Buprenorphine Depression Drug Stumbles

I’ve written a few optimistic lines about ALKS 5461 as a potential solution for people suffering from refractory major depressive disorder.  Those unfortunate will have to keep waiting.
ALKS 5461 is a product in Alkermes’ pipeline that combines buprenorphine with ALKS 33, or Samidorphan.  The combination drug is purported to ‘stabilize opioid pathways’, which is a very simple explanation for a complicated, poorly-understood system.  The results of two late-stage trials were disappointing, in part– according to Alkermes– because the placebo groups did better than usual.  Beating the placebo is a common problem in trials involving antidepressants, because of the high susceptibility to the placebo effect in the patients in such trials.  Over half of patients get better from taking the sugar pill, so a medication that helps half the patients will not move the needle to signal success.
I receive emails now and then from patients treated with buprenorphine for depression.  If the emails are any measure of reality, buprenorphine is not going to cure the world of depression.  While I occasionally read success stories, I just as often read angry descriptions from people complaining that they were never warned of the difficulty of stopping the medication.   I’ve written before that for that reason, I am reluctant to start buprenorphine for depression alone, in patients who are not already opioid-tolerant.  I have patients who struggled with depression before becoming addicted to opioids, and I believe the drug benefits their mood symptoms.  But I continue to hold back in a couple patients who have very severe depression, who have failed traditional treatments.  The news from Alkermes doesn’t push me in either direction.
I’ll take a moment to respond to the angry person who recently commented on one of my other blogs about this topic, who wrote that ‘depressed people are no more likely to get addicted than other people’, and ‘buprenorphine makes people happy and productive’ and therefore should be used for depression.  People with histories of depressive disorders DO have a higher incidence of addiction, but that is not the major issue holding me back from using buprenorphine for depression.  I would also disagree that buprenorphine makes everyone happy and productive.  The mood effects of buprenorphine, like all opioids, are subject to tolerance…  which gets closer to my concern.  I fear that the effects of buprenorphine would fade with tolerance, leaving patients stuck on an ineffective drug.  And we all know what happens to mood during discontinuation of buprenorphine.
ALKS 5461, though, works by a mechanism that may not be susceptible to tolerance.  Buprenorphine is a partial agonist at mu receptors and a kappa-receptor antagonist, and the latter effect is thought responsible for the effects on mood.  Samidorphan selectively blocks mu receptors, so that the combined drug is left with only the kappa effects.  Patients are supposedly spared from mu-receptor activation, tolerance, and withdrawal.   I wonder if it is really all that simple, or if the competition between buprenorphine and Samidorphan at mu receptors will create other problems.    Opioids cause a number of side effects, especially in patients who tend to focus on somatic symptoms, as some depressed patients do.   Starting an antagonist in the presence of an agonist, such as inducing with buprenorphine in patients on methadone or fentanyl, triggers a great deal of misery.  And even stable patients on buprenorphine alone tend to struggle with dry mouth, hot flashes, and GI complaints, most-commonly constipation.  But then again, major depression is a horrible illness.  I’m sure there are many people out there who would make the trade without regret– IF the ALKS 5461 works.
Alkermes continues to study ALKS 5461.  The higher dose ranges in the study, using 2 mg of buprenorphine, appeared to work better than the 0.5 mg dosage, so future studies will focus on buprenorphine doses of 1 and 2 mg per day (paired with equal doses of Samidorphan).  If you’re a believer, the stock is selling pretty cheap these days.  This is not an investment blog…. but I’m betting on Apple instead!

Post-op Pain on Suboxone

Many patients on Suboxone or buprenorphine eventually require pain treatment, just like people who aren’t on buprenorphine products.  I’ve written about post-op pain control several times, but I continue to get emails from patients who haven’t seen my comments and who view an upcoming surgery with the same fear experienced by patients before the early 1900’s, when the OR was correctly seen as a horror-chamber.
These patients are often torn between following the treatment plan vs. doing what they have learned may work better.  In all cases, I tell patients that they cannot act in ways counter to what their physician prescribes.  But I often support their intent to ask their doctors to clarify or modify their treatment plans.

Patients write about ‘the look’– the way doctors, nurses, and pharmacists react when patients ask about pain control.  As a recovering addict myself, I know what they are referring to.   Doctors encourage other patients to discuss concerns about pain control, and as long as they have no piercing or tattoos, patients will usually be comforted with assurances that their doctors will take their pain seriously.  But people on buprenorphine often see their doctors roll their eyes, or even say that the opposite is true– that if they have pain, they had better not bother the doctor about it!    Doctors who act that way are asses, of course, and I urge patients to avoid them if possible.  This post is not for those doctors, as they are not likely to ‘get it’ after reading the comments of another doctor— if they would ever read them in the first place!

I’m writing for the doctors who are open to hearing about new ways to help their patients.  I intend to use this post, going forward, to answer the emails from patients about this topic   If you are a physician who received this from a patient, please consider my comments– as I have found the approach described below far more helpful for surgical patients on buprenorphine products than the alternatives described elsewhere.  There was an NIH consensus paper a few years ago for example that described several alternatives, but mostly focused on discontinuing buprenorphine before surgery, then restarting buprenorphine at some point through a standard induction that includes 24 hours of withdrawal in patients already weakened by surgery.  Standard doses of opioid agonists were recommended for pain.  That approach was also described in a flashy article in one of the throw-away journals a month or two ago (i.e. Autumn of 2015).

