Ten Gripes of Buprenorphine Doctors

I recently gave a lecture to medical students about opioid dependence and medication assisted treatment using buprenorphine, methadone, or naltrexone. I was happy to see their interest in the topic, in contrast to the utter lack of interest in learning about buprenorphine shown by practicing physicians. In case someone from the latter group comes across this page, I’ll list a few things to do or to avoid when caring for someone on buprenorphine (e.g. Suboxone).

1. Buprenorphine does NOT treat acute pain, so don’t assume that it will. Patients are fully tolerant to the mu-opioid effects of buprenorphine, so they do not walk around in a state of constant analgesia. Acute pain that you would typically treat with opioids should be treated with opioids in buprenorphine patients. Patients on buprenorphine need higher doses of agonist, usually 2-3 times greater than other patients. Reduce risk of overuse/overdose by providing multiple scripts with ‘fill after’ dates. For example if someone needs opioid analgesia for 6 days, use three prescriptions that each cover two days, each with the notation ‘fill on or after’ the date each will be needed.

2. Don’t say ‘since you’re an opioid addict I can’t give you anything’. There are ways to provide analgesia safely. If you do not provide analgesia when indicated, your patient will only crave opioids more, and may seek out illicit opioids for relief. Unfortunately nobody will criticize you for leaving your patient in pain, but they should!

3. Don’t blame the lack of pain control on laws that don’t exist, for example “I’d like to help you but the law won’t let me.” Patients deserve honesty, even when the truth makes us uncomfortable. We get paid ‘the big bucks’ for tolerating the discomfort that sometimes comes from frank discussions with our patients.

4. Don’t assume your patient can or cannot control pain medications. If a patient has been stable on buprenorphine for years, he/she may have a partner or family member who you can trust to control pain medications. Some patients stable on buprenorphine can control agonists used for acute pain, but I wouldn’t stake my life, or theirs, on that ability. A useful compromise is to prescribe enough pain medication to cover 1-2 days of analgesia on each of several prescriptions, each with a ‘fill after’ date, to reduce the amount of agonist controlled by the patient at one time.

5. Don’t tell your patients that ‘opioids don’t work for chronic pain.’ I see stories on such great medical sources as the ‘Huffington Post’ explaining that ‘opioids never help chronic pain’. In reality, your patients know that opioids DO treat chronic pain, so they will consider you a liar or an idiot if you clam they don’t. The challenge is explaining the risk/reward equation to your patients, and explaining why treating chronic pain with opioids often leads to greater problems, as the risk/benefit equation is changed by tolerance.

6. I know this will cause heads to explode, but don’t assume that chronic pain is always less severe than acute pain. What if your patient’s chronic pain is worse than the typical pain after cholecystectomy or ACL repair? Most doctors would gasp at the idea of recovering from major surgery without opioids. What if the pain from failed back syndrome is worse?! I have had a few patients who, I’m certain, experience a great deal of suffering, and have gone so far as to have brain or spinal cord implants to get relief. I’m not arguing that we treat chronic pain in the same way as acute pain. But we shouldn’t jump to the conclusion that chronic pain isn’t severe enough to warrant opioids in order to dismiss those complaints more easily.

7. Don’t tell your patient to stop taking buprenorphine unless you’ve talked with the doctor who is prescribing that medication, and realize that the doctor you are calling knows more about buprenorphine and addiction than you do.

8. Don’t ask patients ‘how long are you going to take that stuff’ or criticize patients’ use of buprenorphine medications. Likewise psychiatrists shouldn’t tell patients scheduled for knee arthroscopy that the procedure is controversial, or talk patients out of hernia surgery.

9. Don’t assume that the doctor prescribing buprenorphine knows what YOU are doing. Too often patients will tell me about surgery that they failed to discuss in advance, even calling about pain hours after getting home from a procedure they failed to mention. Some people seem to believe that doctors regularly collaborate on their care, even though the opposite is closer to the truth.

10. Don’t assume that unusual or atypical symptoms come fromo buprenorphine. One truism of medicine is that doctors tend to blame unexplained symptoms on whatever medication they know the least about. Fevers of unknown origin, mental status changes, or double vision are not ‘from the buprenorphine!’

Those are the gripes at the top of my list. Did I miss one of yours? Or for patients, have you suffered from breakdowns in the system?

