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.

Benzos and Buprenorphine

The high safety of buprenorphine, except when combined with a benzodiazepine, has been twisted in comments about the drug (and in the minds of regulators) to buprenorphine being uniquely dangerous when combined with benzodiazepines, which is not true.

I’ve heard more and more from insurers, regulators, and well-meaning agencies about the dangers of combining buprenorphine and benzodiazepines.   Some insurers protest paying for buprenorphine if patients are taking benzodiazepines.  Medicaid recently sent a letter that described a ‘severe risk’ of using benzodiazepines in patients on buprenorphine.  And the state drug database contains a graph for each patient of the morphine-equivalent narcotic dose over time, and shades the data in red if benzodiazepines are also prescribed.
Readers of my blog know I’m no big fan of benzodiazepines (read this for example).  But in an era of ‘fake news’, I’m even less of a fan of incorrect statements by doctors.   The drug database also ignores the ceiling effect of buprenorphine, and extrapolates the morphine equivalency of low doses of buprenorphine as if the dose response ‘curve’ was a straight line.  That ridiculous calculation leads the graph of opioid use to show buprenorphine patients as taking the equivalence of 900 mg of morphine per day.  The harm is minor I suppose by limitations on access to the database, but the error leads to misperceptions among doctors, and could potentially lead to mistakes in treatment decisions.
Benzodiazepines are respiratory depressants, especially when added to opioids.  The combination is dangerous when patients take doses of either class of drug that are higher than their tolerance levels.  The ceiling effect of buprenorphine eliminates that risk in patients who are stable on addiction-level doses of the drug, i.e. doses above the ceiling threshold.  A patient taking a maximal amount of buprenorphine CANNOT take a dose of buprenorphine that will cause respiratory depression.  Note the word ‘maximal’, not ‘maximum’.   By maximal, I mean a dose above about 8 mg per day, beyond which further doses will have no increase in mu receptor activity.
It is very difficult, and rare, to die from buprenorphine.  A person who lacks tolerance to opioids can die from buprenorphine, but deaths in that case are rare unless a second respiratory depressant is added– usually a benzodiazepine.  The high safety of buprenorphine, except when combined with a benzodiazepine, has been twisted in comments about the drug (and in the minds of regulators) to buprenorphine being uniquely dangerous when combined with benzodiazepines, which is not true.  Benzodiazepines are much, much more dangerous when combined with opioid agonists.  That risk is almost completely mitigated by buprenorphine, providing the person is tolerant to buprenorphine.
Buprenorphine rarely causes overdose unless combined with benzodiazepines in patients who are not tolerant to opioids.  Valid questions over benzo use should not be confounded by fears over buprenorphine.
Below, I will paste a letter I recently sent to one insurer who refused to cover buprenorphine in a patient on benzodiazepines.  Comments, of course, are welcome– and encouraged.
Re: XXX XXXX
XXX XXXX is treated with Suboxone for opioid dependence, and with a combination of medication for depression and anxiety that includes clonazepam and a shorter-acting benzodiazepine, currently lorazepam.    He has a history of (a significant anxiety disorder that I won’t disclose here).
The issue of benzodiazepine use in combination with opioids is complex, but fairly predictable in people who use benzodiazepines correctly (e.g. at regular intervals, rather than taking a month’s supply in three days and then going without for several weeks).
I am experienced in the use of medications that have respiratory depressant properties.  I am Board Certified in Anesthesiology and also in Psychiatry, and I worked as an anesthesiologist for over ten years before training in psychiatry.  I also have a PhD in neurochemistry, and I teach the section on opioids at the Medical College of Wisconsin.  I will take some time to explain the interaction of benzodiazepines and buprenorphine—so I hope you will read my comments and take them seriously.
Buprenorphine has been known to be a very safe medication for the past 3 decades.  Review of the pharmacology literature will show that deaths from buprenorphine are rare. While over 30,000 Americans die from overdose each year, only about 40 of those deaths occur in people who have buprenorphine detected in the bloodstream.  Of those 40 deaths, almost all were from opioid agonists, with buprenorphine NOT acting as a contributor to the death—and in most cases the death would have been prevented had MORE buprenorphine been present in the bloodstream.
The few deaths attributable to buprenorphine each year in adults require 1. An absent or low opioid tolerance, AND 2. the presence of second respiratory depressant that the person also lacks tolerance to.  Because of the ceiling effect, which caps the CO2 response-shift from mu-receptor activation,  deaths from buprenorphine alone are rare in adults.   Death is possible in adults naïve to opioids–  but only if a second respiratory depressant is present.
The fact that death from buprenorphine can only occur in the presence of benzodiazepines has been misinterpreted at times, in warnings about opioids, as the idea that benzodiazepines and buprenorphine are uniquely dangerous when combined.   Understand that patients tolerant to buprenorphine have a partial-pressure of carbon dioxide equal to 40 mm mercury (the normal level).  Because of the ceiling effect, additional doses or amounts of buprenorphine cannot shift the carbon dioxide response curve.  For that reason, patients who have been maintained on buprenorphine doses above the ‘ceiling threshold’ for over a couple weeks have no respiratory depression from the drug.  Such patients have similar respiratory responses to benzodiazepines as those of normal patients.
Mr XXXX is fully tolerant to the cap effect of buprenorphine, so he is not at risk of respiratory depression from the drug.  Frankly, he is in a much safer position than other patients contemplating benzodiazepines, because if he used opioid agonists their effects on respiratory function would be blocked.
I am not a big fan of benzodiazepines, and for that reason have tried to taper Mr. XXXX off of them in the past.  But when we have attempted to taper them, the insomnia and anxiety symptoms become more severe, causing him to isolate from others and miss work.  I am fearful- for good reason—that attempts to reduce benzodiazepines at this point would result in another significant depressive episode, resulting in hospital admission.  My goal has been to avoid any further increase in his dosage—something we have been able to do over the past two years.
Understand that the risk of respiratory depression comes down to tolerance, for both opioids and benzodiazepines.  Mr. XXXX uses the same amount of each medication every 24 hours, and does not stockpile medications or use medications impulsively.  His tolerance to BOTH medications, along with the cap on opioid effects intrinsic to buprenorphine, provides a significant margin of safety.