There are so many problems with that approach:

  • Patients forced to stop buprenorphine before surgery and enter surgery dehydrated and weakened (IF they even managed to stop, as many patients end up staying on buprenorphine covertly– NOT a good situation for surgery.)
  • Buprenorphine discontinuation not an option for emergency surgeries;
  • Constant opioid levels are necessary to avoid withdrawal, before even considering pain control;
  • Buprenorphine is erroneously considered gone, when the long half-life actually assures that buprenorphine is still present;
  • Patients fret and argue over pain control every time the nurses change shifts;
  • Buprenorphine re-induction at some point after surgery, requiring patients to go through withdrawal symptoms;
  • Agonist treatment alone causes tolerance to rise very rapidly, requiring high doses of narcotic at hospital discharge;
  • An increased risk of overdose from narcotic pain medication in patients off buprenorphine;
  • And many other reasons.  Using the ‘discontinuation’ approach, patients end up on a Hellish roller-coaster ride where pain is grossly under-treated and withdrawal symptoms are only 4 hours away, day after day.

I’ve read emails from people whose buprenorphine doctors recommended taking more buprenorphine for post-op pain, or dosing more often.  I’ve read about suggestions to use Tramadol for pain after major surgery(!)
Earlier today I sent a letter in response to a woman who is planning a series of painful procedures.  I’ll share that letter to spare myself some time:

Dear A,

You’ve been through enough misery, and I hope you convince your physician to consider a different approach to your pain. I’ve had patients on buprenorphine go through many surgeries including thoracotomy, nephrectomy, open cholecystectomy, total knee replacement, and rotator cuff repair– all very painful surgeries.  My experience as an anesthesiologist piques my interest in post-op pain control.

My favored approach is very simple.  Maintain buprenorphine, and use oxycodone or other agonists to out-compete buprenorphine at the mu receptor as needed for pain relief. The benefits of the approach are obvious once the prescriber opens his/her mind to the realities of ligand competition.  There is no need to go through withdrawal, no need for ‘comfort meds’ to tolerate the withdrawal, and no need to enter surgery in an already-weakened state. As you know, even minor withdrawal causes people to feel very depressed, lose their appetites, stop sleeping…. is that really any way to go into surgery?

As an aside,  buprenorphine alone does not provide ‘real’ pain control in patients who take chronic buprenorphine.   Yes, buprenorphine seems to reduce pain in people with minor pain issues.  But it is of no use for the pain of major surgery.  Of course in theory, why would buprenorphine treat chronic pain in patients with complete mu tolerance to a medication with a ceiling effect?

A few years ago, an NIH consensus paper described a few approaches to acute pain in patients on buprenorphine. I don’t know who was on that panel, but the paper suggested stopping buprenorphine for several days before surgery and then using agonists. The panel mentioned the approach that I favor near the end of the paper.   I also described my favored approach at an annual meeting of ASAM, in a talk that was very-well received. I was optimistic that the discussion would open enough minds among prescribers to follow the neurochemistry, instead of focusing on the misplaced fear of combining an agonist and a partial agonist.   There are other papers out there– and book chapters– about the effects gained by combining an agonist with a partial agonist. You can find my ASAM slides at www.slideshare.net by searching for ‘junig’ and ‘uncoupling analgesia’.
The ‘uncoupling’ part BTW is what makes my favored approach so valuable, but that gets into the area of chronic pain, which is not entirely relevant to this discussion.  In short, opioid analgesia has always been limited by tolerance and dependence.  I believe that those limits can be removed by combining mu receptor agonists with partial agonists, allowing for pain relief from agonists while partial-agonists prevent euphoria and anchor tolerance at a lower level.

My approach is to reduce buprenorphine to about 4 mg per day.   Higher doses in my experience get in the way of pain control.  I then treat post-op pain as I would in any patient, but using 4 times more agonist (warning– see * below).  I typically prescribe oxycodone, 15 mg tabs,* and direct patients to take one tab every 4 hours as needed. When patients no-longer needs narcotic analgesia, I stop the agonist and have them resume their regular doses of buprenorphine. That’s it.  No tapering, and no withdrawal… just treating patients as I would any other patients, but realizing that mu receptors are competitively blocked, and effective doses of oxycodone must out-compete buprenorphine.

Dilaudid or fentanyl are not necessary. You could approach post-op pain in a very elegant way in a hospital using sublingual buprenorphine, fentanyl infusion, and PCA, but that gets a bit complicated. Oxycodone works fine.   In rare cases my patients required higher doses of oxycodone, but I’ve never had reason to use more than 30 mg.   Oxycodone is typically used every 4 hours.  My buprenorphine patients have found good pain relief from total daily doses of 60-120 mg of oxycodone.  The patients who went to a hospital where I couldn’t control their analgesia, who were told to stop buprenorphine, ended up on much higher doses of oxycodone at discharge.

