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.

 

Newborn Buprenorphine Abstinence: Get Real!

First Posted 2/6/2014

A few weeks ago I wrote about the differing standards of care for women who deliver babies while treated with buprenorphine for opioid dependence.  Some hospitals require newborns exposed to buprenorphine to stay in the neonatal ICU for arbitrary length of time.  Intravenous infusions of opioid agonists are given to infants whose first yawns or cries are interpreted as neonatal abstinence syndrome.  Other hospitals allow women on buprenorphine to take babies home at the regular schedule, allowing a natural taper from buprenorphine by breast-feeding.

Regardless of hospital policy, many women on buprenorphine enter into the delivery process with a sense of dread, knowing they are harshly judged by doctors and nurses.  Doctors warn women that their babies will suffer from withdrawal if they don’t taper off their medication before delivery.  And members of the media decry the selfishness of women treated for addiction who become pregnant, suggesting the more responsible expectant mothers would use ‘will power’ to avoid all substances.

Even while experts recommend that women treated for addiction stay on medication treatment regimens during pregnancy, society looks negatively on women who do the right thing.   A new mom on SuboxForum recently wrote about how horrible she felt, for putting her baby through such a difficult time.  But should women compliant with recommended treatment for opioid dependence feel so guilty?

Until 30 years ago or so, newborns having major surgery often received paralytic agents with little or no anesthesia or pain medication.  Surgeons and anesthesiologists did not think babies with heart anomalies would survive anesthetics, and saw no reason to anesthetize a brain that lacked a ‘record’ function.   Now, most babies having major surgery receive anesthesia.   But in many situations, non-medicated babies are simply restrained during procedures that would be painful in adults, ranging from awake intubation to circumcision to multiple attempts at IV access (the latter is required when doctors insist on treating neonatal abstinence with morphine infusions).

I did not enjoy working on newborns in those settings back in my anesthesia days, especially after having three children.  But there will always be times when anesthesia is too dangerous or impractical, leaving no choice but to tune out the baby’s cries and focus on safety.  In these cases, do babies experience pain?  We know that babies react to stimuli that adults would find painful, and generate stress responses to those stimuli.  But the answer to the question about pain is far more complicated than a simple ‘yes’ or ‘no.’

People having conscious sedation for colonoscopy, gastroscopy, or some emergency procedures (like reduction of a displaced fracture, emergency D and C, or insertion of a chest tube) often appear awake while appropriately sedated.  Patients who will later think that they were blissfully sleeping, in reality, carry on conversations and move about as directed on the OR table.  Depending on the anesthetic used, patients may react strongly to pain.  Patients who can’t be fully anesthetized because of the risk of aspiration or airway obstruction may yell out in response to the injection of local anesthetic, even when administered enough Versed and Ketamine to guarantee full amnesia.   They moan in pain throughout the procedure, and then thank their anesthesiologist for keeping them completely ‘asleep’.  Similar experiences are the norm in every GI suite across the country.

In this common scenario, do patients experience pain?  When someone sedated beyond the point of recall complains of discomfort, did the discomfort really happen?   Did the patient feel pain and then forget it?  How do we know?  Before my endoscopy, I knew that I would experience pain going forward in time.   But afterward, when I thought back about the procedure, it was a piece of cake.  Did I suffer?  Not at all.

Similar experiences occur in newborns.  Babies are not capable of remembering those first weeks or months.  One could argue that repeated discomfort creates brain pathways that lead to a heightened stress response in later years… but if that is true, how does the brain differentiate ‘normal’ pain experiences of the newborn from ‘abnormal’ pain?  The baby’s head is squeezed hard enough during delivery to change the shape of the skull.  That has to hurt… not to mention the discomfort of being squeezed inside a uterus during the last 4 weeks before delivery.  During delivery, the baby is transferred from a 37 degree uterus, where oxygen is delivered through the umbilical cord, to a bright, cold, environment where getting oxygen requires gasping for air, with every bit of strength.  Sounds traumatic to me!  During deliveries, babies sometimes experience dislocated shoulders and major nerve damage (shoulder dystocia).  Forceps or suction cups may be used to pull the baby, by the head, from the birth canal.