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

A New Way to Stop Suboxone?

Originally Posted 10/27/2013
I usually have my wife/business partner review my posts and provide her opinion whether my arguments are sound.  For the record, she tells me that this post is technical and boring.  I disagree, but we aren’t planning to separate over the issue.  A valid criticism, I think, is that I’m doing a lot of guessing and wondering in this post.  This post is an example of the things I waste time wondering about.   I try to avoid writing things that are somewhat speculative, but I wanted to give it a shot for two reasons.  First, because there may actually be something to the idea I am about to describe.  But more important, I wish to point out some of the many ideas in the addiction world worth exploring…. And I hope that pharma continues to search for answers (i.e. spend money) in this area of medicine.
So I’ve been thinking more about ALKS 5461, the Alkermes pipeline medication that is a combination of buprenorphine and ALKS 33, which is a mu opioid antagonist also called Samidorphan with the structure shown at the left. ALKS 5461 is being developed by Alkermes for the treatment of major depression.  I don’t know much about the clinical actions of ALKS 33, (a proprietary molecule), except that it comes from a family of drugs that bind with high affinity and specificity to mu or other opioid receptors.  Samidorphan, a mu receptor antagonist, allows investigation of buprenorphine’s potential therapeutic effects at kappa and delta opioid receptors by blocking effects at the mu receptor.  Drugs with actions at other opioid receptors have be developed, and in some case patented.Until recently, theories about depression revolved around abnormalities in brain monoamine pathways or deficiencies of monoamine neurotransmitters.  Monoamines include serotonin, melatonin, and the catecholamines (noradrenaline, dopamine, and adrenaline). Most modern antidepressants act at serotonin or catecholamine receptors or reuptake sites. The new Alkermes medication ALKS 5461 is the first serious effort that I am aware of to treat depression from the opioid perspective.
Our brains contain natural opioids called endorphins and enkephalins.  Endorphins and enkephalins are neurotransmitters in pathways with a wide range of actions, including blocking pain and raising mood during injury or sexual activity. Pain pills such as oxycodone displace endorphins and hijack the natural endorphin pathways, providing euphoria without the trouble of buying flowers.  Of course, a relationship with self-administered opioids always becomes more destructive than even the most codependent partnership!
As an aside, when I presented for addiction treatment 13 years ago I told the addictionologist about my background in neurochemistry, and went on to explain that I was fairly certain that I suffered from a deficiency of natural opioids.  That doctor got a kick out of my story, and I would enjoy a sense of justification if my hypothesis someday proved to be correct.
When one considers using treating depression with buprenorphine, the obvious deal-breaker is the same issue that has prevented every other serious consideration of treating depression with opioids, namely the development of tolerance at the mu opioid receptor.  Because of tolerance, anyone who finds relief from depression with buprenorphine would be cursed by the need for eventual withdrawal, as well as other consequences of opioid dependence. I assume that Samidorphan is added to ALKS 5461 to prevent mu activation and tolerance.  Beyond partial agonist effects at the mu receptor, buprenorphine antagonizes (blocks) delta and kappa opioid receptors.  These blocking actions are not subject to tolerance, and may provide avenues for treating pain and/or depression.
Depression causes significant morbidity throughout the world, so there are huge profit incentives for new antidepressant medications. Addiction creates a large market as well, but companies rarely go as far out on a limb for addiction products as they do for other diseases. The need for new antidepressants is acute, but in an alternate universe where pain and addiction treatment take priority, Samidorphan and related opioid molecules might have a number of benefits. I’ve posted, for example, about my experience treating severe chronic pain by combining buprenorphine with an opioid agonist.  I expect the combination to be exploited eventually given the need for effective pain treatments, perhaps using an analog of Samidorphan.
Doctors use buprenorphine to treat opioid dependence.  The goal of buprenorphine treatment is to block the cycle of use and reward for some period of time, and to allow patients to create support systems, establish self-sufficiency, regain self-esteem, and practice living ‘life on life’s terms.’  The amount of time that it takes to accomplish these goals likely varies depending on the individual’s premorbid function, life experiences, insight, genetics, and other factors, but studies suggest that a year is not long enough to make meaningful headway.   It is possible that for some people, opioid dependence is a relatively permanent condition that is best controlled with life-long maintenance treatment.   But for those who would like to try to maintain sobriety off buprenorphine, the tapering process reignites the circuits that were set up by the initial addiction, causing cravings, withdrawal, and the constant obsession to delay the taper and resume the prior day’s dose of opioid.
If ALKS 33 has a long half-life and blocks buprenorphine in a dose-dependent manner, I could picture an alternate strategy for stopping buprenorphine where the antagonist (ALKS 33) is introduced to buprenorphine patients at a gradually-increasing dose.  The goal would be to eventually have the person on a daily dose of Samidorphan sufficient to block all of buprenorphine’s effects at the mu receptor, at which point the person could discontinue buprenorphine without withdrawal.  I suspect that the patient would experience withdrawal in response to each increase in dose of Samidorphan, although withdrawal would be reduced by introducing the drug at a measured pace.
What is the value in tapering in such a ‘reversed’ way?  Why would adding an antagonist be preferable to the current process, i.e. simply reducing the dose of buprenorphine over time?  The answer comes from an understanding of the nature of addiction.  A person stopping buprenorphine by gradually adding Samidorphan would face the decision once per day, whether to take the next dose of Samidorphan.  Compare that once-per-day decision to the current method of tapering buprenorphine, where the person must decide, thousands of times per day, to NOT take more buprenorphine.  I would expect that deciding to take an antagonist once per day would be more likely to succeed then CONSTANTLY deciding NOT to take buprenorphine all day long, throughout all of life’s ups and downs—times when the patient was conditioned to take opioids.
We will learn more about Alkermes new medication in coming months. I hope that someone in a power position will consider some of the other diseases that might respond to these interesting chemicals, including opioid dependence.