Addendum: 11. When treating post-surgical pain in buprenorphine patients, choose one opioid and stick with it. What often happens is that doctors will use one opioid, say morphine… and when nurses call a few hours later to say the patient is still screaming, they change to a different opioid, then another after that. As a result, the patient is placed on insufficient doses of several opioids, rather than an adequate dose of one medication.

There are two critical issues in treating such patients effectively. First, providing pain relief comes down to competition at the mu receptor. A certain concentration of agonist in the brain and spinal fluid will out-compete buprenorphine and provide analgesia. You cannot get there by adding other opioids together. If you use oxycodone for an hour and then change to dilaudid, you are starting over. Instead, choose one drug, preferably something that can be given intravenously, and stick with it. Morphine is not a good option btw, because of the low potency and histamine releasing properties of that drug.

Second, remember that analgesia and respiratory depression travel together, both mediated by the mu receptor. Anesthesiologists know this principle well… opioid medication can be titrated to respiratory rate, providing that the medication is given IM or IV. If a patient is breathing 28 times per minute, he/she is in pain. If the patient is breathing 6 times per minute, pain is not a problem, and the patient should be monitored for respiratory depression and possible overdose. When treating pain, doctors should aim for a respiratory rate of 14-18 breaths per minute, making sure that the medication is actually getting into the bloodstream (the risk comes when patients are given SQ injections or oral doses of narcotic that enter the bloodstream later, causing toxic blood levels).

Opioid Induced Hyperalgesia Prevented by Buprenorphine?

“Buprenorphine is a kappa receptor antagonist. For these reasons, buprenorphine might be unique in its ability to treat chronic pain and possibly OIH.”