Newborns have immature nerve supply to the gut, so early peristalsis– the coordinated contracting that propels digestible material downstream in the fully developed intestine– creates cramping and ‘pain’ in infants (sometimes called ‘colic’).  Limb muscles are spastic, and the spasticity would likely be painful in an adult.  Choking or coughing on breast milk is a normal part of the newborn experience.

How does ‘withdrawal’ compare?  What is the worst part of withdrawal— diarrhea?  Cramping?  Body aches?  Anxiety?  Depression?  Compared to the normal experience of a newborn, how do these symptoms rate?  Babies do not feel embarrassed or ashamed of their condition.  They don’t feel guilty or remorseful.   And after raising children through, I don’t think a baby coming off buprenorphine could be more ‘depressed’ than other babies.  Can a baby who turns purple crying his lungs out, feel any worse?  Normal infants get pretty miserable at baseline!

Like most parents I have always been willing to put my life or discomfort before that of my kids, if that were possible.  I don’t lack empathy for babies experiencing pain.  But ‘to keep it real’, writing about those ‘poor babies going through withdrawal’ is an emotional response, not an accurate understanding of the newborn experience.

Most new moms torture themselves enough with fears about their mothering skills, without the medical profession piling on.

Newborn Buprenorphine Abstinence: Standard of Care

First Posted 2/1/2014

The topic of newborn abstinence syndrome from buprenorphine provokes strong emotions.  Expectant mothers anticipate harsh attitudes from doctors and nurses.  They worry that their use of buprenorphine will cause their babies to suffer from withdrawal.  They hear about the experiences of women reported to CPS after delivery, or whose babies were kept on inpatient opioid tapers for weeks.

A member of SuboxForum recently wrote that the hospital she planned to use, in downstate NY, required mothers on buprenorphine to sign a formal policy regarding the care of their newborn infants.  The policy stated that all babies of mothers on buprenorphine must go to the NICU for at least 10 days after delivery, regardless of condition. Mothers were not allowed to refuse that level of treatment for any reason.

Last week, one of my buprenorphine patients came to her appointment with her 5-day-old baby, after both she and her baby left the hospital less than 48 hours after delivery.   Her discharge struck me as premature, not because of anything to do with buprenorphine, but because new moms are frequently anemic and sleep-deprived and can use a bit of rest before taking on an infant’s schedule.

How can the ‘standard of care’ vary so greatly?  What role does insurance coverage play in decisions about opioid tapers, NICU admissions, and discharge schedules?  After having dozens of patients go through the process uneventfully without intervention by neonatologists, I wonder if newborns are always positively served by their interventions. I also question the wisdom of using opioid agonists to taper from a long-half-life, partial agonist, i.e. buprenorphine.

In blinded studies, only half of babies born to women on buprenorphine show objective signs of ‘withdrawal’, which is a misleading word for describing the experience of an infant.  I have no doubt that in the typical non-blinded nursery, neonatal abstinence symptoms are grossly over-diagnosed.  Mothers on buprenorphine describe a biased diagnostic approach to their newborns, where babies who cry are ‘too agitated’, and babies who sleep are ‘too sedated’.

In the case of babies who truly show symptoms of NAS, do the symptoms always warrant ten days in the NICU?  Is a baby distressed by mild neonatal abstinence better off in mom’s lap nursing with breast milk containing small amounts of buprenorphine, or lying alone in a plastic incubator under fluorescent lights, with multiple IV lines? Some docs and nurses in my area allow moms on buprenorphine to nurse, a policy that makes sense from an anatomical and developmental perspective.   As the baby’s liver matures, ingested buprenorphine is eventually completely destroyed through first-pass metabolism.  The process allows for a gradual, natural taper, without the misery and cost of IV infusions and monitoring systems.

