Withdrawal Archives - Suboxone Talk Zone

Tapering off Buprenorphine or Suboxone, Pt 2

In the last post we discussed some of the misconceptions about tapering off opioids. Today we will discuss a couple basic principles, and then describe the approach I recommend for my patients tapering off buprenorphine.
Opioids act at receptors that normally bind endorphins, which are released by neurons in response to a range of stimuli including trauma and rewarding behaviors such as eating a good meal or using addictive drugs. Endorphin pathways elevate mood, reduce sensation of pain, and impact urine production, immune function, intestinal motility, and other bodily functions. Endorphin pathways have a certain baseline activity or ‘opioid tone’ that is directly related to opioid tolerance. When opioid stimulation is greater than one’s tolerance, opioid tone is increased. When opioid stimulation drops below one’s tolerance, opioid tone is reduced, causing withdrawal symptoms.

The goal of any taper off opioids is to recover original or native opioid tolerance. Some people focus on getting rid of the opioid, and even use substances or behaviors to ‘flush buprenorphine from the body’. Products marketed as detox agents have minimal impact on the clearance of buprenorphine or other substances. And even if they could increase the rate of clearance, they would only make detox harder by increasing the severity of withdrawal symptoms. The relatively slow metabolism and clearance of buprenorphine provides a cushion by slowing the loss of opioid tone.

Prolonged use of any opioid changes opioid receptors. The changes are not fully understood but include a decrease in number of receptors and changes in binding properties that reduce receptor sensitivity to opioids, including endogenous opioids (endorphins). Recovery from a state of tolerance takes 2-3 months, and is initiated by reduced opioid tone. Withdrawal symptoms reflect the reduced opioid tone that provokes eventual recovery of native tolerance.

Recovery of native tolerance is the rate-limiting step when tapering off any opioid, including buprenorphine. When the dose of buprenorphine is reduced, the amount of buprenorphine at opioid receptors decreases over the next 5 days and then stabilizes at a lower level. In response, opioid tone (the summation of current flow through opioid receptors) drops below normal. If the dose of buprenorphine is maintained at that level, opioid tone will recover to normal in about 2-3 months. If buprenorphine is suddenly and completely discontinued, opioid tone will decrease to very low levels and cause severe withdrawal that lasts for 2-3 months. If buprenorphine dose decreases more slowly, opioid tone will decrease more slowly, lessening the severity of withdrawal. But it still takes 2-3 months for opioid tone to return to normal. So for any taper, patients must decide whether to decrease their dose quickly and be done in 2-3 months, at the cost of greater withdrawal, or instead to taper more slowly to reduce the severity of withdrawal.

The relationship between buprenorphine dose and opioid activity is linear up to about 2-6 mg. Beyond that point further increases in dose have less impact on opioid tone. The reverse occurs when tapering, so that opioid tone decreases only slightly as dose is reduced from 16 mg per day to 4 mg per day. The non-linear dose/response relationship allows for rapid decreases in dose early in the taper process with limited or no physical withdrawal symptoms. Since the early challenge is mostly psychological, I use the early part of a taper to help assess whether a patient is truly ready to take on the tapering process.

I like to have patients lead the way in tapering off buprenorphine. I’ve found that if I lead and reduce the amount of prescribed buprenorphine for the next month, patients often fail to make reductions and end up out of medication before the end of the month. So instead I ask patients to tell me when they are certain that they are ready to stay at the lower dose.
During a taper, I recommend dosing buprenorphine twice per day. Patients start by removing 2 mg from the evening dose. After at least two weeks 2 mg can be removed from the morning dose. This sequence is repeated at intervals of at least 2 weeks until the total dose is 4 mg per day. In my experience patients who get to that point are usually in a good mental position to begin the second, more difficult part of the taper.

Most people will be able to continue working when opioid dose is reduced by 5% or less every 2 weeks, or 10% every month. That number is a good general guideline when deciding how fast to taper. Suboxone film makes tapering relatively easy. Patients purchase a weekly med organizer, and start the week by opening and stacking 7 films. A scissors or razor is used to cut a millimeter from the end of the stack, and one film is placed in each compartment of the organizer for that day’s dose. When the patient is comfortable with that dose, slightly more is removed for the next week. The process continues every 2-4 weeks, eventually changing to the 2 mg films. I recommend that patients continue tapering until the dose is 300 micrograms (0.3 mg) per day or less before stopping buprenorphine completely. It is fairly easy to guesstimate where to cut the film in order to reduce by 10%; just measure half, then half of that, then half of that.