Withdrawal from Suboxone or Buprenorphine

I received a question from a reader about withdrawal symptoms from stopping buprenorphine. My answer has relevance to opioid withdrawal in general, and to a common misconception about the duration of withdrawal symptoms.
The message:
Basically I quit Suboxone about 18 days ago. When I decided to quit I was taking about 8 to 12mgs per day. I got into taking Suboxone from trying to quit a Percocet habit that developed after a car wreck. I was stuck on Suboxone for near 3 years before I finally realized the person I thought I was really wasn’t the person I expected myself to become. So I decided I had enough and quitting Suboxone should be easier than quitting Percocet. I still laugh over that because I should have educated myself better before I landed myself where I am now. I am starting to feel marginally better but I have zero energy and my depression is off the charts. . . My question is because Suboxone has such a strong half-life being a partial instead of full agonist, how many more days weeks months do I have to suffer through before I can expect to return to normal? I am terrified of relapsing and have set a zero tolerance for myself. Hopefully I am strong enough and smart enough to stay away but is there anything extra I can do to help ease anxiety and the depression? Honestly I feel like I live in a personal hell no one gets or understands. I was just hoping u could give me some advice. Thanks for reading my message.
My answer:
There are many misconceptions about withdrawal and buprenorphine. Many people make the mistake of thinking that the long half-life of Suboxone lengthens withdrawal. The long half-life of buprenorphine reduces the intensity of withdrawal, but has a very minor effect on the duration of withdrawal symptoms.
Before going there, though, I’ll comment about where you are, and where you came from. I admit to feeling a bit annoyed when people write about being ‘stuck on Suboxone.’ I’m not sure why it bothers me as much as it does; I don’t receive kickbacks from Reckitt Benckiser, and I certainly had no part in inventing Suboxone. If I put words on my annoyance, it would be something about looking a gift horse in the mouth—a saying that nobody seems to say anymore.
Suboxone didn’t cause your problems; YOU caused your problems, or perhaps Percocet did. Suboxone bailed you out; it allowed you to live to fight another day, rather than go down the tubes and end up in prison or dead, from oxycodone addiction. People often write the same thing— about being stuck– on my forum, and I have the same reaction there. It seems to be so unappreciative or irresponsible, to blame the very thing that kept you alive.
For the people who write ‘I should have just stopped oxycodone without taking Suboxone’, I point out that it is clearly easier to stop Suboxone than oxycodone. How do I know? I know because we are having a discussion about tapering Suboxone! Nobody addicted to opioids tapers off oxycodone (everyone tries, but nobody is successful). At least SOME people CAN taper off Suboxone. Don’t believe me? Think it would have been easier to taper off oxycodone? Then you can just change to oxycodone and get on with the taper! NOTE—I do NOT recommend doing so; oxycodone is MUCH more addictive than buprenorphine, and much more likely to kill you!
The other reason the attitude bothers me is because after treating people addicted to opioids for the past 7 years, I’ve watched so many people from utter despair to stabilized on Suboxone, and then become convinced that they aren’t ‘clean enough’ on Suboxone. I’ve watched them taper off, and I’ve seen their obituaries a few years later, or received desperate emails describing the loss of a 70 K per year job because of a recent felony conviction. Meanwhile I have a number of patients who are content to treat their addiction for years, as their lives get far better than they ever dreamed.
For those still reading, I’ll explain why half-life is not a big contributor to the duration of withdrawal. If we took any person on any opiate, then suddenly and completely removed the opiate from the body, the brain pathways that are stimulated by opiates (the endorphin pathways) would suddenly become quiet. As those pathways stop firing, the person feels horrible. After all, the pathways help keep everyday-sensations from being painful and help elevate mood, so the opposite happens when they stop.
As the person used higher and higher doses of opioids over time, tolerance developed at the receptor level. In essence, the receptor for opioids became less sensitive to ALL opioids. Receptors that are not sensitive to oxycodone, are also not sensitive to hydrocodone, and not sensitive to the brain’s own opioids—endorphins. In a withdrawing person, there is little or no activity in opioid pathways because the receptors, where endorphins usually act, are no longer responding to endorphins.
In order for withdrawal to end, the body must make NEW receptors, and implant the receptors in the cell membrane. That takes weeks to occur. The process is initiated by withdrawal itself. When the neurons in endorphin pathways are not firing at their normal rate, the neurons respond to that lack of firing by turning on the machinery involved in making new receptors. In other words, the pain of withdrawal MUST occur, if receptor renewal is to be triggered.
The duration of withdrawal is a function of how long the body takes to make new receptors– NOT the amount of time to clear the body of the substance. Some people mistakenly think that withdrawal ends when the drug is gone– and that it is ‘stuck in the bones’ or things like that. All of that makes interesting reading, but it is not what is going on. It takes 8-12 weeks for the body to make new receptors, so that is how long opiate withdrawal usually lasts.
Suboxone DOES have a long half-life. That long half-life causes the initial withdrawal to be less severe because instead of turning off instantly, the opioid pathways become less and less active over days. So instead of the sudden onset of severe symptoms, the misery takes several days to peak. This may result in the entire process lasting an extra day or two, but that extra time is not relevant compared to the weeks that it takes to generate new receptors.
I imagine that people get different impressions of withdrawal because of the different patterns of misery from different opioids. When I came off fentanyl, I was very, very sick for the first few days. I could not walk, literally, and my systolic blood pressure never got above 90. A week later, I could walk, and so things seemed a lot better. But I still got winded after 20 feet, and I couldn’t eat for many weeks. I lost 30 pounds in the process, and I was skinny to start! Buprenorphine withdrawal starts more slowly, but then ramps up higher after a few days, and then slowly goes down. I see people come off all sorts of opioids; the pattern of misery varies, but the total misery is about the same in each case.
Specific to the writer, one should anticipate 2-3 months of fatigue and loss of appetite after stopping buprenorphine, similar to other opioids. The first few days are a bit less severe with buprenorphine than with, say, oxycodone, because the drug is leaving the body more gradually.
A final comment—I worry whenever I read that a person’s strategy for staying sober involves being ‘smart’ or ‘strong’. The only way I know to stop opioids is by coming to the full realization of one’s powerlessness over them, as in the first step of AA/NA. Being too strong or smart only gets in the way of that realization. In my opinion fear is the best approach, as in ‘if I try, even once, I will die— and it will ALWAYS be that way.’
I wish you well,
J