Decisions about monitoring and discharge should, of course, revolve around safety.  I question whether the various approaches to buprenorphine abstinence in the newborn are based on informed, intellectual consideration, or are instead liability-motivated rules supported by ‘best guesses’ by people who don’t understand buprenorphine.  Given the 180-degree difference between the approaches of different hospital systems, somebody is clearly doing it wrong.

I’ve griped about how research studies about drug addiction are so-often focused on demographics, where the data does more to describe the past than to improve care going forward.  The best approach to babies born to mothers on buprenorphine should be near the top of the list for research funds.  The hard part of such studies will be identifying (and following) the conclusions that are derived from science, vs. those that come from concerns about litigation, where the costliest and most-intense treatments always win out.

How and When to Stop Buprenorphine or Suboxone

First Posted 12/15/2013

People know my bias—that buprenorphine is best-considered a chronic, perhaps life-long treatment for a chronic, life-long disease.  That said, I am aware of how many people out there are convinced that they need to be ‘off everything,’ no matter the misery opioids have caused in their lives.  I don’t get it; my perspective over the years has been seeing obituaries of patients who were doing great on buprenorphine or Suboxone for years, until well-intentioned relatives convinced them that they weren’t really clean.

But I’ve written all of this before.  For those of you who are still intent on stopping buprenorphine, I’ll share my observations after watching hundreds of people stop the medication—some intentionally, and some before going back to H for some crazy reason.

First off—there is NO truth to the idea that ‘the longer you take it, the harder it is to stop.’  The idiots who peddle that line are the same people who are on and off buprenorphine, or perhaps who have run out of doctors willing to see them and now hoping that company will join their misery.   The opposite is true.  The patients who have done the best are the people who stayed on buprenorphine or Suboxone for at least 2-3 years, and came to a point where they just knew it was time to stop.  The ones that have done well—stayed clean—are the ones who made gains during their time on buprenorphine.  They got educated.  They got promoted.  They started families in a responsible manner (i.e fell in love first, and then had the family).

I’ve seen so many people stop Suboxone after 3 months, 8 months, or a year—and what I’ve seen mirrors the studies that show 90% relapse rates within one year of stopping buprenorphine.

I’ve developed a set of indicators that are associated with maintaining abstinence after buprenorphine.  In very-rough order of importance, they are:

  1. Taking buprenorphine once per day or at MOST twice per day, not in response to depression, fatigue, emptiness, insomnia, or urge, but completely ‘by the clock’—as they would take blood pressure medication.
  2. Having month after month with no extra calls reporting lost or stolen buprenorphine, having no ‘very bad weeks where everything went wrong that forced them to take a little extra’.
  3. No use of intoxicants, especially for treating mood or anxiety—i.e. the ability to live ‘life on life’s terms.’
  4. Age over 30.  Not sure why—but I have my theories.  Age brings wisdom, persistence of intent, insight into emotions, and the realization that life is temporary and precious.
  5. No history of depression or anxiety.  Not always controllable, unfortunately.
  6. Stable job, stable finances, and stable relationship, and preferably one or two hobbies.
  7. Complete loss of using contacts, and NO immediate access to opioids (no spouse on pain pills or Xanax;  no dealer calling every few days).
  8. Absence of a chronic pain condition- or acceptance that one will have to tolerate one’s pain.
  9. Being on a regular exercise schedule.
  10. The recognition that opioids kicked the snot out of them, multiple times—and a strong fear of relapse.

People who lack one or more of these items should strongly re-evaluate a decision to stop buprenorphine.  There are other factors—but it is late, so cut me some slack.

When someone wants to stop taking buprenorphine and I’ve educated that person about the numbers and risks, my next step is to ask the person to cut from 16 mg of buprenorphine (if on that much) to 8 mg.  That change done correctly will cause no physical withdrawal, but creates enough mental pressure to separate those who are ready from those who are not.

Remember at this point that all of these things are used in my own practice;  they are not intended to direct people who are not my patients, but rather to stimulate discussion with your OWN doctor(!)

