ‘are you sure you want THIS MUCH?’  Then the nurse won’t want to  give such a large dose, especially without monitoring– meaning that he/she will suddenly be pushing to get you transferred to the ICU.  The pharmacist may nix the whole thing, and simply say that ‘he isn’t going to risk his license by releasing so much narcotic’. Meanwhile, you will be writhing in pain as the hours go by.

The lower you can get your daily dose, the less buprenorphine you will have in your body to block the post-op medications.  Yes if you stop entirely three days in advance, you won’t have significant withdrawal for a few days… and by that time you will be getting the post-op pain meds.

A couple things… an anesthesiologist wrote and said that in his experience the lipid-soluble and high-potency opiates seem to ‘compete’ more effectively at he opiate receptor, and that they therefore are better choices for post-op pain.  Remember, though, that you will have TWO problems with getting pain relief;  the first is the competetive block of your opiate receptors, and the second is the high tolerance you will be left with, even after the buprenorphine is gone.

Your last question about how long it would take to ‘feel’ agonists after Suboxone… it would depend, of course, on the dose of agonist, the type of agonist, and the dose of Suboxone.  The bottom line is that it always takes much longer than people expect.  I have had a couple people who needed to go back to agonists for pain, and they said something similar to each other– that even after weeks off the suboxone, they could never get the same old ‘euphoric’ feeling again.  I don’t know if that is from some small lingering amount of Suboxone, or from the remaining elevated tolerance persisting for a long time after stopping the drug… But whatever it is, it will be difficult to get relief from opiate agonists for some time after stopping Suboxone.  And the people who stop Suboxone for a day, hoping to catch a buzz from a couple 40′s, will be disappointed!

The questions:

I am having surgery and my doc was unaware of some things and I thought that you could confirm them for him?  Could you advise him to take me off the Suboxone 10-14 days prior to surgery?  I have been researching this religously and I have come to the conclusion that it would take 2 weeks to get the Bupenepherine 100% out of my system so that there is no blockage, unless you think otherwise?  Also could you tell him about the oxycodone to keep me out of withdrawal and to help me cope with the pain?

Note:

I had also received a note from the doctor, saying that he was going to change the patient from Suboxone to Subutex before the surgery, and then back again at a later point.  This is fine, but not enough– the naloxone isn’t the problem– the buprenorphine alone is a partial agonist i.e. an antagonist at the mu receptor.  The buprenorphine alone will block other opiates, and since the patient is tolerant to the buprenorphine, it will not serve any role as an analgesic medication.  The patient needs additional opiate activity in order to have analgesia– and since his tolerance is high, he needs significant doses of a potent opiate.

My comments to the doctor:

Hi Dr. XXXX,

I don’t want to complicate your treatment of Mr. XXXX—he reads my blog about Suboxone at http://suboxonetalkzone.com where I write quite actively about my experiences treating patients for opiate dependence.  I am a (blah blah blah blah– you all know this stuff by now)

I have helped a number of patients through surgery.  The naloxone isn’t so much the problem as is the buprenorphine–  naloxone has a very short half-life and will cause a couple hours of withdrawal if injected IV, but buprenorphine is a partial agonist, and has very potent antagonism at the opiate receptor that lasts for days and days.  The half-life of buprenorphine is about three days;  when we treat addiction we are using supra-maximal doses of buprenorphine.  When I gave buprenorphine IV to treat labor pain as an anesthesiologist I would give microgram doses;  even just 8 mg is enough to block ordinary doses of opiate agonists for several days.