Advantages of Combined Approach:

There are many advantages to maintaining buprenorphine throughout the perioperative period. The entire process is much simpler, and the patient’s experience is better because there is no euphoria, and no warm rush from oxycodone to rekindle addiction. The pain is relieved, but the reinforcing effects of oxycodone are eliminated.  I assume the that the limits on mu effects by buprenorphine are like a ‘governor’ that limits the speed of fleet vehicles. You can get only so much opioid effect in the presence of buprenorphine, and not enough to cause a ‘high.’

The combined approach also prevents tolerance, which is a greater issue with chronic pain than with post-operative pain. Buprenorphine anchors tolerance at the level yielded by the ceiling effect, allowing agonist effects to continue over time. I’ve treated people with the combination of buprenorphine and oxycodone for over 2 years, and the combination continues to work as well as it did on the first day.

Some prescribers and pharmacists worry about ‘precipitated withdrawal’, but that is not an issue as long as buprenorphine is continued every day. The only way to precipitate withdrawal would be to stop buprenorphine for at least a few days, boost tolerance higher with an agonist, and then give buprenorphine– which would ‘yank’ tolerance back down again. Patients who stay on buprenorphine can add agonists without fear of precipitated withdrawal.

I’ve convinced a few doctors to try this approach, and I’ve received a number of positive reports about the approach.   I’ve described the idea to several pharmaceutical companies as an approach that would revolutionize pain treatment.  Can you imagine pain relief without addiction, without tolerance, and without euphoria?   I realize that the large number of deaths caused by opioid overdose limits interest in opioid analgesia.  But I suspect that a product that combines buprenorphine and an agonist would go a long way to reducing opioid dependence, providing that the two medications were irreversibly bonded together in a combination product.  I have some thoughts about how to do that… but that’s for another day.

It is NEVER safe to prescribe one’s self opioids or other controlled substances, so this discussion is intended to provoke discussion between patients and their doctors.  Patients must realize that there are many things that go into decisions about post-operative analgesia, and NO approach is the right approach for everyone.  Any individual patient may have features to his/her history that make the combination approach inappropriate, or even dangerous.

*Doses described in this post are intended as approximations for consideration by trained and licensed medical professionals.  Doses described may not be safe in some patients, including patients at the extremes of age, patients with respiratory or other chronic illness, patients with central nervous system disorders, or patients on other respiratory depressant medications.

NEVER use opioids except as directed by your own physician.

What’s Up with Buprenorphine?

I think about a joke my dad used to tell over and over.  A guy is upset because his kid has never talked in his entire life.  He has taken his kid to all the specialists, but nobody has an answer.  Then at his 18th birthday party the kid blurts out “we’re having ham AGAIN?!’    His family breaks out in tears of joy, and eventually his dad asks him why he hasn’t talked for so long. The kid pauses, and then says “up to now, everything was OK.”
A dumb joke… but then again I just saw a PBS show about the life of Joan Rivers, and I was struck by how so many comedians make a living by saying things that are simply disgusting, and passing them off as ‘comedy’.  Joan’s disciples all have the same type of humor… what’s the name of that red-headed woman who did a brief stint on Seinfeld?  Just say something shockingly rude to a crowd who paid to see you, and they laugh.
Got off track.  My point was that I’m sorry for being gone so long, and I wish the reason was because there was nothing to complain about.  Unfortunately, there are still plenty of things to complain about…. the cap on doctors prescribing buprenorphine products, the large number of overdose deaths, the spread of hepatitis C and other blood-borne illnesses, the ignorance of the media and among some DA’s and law enforcement agencies…
Frankly, I took a break from writing because I was tired of being so angry all the time.  But over the past few months, I’ve received daily messages from people suffering from addiction and looking for answers.  I appreciate those of you who continue to stop by the web site and the Forum, and I’ll try to get over my anger and get some new content out here.
I have at least a few things that I’d like to address at this point– but please feel free to help me out by sharing a question, an interesting situation, or anything else that you find interesting.. and I’ll use it as a starting point for a post.  Send me an email, or leave a comment… and I’ll be back!
BTW, hope everyone had a nice summer!

The Pain Clinic: Your Money’s Worth?

Originally Posted 7/18/2013
Like most of you, I’m not thrilled with modern healthcare.  I miss how things were twenty years ago, when I had a sense of ‘having a doctor’ who actually knew me, who had my best interests in mind.  I remember my father, a defense attorney in a small town in Wisconsin, telling me about the state’s ban on advertising by lawyers – a once-debated issue that is hard to visualize in the current era.  He believed the ban was a positive thing, helping keep the legal profession honest and avoiding the appearance of impropriety.   I remember comparing the situation to medicine and thinking ‘of course the ban is a good thing; just think of what society would think about DOCTORS, if they hung billboards for their services!
Those debates must appear bizarre to young people now, who can’t drive a mile without hearing or seeing ads urging people to sue over work grievances, accidental injuries, discrimination, medication side effects, malpractice… while hospitals and doctors compete for space for their own ads for pain clinics, wellness centers, hip and knee replacements, or robotic surgery.
Billboards announce the next great thing that one hospital has that others don’t, one medical gimmick replacing another.  ‘Pain treatment’ is one of the biggest healthcare scams of the past 20 years, with ads promising treatment for chronic pain in an ‘advanced’ or ‘collaborative’ manner.   The scam is easy to see if one drops all positive assumptions about medicine—and health insurance– and observes what happens to patients who use pain clinics.  Follow two hypothetical patients, one with insurance and another with no money or insurance, with the exact same injury—let’s say back pain from lifting crates in a factory every night for several years. Their experiences will demonstrate why being insured is not always in one’s best interest.