A Save with Suboxone?

I’d like to share a recent email exchange with a reader. The post is long, but there are several interesting aspects to the discussion. I’ve removed the conversational parts, as well as the identifying information.
The initial message:
I was an intravenous heroin user for three years. After treatment I was able to stay clean for 6 months… Well apparently to most people I was not clean because I was on Suboxone, but to me I was clean. People are so very discouraging when you tell them you’re clean and they find out you are on Suboxone. It hurts because of how much hard work you put in. I did well for six months, but then I relapsed and used for 5 days. After a short binge I again stopped, continued Suboxone and used once more for one day alone.
All of these relapses were with my girlfriend, and she used one extra time while I was working. She overdosed all three times she used. Her mother found her the second time in her room almost lifeless, and I was with her the other two times. I acted very quickly, giving her CPR immediately and calling 911 without the least bit of hesitation, as did her mother.
My girlfriend) is not on Suboxone, but I stayed on every day other than the times we used. I am pretty educated about opiates in general and I understand that she overdosed because of her lack of tolerance. I have read something you said before: A person on Suboxone maintenance has the tolerance of someone who takes 100mg of oxycodone a day. I need to know, for the sake of her life, my life or someone else’s life, if ever in a dire, life threatening situation and for some crazy reason 911 isn’t an option, could you melt down a Suboxone strip and inject the overdosed person and use it like Narcan if you absolutely had to? Or do you think I’m nuts for even asking?
One more topic… I obsess over heroin every day. It’s so bad that I sit with a calculator and tell myself, “alright, if I stay clean for these next two years and I finish my degree and start my career making this much salary then I can spend this much a day on heroin and it will total x amount of dollars a year and subtracted from my salary I will still have more than enough to survive.” How sick is that? It’s disgusting. It’s an absolute obsession of the mind. I seriously convince myself that with the right amount of steady income I could actually be a functioning addict.
Thank you so much for your time. I appreciate it so much.
My Reply:
Your email shows the incredible danger associated with use of intravenous opioids. I remember how impressed I was, when I was a resident in anesthesiology, over how the human body is SO strong and restorative, that we can survive and recover from horrible injuries… yet how fragile we are, that a lack of oxygen for only several minutes can cause death. Injecting opioids is a very effective, targeted way to kill a person. Doctors and nurses do not inject narcotics unless the patient is being monitored, usually using a ‘pulse oximeter’ to monitor the level of oxygen in the blood. Yet people with far less training are injecting the same drugs, not only without monitoring, but even in the absence of a non-impaired observer. It is no wonder that there are so many deaths from opioid dependence.
You probably know how I feel about being ‘clean’; people on buprenorphine are clean enough, in my opinion, to be considered sober. People on buprenorphine become fully tolerant to the effects at the mu receptor; there might be very minor effects at the kappa receptor, that may or may not have very minor cognitive effects…. but people take chronic medications for MANY illnesses, and some degree of sedation occurs with most of them, including medications for high blood pressure, migraine headaches, and seizure disorders. Should we consider all of THOSE people to be ‘not really clean’ too?
The question about using Suboxone to reverse overdose is very interesting– and shows that you have a good understanding of what is going on with medications like buprenorphine (in Suboxone).
One of my patients has described how he saved his girlfriend’s life by injecting Suboxone. He says that she was unresponsive and barely breathing, and out of desperation he put an 8 mg tablet of Suboxone in her mouth. When she didn’t respond after a minute or two, he quickly dissolved a tablet of Suboxone and injected it into her arm. He claims that she woke up 30 seconds later.
I’m glad his girlfriend survived, but I do NOT recommend that anyone rely on this approach to save a life. The most appropriate action, of course, is to do whatever one can to find appropriate treatment, and stop accepting the huge risks associated with IV injection of opioids. If a person has overdosed, call 911 immediately. The brain starts to die in about 3 minutes. Some parts of the country have instituted programs that provide naloxone injection kits for people addicted to opioids; injecting a pure antagonist like naloxone (Narcan) is much safer than injecting the partial agonist, buprenorphine.
The outcome after injecting Suboxone depends on a number of factors, including the person’s tolerance level and the presence or absence of other respiratory depressants. If a person has only used opioids– no benzodiazepines or barbiturates or alcohol— then in theory, injecting Suboxone would rescue the person from overdose. Both parts of the medication would contribute to reversing the effects of opioids; the naloxone (to a small extent) and the buprenorphine, which would have most of the effect. The ceiling effect of buprenorphine should prevent respiratory arrest in any person, as long as no other respiratory depressants are around.