Buprenorphine tablets, of course, are much harder to divide. Zubsolv did people a favor by coming out with a range of doses, and hopefully other brand and generic manufacturers will eventually follow suit. For now I usually have patients use the tablets to taper as far as possible, using the 2 mg tablets in the lower dose range, and then pay the extra cost for the film for the final month or so. A 12 mg film can be divided into 24 half-milligram pieces without too much effort, so the cost doesn’t have to be prohibitive.

I have had many patients taper successfully off buprenorphine. Fear is common and normal for a number of reasons, but the fear usually gives way to a sense of confidence and optimism when a taper is done correctly.
Things to keep in mind:

Be patient. Tapering by too much, or too quickly, causes withdrawal symptoms that lead to ‘yo-yos’ in dose.
Buprenorphine products are very potent. A sliver of Suboxone Film may contain enough buprenorphine to harm or kill an animal or small child. Take care to divide the medication in a well-lit setting, and clean up very carefully.
Buprenorphine is used to treat pain in microgram doses. If you jump from 1 mg, you will have considerable withdrawal symptoms.
If you are still running out of medication early, it is not time to taper off the medication.
People on buprenorphine for a year or less have rates of relapse over 90%. In my experience patients are more successful tapering off buprenorphine if they have been on the medication for 2-5 years or more.
If you struggle in tapering down to 8 mg, consider going back to your stable dose, waiting 6 months, and trying again.
People addicted to opioids often substitute other drugs for their drug of choice. Do not start a new addictive substance in order to get off buprenorphine.

Good luck!

Tapering Off Buprenorphine or Suboxone pt. 1

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

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

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

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

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

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

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

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

This Suboxone Doesn’t Work!

Today on SuboxForum people were writing about their experiences with different buprenorphine formulations. Doctors occasionally have patients who prefer brand medications over generics, but buprenorphine patients push brand-loyalty to a different level. The current thread includes references to povidone and crospovidone, compounds included in most medications to improve bioavailability. Some forum members suggested that their buprenorphine product wasn’t working because of the presence of crospovidone or povidone. Others shared their experiences with different formulations of buprenorphine and questioned whether buprenorphine products are interchangeable, and whether buprenorphine was always just buprenorphine, or whether some people respond better to one product or another.
My comments, including my observations about patient tolerance of specific buprenorphine products, are posted below.
Just to get some things straight about povidone and crospovidone (which is just another synthetic formulation of povidone), both compounds are NEVER absorbed, by anyone.   They are part of a group of compounds called ‘excipients’, and are included in many medications to help with their absorption. They act as ‘disintegrants’– meaning they allow the medication to ‘unclump’ and dissolve in liquids, such as saliva or intestinal secretions.
Molecules tend to clump together, sometimes into crystals, sometimes into other shapes. A pile of powdered molecules molded, packed, and dried into pill form wouldn’t dissolve in the GI tract if not for povidone or other disintegrants. I remember reading somewhere about cheap vitamins that could be found in the stool, looking much the same as they did when they were swallowed. Not sure who admitted to doing the research for that article..
Buprenorphine IS buprenorphine. Period. The absorption isn’t affected much by excipients, because nobody ever complains that their Suboxone or buprenorphine won’t dissolve. Povidone or crospovidone are also added to increase the volume, because an 8 mg tab of buprenorphine would be the size of 100 or so grains of salt. Excipients like povidone and crospovidone also help some drugs dissolve, especially drugs that are fatty and don’t usually dissolve well in water-based solutions.   This last purpose does NOT apply to buprenorphine, since buprenorphine is very water-soluble. Zubsolv is supposedly absorbed more efficiently in part because it dissolves very quickly, and maybe that is due to excipients.
I realize that when I write ‘bupe is bupe’ it sounds like I don’t believe those who complain about their medication. But honest, I work with people over this issue every day… I have an equal mix of people who insist Suboxone doesn’t work for them and people who insist ONLY Suboxone works for them.    Today I was reading TIP 43– a guide about medication-assisted treatment put out by SAMHSA and the Feds that is over 300 pages long, very well-cited– in a section that cited studies about the psychological triggers for withdrawal symptoms. TIP 43 and other TIPs can be downloaded for free… just Google them. TIP 43 is primarily about methadone, but some of the information applies to methadone and buprenorphine. The pertinent section was around page 100, if I remember correctly.
The TIP information mirrored what I see in my practice. For years, I’ve noticed that patients will complain about withdrawal symptoms even at times when their buprenorphine levels are at their highest. Patients also report that their withdrawal symptoms go away ‘right away’ after dosing, when in fact buprenorphine levels won’t increase significantly for 45-60 minutes. People who have been addicted to opioids may remember how even severe withdrawal mysteriously disappeared as soon as oxycodone tabs were sitting on the table in front of them.   The bottom lline– withdrawal experiences are remembered, and those memories are ‘replayed’ in response to triggers or other memories.
In my experience as a prescriber, I’ve come to believe that patients with an open mind will learn to tolerate any type of buprenorphine (the exception being the 1 patient I’ve met who developed hives from meds with naloxone– hives that appeared consistently on three distinct occasions). But withdrawal symptoms seem to be triggered, in many people, by the expectation of withdrawal symptoms. So someone convinced he will never tolerate Zubsolv, Bunavail, or Suboxone Film will probably never tolerate those medications.
As for buprenorphine, it IS just buprenorphine. Molecules with a certain name and structure are always identical to each other. They are not ‘crafted’ products like bookcases or tables; some buprenorphine molecules aren’t made with a quality inferior to other buprenorphine molecules. And once a molecule is in solution, I don’t see much role for excipients. Of course a tablet or strip could contain too much or too little active drug, but that is an FDA issue, not an excipient issue.