Epidural injection
Are epidurals worth the money for chronic pain treatment?

Our uninsured man develops pain in his lower back that does not extend into his legs, without leg weakness or incontinence.  He goes to urgent care and pays cash for the visit, and tells the doctor that he can’t afford to be referred anywhere.  The doc tells him to avoid heavy lifting for a week, and when he returns to work, to lift with his legs and knees instead of bending his back.  He is told to stretch at least 30 minutes every morning and evening and to exercise each day.  Back pain usually comes from a combination of ‘pain generators’ in muscle, bones, tendons, ligaments, and nerves in the lower back.   But the body has amazing recuperative powers, and if our hypothetical patient stretches, exercises, and avoids repeat injury, he will get better over several weeks.  Not a bad outcome for $150!
The guy with insurance goes to his doctor, who prescribes 90 tablets of Percocet and schedules an MRI.  This doctor doesn’t explain the need for stretching, assuming that the patient will hear all that from the next doc he is referring to… or maybe he recommends stretching and exercise, but the Percocet helps the patient feel less restless while sitting in front of the TV, reducing the stretching or exercising that would have helped him feel better.  When the MRI shows ‘degenerative disk disease’ (as it always does in people over 40), the doc refers him to a neurologist for EMGs.  The patient meanwhile sees his chiropractor for 5 ‘adjustments’ per week.  The neurologist refers him to a physical medicine and rehab doc, who orders physical therapy.  All of these steps in the process extract their pound of flesh, paid by either the patient or society (through higher insurance rates).
The people who are getting rich in medicine know that it’s all about PROCEDURES.   Our insured patient already paid over $1000 for his share of the costs for a lumbar spine MRI (not to mention the plain films and a CT scan done first, just in case they might be helpful).  He or his insurer paid another grand for the EMG.  The chiropractor cost another 1-4 grand, depending on the patient’s zip code.
The money really starts to flow when the rehab doc sends him to a pain clinic.  The pain clinic starts with more x-rays, CT, and MRIs, claiming that THEIR techniques will give a better look at things that the others may have missed.   For the most common diagnoses—degenerative disc disease, lumbar strain, or facet arthropathy– treatment choices include lumbar epidural steroid injections, selective nerve root injections, and local anesthetic ‘trigger point’ injections to relax tightened muscles.  The doctor’s charge to do an epidural or nerve root injection?  About $500-$1200, for a procedure that takes about 15 minutes.  An efficient doc could easily do 10-12 injections per day.  If the doc attended one of those meetings that teach ‘maximizing reimbursement’—meetings often held on cruises or tropical islands—the doc calls his office an ‘ambulatory care center’ so that he can bill ‘facility fees’, turning a $700 epidural into a $5000 ‘short stay.’
I hear what you’re thinking—that relief from back pain is WORTH the $5,000-$10,000 cost for this patient.  What if the procedure provides only partial relief—the typical result?  Or What if the epidural steroid injection only MIGHT provide pain relief— but probably WON’T?  Is it still worth as much?  What if the pain relief won’t start for a few weeks and only lasts a month or two, and then the shot must be repeated?  What if the injection can be done only 3-4 times per year, and the patient has less than a month of relief each time.  Is 3 months of moderate reduction in pain worth $15,000?
The scam is aided by a simple fact that patients often forget: most minor injuries will heal on their own without medical intervention, as long as re-injury is avoided.   It is no coincidence that many medical procedures or treatments take ‘a few weeks’ to work, the amount of time most often associated with natural healing.  You’ve heard the joke….  With treatment, you’ll improve in 14 days; otherwise a couple weeks!  Present-day back injuries last about as long as they did 50 years ago—even though we now spend tens of thousands of dollars per injury, rather than a few weeks of ‘taking it easy.’
I’m taking care to present examples that give medicine the benefit of the doubt.  I’m not mentioning the many injections done on people despite clear evidence, on exam or MRI, that the injection will do nothing for their pain.  I’m not talking about trigger injections (done thousands of times each day throughout the US) that hurt like blazes during the shot, giving the illusion of pain relief (and nothing else) when the needle is removed.  I’m not talking about the many MRI’s, ultrasounds, CTs, and EMGs that could be replaced by a smart doctor with basic physical examination skills.
And I’m not talking (until now) about the people who suffer from iatrogenic addiction—- those who go to pain clinics for aches and pains that will either gradually go away or won’t ever go away, that in either case have a trajectory of recovery that can’t be altered by the pain clinic.  The patients are prescribed opioids, and asked to return for one procedure after another.  The patients notice that the procedures are doing nothing for the pain, but they return over and over for refills on the pain pills that they now physically depend on.
The insurer eventually balks at paying for more procedures… and at this same point the pain clinic docs decide that further attempts at pain relief would be pointless.  The doc tells the patient that since he is doing nothing but prescribing pain pills, the patient should go back to his primary care doctor and never return to the pain clinic (unless a new, reimbursable injury comes along).  The referring doctor is not comfortable prescribing the same large dose of narcotics, and tells the patient to ‘taper off the pain pills’—- something that most people just can’t do.  The patient inevitably violates the opioid treatment contract by asking for early refills, smoking marijuana, missing an appointment, running out of money to pay for visits, seeing another doctor, using the wrong pharmacy, etc…. allowing the doctor to blame the patient for breaking the rules, requiring discharge.