With my patients, or when recommending other physicians, I suggest first getting the patient to a lower dose of buprenorphine—on the order of 8 mg per day.  If you were to lower Mr. XXX’s dose tomorrow, he wouldn’t get down to a new steady-state level for at least a week or two;  he would have very little withdrawal, because the ‘ceiling effect’ occurs at a dose of about 4 mg per day, so any dose above that will have almost the same opiate activity.  From the 8 mg daily dose (usually once per day, in the morning) I stop the buprenorphine at least 3 days before surgery.  It will still be very difficult to treat post-op pain, because three days later the person will still have significant buprenorphine in his system, which has a very high affinity for the receptor.  It is important to remember that even if all of the buprenorphine was gone, the patient will still have a very high tolerance—equivalent to being tolerant to 30 mg methadone or 60 mg oxycodone.  That means that 60 mg of oxycodone only gets the patient to ‘neutral’;  higher doses are required to provide analgesia.  I usually give patients either 15 or 30 mg oxycodone tabs, to take 2 (or more) every 4 hours as needed.  At the time when the surgeon would typically stop narcotics, I change the patient back to Suboxone or Subutex—either one, as they both work the same in a person not injecting.

It is important to focus on the pain, not on the dose of narcotic. The dose is meaningless in a tolerant patient;  I have had patients require doses of morphine greater than 50 mg every 2 hours after c-section, for example.

On my blog I have a number of comments about anesthesia and surgery;  if you go to http://suboxonetalkzone.com and search for ‘anesthesia’ or ‘surgery’ you will find them.

Thanks for writing, and good luck,

SD

Addendum for the blog readers:

I am aware that the person having surgery requested medication to prevent withdrawal; I did not mention this to the surgeon because it is a ‘touchy subject’. It is in fact illegal to prescribe or administer an opiate for the sake of treating withdrawal, with the exception of methadone clinics—and now Suboxone. For that reason, I don’t usually stop the Suboxone 10 days in advance—I stop it 3 days in advance. Most people seem to take about three days to go into withdrawal, so that usually works pretty well.

I have had a couple discussions with this writer, and I hope things work out well for him. Many doctors out there have their own ways of doing things, and most doctors consider themselves up on what they need to know; it is hard to just tell a doctor to ‘do it this way’. I know I wouldn’t like it either. Let’s all hope for a little extra consideration and sensitivity from his physician.

SD

http://suboxonetalkzone.com

I’m in a bad mood tonight– squabbling with my 13-y-o daughter will do that to me– so I’m going to cheat and copy an e-mail that I recently sent to a reader.  She takes Suboxone and will be having surgery;  she did everything correctly, tapering her dose and then stopping the Suboxone for a few days before surgery.  Ideally her addiction doc or her surgeon would prescribe her a large dose of oxycodone to treat the post-op pain, but instead she was told that she is already treated for pain from being on the Suboxone, so she doesn’t need anything more.  After her appropriate objection, he told her that he would recommend that the surgeon prescribe– of all things– fentanyl patches.  Never mind that fentanyl patches have a ‘Black Box Warning’ by the FDA, that they are contra-indicated for treatment of post-op pain!.

As I mention in the e-mail, fentanyl was my ‘drug of choice’– it is a staple of the anesthesiologist’s ‘sleep kit’.  I have had a number of patients who abused fentanyl;  one person was drying and smoking the stuff that she scraped from the patches (it gets even more disgusting– she collected used patches from the backs of old people in nursing homes, pooling them together to  get enough used-up resin to get high (the patches are sometimes put on the mid-back area of demented, elderly patients so they don’t peel them off and throw them away).  I wouldn’t normally write about something that would provide a ‘tip’ about how to use– please continue reading.  She smoked this dried mess, and the vapors from whatever chemicals it consisted of trashed her lungs.  She developed ARDS (Adult Respiratory Distress Syndrome) and almost died, eventually leaving the ICU with permanent pulmonary problems (try saying THAT three times real fast!).  So don’t smoke that garbage.

OK… my message, filled with righteous indignation:

Yes, just to validate what you already know, you DO need extra opiate to compensate for pain—people on Suboxone are on that level of opiate as their ‘baseline’, and so of course you need something more potent when pain control is needed!  I wonder—does your Suboxone think that everyone on the medication is covered for all their pain control needs?  Is there ANYTHING he would consider providing pain medication for?!  I worry about this type of situation, since the people who end up treating addiction and prescribing Suboxone are not the same docs who have experience in prescribing pain medication.