The opioid crisis has been fueled by the use of opioids to treat chronic pain.  Practice patterns have changed, but doctors are still criticized for their roles in the overuse of opioids.  I’ve sat through community ‘heroin forums’ (sometimes on stage) as sheriffs, politicians, and ‘recovered addicts’ firmly pointed fingers at health professionals.  I, meanwhile, kept my finger under the table, but had the thought that some of the people pointing would be the first to complain if they were forced to stop pain medication prematurely for their own good or ‘for the good of the community.’
Doctors can’t see into the future.  I suspect most cases of opioid overuse began with well-intended efforts to provide temporary pain relief.   But then for a variety of reasons things didn’t go as planned.  Maybe the planned knee or back surgery never took place because of patient indecision or insurance problems.  Maybe the lumbar strain didn’t heal after 6-8 weeks the way it was supposed to.  In any case, doctors who work with pain patients know what happens next.  Before the next appointment, the doctor plans to tell the patient that the time has come to stop opioids.  But after that suggestion, the patient replies that the pain is even worse now than when the pain meds were started.  “Actually (says the patient) I was going to ask you to increase the pain medication!”
Some doctors hold fast to their plan and initiate a taper.  Some doctors argue over the issue, and some manage to create enough fear in the office that no patient would dare talk back. Too often, patients are suddenly cut off high doses of opioids, precipitating withdrawal symptoms that drive them toward illicit pills or heroin.  Patients who manage to maintain scripts for opioids embark on a miserable journey that often ends badly.
I’ve converted many pain pill patients to buprenorphine patients over the years.  I could save time using a rubber stamp to document their histories:  (blank)-year-old man was started on pain pills after (blank) injury (blank) years ago; dose was increased over time using oxycodone then OxyContin then fentanyl patches; patient lost the ability to control the medications and ran out early, resulting in discharge from treatment.  Patient presents asking for treatment with buprenorphine.
Many past patients fit this description, riding the gray area between opioid dependence and pain.  Lawmakers and policy-writers seem to believe that most patients are either addicts or pain patients.  Doctors who work in the field know that most patients sit in the middle, with smaller groups on each side. **
I’ve been surprised at how well those pain patients do after changing to buprenorphine.  They usually feel much better overall, which is no surprise given the misery of living according to a cycle of relief and withdrawal.  More surprising is that their pain is reduced, sometimes completely.  I assume the reduction in pain relates to stopping the cycle of relief and withdrawal, although I don’t know the mechanism beyond that idea.  People who take opioids become more ‘somatic’ over time, more and more focused on symptoms including those that warn of impending withdrawal; perhaps buprenorphine reduces that tendency toward somatization.
Which brings us to opioid-induced hyperalgesia or ‘OIH’, where prolonged use of opioids makes pain symptoms worse.  I’m reluctant to go ‘all in’ on OIH, just as I reserved full judgement of the full range of symptoms blamed on TMJ, EBV, IBS, CFS, FM, MCS, WPW, PMS, PMDD, RSD, CRPS, RLS, GAD, SAD, DID, IED, and other ‘initialed diseases’ that have garnered headlines over the years.   (Can you name them all? *** Try THESE )   Attention on OIH has waxed and waned over the years, and is gaining attention now as PROP, the CDC, and SAMHSA talk down opioid use.
LOL.
But seriously, my problem with OIH starts with awareness that pain sensation is very complicated.  Different people describe varying pain intensity for the exact same stimulus.  And even within one patient, intensity varies according to mood, fear, the duration of the pain (expected and actual), the perceived reason for the pain, the perceived harm from the stimulus, the setting (e.g. home vs. laboratory), and many other variables.  It is one thing to see how long it takes a rat to flick its tail when placed over a heat lamp, but another when a human fills out a pain scale.
I also take note of selection bias, a phenomenon that occurs whenever science bumps into political forces where studies citing the occurrence of a phenomenon are more likely to get government funding and editor approval than studies denying the phenomenon.  And no, I’m not a denier—of anything.  But I know bias when I see it. I’ve seen articles that conclude ‘there is not enough evidence to rule OUT the existence of OIH’, which is the opposite of how good science is supposed to be conducted.
You’ll find a great review of OIH here: http://www.painphysicianjournal.com/current/pdf?article=MTQ0Ng%3D%3D&journal=60
A cautious reader of the literature will note that at best, OIH is more of a ‘basic science’ phenomenon than a ‘clinical phenomenon.’   Increased pain sensitivity in response to opioids is subtle.  If it wasn’t, it would have been described decades, even centuries ago.  The linked material references older comments that the authors suggest came from observations of OIH, but to my reading the comments more likely referred to the withdrawal that follows opioid use.  You’ll also notice, if you read the linked article, that most of the studies of OIH in humans look at pain sensitivity in long-term methadone patients.  But you’ll also read that in theory, methadone is one of the least-likely opioids to cause OIH.
Interestingly, the other opioid agent with lower likelihood to cause OIH is… buprenorphine.  From the link above:  Buprenorphine has been shown to be intermediate in its ability to induce pain sensitivity in patients maintained on methadone and control patients not taking opioids. Buprenorphine showed an enhanced ability to treat hyperalgesia experimentally induced in volunteers compared to fentanyl. And spinal dynorphin, a known kappa receptor agonist, increases during opioid administration, thus contributing to OIH. Buprenorphine is a kappa receptor antagonist. For these reasons, buprenorphine might be unique in its ability to treat chronic pain and possibly OIH.
In short, long term use of opioids appears to increase pain sensitivity.  But we are a long way from understanding the extent of that phenomenon.  Some studies suggest that all opioids are not equal in regard to OIH, and I wonder if the reported decrease in pain from relatively minor injuries such as lumbar strain, when people change from opioid agonists to buprenorphine, is caused by a decrease in opioid-induced hyperalgesia.
But then again, maybe those patients just thought they had pain because of a subconscious (or conscious) desire to get pain pills.
For whatever reason, people with chronic pain seem to do well on buprenorphine.  Hopefully all of the concerns over opioids will leave us at least that one treatment option.  Give the extreme safety of buprenorphine, that should be a no-brainer!
**At least that was the case until several years ago, when I began seeing more and more patients who ‘started heroin recreationally’- an oxymoron if there ever was one.
***TMJ = temporomandibular join disorder, blamed for chronic headaches and other symptoms; EBV = Epstein Barr Virus; IBS = irritable bowel syndrome; CFS = chronic fatigue syndrome; FM = fibromyalgia; MCS = multiple chemical sensitivity; WPW = Wolf Parkinson White; PMS = premenstrual syndrome; PMDD = premenstrual dysphoric disorder; RSD = reflex sympathetic dystrophy;  CRPS = complex regional pain syndrome; RLS = restless leg syndrome; GAD = generalized anxiety disorder; SAD = seasonal affective disorder; DID = dissociative identity disorder; IED = intermittent explosive disorder.