Suboxone and Tooth Decay

Originally posted 10/21/2012
I have received a several emails over the past few years from people who experienced deteriorating dental health while taking buprenorphine or Suboxone.  I also have patients in my practice who have had extensive dental work, and wonder if Suboxone is to blame for their cavities or other problems.
I wrote about this issue several years ago.  At that time I wrote that there was no evidence that sublingual buprenorphine or Suboxone cause or accelerate tooth decay.  After writing the article I received a number of angry emails from people who insisted that I was wrong.
Let’s step back for a moment to highlight the difference between thinking something vs. proving something.  Some people misunderstood my comments about tooth decay and Suboxone, thinking that I was arguing that Suboxone does not harm teeth.  That was not what I wrote.  My point was that as of that time, there was no evidence that Suboxone or buprenorphine caused tooth decay.  When I write about the science of buprenorphine, I try my best to distinguish between what I think is true vs. what was established through scientific study.
I recently met with a patient who has had extensive dental work over the past few years, the same time that she was taking sublingual buprenorphine.  She asked if I thought that the two were related.   I made a few comments (that I’ll be getting to), but also promised her that I would do a literature search, to see whether any connection has since been established.  Ironically, a case report of a woman on Suboxone who required extensive dental work was just published yesterday.  The case report is in the latest issue of The American Journal on Addictions, and the same case is cited in the October 20, 2012 edition of Reactions Weekly.
The world of science is not efficient.  Knowledge moves forward slowly, based on findings amassed from many studies, often repeated multiple times.  Case reports are not intended to prove something.  In fact, case reports are often unusual clinical examples that defy the norm.  They are often published to point out an area that deserves more study.
I cannot copy the case report here because of copyright laws.  But the case described a 35-y-o woman who used oxycodone for about a year at doses up to 160 mg per day, and then went on buprenorphine/naloxone.  After 18 months, her dentist told her that she had extensive decay of 4 molars requiring root canal.  She reportedly had minimal history of dental problems before starting opioids or buprenorphine.
The author of the case report hypothesized that if there is a connection between Suboxone and tooth decay, one reason could be xerostomia, i.e. dry mouth, caused by buprenorphine.  The lack of saliva was my thought, too, as a mediator of any possible effects of buprenorphine on teeth.  Saliva serves an important role in dental health, including rinsing away food particles and acting as a buffer.  The patient in the case report did not report a dry mouth, so the author pointed out that all opioids have some ability to suppress the immune response, and perhaps buprenorphine and/or naloxone reduce the immune response, allowing for greater destruction of teeth by bacteria.
The case report, surprisingly, did not say which buprenorphine product(s) the patient had used, e.g. tablets, film, or generic buprenorphine.
What needs to happen next is for someone to do a case-control study of patients on buprenorphine, to see if they are more or less likely to have tooth decay.  The most valuable study is usually a prospective, randomized clinical trial;  that would not be proper here, since it would not be appropriate to randomize subjects to buprenorphine vs. no buprenorphine.  But a close second would be a case controlled study, where patients on buprenorphine are matched to ‘controls’ with similar characteristics— age, sex, eating habits, income level, education, etc.– and the dental outcomes are followed forward over a number of years.  A less-costly, less-reliable study is one that looks backward, comparing patients on buprenorphine with those not on buprenorphine to see which group has a higher incidence of dental caries.
We are not much better off at this point in our knowledge of whether Suboxone or buprenorphine predispose toward tooth decay.  The case report only mirrors what I see in my practice.  But as I often tell patients, I have other patients who are not on buprenorphine or Suboxone, who have tooth problems.  I also have patients on Suboxone with great teeth.  Hopefully some ambitious PhD candidate will sort through the issue soon.