Baby’s Buprenorphine Withdrawal

This morning I responded to a woman at SuboxForum. Her baby was taken to the NICU for ‘withdrawal’, which is better identified as neonatal abstinence syndrome. She said that the baby is eating well, but there is concern that the baby sleep only 2 hours at a stretch. The baby is on morphine, and mom is wondering when they both can go home. She is kicking herself for not trying to stop buprenorphine before the delivery. I spent a while responding, so I decided to post my response here as well, in case a mom in a similar situation stops by.

My comments:

I have written a number of posts about neonatal abstinence, and I invite you to read a post in my blog about the guilt you are feeling.

First of all, you did the right thing. Period. Every medical specialist, study, or text will say the same thing: that women addicted to opioids should be maintained on a long-acting opioid until the baby is born. Traditionally, that opioid was methadone. But women on methadone who are pregnant often end up on very high doses of that drug– pushing their tolerance to high levels, so that virtually all their newborns have significant withdrawal. Of course, the babies do fine in the long run— and the experience of withdrawal is not among the worst things that a baby experiences, by far.

People see a shivering newborn and somehow imagine that the baby just ‘came to be’, at that moment. In reality, a couple hours earlier the baby was in the birth canal, squeezed so tightly that shoulders are sometimes broken, probably experiencing a sensation akin to suffocation. I say that because while oxygen is being delivered via the umbilical cord, during deliver the cord is often compressed, causing changes in oxygen and carbon dioxide that would cause the same physiologic sensations as asphyxiation. The low oxygen tension and high carbon dioxide levels stimulate the ‘preborn’ to breathe, a hopeless challenge when the baby’s face is tightly wrapped by the birth canal!

And of course before that, the baby was upside down, getting pushed, squeezed, bounced… we picture this wonderful intra-uterine environment, but in reality we have no idea what it ‘feels like’ to the fetus. All the things we see after the birth were before birth, except perhaps the shivering. When the baby is born, there is no ‘on switch’ that suddenly starts recording his experiences!

