Does Suboxone Stop Working Over Time?

First Posted 12/31/2013
Buprenorphine is relatively unique among opioids in having a ‘ceiling’ to mu opioid effects.  There are other known molecules that act as partial agonists at mu opioid receptors, but buprenorphine is the most useful, at this point, because of other traits of the molecule– such as having few side effects from actions at non-mu receptors.
As most opioid users soon realize, opioid agonists increase tolerance over time to what appears to be an infinite degree.  The mechanisms of tolerance are complicated. I often describe tolerance as a process where receptors become less and less sensitive to opioids with stimulation, to the point where native opioids (endorphins and enkephalins) no longer activate opioid pathways.  Some of the change in sensitivity is caused by the binding of phosphate molecules to the intracellular portion of receptors, causing changes in conformation. Tolerance development is likely far more complicated, though, and includes other changes in synaptic transmission through different mechanisms.

Opioid Effect vs. Dose of Drug
Opioid Effect vs. Dose of Drug

The best model to understand the effects of buprenorphine, in my opinion, is to plot the curve with ‘mu effects’ on the y axis and ‘blood drug level’ or ‘dose’ on the x axis.  Opioid agonists yield a straight line with a slope that correlates with drug potency.  Buprenorphine yields a straight, sloped line in microgram doses and low blood levels, but a horizontal line in high doses.  At a sufficient blood level, buprenorphine essentially sets the tolerance at the degree of opioid effect predicted by that horizontal line.
We could also graph the development of tolerance over time, to high doses of opioids.  Agonists would yield a sloped line that eventually flattens, providing the dose of drug is held constant.  In increase in dose of agonist would cause the line to slope upward for more time, and flatten at a higher level.  With buprenorphine, on the other hand, the slope would flatten at a level that remains constant, even if dose of buprenorphine was increased.
This second graph answers the question of whether buprenorphine or Suboxone stop working at some point in time. From a theoretical standpoint– which is mirrored by clinical experience– tolerance from high-dose buprenorphine does not change beyond the increase in tolerance over the first few weeks of use—- or beyond the decrease in tolerance that was caused by higher amounts of an opioid agonist.  If we graphed the development of tolerance to high dose buprenorphine (say 16 mg per day) vs. time, the graph would be different for opioid-naive persons than for people taking high doses of agonists.  In the former group, the line would slope upward and flatten in days to weeks.  In people taking high doses of opioid agonists, the line would slope steeply downward over the course of minutes, and flatten at the same level as for the first group of patients.  The steep, downward-sloping line would represent the forced-lowering of tolerance by buprenorphine, which is experienced as precipitated withdrawal.  In precipitated withdrawal, buprenorphine is ‘yanking’ tolerance down suddenly.  The graph would be similar for the mu antagonists naltrexone or naloxone, but the point of leveling off would be lower– theoretically at the level of zero, if enough antagonist is used.
I realize that it is difficult to develop mental images from another person’s written descriptions… but I encourage people who want a better understanding of buprenorphine to give the mental images a try.  Once a person can picture the flattening of opioid effect with increased dose or blood level of buprenorphine, the mechanism of action of buprenorphine is easily understood.  As long as the blood level remains above the point where the line becomes horizontal, the opioid effect does not decrease– and so from the brain’s perspective nothing wears off, and nothing ‘comes on’.  Tolerance develops to that level of opioid effect within days to weeks, removing any subjective opioid effect.
After the initial days to weeks on buprenorphine, the tolerance level remains constant– even if the dose of buprenorphine is raised or lowered, as long as the dose remains above the critical level that yields the ceiling effect of the drug.
For those who want ‘just the facts’, the response of opioid receptors to high-dose buprenorphine does not change over time.  Buprenorphine and Suboxone therefore do NOT stop working over time, and there is no need for the dose to change over time.  If anything, my patients tend to move to a lower dose with time, as they find the minimum dose necessary to produce the ceiling effect of buprenorphine throughout the entire dosing interval.
The graphs also explain why there is no truth to the common internet comment that ‘the longer you take buprenorphine, the harder it is to stop’.  Tolerance remains constant, so from a physical standpoint the journey off buprenorphine is the same in three months or three years.  My own clinical experience suggests that people find it progressively easier to stop buprenorphine the longer they take the medication. I have no proof for if or why that occurs, but I suspect that a number of psychological factors are responsible—including the transformation to a new, non-using identity that allows withdrawal symptoms to act aversively and remind people of their desire to stop opioids.
In other words, I suspect that being on buprenorphine for a long time reduces the cravings during withdrawal, instead causing cravings

Why do some docs kick patients off buprenorphine?