Cannabinoid Hyperemesis: How Rare?

I recently read a CBS news story about CHS, or Cannabinoid Hyperemesis Syndrome, describing a 100% increase in cases in Colorado since the legalization of marijuana there. A search for ‘THC’ and ‘CHS’ pulls stories from a range of sources including High Times, Wikipedia, Fusion.net, and Current Psychiatry. A broader search reveals articles calling the disorder ‘fake news‘.

Most articles about CHS describe the condition as rare, but becoming less rare as the legalization movement takes root and grows. The syndrome occurs in heavy, long-time users of marijuana who first notice reduced appetite, mild nausea, and sometimes weight loss. Those symptoms, and the symptoms that follow, are relieved by smoking marijuana, leading those with the condition to become heavier users who come to see marijuana as beneficial to their health.

Over time the symptoms worsen to include paroxysms of severe abdominal pain, nausea, and vomiting. Patients often seek help from a number of health practitioners, including alternative health treatments. Tests come up negative, and patients continue to turn to marijuana to treat the symptoms– along with hot baths and showers, which for some reason make the pain and nausea more-tolerable.

Since we live in an era of social media I’ll point out that I have no strong feelings toward marijuana. I don’t kick people off buprenorphine products for testing positive for THC, as it makes little sense to stop treating a potentially fatal disease because the patient smokes pot. I doubt doctors would withhold cancer treatment because of marijuana use either. I’m describing my observations only to get the word out about something that doctors are missing. Over the past 2-3 years I’ve had several patients with symptoms identical to those described in stories about CHS, so I suspect the condition is more common than thought.

The Current Psychiatry article describes possible mechanisms for symptoms of CHS. The nausea and vomiting may be caused by accumulation of cannabinoids in the lipid tissue of the gut, causing activation of the CB1 receptor in the intestine to override the anti-emetic effects of CB1 activation in the hypothalamus. Activation of CB1 receptors in the gut slows peristalsis (the motion of the intestines that propels food forward) and dilates the blood vessels to the intestinal system. Hot baths and showers may provide relief by dilating blood vessels in the skin and redirecting blood flow away from the gut. Other possible causes relate to the effects of specific cannabinoids, or perhaps herbicides or pesticides.
One of my patients had classic symptoms of CHS for several years. A year ago I had not yet heard of the condition, but noticed that he repeatedly talked about marijuana being a ‘wonder drug’ for disabling stomach pain and nausea, even as he lost weight and his general health deteriorated. When I asked if he considered that marijuana may actually be harming his health he became angry and defensive, and never returned for follow-up.

Another patient talked about his spouse’s health problems, hoping I would have ideas about the cause of her symptoms that weren’t found through visits to many specialists. Marijuana wasn’t even part of the discussion as he described her severe pain and nausea over the past year that caused her to go to the ER several times each month. At his last appointment, armed with new knowledge about CHS, I asked him if his wife smoked marijuana.

He said that she not only smoked it, she recently got her ‘medical marijuana’ card because smoking was the only thing that relieved her nausea. I asked if she ever felt better after a shower, and he said “oh my gosh, she is in the shower for three hours or more every day with the hot water turned up!”

The big question, of course, will be whether people with similar symptoms will try going without pot for a month, the length of time required for symptoms to fade, and whether clearing their systems of THC actually relieves their symptoms. But other heavy marijuana users with pain and nausea should read up on CHS, and consider a trial off THC. One month without pot isn’t going to kill you.

Prince Missed Suboxone Lifeboat by 12 Hours

One of the links from this page connects to the ‘OD Report‘. I set up the connection to highlight the epidemic of overdose deaths, not to sensationalize the issue. But the Prince story is sensational and tragic at the same time. And the connection to buprenorphine only magnifies the tragic circumstances that are wrapped around the use of a potentially-life-saving medication.

I read some time ago about Prince’s chronic pain problems, primarily involving his hips and secondary to years of dancing in high-heeled shoes. Shortly after his death, TMZ reported that Prince’s plane made an emergency stop in Moline Illinois on his way home from Atlanta. They reported that he received Narcan at the airport after landing, and then was treated and released at the hospital before flying home to Minneapolis. TMZ later reported that Prince was taking large amounts of prescription opioids that contributed to his death.