 

The method I usually recommend is for the person to go to twice per day dosing—8 mg AM and 8 mg PM, and then change to 8 mg AM and 6 mg PM for two weeks, then to 6 mg/6 mg for two weeks, then 6 mg/4 mg for two weeks, then 4mg/4 mg.  If the person can do that without any problems, I am willing to help with the taper.

I usually have patients to make small reductions at their own pace every few weeks.  The goal is to move slowly; one common misstep is to make a reduction before arriving at a stable blood level from the last reduction.  A dose should be maintained for at least a couple weeks before dropping lower.

Most people benefit from more-frequent dosing during tapering, since the effective half-life of buprenorphine is shortened when blood levels drop below the ‘ceiling level.’  I’ve had some patients claim to do better dosing 3 times per day during tapers. My only concern about dosing that frequently is the risk of returning to conditioned addictive behavior. I suppose the other issue is that more-frequent dosing requires smaller doses, that are more difficult to keep consistent.  The 2 mg film is very helpful for tapering at lower levels, can with a razor or hobby-knife.

Patients on buprenorphine for pain treatment can avoid violating the Hamilton Act and progress down a series of Butrans patches—a process that is technically illegal for non-pain patients.    The biggest patch releases about 0.5 mg of buprenorphine per day, which seems like a big step from 2 mg of oral buprenorphine until you remember that only 30% of an oral dose is absorbed.  So 2 mg of oral buprenorphine yields about 0.7 mg of buprenorphine in the bloodstream—close to the amount delivered by the largest Butrans patch.

It is illegal to taper opioid addicts using Butrans, according to the Harrison Act.  I realize that the situation is not fair… but sometimes Presidents create laws, even put their names on them, thinking the law is a good idea… and then the future ends up showing what a bad, bad idea the law was. Just speaking of Harrison, of course…

When patients fail a taper by using opioid agonists or returning to a higher dose of buprenorphine, I suggest they go back to a comfortable dose, and try again in a year.  The hardest part of tapering is mental, but the physical symptoms are nothing to sneeze at.  When tapered slowly, the physical withdrawal from buprenorphine isn’t all that much worse than having a bad cold.  The goal is to stay in the game, hour after hour (after hour).

I recently met with a patient who stopped ‘cold turkey’ from 16 mg, who shared his experience in detail.  He worked every day in a factory job, and managed to stay at work throughout the entire process. He swore by the 5-hr energy drinks, and said that they kept him working on the worst of days.  His symptoms peaked at 11 days, and at 3 months he felt fully recovered.  He carried pictures of his kids, and looked at them every time he felt a hot flash or was stuck on the commode.

I believe that he will do well because he knows that addiction is truly cunning, baffling, and powerful, and understands that he must always be alert for some crazy, cocky idea to enter his thought process.   One interesting thing in this particular patient was that the entire time he went through withdrawal, he never experienced cravings.  He had been on buprenorphine for a number of years, and just felt ‘done.’

Finally… most of us were brought to addiction by our best ideas.  Sobriety requires CHANGE, and change is not comfortable or pleasant.  Nobody wants to attend his/her first meeting.  And everyone who loves meetings has many, many days when meetings are the last thing they want to do… but they go anyway.  THAT is what change is all about.

Withdrawal Work-Up II

First posted 11/11/2012

In my last post, I wrote about the work-up of a patient who experiences symptoms similar to opioid withdrawal that start about an hour after each dose of Suboxone.  We decided that the symptoms were signs of withdrawal—i.e. reduced activity of mu-opioid pathways—and that the symptoms were triggered by taking a daily dose of Suboxone (buprenorphine/naloxone).

Note that I wrote that the symptoms seemed to be caused by reduced mu activity, i.e. not necessarily by reduced mu-receptor binding. Endogenous opioid pathways are very complex.  Decreased activity in opioid pathways may arise from decreased binding of agonist at the receptor, or from changes in a number of other chemical or neuronal pathways.