I often receive e-mails from people that go something like this: I was addicted to oxycodone and heroin for 5 years, and lost my marriage, several jobs, and the trust of my children. I was completely broke, and considering suicide. Then I heard about treatment with buprenorphine and found a doc who prescribed it. Since then everything has been going much better; I have a job, I’m putting some savings away, and I have been starting to reconcile with my family. But my doctor says he wants me off Suboxone and is making me taper, and I’m definitely not ready. I am starting to panic because I know that if I have to go off buprenorphine I’ll only end up using again. Is there a way to make him keep me on buprenorphine?

Why the rush off buprenorphine? Suboxforum.com
Why the rush?

I have described my approach ad nauseum on this blog. I look at the ‘givens’:
– Despite everyone’s wish that addicts stop using opioids and ‘get off everything,’ it just doesn’t work that way. The relapse rate after stopping opioids is very high, whether stopping buprenorphine or any other opioid substance.
– Opioid dependence is a chronic illness that never goes away. People relapse even after years of sobriety.
– Traditional treatment suffers from very high costs and very low success rates, and requires a large time commitment. Traditional treatment does NOT offer any ‘long term protection’ against relapse; if a person stops attending meetings, the rate of relapse becomes similar to those who never went through treatment.
– Buprenorphine can hold opioid dependence in remission in motivated addicts. It is not just a ‘substitution’ of one drug for another, as the ‘obsession’ which is the essence of addiction is reduced, allowing personality to improve and for other interests to return.
– The side effects and risks of taking buprenorphine are not significant, especially when compared with treatments for other life-threatening conditions.
– Even a short relapse can have unpredictably severe consequences, including legal trouble, loss of career, loss of key relationships, and death.
I could go on and on with this list, but you get the idea. My own conclusion then has been that buprenorphine should be considered a long-term treatment for a long-term condition.
Why do some doctors insist on a short-term approach? One reason is simple ignorance, and not understanding the nature of opioid addiction. Many docs persist in seeing addiction as a ‘choice’, and fall into the same silly thinking that some addicts initially believe, that the main barrier to sobriety is withdrawal. Addicts who become miserable enough to get through withdrawal quickly learn that the withdrawal is NOT the problem—at least not the MAIN problem—as even after the symptoms go away, the addict relapses. This is maddening to the addict’s loved ones, and some doctors see this situation and become angry at the addict, rather than understanding the nature of addiction. At least there are now studies showing the high rate of relapse, and hopefully the data will change the behavior of physicians prescribing buprenorphine.
Another reason for short-term prescribing is because the buprenorphine is being used as detox, for entry into a ‘total sobriety’ treatment center. I won’t get too upset about such a situation, except to point out that such treatment centers commonly mislead patients about their chances. At the treatment center where I used to work, Nova counseling services in Oshkosh, WI, the counselors would get very excited about patients who looked good on their way out the door. But nobody seemed to feel any responsibility if that same patient relapsed and returned—or died—six months down the line. Of course many patients never made it to the end of treatment, getting thrown out early or leaving on their own. The counselors blamed those failures on the patient—instead of recognizing a failing treatment strategy. THIS IS A VERY SERIOUS PROBLEM, by the way, with residential, traditional treatment programs—a problem that exists because of stigma about addiction, and a sense that addicts are less deserving of good health than ‘normal people.’ How can I say that? Think of it this way—what if any other illness was managed in this way? If heart disease or diabetes simply failed to make people better most of the time, and the doctors routinely blamed the patients for the lack of success, how would THAT fly?
My biggest concern is that there are motivations to get patients off buprenorphine that come from the requirements placed on physicians who prescribe the medication. Physicians can treat only 30 patients at a time with buprenorphine. After a year they can apply to raise that limit to 100 patients. Ironically there is no limit at all on the number of patients a doctor can treat with opioid agonists! In a typical practice, patients are seen less often as they become more ‘stable’ on buprenorphine, resulting in a situation like mine– I have about 100 patients who have done well on buprenorphine for some time, many of whom had multiple attempts at ‘traditional treatment’ and some who were on buprenorphine from other docs, who would like to stay on buprenorphine long-term. That’s fine with me; buprenorphine patients are a small part of my practice. But if I wanted to make significant income from patients on buprenorphine, I would need to clear out spots for new patients who are seen at greater frequency, and who would pay the initial intake fee.
In other words, doctors are rewarded for high patient turnover, and the growth and earning power of their practices are limited by the cap on the number of patients they can treat. I understand the reason for the cap; we don’t want to suddenly have thousands of patients on buprenorphine without adequate treatment and supervision. But there is always a downside to any regulation, and rapid turnover in some practices is a downside to this particular regulation.
I don’t have any particular advice for people who are being forced off buprenorphine for no fault of their own, other than to seek out a new physician. Patients who are considering starting buprenorphine may want to ask the doctors in their area about their attitudes toward long-term maintenance. Hopefully over time at least some of the motivations for pushing people off buprenorphine will become less significant. For the docs who are doing the pushing, I encourage you to examine your own motivations. I realize that everybody wants to get back to how they were before becoming addicted to opioids… but it is important to remember that nobody can predict the outcome of a relapse, and some people die.