Suboxone Withdrawal in Newborns

One of the top search terms for Suboxone relates to pregnancy, and fear that the baby will experience withdrawal; official name ‘neonatal abstinence syndrome.’  I wrote this post a couple years ago, and I think it is worth reposting. Since the first time around, several studies have shown that withdrawal symptoms occur in about half of babies born to mothers on buprenorphine. The symptoms, when they do occur, tend to be milder than the symptoms in babies born to mothers on methadone or other opioid agonists.
Headlines grasp for attention with words like ‘addicted babies.’ Realize that there are many differences between physiological dependence and addiction to substances. For example, people who take Effexor are dependent– and will have significant discontinuation-emergent side effects– but they are not ‘addicted’, which consists of a mental obsession for a substance. The same is true of beta-blockers, in that discontinuation results in rebound hypertension, but there is no craving for propranolol when it is stopped abruptly.
We have no idea of the ‘cravings’ experienced by a newborn, but I cannot imagine a newborn having the cortical connections required to experience anything akin to the ‘cravings’ experienced by opiate addicts, which consist of memories of using and positive reinforcement of behavior—things that are NOT part of the experience ‘in utero’.
It is also important to realize that the withdrawal experienced by addicts consists of little actual ‘pain’ (I’ve been there—I know). Addicts talk about this subject often, as in ‘why do we hate withdrawal so much?’ It is not physical pain, but rather the discomfort of involuntary movements of the limbs, depression, and very severe shame and guilt. The normal newborn already has such involuntary movements as the result of incomplete myelination of spinal nerve tracts and immature basal ganglia and cerebellar function in the brain. And the worst part of withdrawal—the shame and guilt and hopelessness—are not experienced in the same degree in a baby who has no understanding of the stigma of addiction!
Finally, if we look at the ‘misery’ experienced by a newborn, we should compare it to the misery experienced by being a newborn in general. I doubt it feels good to have one’s head squeezed so hard that it changes shape—yet nobody gets real excited about THAT discomfort—at least not from the baby’s perspective! I also doubt it feels good to have one’s head squeezed by a pair of forceps, and then be pulled by the head through the birth canal! Many hospitals still do circumcisions without local, instead just tying down the limbs and cutting. Babies having surgery for pyloric stenosis are often intubated ‘awake’, as the standard of care– which anyone who understands intubation knows is not a pleasant experience. And up until a couple decades ago—i.e. the 1980s (!), babies had surgery on the heart, including splitting open the sternum or breaking ribs, with a paralytic agent only, as the belief was that a baby with a heart defect wouldn’t tolerate narcotics or anesthetic. I don’t like making a baby experience the heightened autonomic activity that can be associated with abstinence syndrome, but compared to other elements of the birth experience, I know which I would choose!
My points are twofold, and are not intended to encourage more births of physiogically-dependent babies. But everyone in the field should be aware of the very clear difference between physiological dependence and addiction, as the difference is a basic principle that is not a matter of opinion—but rather the need to get one’s definitions right. Second, the cycle of addiction and shame has been well established, and there is already plenty of shame inside of most addicted mothers. If there are ten babies screaming loudly, only the whimper from the ‘addict baby’ elicits the ‘tsk tsk’ of the nurses and breast feeding consultants. My first child was born to a healthy mom years before my own opiate dependence, and he never took to breast feeding; he his mother been an addict, his trouble surely would have been blamed on ‘addiction’ or ‘withdrawal’. Unfortunately even medical people see what they want to see—and sometimes that view needs to be checked for bias due to undeserved stigma—for EVERYONE’S good, baby included.
Addendum:  Another of my posts, including a response to a mother’s comments and several references, can be found here.