As buprenorphine has become more-available, the trend has been to use buprenorphine instead of methadone. There are several advantages– the tolerance of the mother is much lower, meaning any withdrawal in the baby will likely be less severe. According to a number of studies, about half of babies born to moms on buprenorphine show signs of neonatal abstinence syndrome, compared to almost all babies born to moms on methadone. Studies show no benefit to tapering buprenorphine to lower doses before delivery, but I tend to think that there must be value in doing so. I wonder if those studies truly had good control over the doses that study subjects were taking. My patients seemed to benefit by reducing to 4- 8 mg during pregnancy– but perhaps my impressions are biased.

Another biased impression of mine is that babies have experiences largely dictated by the sensibilities of their neonatologists. Almost all of my patients who delivered at the local, small community hospital did great, and moms and babies went home at the regular time. If there was any withdrawal, it wasn’t noticed. Maybe it was treated by the buprenorphine in breast milk, because all of the mothers were encouraged to breast feed. Nursing while on buprenorphine seems to me to be the ideal way to wean a baby off the medication; the baby’s immature liver gets better and better at metabolizing medications after birth, allowing the amount of buprenorphine in the bloodstream to decrease over time.

Hospitals with neonatologists and a neonatal ICU are going to USE those things. The regular OB nurses in those environments tend to become less-familiar and less-comfortable with anything other than ‘normal’, and watch for reasons to send babies to a higher level of care. Every nurse on the OB unit knows that this baby’s mom is an addict. If the baby cries along with all the other babies, the nurses will believe that ‘this’ baby is suffering from withdrawal. And when the baby is sleeping along with all the other babies, the nurses will think ‘this’ baby is sedated from buprenorphine.
They will transfer the baby to the neonatal ICU, where the environment makes ANY baby look sick and miserable, opioid withdrawal or not. Just look at the environment, and all of the little ways that mom’s experience changes…. instead of smiling nurses wheeling the baby into the room, congratulating mom repeatedly in front of smiling family, you have busy, serious-faced nurses and doctors bent over charts or computers. When they take time to talk with mom, the conversations are serious, and certain to instill guilt and fear. The baby is attached to wires or tubes, perhaps wearing oxygen, under unnatural lighting that changes skin color from healthy-looking to some type of medical specimen.

The baby will remember none of this, just as the baby won’t remember the difficult journey down the birth canal… or the circumcision! Rest assured that all of the pain and misery will reside completely in mom, which is probably where the doctors and nurses intend for it to go. I realize, of course, that there are good doctors and nurses out there… but I know that when you get a group of people together, the urge to look down their noses at people with addictions often becomes too powerful to avoid.

Most important of all: a couple years ago I did a talk for a large group of public health nurses, social workers, and AODA professionals about the impact of opioid dependence on pregnancy and on children born to women addicted to opioids. I did an extensive literature search to prepare for the talk, and I was glad—and surprised— to find that there are NO known long-term effects on children from methadone or buprenorphine treatment during pregnancy. There ARE problems in some children born to addicted moms, but when the studies are controlled for cigarette smoking, poor or absent prenatal care, use of alcohol, and other factors, the use of opioids has no long-term developmental impact. That is VERY good news.