The OD Report contains newsfeeds about opioid overdose. An article published today describes the circumstances surrounding the discovery of Prince’s body by Andrew Kornfeld, the son of an addiction doc from Mill Valley, California. According to the article, an emergency addiction treatment plan was arranged with a program called ‘Recovery Without Walls’ based in Mill Valley, California. The physician who founded and medically directs that program, Dr. Howard Kornfeld, was not able to make it to Prince and instead sent his son, Andrew Kornfeld, a premed student who worked as a ‘spokesman’ for Recovery Without Walls.

Here is where it gets interesting… Andrew Kornfeld travelled to Prince’s home with a small supply of buprenorphine. The intent of the people involved cannot be known, of course, but one could surmise that the buprenorphine was provided in order to get Prince started on the medication. Andrew Kornfeld was the person who reportedly called 911 after he arrived at Paisley Park, prompting security personel to summon the singer and eventually find his body in an elevator.

Putting aside for a moment the legal and ethical lapses of a premed student delivering buprenorphine to a person in another state. one thing is clear: Had Prince taken the two tablets of buprenorphine found with Andrew Kornfeld, he would never have died from opioids– unless, at some point, he decided to stop taking the medication. If you have trouble believing that simple fact, then I suggest you do some more research about buprenorphine treatment. You’ll find that while 30,000 people die each year from opioids without buprenorphine in their bloodstream, only 40 die with buprenorphine in their system– and almost all of those people died from other agonists, and would have lived if more buprenorphine was present.
It is almost impossible to die from opioids if a person is taking buprenorphine or the combination drug, buprenorphine/naloxone.

I don’t know how the media will interpret the story, or who society will hold at fault. From my perspective, the story is tragic in how predictable things played out. Prince had the resources to determine the truth about opioid dependence– i.e. that abstinence-based programs rarely work, especially for patients with chronic pain. He likely learned that his options included 1. a stay in rehab, including a painful withdrawal, followed by a high risk of relapse, or 2. finding a doctor to treat his chronic pain and opioid dependence using buprenorphine or a buprenorphine/naloxone combination medication (as they are essentially identical), which would almost immediately place his ‘opioid problem’ in remission. It is not clear how much of his problem was ‘addiction’, and how much was ‘pain treatment plus tolerance.’ The difference between the two conditions is often in the eye of the diagnosing physician. But the good news for such patients is that is doesn’t really matter. Buprenorphine products provide almost immediate resolution for pain patients tolerant to opioid agonists, removing cravings and providing relief from withdrawal.

In a sane world, Prince would have called the doctor down the street to get started on buprenorphine immediately. But doctors who prescribe the medication are hard to find, and the few doctors who do prescribe the medication are stuck at the 100-patient cap, waiting for President Obama to make good on his promise to change the rules so that more people can be treated.

Instead, the 100-patient limit remains in place– and patients desperate for help search throughout the country for doctors with openings. I myself receive several emails and calls every single day from people across the country who are begging for help. I tell them the same thing I would have told Prince: I’m stuck at the cap. I wish I could help.

Opioid Analgesia Without Addiction

I don’t have pull with the addiction-related organizations out there. I’m never been a joiner, and I tend to notice the problems caused by medical societies over the good things that they supposedly accomplish. For example PROP, or ‘Physicians for Responsible Opioid Prescribing’, have a specific mission. Once a group has a mission, any considerations about individual patients go out the window. PROP has propagated the message that opioids are NEVER beneficial for patients with chronic pain.

Legislators with no knowledge of clinical medicine hear that message, and respond by passing draconian laws that interfere with any considerations of individual patients. I would guess that the people of PROP pat themselves on the back for encouraging laws that remove physician autonomy. I’m sure they figure that they are smarter than all the family practice docs out there. But in reality, they are only destroying the control of doctors over patient care, and handing that care over to politicians. Way to go, PROP.

In the same way, the societies that hold meetings about meetings, that elect Secretaries who become Vice Presidents who become Presidents, get to publish the articles that describe clinical protocols. The doc who spends every day talking with patients has no access to these sources, and little ability to influence those protocols. Sometimes the societies and organizations get things right… and sometimes they get things wrong. The latter is the case with post-op pain control in patients on buprenorphine products.