I like your idea of letting the surgeon see the recommendation and then asking for something a bit less potent.  I don’t think the fentanyl patch would kill you (how reassuring that must sound!), and there are things you can do to make it safer–  there actually have been deaths associated with the patch, and I think there might even be a warning that comes with it now that it is not to be used for post-op pain—but by understanding some things about the patch you can make it a bit ‘less inappropriate’.  The first thing is to never cut the patch in an attempt to make it less potent.  Different brands have different things inside—some have gels, some have a semi-solid matrix, some have liquid—and some are safe to cut, but most aren’t, so just don’t do it.  The risk is when it is cut, the fentanyl leaks out and gets absorbed through the skin at a much faster rate than 100 micrograms/hour, leading to respiratory arrest.  The second important thing is to avoid heating the patch when it is against your skin, as that will increase skin blood flow which will cause greater absorption of fentanyl… again leading to respiratory arrest.

Fentanyl is an interesting drug—so interesting that I made it my drug of choice during my days as an anesthesiologist!  I was ‘outted’ (is that the right spelling?) by Men’s Health magazine—Google ‘men’s health’ and ‘junig’ and you will find the story–  and in the article they suggest that anesthesiologists breathe vaporized fentanyl that leaves the body of the unconscious patient through the opened abdomen, and they cite a study that found plasma levels of fentanyl in anesthesiologists just from a day’s work.  The guy who interviewed me for the story, Chris McDougall, suggested that this is why anesthesiologists become addicted to opiates.  I told him I thought the idea was silly—but he wrote about it anyway.

In small IV doses, fentanyl (which is a fat-soluble molecule) hits the brain and then ‘redistributes’ into the fat compartments of the body, so that the level in the bloodstream and at receptors rapidly decreases.  As you give more and more fentanyl, eventually the fat compartments become filled with fentanyl, and there is no place for it to ‘redistribute’ to.  At that point the blood level builds up, and is any decrease is dependent on breakdown at the liver—a slow process.  So in some cardiac anesthetics, where very large doses of fentanyl are given, the patient remains on a ventilator for up to 24 hours and sometimes even longer.

Wearing a fentanyl patch has effects similar to being on an IV infusion of fentanyl.  Initially, the fentanyl enters the blood and at the same time leaves the blood by entering fat compartments of the body.  After a few days, the fat compartments become saturated and there is nowhere for the fentanyl to go… and the blood level therefore rises.  The deaths from fentanyl patches often occurred after several days, because of this phenomenon.  Overdose from opiates occurs from respiratory depression, and the degree of depression can be measured by the respiratory rate.  I should add that benzos like Valium or Xanax greatly increase the respiratory depression from opiates.  You can help reduce the risk of overdose by having someone count your respirations when you are at rest or sleeping—you can’t count your own because you will change the rate if you pay attention to it!  The way doctors do it during exams (I am giving away a secret here!) is to hold the patient’s wrist and pretend they are counting the heart rate, and watch or listen to the patient’s breathing and count that instead, while watching the second hand on their watch.  Anyway…  if someone follows your respiratory rate while you are resting or sleeping, a normal rate is about 16;  the rate of a person in pain is usually above 24;  a person who is getting too much narcotic will have a rate of 12, then 10, then 8, then 6…  and after that they might just stop.  People who snore are at greater risk, because as the drive to breathe goes down, they are more and more likely to stop moving past the obstruction.  From a practical standpoint, if your respiratory rate drops below 12, I would suggest removing the patch, and keeping if off until you are alert and the pain has returned.  There will be a lag time with patches—it takes an hour or two for them to start working, and after removing them there will still be some absorption of fentanyl from the skin for an hour or two.

I had better send this off.  Again, I’m sorry your doc isn’t more enlightened.  Be careful out there… and keep us up on how things go!

SD