High Dose Buprenorphine (HDB) and Toxicity Concerns

Several weeks ago an article with a provocative title was posted at Suboxone Forum. I don’t remember the exact title, but it was something like ‘Toxicity from High Dose Buprenorphine (HDB). Before everyone gets too excited, there was nothing all that new in the article, which consisted of three case reports about deaths of people taking buprenorphine. One case consisted of a suicide from very large doses of buprenorphine, one was a death from combining buprenorphine with other respiratory depressants, and the third death was in a person with liver failure who took buprenorphine with other psychotropic medications. There are a couple issues brought up in the article that are worth mentioning.
First, I appreciate their use of the term ‘high dose buprenorphine,’ and this was the first time I came across the distinction between the historical use of buprenorphine in microgram doses for treating pain and the more recent use of milligram doses for treating addiction. Buprenorphine is an extremely potent opiate; the ceiling effect protects from overdose in the absence of other respiratory depressants (with some exceptions– see below) and places a ‘cap’ on tolerance to the medication, but buprenorphine reaches maximal effect at a very low dose. The potency of buprenorphine is more similar to that of fentanyl or sufentanil than to morphine or oxycodone. Transdermal formulations of buprenorphine used for pain release doses of buprenorphine between 5 and 75 MICROgrams per hour. The most popular dose of buprenorphine used for opiate dependence in the US is the 8 mg Suboxone tablet, which contains 8000 micrograms of buprenorphine! It is likely that one reason for the occasional death from buprenorphine ingestion relates to fact that a fraction of an 8 mg tablet is about as potent as an entire 8 mg tablet, and novices to buprenorphine make the mistake of thinking that a very small piece will be less likely to kill them than taking an entire tablet. Because of the ceiling effect and high potency, there is little if any protection in taking a small piece of a tablet.
While the ceiling effect offers some protection against overdose from buprenorphine, there is no protective ceiling effect to the actions of the drug’s primary metabolite, norbuprenorphine. There have been deaths attributed to the ingestion of very large doses of buprenorphine where the metabolite accumulated to levels that caused respiratory arrest. It appears that norbuprenorphine does not accumulate to levels sufficient to cause respiratory arrest in people with intact liver function who are taking standard, FDA-approved doses of Suboxone. But there are a number of medications that inhibit certain liver enzymes, and it is conceivable that the right combination of medications and a large dose of buprenorphine could result in potent respiratory depression. A number SSRI’s interfere with liver enzymes, the most potent perhaps being fluoxetine or Prozac, but in the case of SSRI’s the enzyme affected converts buprenorphine to norbuprenorphine. Fluoxetine may in fact then offer a protective effect by preventing conversion of buprenorphine to the more-dangerous metabolite norbuprenorphine.
The respiratory depression potentially caused by norbuprenorphine again draws attention to the fact that very high doses of buprenorphine are used when treating opiate dependence. We know much about the metabolism and actions of microgram doses of buprenorphine, as the medication has been around for over three decades. But a number of attributes of the medication change at very high doses. One very significant change is in the half-life of the medication. Microgram doses are metabolized in several hours, but at milligram doses the metabolizing enzymes become overwhelmed, increasing the half-life to one to three days. This increase in half-life is very useful when using buprenorphine to treat opiate dependence… but can be cumbersome when trying to rid the body of buprenorphine, say before elective surgery.
The most frightening question about HDB is whether there are toxic effects from such use that have not been apparent after years of microgram dosing of the medication. Because of this blog I receive a number of messages from people who take buprenorphine. I have heard of several cases of neurological illness in people taking buprenorphine, but I have no idea whether the reports represent higher frequencies of illness than would be expected in the general population. Specifically, I have heard about a person with dementia, a person with encephalopathy, and a relatively young young person who developed symptoms of Parkinson’s Disease. In all cases, the person was taking buprenorphine for several years.
At this point I must say DON’T HAVE A COW. To date, several hundred thousand patients have been treated with HDB; we would expect a number of those people to come down with these conditions in the ABSENCE of any connection between buprenorphine and neurological illnesses. I continue to prescribe buprenorphine, and I believe WITHOUT RESERVATION that the medication is the best, most appropriate treatment for MOST cases of opiate dependence. I think it is probably clear to most readers by now that I am not in bed with Reckitt-Benckiser; I will always write about any concerns that I come across about the medication without delay. I regularly scan the literature for articles about buprenorphine, and I run literature searches in response to any serious concerns by people in my practice or on the forum. I also ask that if anyone is aware of a case of neurological illness in a patient who takes buprenorphine, that they contact me so that I can report the information to the FDA.
JJ