But– one CANNOT expect the ceiling effect’s protection in the presence of other respiratory depressants. If other depressants are present, opioid tolerance becomes a big issue. I’ll describe two cases to demonstrate:
– Let’s take the low-tolerance scenario, with a person who has never used opioids or benzodiazepines, who ‘sniffs’ 40 mg of oxycodone and 10 mg of alprazolam. The risk of overdose would be high in that situation. And if, during overdose, someone injected Suboxone, the opioid effects of buprenorphine would be as great, or greater, than the opioid effects of oxycodone— so the person’s condition would likely worsen. (Note that I’m ignoring the effects of naloxone. Naloxone’s clinical effect last only about 20 minutes. That effect might help the person in this scenario, but it is hard to predict whether the naloxone would out-compete the buprenorphine that is also being injected. People who have injected Suboxone in the past tell me that they found are no difference between injecting Suboxone vs. injecting plain buprenorphine. That wouldn’t surprise me, given the high-affinity binding properties of buprenorphine.
– For the high-tolerance case, let’s take someone who is using 150 mg of oxycodone per day, but on this occasion took an amount of heroin equal to 300 mg of oxycodone. Let’s assume that there are no other depressants on board. In this case, injecting buprenorphine would be expected, theoretically, to block the effects of heroin, and not only wake the person, but precipitate withdrawal. Even if other respiratory depressants are on board, the buprenorphine would likely save the person from overdose, because the opioid effects of buprenorphine are significantly BELOW the person’s tolerance level, and below the effects of the heroin that is causing overdose.
Essentially, the high-affinity binding of buprenorphine displaces other opioids, causing an opioid effect equivalent to 60-100 mg of oxycodone. If the person’s tolerance is higher than that, the result will be precipitated withdrawal. If tolerance is lower, the result will be greater opioid intoxication.
I will stress, again, that the thing to do in case of overdose is to call 911. An even better thing to do would be to get help for anyone you know who is injecting heroin, and get help NOW—as the risks of IV drug use are very high, and nobody believes that he/she will be the next person to die. If you are in a situation where someone else is overdosing, and you inject that person with Suboxone or any other substance other than Narcan, you will likely be prosecuted, and convicted, for manslaughter.
The obsession described in your message is typical, and is the hallmark of opioid dependence. In my opinion, we (psychiatrists) should see ‘obsession’ as the primary defect in cases of addiction, as obsession is what destroys personality, undermines self-esteem, and crowds out other interests and interpersonal relationships. As I’ve written before, buprenorphine’s unique properties allow it to reduce or eliminate the obsession for opioids. Buprenorphine, I believe, is an effective, targeted way to treat opioid dependence.
His message back:
Being a psychiatrist, what are your thoughts on that obsessive thinking? I hate meetings and the 12-step programs. I lived in a half-way house for a month and a half that required 3 meetings per day. I agree with you that they create a fabricated sense of happiness and self-worth. Do you recommend staying on Suboxone for an extended period, especially during a time where i am still having these thoughts? And because of the way I feel toward meetings should I seek a psychiatrist and try to explain my thought process in order to try and change it? What would you recommend to someone in my situation who obsesses to that degree, and hypothetically plans his future around heroin?
Me Again:
I have seen SO many people who stopped Suboxone, then relapsed years later and lost a great deal. I’ve seen obituaries of former patients who used to be on Suboxone. If a person can take the medication without too much hassle— i.e. has a doctor who allows ‘remission treatment’ without making the person feel like a second-class citizen– then long-term Suboxone provides for the best chance of doing well in life, in my opinion.
Other than buprenorphine, the best ‘treatment’ for the obsession, in my opinion, is fear. Step programs tap into that fear, by emphasizing powerlessness— the realization that using even one time will definitely, without a doubt, lead to your destruction. Every thought about using should be confronted with that reality— that if you use, you will die. Relapse often starts with the idea that maybe the person can get away with it, maybe just once… so to stay sober, the person must KNOW that there is no way to try it, even once. That is a bummer, but not the end of the world! Humans love to feel powerful, but attendance at meetings helps reinforce the reality, and the value, of powerlessness. I’ve written about my own experiences back in 1993, when the realization of my powerlessness caused my desire to use to suddenly disappear. If only I could have remembered that powerlessness, even as my life got better!
I do not think that psychotherapy is all that helpful for obsessions. In fact, I think that psychotherapy can be dangerous, if it leads to the thought that you have everything figured out— a thought that the addicted personality loves to run with!
The challenge when treating with buprenorphine is to instill and reinforce the knowledge of powerlessness, even while treating the obsession for opioids with a highly-effective medication. The thought process becomes a little more complicated, but not impossible to grasp.