Opioid Withdrawal Treatments

A post on the Forum asked about the best remedies for opioid withdrawal.   I will review the medications and other treatments for opioid withdrawal that I have heard discussed by physicians or by people on the internet. Hopefully readers will leave comments about medications or approaches that they have found useful. Likewise, if you are a physician, please weigh in with the approaches that you have found to be useful.
For readers, it is very important to understand a couple things about this post. First, the medications listed here are not FDA approved for treating opioid withdrawal. They have not been systematically tested for that purpose. Most of the medications that I will list are available only by prescription— and must be taken ONLY by prescription. They all have interactions with other medications, and they all have toxicity in certain doses, and in people with certain conditions. Do NOT take them other than through guidance by your doctor. This post is intended to spark discussion with your doctor— and to help doctors learn about approaches that they have not heard about elsewhere.
I will encourage doctors or other contributors to this post to avoid discussion specific dosages. These medications must be prescribed by physicians who understand them, or who know how to become knowledgeable about them.
One problem for doctors is that CME meetings generally discuss treatments that are FDA indicated. I do not know of any medications that have been approved or marketed specifically for opioid withdrawal, and I do not have the sense that the field of medicine views opioid withdrawal as a pressing issue. But I am aware that for buprenorphine patients, the treatment of withdrawal symptoms has the highest priority of any medical concern.
With those caveats, here are the medications that I have heard the most about, roughly in the order of what consider their usefulness:
– Clonidine: Available by tablet or by patch. The medication reduces CNS excitability, and relieves all opioid WD symptoms to some extent. Side effects include sedation (which may be useful), dry mouth, and hypotension.
– Gabapentin: An anticonvulsant that some people find relieves anxiety and perhaps the sweating during withdrawal.
– Benzodiazepines: A controversial topic. They are potent sedatives, but they are also potent respiratory depressants when combined with opioids. Most overdose victims have these drugs on board. They relieve anxiety, insomnia, and muscle tension, and cause fatigue. Should NEVER be combined with opioids unless under very careful supervision (i.e. ‘self treatment’ = NO treatment).
– Phenobarbital: A Forum participant wrote that his/her doc prescribed phenobarbital for opioid withdrawal with great success. All barbiturates act similarly to benzodiazepines, and have potent respiratory depression, especially with opioids. Again, must NOT be used except under close supervision. Have effects similar to benzodiazepines. Dangerous if combined with alcohol.
– Quetiapine: AKA Seroquel. A potent sedative, used to treat psychosis, bipolar mania, depression… and off label, insomnia. Side effects include dry mouth and sleepiness.
– Natural ‘remedies’: A variety of withdrawal remedies are advertised on opioid-related web sites. I’ve had patients who tried most of them, and I’ve never heard anyone say they were useful. Some come in ‘daytime formula’ and ‘nighttime formula’. Always read the ingredients– and if you see a long list of herbs and roots, realize that there is NO oversight of the claims that are made. You could put bundles of dandelions into empty capsules and sell them over the internet, making the same claims. How hard do you think it would be to find a people to write ‘testimonials’ for twenty bucks? Or you could just write them yourself! Buyer beware.
– Amino acids: Again, advertised on the internet, and offered at steep cost by ‘select’ doctors. One of the ‘pioneers’ of amino acid treatments for withdrawal was convicted of fraudulent practice in Texas, and now offers the same as he did in Texas, but safely across the border, in Mexico. He has clinics in the US, run by other doctors, who boast of using his methods. The appeal of buying into a treatment that was proven fraudulent in court escapes me. But the treatment of opioid dependence is strongly influenced by perception, and so is strongly subject to placebo effects. The appeal of snake-oil remedies has created a living for many, many charlatans over the years, and a sucker is born (at least) every minute.
– General sedatives: Insomnia is such a big problem that anything that helps with sleep will help during opioid withdrawal. Meds include diphenhydramine and hydroxyzine (antihistamines), zolpidem and zopiclone (short-term sleep meds), and trazodone and mirtazapine (sedating antidepressants).   Cyproheptadine is a sedating antihistamine that reduces nightmares, and stimulates the appetite.
– Stimulants: I’ve read of people using them to fight the depression and fatigue during withdrawal. That use of a schedule II medication may be illegal in some states, and is probably frowned-upon by agencies that regulate medical practice. The energy and mood effects from stimulants are temporary, and must be ‘paid back’ with fatigue and depression when the stimulants are discontinued.
– Naltrexone: An opioid antagonist that has been used to speed the reduction of opioid tolerance. Naloxone and naltrexone are used during rapid detox, under strong sedation or anesthesia, but I believe that some have used naltrexone in very low doses in awake patients. If you are a doc who knows about this approach, I’m all ears…
– Antidepressants: Depression is one of the worst aspects of opioid withdrawal. Antidepressants would seem appropriate… but I know of no antidepressant medications that have a chance against the severe depression caused by opioid withdrawal. I’ve used them for patients after the withdrawal ends, when depression lingers… but I see little use for them during acute withdrawal.
Gosh, I thought my list would be longer. Given how many people suffer through discontinuation of opioids, our approach to easing misery is pretty limited.   I will remind readers– most of the medications listed above will cause serious harm, if taken without doctor supervision.
If you are a doctor who has found success with other medications, or if you are a patient of such a doctor, leave a comment to help spread the knowledge. If you are not comfortable with leaving a post, send me an email, or a message through LinkedIN.