Clean Enough

In regard to my last post
There are many directions that we could take as we review that message.  My overall impression, as I read the letter, was of a person struggling to accept the reality of his condition.  Over and over, the person repeated the same behavior, starting Suboxone, stopping, and thinking this time will be different.
One thing I’ve learned as a psychiatrist, more than anything, is that change is difficult, and rare.  The writer ends with the thought that maybe this time will REALLY be different.  I have no idea if it will be, and for his sake, I hope it is… but unfortunately, the odds are that history will repeat itself.
Why, then, bother taking Suboxone—if everything just goes back to how it was?  The problem is not that Suboxone ‘doesn’t work’; the problem is in the expectations of some of those who take or prescribe the medication.  The active part of Suboxone—buprenorphine—is not a cure for addiction, but rather is a very useful tool.  Buprenorphine is a chemical that essentially tricks the mu opioid receptor.   Because of the ceiling effect—at higher drug levels, effects at the receptor remain constant as drug concentrations vary—the receptors function as if nothing is ‘coming on’ or ‘wearing off.’  That, in turn, eliminates cravings for the drug, and prevents the ‘reward’ for taking the drug.
Buprenorphine appears to work very well for the writer.  When on buprenorphine, he is able to avoid using opioid agonists.  The problem comes in the expectation that when buprenorphine is stopped, the condition of opioid dependence will somehow be gone, and will stay gone.   That is a completely different matter!
Opioid dependence is a complicated condition that can be viewed from different perspectives; behavioral, neurochemical, social, etc.  Some factors that contribute to ongoing addiction are addressed by buprenorphine, but most are not.  At one point the writer refers to being ‘stabilized on buprenorphine;’ the best way, I think, to view what happens with the medication.
During active addiction, a person finds that unpleasant emotions, thoughts, or feelings can be blunted by taking a substance.  In the long run, the consequences of using a substance become more and more negative, but the active addict cannot see beyond the pressing needs of the moment.  These pressing needs become worse, once addicted, because physical withdrawal – including depression, pain, and dread—are added to the other pressures of life.  Buprenorphine removes the neurochemical pressure to take opioids—i.e. the constant obsession to improve one’s subjective state.
Hopefully, relieving that obsession allows the patient to change the course of his life; to change social networks, to improve occupational standing, to improve self-discovery and personal insight.  If a person insists on stopping buprenorphine, the hope is that there will be enough changes in these other areas, so that the person will somehow be able to avoid responding to the urge to medicate the moment.
I think we are at a point where we need to consider the true nature of addiction.  Many treatment programs and physicians and treatment programs have an idealized image of how things should proceed after starting buprenorphine.  Patients ‘should’ be able to avoid all other substances, and patients ‘should’ be able to taper off buprenorphine at some point.  Through a process known as ‘counseling,’ patients are supposed to develop insight into their thoughts, emotions, and behaviors, so their lives follow a different course when the buprenorphine is eventually discontinued.
But what if patients CAN’T taper off buprenorphine?  What if patients eventually relapse, after stopping buprenorphine? What then?  Contradictions are apparent, when one looks for them.  We know that opioid dependence is a chronic, relapsing condition.  We know that relapse is more the rule than the exception.  We know that addiction is a process, not an event—and that ‘cure’ is not an accurate concept. Yet program after program requires people to eventually stop buprenorphine.  Talk about a set-up for failure!
To truly understand addiction and the role of buprenorphine, one must realize that addiction is a conditioned or learned phenomenon.  Parents of teens addicted to opioids will sometimes tell me ‘I just want my daughter back.’  I’ll ask the parent when he last rode a bicycle— and point out that even if the last ride was 20 years ago, he could still ride today.   And even if he hasn’t been to his childhood home for 20 years, he could likely drive straight to his front door.  THAT’S the challenge of ‘curing’ addiction!
Other thoughts…
About the ‘utilitarian’ approach… the way I suggest we view buprenorphine is the best way to consider other psychiatric medications as well, in my opinion.  We don’t think of SSRI’s as ‘curative’ for depression; rather they reduce obsession and worry, contributing to changes that allow recovery from depression.  Anticonvulsants do not ‘cure’ bipolar; rather they reduce the likelihood or severity of symptoms of mania.  Antipsychotics do not ‘cure’ schizophrenia; they prevent or reduce psychotic symptoms.
About anxiety… does the writer REALLY have it more difficult than others?  Maybe– or maybe not.  It really doesn’t matter.  Most patients who I see for opioid dependence believe they were dealt an unfair hand in life, from an emotional perspective.  Most feel that their subjective experiences are more difficult than the experiences of others.  Many say that they are ‘shy,’ or that they experience significant depression most of the time.  Most say that opioids relieved those uncomfortable emotions or sensations very effectively—at first, anyway—and that is why the addiction started.
Whether our load is truly heavier than someone else’s doesn’t matter, since we only experience our own load.  In other words, who would hurt more if his arm was severed, you or me?  It doesn’t matter—it hurts both of us ‘enough!’  At the same time, no amount of personal distress logically warrants taking something that only makes things worse.  If only addiction was logical!
About being able to choose the course of our lives… ‘Choice’ advocates–people who say that addicts choose to use drugs, and that they should simply choose NOT to use—say that addicts are weak in needing to medicate themselves through life.  In reality, there are few discreet ‘choices’ in life.  Our behavior flows seamlessly from one thing to the next.  ‘Choosing’ consists of a million tiny thoughts, sewn together and spread over a wide range of time.  The actual ‘choice’ to use occurs long before a person literally picks up the drug—- in a million subtle decisions and behaviors that the person may or may not have insight into.  Avoiding opioids, without the help of buprenorphine, requires constant awareness and engagement of insight.  Sober recovery is not effortless, and is not possible for everyone— just as some people cannot avoid depression without using SSRIs, and some diabetics cannot control their blood sugars without using exogenous insulin.  There is no shame in having one’s addiction treated!
Comments, as always, are welcome.  And to the writer, thank you for sharing your story, and provoking this discussion.  I can’t say whether it is time to stop Suboxone, or whether you will ever do well off the medication.  But in any case, I encourage you to appreciate life as best you can, and cultivate enough interests so that the buprenorphine issue falls into the background.  That, in my opinion, is the best way to use buprenorphine; to allow people to live life as if they had never become addicted, and to learn to tolerate life on life’s terms, as best they can.  For some people, maybe that’s ‘clean enough.’