Questions, Excuses, Krokodil

I’ve been in more of a chatty mood lately, as regular readers have likely noticed.  I find it interesting that weeks will pass when I have little or nothing to say… and at other times, I have all sorts of random thoughts to discuss.
Excuses first– I’ve been tinkering with ads for the past few days, and I apologize to those of you who tried to read a post while I was activating and deactivating Wordpress plug-ins.  After experimenting with different colors I’ve decided that basic grayscale is the best.  For those who don’t blog, ‘plug-ins’ are small, add-on programs that add a range of functions to a blog.  There are literally thousands of them out there;  some free, some for a small charge.  A couple dozen plug-ins are designed to add the code for Google Adsense to a blog, with a range of features including adding ads randomly to old posts, etc.  I’ve found that some work better than others; a couple of them really messed up the other blog functions, causing the top banner to appear at the bottom and vice versa.  I THINK I have things working OK now;  if you are having trouble, please send me an email (drj at Suboxonetalkzone dot com) and tell me the nature of the problen, and the browser and operating system you are using.  Thanks!
Another neat feature of WordPress is that you can review a number of different statistics for a blog, including the keyword that each viewer searched for before arriving at the site.  I see certain questions posted over and over;  I presume those questions are about things that come up often in the lives of people on Suboxone.  I used to do ‘questions and answers’ on a regular basis;  I’ll try to get back to those now and then, using the most popular queries as starting points.
Yesterday, several people searched for phrases related to buprenorphine and workplace drug testing.  I’ve received a number of questions by email about that same topic.  People wonder if Suboxone (buprenorphine) shows up in drug testing, and whether they should disclose that they take the medication before the test.  This is a very tough issue.  I believe that people who take Suboxone properly are NOT impaired by the medication.  There was an article from the Mayo Clinic Proceedings recently that claimed that people ARE impaired by Suboxone, and therefore certain occupations– notably physicians and nurses– should not work at those jobs, if taking Suboxone.
There were at least two things that made their conclusions… ridiculous.  First, the authors wrote that doctors’ work is so uniquely difficult, that it challenges gray matter so much more heavily than other occupations, that doctors should avoid buprenorphine treatment.  To that, I say that a recovering anesthesiologist taking Suboxone is much safer than a recovering anesthesiologist, holding fentanyl in his/her hand, not on Suboxone!  Even if you take away the risk that the non-Suboxone doctor is using, one must consider the effects of cravings on vigilance.  I’ll take the doc on Suboxone, who is placing all of his attention on ME, over the guy reciting the serenity prayer to himself and pondering the decision over what can be ‘changed’ and what can’t!  Of course, that’s just me…
I was also impressed by the ego of the writers, who think that a pediatrician or radiologist has greater need for an ‘unmedicated brain’ than a jet pilot, or a welder ten stories up, or a long-haul trucker, or a nuclear physicist. Yes– doctor jobs are ‘uniquely’ difficult!  (add sarcasm here).
The conclusions were deeply flawed in other ways.  To determine the effects of Suboxone on performance, they looked at studies that gave people opioid agonists or buprenorphine, and concluded that the effects were similar.  I mean really– people who are not on Suboxone regularly, without a tolerance to opioids, taking buprenorphine?  OF COURSE the people were messed up!  Suboxone has potent opioid effects;  there is no argument to that point.  But the unique ceiling effects of buprenorphine allow the subjective effects to go away, as tolerance is established.  That’s the whole point of Suboxone treatment!
I’m off on a tangent, right?  Back  to drug testing…  I do not think that people on Suboxone, who take it properly, are impaired in any way.  So I do not believe that people should have to disclose their treatment, and their history, to their potential employers.  But my opinions on the matter are irrelevant, unless the new/old President-elect appoints me as Attorney General… and odds are not in favor of that happening.
I can say that I’ve received 20-30 emails over the years, asking about employee drug testing.  In each case I asked the writer to follow-up and let me know what happened.  Some ended up disclosing that they were on Suboxone, and most did not.  To date, nobody has written back to say that they were denied the job over the issue.  I therefore conclude that most employers are ignoring buprenorphine, at least at this point.  That’s the best answer I have;  I can’t recommend any specific course of action.
Finally… today I came across an old post on my forum about a drug that was sweeping across Russia last year, called Krokodil.  The drug apparently is made from over-the-counter codeine tablets, in a process that creates a cheap concoction of opioids in a toxic sludge.  Users of the drug describe withdrawal more severe than opioid withdrawal, that includes seizures.  And within days of starting a habit, users slough off large sections of skin and other tissue from their arms, legs, torso– even from the face.  Not for the faint of heart— if you search the name of the drug under Google Images, you will find horrifying photographs of the damage inflicted on people addicted to the substance.
If anyone really thinks that drug addiction is a ‘choice,’ please tell me what, exactly, those tragic people were thinking.