This diagram shows the processes that are triggered by mu-receptor binding in humans before and after opioid tolerance.  The diagram only shows the complexity of processes within one type of neuron with opioid receptors; realize that each neuron 1. Has receptors for many other neurotransmitters as well, and 2. Receives input from thousands of other neurons.  As we sort through possible causes of our patient’s symptoms, keep in mind the complexity of neural pathways.

While we are on the subject of complexity, the web site linked above is an incredible resource for those interested in biochemistry.  The site includes diagrams of a number of metabolic pathways that describe how different molecules, including neurotransmitters, are manufactured by the human body.  I encourage people to browse the site.  You will gain insight into why the actions of substances are difficult to fully predict.

The withdrawal symptoms experienced by our patient might arise from dysfunction in any one of the many chemical pathways that affect opioid tone. But since a dose of Suboxone contains naloxone, a mu-receptor inverse agonist, it is possible, maybe even likely, that the naloxone is related to symptoms.

Naloxone is less lipid-soluble than buprenorphine and so only a small portion—about 3%– of a dose is absorbed through mucous membranes.  The rest of the naloxone is swallowed, consciously or inadvertently, and eventually absorbed from the small intestine, to pass to the liver via the portal vein.  The entire dose is usually metabolized by the liver before gaining access to the general circulation, a process called ‘first pass metabolism.’  If our patient’s withdrawal symptoms are caused by naloxone, we have to find a way for the naloxone to enter the general circulation, so that it can displace buprenorphine from mu receptors in the brain.

Absorption through oral mucosa is unlikely to vary from one person to the next.  Some molecules become more lipid-soluble in acidic or basic pH environments, but not naloxone.  I suppose that absorption might be increased by removing layers of the oral mucosa by vigorous brushing, but I doubt we could get a significant increase in absorption without considerable painful damage to the oral mucosa.

Likewise, there is little difference in the absorption of molecules by the small intestine in the absence of significant disease processes affecting the GI tract.  Absorption and liver metabolism of some drugs may be changed by surgeries, such as gastric bypass.  But our patient has neither gastro-intestinal disease nor history of surgery to his GI tract.

Naloxone is metabolized by a liver enzyme called UDP-glucuronyl transferase.  The enzyme attaches a molecule called glucuronic acid to naloxone, creating a larger molecule that is easily excreted by the kidneys.  I have been reading up on glucuronidation, suspecting that something may be interfering with that process in our patient to cause an increased blood level of naloxone.  Biochemists are invited to correct me if I am wrong, but from my reading, the glucuronidation process is not limited to specific cytochromes.  Whereas buprenorphine is metabolized by CYP3A4 and CYP2C8, two groups of enzymes that are inhibited by certain medications, the glucuronidation of naloxone is not blocked by other medications.

In layperson’s terms, I suspected that the patient was taking a medication that blocked the breakdown of naloxone at the liver, causing an increased blood level of naloxone that then interfered with buprenorphine activity.  There are a number of medications that block the breakdown of buprenorphine, but none that I could find that block the breakdown of naloxone.  Dead end.

The patient was taking an antihistamine, cetirizine, which is excreted mostly unchanged at the kidneys, but I have not found any evidence that the excretion of cetirizine interferes with the metabolism or excretion of naloxone. Likewise for the Lexapro he was also taking.  Dead end again.

It would have been cool had I discovered a precise explanation for the patient’s symptoms.  Had I found a logical explanation for his symptoms, I would have suggested changes in his medications and submitted the drug interaction to a peer-reviewed journal as a case report.  The patient would feel better, and fame and fortune would be one step closer…

But the true outcome is more instructive, as it is more consistent with what usually happens.  I will explain to the patient that I do not have a good explanation for his symptoms, and whatever we do going forward will be ‘educated guesswork.’    But I hope that after reading this, people will understand that even when we can’t find the answers, it isn’t from lack of trying.  And like other doctors I will continue to read the literature, as our knowledge of med/med interactions, while complex, still has a long way to go.

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