An Addict's Story

I received the following email last week.  I considered trimming it down, but the story is well-written and describes a history that is similar to that of many of my patients.  As usual, I will write a follow-up post in a week or so.
Dear Dr. J,
I have read many of your posts over the past few years. Like many, I started out disagreeing with your comments and insight, while blaming my inability to manage my addiction on the Suboxone treatment. My active addiction to opiate pain medications was brief, about 4 months of hydrocodone/oxycodone use in the end of 2007. In early, 2008), I reached out to my primary care physician who directed me to an inpatient stabilization followed by Suboxone maintenance/addiction therapy. When I entered treatment I maintained the belief that I was not an addict, and my doctor initially supported this attitude. He described my situation as physical dependence stemming from treatment of pain. I was a recent college graduate, I had a wonderful upbringing, a bright future…I believed that “people like me don’t become drug addicts.” So of course I wanted to minimize the seriousness of my illness. I convinced myself that this physical dependence “happened to me,” and I was doing what needed to be done to resolve the issue. So I saw my doctor monthly and went to weekly addiction therapy sessions. I did not use “street drugs,” or any other RX meds, so my UAs were always clear, and eventually I was seeing the doctor for a refill every few months.
At the same time, I was dealing with the onset of some anxiety and panic issues, which I also used to rationalize my initial abuse of the opiates. As college came to an end I began to get very anxious about the future and panic in certain situations. When I was prescribed the Vicodin and Percocet for a knee injury, it was like finding the key that turned off all these negative feelings/physical sensations. My beliefs regarding success and failure fueled my anxiety, and allowed me to rationalize abusing the opiates as self-medication. When I began taking the pain medications I had no understanding of addiction or opioid dependence, and I honestly thought “this is an RX medication, I am prescribed it for pain, it also helps with this anxiety issue, so taking a few extra is fine.” So, as I said, it was very easy to go along with this idea that I was somehow different than all the other addicts.(“terminal uniqueness,” one of my NA friends taught me that term, I have always loved it.)
My starting dose of Suboxone was 16mgs/daily. Between January and August 2008, I tapered down to about 1 mg/daily. However, in July I experienced a major panic attack and was prescribed clonazepam for my anxiety/panic.  In August, I discontinued my Suboxone and was prescribed Bentyl, Tigan, and Clonidine for acute WD symptoms. The withdrawal was really not bad. It lasted about a week; the worst of it was my anxiety, stomach, and exhaustion, which continued beyond the week. I tried to push on through it, however, it was as though I had traveled back in time to the day I had gone into treatment.
The reality was that I had done nothing during those 8 months to understand or manage my addiction or anxiety (beyond medication).  At the time, of course, I didn’t understand this– and was immediately looking to place blame with the Suboxone. “Why the hell did I take the drug if I was going to end out feeling the way I did right when I started…I wasted 8 months delaying this inevitable hell”…the usual retorts from an addict in denial. I tried a number of different SSRIs/SNRIs, as well as amphetamines, to help with my exhaustion and focus. Nothing helped; I lost 35 lbs. by late November 2008.
From the very first follow up after stopping the Suboxone, my doctor suggested starting again. I had never relapsed during my treatment with Suboxone, and I had not used since stopping, so starting Suboxone did not make sense to me at the time. However, I knew that it would make my discomfort go away, and decided to start the Suboxone again in early December 2008. We determined that my decrease from 8 mg to 1 mg over two weeks prior to discontinuing was too fast. I still wasn’t willing to deal with the reality of my anxiety and addiction, and continued to minimize.
I went back on the Suboxone. Over the next year, I stayed on the Suboxone consistently, and just focused on living life. I did not do any NA/AA, addiction therapy, etc. In early 2010, I began relapsing. I would run out of my prescription early and substitute with other pain medication. Still rationalizing that the Suboxone was a pain, and I was just doing what was needed to make it work. It was during this period that my addiction became fully active, and the use became less about self-medicating and more about the feeling/escape.
In late 2010, I checked into a treatment center to detox from all opioid medications. Again, the immediate WD symptoms were very mild and the isolation of the center helped with my anxiety. I was able to isolate and almost hide from the anxiety by being in the center and cut off from the world. I left the center 4 days later, prescribed Gabapentin and clonazepam for anxiety. The day I left, I relapsed on the ride home from the center.
It is amazing, but it still had not clicked for me. The anxiety was in the forefront, and I still thought that the addiction was a symptom or result of those issues. Needless to say, I ended up sleeping all day, exhausted, depressed, with the same stomach issues. I was finishing up business school, and trudging through. I would rationalize taking the pain medications again on days when I had school. And I walked down the same road again. The entire time I cursed Suboxone as the cause of all my issues. “If only I would have gone cold turkey from the pain killers back in 2008….I wasn’t an addict until I was prescribed Suboxone”…again the usual BS.
As you can probably guess I hit the wall again, and ended out back in treatment. However, this time something clicked in me, and I was fortunate to have a team of caretakers who could see through my BS. I realized that I had crossed so many lines that I thought I never would, and could not control myself. Instead of just doing a short-term stabilization, I spent 3 weeks in intensive out-patient treatment following my inpatient stay. I was stabilized back on Suboxone, and then for 3 weeks, 8 hours a day, I was focused on my addiction, and the team at the center was not letting me [email protected]@ anything. I started that program in mid June 2011. I learned about my addiction, and got honest with myself, my family, and my friends (I had hidden my addiction and treatment from everyone in my life except for my mother and father up until last summer).
I was humbled in a major way, and finally got real with myself. I had always thought that saying “I have an addiction” was a cop out. Coming to terms with my lack of control was and continues to be very hard. I feel a great deal of guilt and disappointment towards myself. And there is part of me that still wants to believe that I can control all of this and with enough will-power fix all my issues. Ironically, in a way, I am striving to maintain control and fix these issues every day, as I stay clean and focused on my sobriety. I was always afraid of being defined by my addiction. However, when I got honest, I realized that the more I tried to ignore reality, the more my addiction consumed my life.
Ultimately, I wanted to write this email as a thank you to you and share my story with those who visit your site. It took me 5 years, 3 times off and back on Suboxone, and 2 stays in treatment to realize that I am an addict. In hindsight, I think much of my downfall was classic addict behavior; placing blame, terminal uniqueness, etc. I expected Suboxone to resolve all my issues, without doing any actual work.
Looking back on all of my experiences, I thought this is where I would end out. However, working through my addiction has helped my anxiety immensely. And I am beginning to feel it is time to appropriately taper and discontinue my Suboxone. With all the support I have now, and the skills I have gained I feel very optimistic (cautiously).
Dr. Junig – I would be interested in your advice regarding tapering or insight on my story in general.
Thank you to the writer;  I’ll be adding my thoughts soon!
 

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.