Post-op Pain on Suboxone

I often receive emails from patients on buprenorphine (or Suboxone) who are preparing for surgery or other painful medical procedures. Ideally in such cases, the surgeon would have a discussion with the person prescribing buprenorphine, in order to coordinate the plan for treating postoperative pain. In practice such discussions don’t seem to take place, leaving patients to scramble for effective pain control after surgery– when it is too late to take the steps necessary for a smooth perioperative course.
I am familiar with an NIH article that describes pain control in people who take buprenorphine. I’ve also prepared a handbook that describes the issues that must be considered in such patients; the handbook can be found easily-enough by searching for the User’s Guide to Suboxone.
Even with those descriptions ‘out there,’ I’ll get requests for a short, ‘just-the-facts’ note that patients can give to their surgeons. I realize that unfortunately, the average surgeon will not sit down for an in-depth discussion of post-op pain control, so I have prepared a few paragraphs that lay out the issues. People on buprenorphine who are having surgery are welcome to copy the paragraphs below and give them to their surgeons, in order to facilitate discussion.
Surgery in Patients on Buprenorphine
Buprenorphine is a partial opioid agonist that is used for several indications. In low doses—less than 1 mg—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 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 to do—or by reducing the dose of buprenorphine to 4-8 mg per day, starting the day before surgery and continuing post-operatively. 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 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 report that opioid agonists relieve pain if taken in sufficient dosage, but the subjective experience is different, in that there is no feeling of euphoria.
Quick Notes:
Patients taking maintenance doses of buprenorphine do NOT receive surgical analgesia from the medication, as they are completely tolerant to the mu-opioid effects of buprenorphine after the first week or so on the medication.
Discontinuation of high dose buprenorphine or Suboxone treatment results in significant opioid withdrawal symptoms within 24-48 hours.
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 on buprenorphine. Initiating buprenorphine WILL cause withdrawal in someone who is tolerant to opioid agonists, unless the person is in physical 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.

Tough Choice

I have been struggling with part II, primarily because there are no easy answers to the situation. I realize that I could easily criticize whichever path a doctor suggests for our imaginary patient.
As an aside, I believe that a major reason for the lack of sufficient prescribers of buprenorphine in some parts of the country is the ‘damned if I do, or damned if I don’t’ scenario. All docs are aware of the current epidemic of opioid overdose deaths, and I think most doctors assume that tighter regulations on opioids are appropriate, and are just around the corner. Some addiction physicians and some pain physicians, particularly those who prescribe opioids, fear being grouped by the media, DEA, or a licensing board as part of the problem, rather than as part of the solution. I recently read of a doctor charged with manslaughter for being one of several prescribers for a person who died from opioid overdose. He prescribed meperidine—and outdated and toxic medication—which likely contributed to the charges… but the story creates a chilling atmosphere, regardless. Suboxone and buprenorphine are much safer medications, but when the target population consists of people with addictions to opioids, there will always be some people who use the medication inappropriately— some with disastrous results.
For those late to the party, we are discussing the best treatment approach for someone who cannot control using opioids, but who for now, at least, has a low opioid tolerance. Starting buprenorphine in such a patient will cause opioid side effects, as described in an email that I received from a woman who was addicted to hydrocodone for four years, who stopped taking hydrocodone for 7 days before induction with buprenorphine.
She wrote:
This Suboxone is making me feel like crap. He has me on 8mg/2mg sublingual 2/day. It’s awful…
She had been taking 20-30 mg of hydrocodone up to 5 times per day, stopping them a week before induction. She continued:
Have had a headache in the base of my skull since starting Sub 4 days ago, nausea, vomiting, sweating a lot, face feels like it’s on fire, can’t taste anything, throat hurts, can’t sleep because my face & eyes itch so bad that I’ve rubbed them raw.
These are classic side-effects of over-narcotization from buprenorphine. A person in this position typically feels better holding the buprenorphine, and when the nausea is eventually gone, taking a greatly reduced dose of the medication. The problem is that if the dose is too low, there is no advantage to buprenorphine over other opioids. The whole point of taking Suboxone is to stay on a blood level HIGHER than the ceiling effect, as that essentially tricks the brain, since the opioid effect stays constant even as the blood level falls.
In a few days, the writer’s tolerance will increase to a level where she can take an entire dose of Suboxone without nausea. And by that time, the medication will greatly reduce the desire to take opioids.
Will she be better off on buprenorphine or Suboxone than she was on hydrocodone? Her tolerance will be higher—meaning greater physical withdrawal if she stops the buprenorphine, than she would have had stopping the hydrocodone.
But on the other hand, she tried to stop taking hydrocodone for several years, and couldn’t. She was taking over 4 grams of acetaminophen per day— the other medication present in Norco besides hydrocodone— which is enough to cause death through liver toxicity. And the ups and downs of hydrocodone addiction create a living Hell that eventually demoralizes the person.
I hear from writers who are angry at their physician for getting them ‘stuck on Suboxone’, saying they should have simply tapered off the hydrocodone instead. My answer is that it is easier to SAY ‘I would have tapered of hydrocodone’ than it is to actually taper and stay off hydrocodone!
A doctor seeing the patient I wrote about in part one, or the person above, would face two options:
1. Cause an incidental ‘high’ by administering buprenorphine, and titrating the dose up to a level that eliminates cravings, or:
2. Use an alternate treatment strategy.
Some doctors would opt for the latter, saying they are not comfortable with deliberately intoxicating patients with opioids—something that is unavoidable when starting a low-tolerance patient on buprenorphine (or Suboxone; note that the naloxone component of the medication is irrelevant to this discussion, as it has no action unless injected).
In such cases people are often referred to step-based or other residential treatment centers. I’ve written some pessimistic opinions about those places, but I’m just trying to be accurate. I realize that there are many people dedicating their lives to treating people with addictions in such places—ranging from free, community-supported programs to $80,000 per month luxury rehabs. As dedicated as those people are, the success rate of such programs remains low, and the risk of fatal overdose is present upon discharge. Most people who have gone through residential treatment relapse. And many people have been through rehab multiple times, yet continue to struggle.
Vivitrol, a monthly, injectable form of naltrexone, has been marketed to fill in this space, as a protection against relapse after residential treatment or after several weeks of detox. But for whatever reason, most people opt to forgo that medication, instead placing misguided faith in their own ability to stay clean. So what usually happens is that people with a lower tolerance to opioids repeatedly go through detox, or repeatedly pay for residential treatment, only to return to using opioids. Tolerance increases over time and eventually they present with a tolerance level where Suboxone seems more appropriate.
Assuming, of course, they live that long.