How Long to Take That Stuff?

I ended the ‘85% off’ sale of the recordings listed to the right of the blog; they are also listed at the web page ‘Sober After Suboxone,’ along with some other useful recordings about opiate dependence. I have received good feedback about the recordings, and I think that the ‘how long’ one is the most useful for the people reading this blog; people at other stages of opiate dependence may find other recordings more useful, such as the one that discusses opiate dependence treatment options. The treatment options are NOT just a list of the different options available; they are a list of the options from the perspective of someone (i.e. me) who has dealt with my own opiate addiction for 16 years. They take into consideration the fact that few people will commit to residential treatment, and more importantly they take into account the relapsing nature of opiate dependence in SPITE of residential treatment options.
The ‘how long are you going to take that stuff’ recording is for the people who are always on your case about Suboxone– the people who think you are still getting high, or the people who say you have ‘substituted one addiction for another’ (you haven’t, by the way). I take on these and other issues, such as the fantasy about being ‘clean of all substances’ that comes from NA programs from time to time. I haven’t fully decided on the title of the book I am almost done with, but I like ‘dying to be clean’, as it captures the folly of going off life-sustaining medication to chase after a shame-based goal to be ‘completely clean.’ For parents who keep harping on their children to stop Suboxone, will you feel better when your son or daughter has died from an overdose while trying to avoid the Suboxone that would have kept him or her alive? DROP THE IDEA OF BEING OFF EVERYTHING. Opiate dependence is a horribly fatal illness; if Suboxone is working, count your blessings and appreciate life. Finally, addiction is not the ‘use’, it is the ‘obsession’. Suboxone is unique among opiates in that it addresses the obsession. THAT is what gives you your son or daughter back.
As I said I stopped the 85% off sale, but I did keep a 50% off sale– not actually a sale, but more a permanent 50% price reduction. I hope you will continue to use the recording, either to arm yourself with knowledge or to share the information with others.
As I have said before, consider the $10 purchase as a donation to the cause. I really appreciate those of you who have already purchased one or several of the recordings.
Thanks!

Can't Find Long-Term Suboxone Doctor

An e-mail:
I’m stuck in methadone-land, no one will write long term for Suboxone. I feel trapped and utterly helpless. I’ve been on methadone for a year and a half, and just see no real end in sight. I am tired all the time, and my friend said that he got on Suboxone and it changed his life. I’ve been reading about it and trying to find someone in my city to do it but they all only do 90 day detox programs. What if anything can I do? I’m out of options short of driving several hours to doctors in other big cities. I’m in Wichita Ks and the next closest is OKC or KC.
My reply:
I assume you have tried the physician-finder web sites; in case you haven’t, one is here at Suboxone.com, and the other here at naabt.com. If you haven’t investigated the local practices lately, I encourage you to check them out again; practices have changed, and more and more docs are realizing that Suboxone is best used long term. A few years ago 70% of scripts were for detox/short-term; now 70% are for long-term use.
Consider posting at SuboxForum.com and maybe someone from your part of the country will have some ideas about docs in your area.
SD