I’ve written about this before, as regular readers know. Over the past 8 years I’ve had dozens, if not hundreds, of patients on buprenorphine undergo surgery. The surgeries include coronary bypass, thoracotomy, rotator cuff repair, C-section, nephrectomy, total knee or hip replacement… and a host of minor surgeries with scopes and lasers. I’ve treated these patients in a number of ways, in part because hospitals that provide emergency care have different ways of dealing with post-op analgesia. I rarely have control over what they do acutely– but I almost-always take over pain control when patients are discharged.

In the past few months there have been several ‘articles’ stating that the best way to handle surgery, in people on buprenorphine products, is to stop the buprenorphine before surgery, and treat pain using opioid agonists. This opinion is not supported by any data. It is someone’s opinion– usually someone who has a title, i.e. someone who spends at least some of his/her time in society meetings. That time is removed from the amount of time that could be spent treating and speaking with patients. Frankly, the ‘higher’ a doctor is in society circles, the less time they spend in patient care. That comment will anger the docs who it applies to. I can hear them now– saying I’m only full of ‘sour grapes’. But maybe those same docs should look in the mirror, and wonder how they ended up as ‘President’ of a society.

I’ve used the approach claimed as best practice in the society journals– i.e stopping buprenorphine before surgery– and the same thing always happens. Tolerance to opioid agonists rises very rapidly in the post-op period. Patients are discharged on huge doses of opioid agonists. And at some point, agonists must be discontinued for 24 hours to allow for re-induction with buprenorphine agents. I’ve had several recent patients go through this exact process– and my frustration motivates this post. One guy shot himself in the femur, and the bullet also passed through his lower leg. He needed fasciotomy to avoid losing the leg. His Suboxone was discontinued at admission, and ten days later he was discharged on 30 mg of oxycodone every 2-3 hours– i.e. over 200 mg per day. The other person was in a serious car accident, and had multiple fractures— femur, pelvis, ribs, wrist– as well as internal injuries. After 3 weeks he was released on over 300 mg of oxycodone per day!

On the other hand, I’ve had many patients go through the surgeries listed earlier while maintained on buprenorphine, 4-8 mg per day. In ALL cases, they had excellent analgesia with lower doses of oxycodone than in the people who stopped buprenorphine. Most patients did well on 15 mg of oxycodone every 3-4 hours– a max of 120 mg of oxycodone per day. In a few cases– i.e. in the most painful operations, in the most sensitive patients– I had to use 30 mg of oxycodone every 4 hours.

The most amazing thing about the combination of buprenorphine and opioid agonists is the absence of tolerance to agonists, when buprenorphine is present. I’ve had patients with recurrent injuries that required repeated surgeries, including a woman who tore her rotator cuff and the surgical repair THREE times over three months. She took the same amount of opioid agonist for three months, with no noticeable decrease in efficacy. After the final operation, after three months on significant amounts of opioid agonist, she simply stopped the agonist and resumed her full dose (16 mg) of buprenorphine. She had no withdrawal, and not other complications. She simply stopped the agonist and resumed buprenorphine treatment.

I’ve come to realize that buprenorphine effectively ‘anchors’ tolerance when patients take opioid agonists, as long as the buprenorphine is continued. Patients always say the same thing: that the pain was reduced by the agonist, but that it didn’t ‘feel’ like the agonist they used to take. In fact, patients who could never control pain pills found that they COULD control agonists if they stayed on buprenorphine.

A couple years ago I presented these findings at an annual meeting of ASAM. The slides can be found here. I believe that some day, combinations of buprenorphine and opioid agonists will be the standard approach to pain treatment. The combination allows for opioid analgesia without tolerance, without euphoria, and with little or no risk of addiction. If THAT doesn’t piqué your interest, you have no business reading about opioid dependence!

I picture combinations of buprenorphine and fentanyl… especially since both are now FDA-approved as transdermal patches. Or perhaps a combination of fentanyl lozenges and sublingual buprenorphine. The possibilities are endless. Throughout history, the miracle of opioid analgesia has been cursed by the attachment to tolerance, dependence, and addiction.

Imagine if that curse was lifted from opioid analgesia. Can you even dare to imagine that world? I’m telling you… it is closer than you think—- and there for the taking.