Hydrocodone (Vicodin) Addiction and Buprenorphine

I recently accepted a young man as a patient who was addicted to hydrocodone (the opioid in Vicodin), prompting a discussion about treatment options for someone who hasn’t been using very long, and who hasn’t pushed his tolerance all that high. Perhaps it will be informative to share my thought process when recommending or planning treatment in such cases. In part one I’ll provide some background, and in a couple days I’ll follow up with a few more thoughts on the topic.
Most people who have struggled with opioids learn to pay attention to their tolerance level—i.e. the amount of opioid that must be taken each day to avoid withdrawal or to cause euphoria (the latter about 30% more than the former). For someone addicted to opioids, the goal is to have a tolerance of ‘zero’—meaning that there is no withdrawal, even if the person takes nothing. That zero tolerance level serves as a goal, making having a high tolerance a bad thing, and pushing tolerance lower a good thing.
Tolerance is sometimes used as part of the equation when determining the severity of one’s addiction. But looking at tolerance alone can be misleading. Tolerance is a consequence of heavy use of opioids, and also a cause of heavy use of opioids. Tolerance usually goes up over time, so having a high tolerance probably correlates with length of addiction in some—- but not all— cases. Tolerance is also strongly related to drug availability. A person with a severe addiction, who only has access to codeine, will likely have a lower tolerance than a person with a more mild addiction, who has free access to fentanyl, oxycodone, and heroin.
I think it is more appropriate to measure the ‘severity of addiction’ by the degree of mental obsession that the patient has for opioids. Tolerance is one piece of information in determining that obsession, but tolerance alone can be misleading.
To get a sense of the obsession for opioids, I look at many factors. Has the person committed crimes to obtain the substance? Violent crimes? What has the person given up for his addiction? Has he been through treatment? How many times? How long did he stay clean after treatment? Have his parents or spouse thrown him out of the house, and if so, does he still use? Did he choose opioids over his career? Over his kids?
Answers to these questions provide a broad understanding about the addicted person’s relationship with the substance—an understanding that is necessary when considering the likely success or failure of one treatment or another. It is also important to consider the person’s place in the addictive cycle—i.e. early, likely in denial, cocky, with limited insight– or late, after many losses, more desperate—and perhaps more accepting of treatment.
I am a fan of buprenorphine as a long-term treatment for opioid dependence, as readers of this column know. I consider opioid dependence to be a chronic, potentially-fatal illness that deserves chronic, life-sustaining treatment— and buprenorphine, in my experience, is a very effective treatment in motivated patients. But tolerance becomes a factor, when considering buprenorphine for THIS patient.
Buprenorphine has a ‘cap’ or ‘ceiling effect’ that allows the medication to trick the brain out of craving opioids. In short, as the blood or brain concentration of buprenorphine drops between doses, the opioid effect remains constant, as long as the concentration is above the ceiling level. In order to achieve the anti-craving effects of buprenorphine, the dose must be high enough to create ‘ceiling level’ effects. If buprenorphine is prescribed in lower amounts—say microgram doses— the effect is identical to the effects of an agonist, since the dose/response curve is linear at lower levels.
Buprenorphine is a very potent opioid, and the effects of the medication are quite strong at the ceiling level. Comparisons to other opioids will vary in different individuals, but in general, a person on an appropriate dosage of buprenorphine develops a tolerance equivalent to that of a person taking 40 mg of methadone per day, or approximately 60-100 mg of oxycodone per day.
A person taking even a dozen Vicodin per day has a much lower tolerance to opioids. Such a person who starts buprenorphine treatment will obtain a very significant opioid effect from the drug— unless the dose of buprenorphine is raised very slowly over a number of days. And in that case, the person’s tolerance level would be pushed much higher.
So if our current patient starts buprenorphine, he will have a much higher opioid tolerance if/when the buprenorphine is eventually discontinued. I receive emails now and then from patients who are angry at their doctor for starting buprenorphine, feeling trapped by the considerable threat of withdrawal from stopping the drug. But at the same time, taking hydrocodone and acetaminophen in high amounts creates the risk of liver damage from the acetaminophen, as well as the considerable risks from opioid dependence.
And so the dilemma. Should buprenorphine be considered in such a case?