Where’s the Buprenorphine asked Mr. Obvious? Thanks, CDC!

A quick note tonight, hopefully with a longer post to follow this weekend…

I’ve been frustrated by the people behind the Wisconsin PDMP, or Prescription Drug Monitoring Program, for their mistakes related to buprenorphine. Whoever came up with the numbers made a rookie error when calculating the equivalent morphine dose of patients taking buprenorphine products. The error is easy to notice by anyone who works with the drug, but apparently difficult to grasp by anyone with the power to correct the database figures.

Those people include, by the way, the folks at Brandeis University who give the numbers to Wisconsin, and the people at the CDC who give them to Brandeis. I’ve written to all of them; the bright folks at the CDC skimmed my explanation of their error and responded with a form-email that provides a link to where I can get ‘answers to my questions’.

Thanks, CDC!

In short, the people doing the calculation take a low dose of buprenorphine– say 200 micrograms– and extrapolate out in a straight line to 16 mg, ignoring the ceiling effect of partial agonists like buprenorphine. The calculation causes the PDMP to display a graph showing that people on buprenorphine are on the equivalent of 1200 mg of morphine. Any physician who sees that data (and all WI physicians are required by law to use the PDMP effective April 1) will think that the buprenorphine patient needing post-op pain is on THAT dose of opioids. Talk about an April Fool’s joke– nothing like hypoxia in the recovery room to brighten everyone’s mood! Don’t worry though– in their email they pointed out the disclaimer in fine print that the site shouldn’t actually be used to compare or convert opioid doses.

Then why make the calculation and show the graph, asks Mr. Obvious?!

This is getting longer than I intended… Another annoying State tidbit is the series of letters to Wisconsin physicians warning about the severe risk of harm from prescribing benzodiazepines to patients on buprenorphine. I’ve written to those folks as well, pointing out that combinations of benzodiazepines with opioid agonists are much, much, much more dangerous than with buprenorphine. I’ve explained how somehow, sometime long ago, the phrase ‘buprenorphine can only cause death in adults if given to someone without opioid tolerance AND combined with a second respiratory depressant, to which the person also lacks tolerance’ (a true statement) was changed to ‘buprenorphine is dangerous when combined with benzodiazepines’ (mostly ‘fake news’).

I haven’t written as many letters over this second issue because I’m no big fan of benzodiazepines. But both issues annoy me greatly, maybe because the errors of logic in both cases are SO obvious. Even for government work!!

Speaking of government work, the Milwaukee County Common Council released figures about the surge in overdose deaths, including a breakdown by ethnicity, age, county region, and drugs found at autopsy. Mr. Obvious has a question for the people writing to doctors to tell them about the SEVERE risks from buprenorphine: ‘What drug is NOT on the list of the 8 most-common drugs found in toxicology tests of overdose patients?’ A hint: It starts with a ‘B’!

Buprenorphine Overdose After Naltrexone Treatment

Naltrexone induces mu-receptor hypersensitivity.  Buprenorphine’s protective ‘ceiling effect’ may not prevent overdose in patients with this ‘reverse tolerance’.

A new patient described his recent history of respiratory failure several days into buprenorphine treatment.  He was told by his doctors that he experienced an allergic reaction to Suboxone. The rarity of buprenorphine or naloxone allergy led me to look deeper into his history, and my conclusion differs from what he was told by his last treatment team.

The patient, a man in his mid-50s, has a history of significant opioid use over the past 20 years.  He used a variety of opioid agonists over the past year, mostly prescription opioids, with an average daily dose greater than 200 mg of oxycodone per day.

Three months ago he went through hospitalization and detox, and after a week he was discharged on oral naltrexone.  He sought further treatment at a different institution that offered buprenorphine.  He was told to stop the naltrexone two weeks before induction with buprenorphine.

He avoided all opioids for that two weeks, and then started buprenorphine, 2 mg twice per day as directed by his physician.  The patient became progressively sleepier after each dose of buprenorphine, and after 24 hours could barely maintain wakefulness.  His complaints resulted in his admission to the hospital intensive care unit.

In the ICU he had a rocky course that included several episodes of apnea, hypoxemia and bradycardia.  The patient does not currently have the records from the hospitalization, so the course of events is based only on his recollections from several weeks ago.  He blacked out several times, and was told by doctors and nurses that his ‘heart stopped on the monitor’ during those times.  He says that his oxygen level was very low at those times according to the monitors, and according to what he was told.

After the episodes when he lost consciousness, he was told that since his heart stopped he needed emergency implantation of a pacemaker.  He said that a short time later those concerns were dropped, and no pacemaker was inserted.  He was discharged from the hospital in good condition after several days.  Follow-up with a cardiologist was not deemed necessary. He was told by his hospital physician that the episodes of lost consciousness were caused by an allergic reaction to Suboxone.  He had no rash or pruritus (itching).

I’m writing about this patient’s care in the form of a ‘case report’.  The patient does not have access to his records.  If he did, I would review them and write a formal case report for publication.  Since I’m relying on the patient’s perceptions and memories, I’ll use this blog.  I will say that I have no axe to grind, and my purpose in sharing this case is to help people avoid a similar situation.  And, of course, to keep readers of this blog entertained!

As the patient shared his story, I assumed that he had an opioid tolerance well-below the ceiling actions of buprenorphine.  When I mentioned my hypothesis, the patient smiled, and told me he had been using over 200 mg of oxycodone each day, blowing that theory to pieces.

But I returned to the same theory when he said that he followed the doctor’s orders very closely, including avoiding opioids completely for two weeks before induction.  I wondered, could a 2-week interval of abstinence lower tolerance so dramatically that buprenorphine resulted in overdose? Then the patient mentioned, in an offhanded way, that ‘he even stopped the naltrexone’.

I’ve written about the increased incidence of opioid overdose following treatment with naltrexone, a risk that is unreported and largely unknown beyond brief reports from Australia cited in the linked post.   Opioid antagonists, including naltrexone (the drug that makes up Vivitrol injections), induce ‘reverse tolerance’ in mu opioid receptors to cause a heightened response, and heightened respiratory depression, from subsequent exposure to opioid agonists.  Anyone close to the field of opioid dependence notices the increased frequency of overdose in patients newly released from confinement, whether in jail or in abstinence-based treatment.  The increased risk of death after a period of abstinence is related to the resetting of tolerance during abstinence.  A return to ‘normal’ use creates significant risk of overdose.

That risk is multiplied if the period of abstinence includes treatment with naltrexone.   Imagine a person who is using six ‘30s’ of oxycodone—180 mg—every 24 hours.  If that person waits a week and then goes on naltrexone, tolerance drops to zero and then to negative levels.  After a couple of weeks on naltrexone, a tablet of Vicodin has the potency of a tablet of Percocet.  That 180 mg of oxycodone now has the potency to cause respiratory arrest and death.

Buprenorphine is a partial agonist with a ceiling effect that prevents overdose in almost all patients who have even small degrees of opioid tolerance.   Almost all deaths from buprenorphine occur in people with limited or no tolerance to opioids.  In the presence of inverse or negative tolerance, the ceiling on buprenorphine’s opioid effect has less protective value.  Such was the case in the patient who is the subject of this discussion.

So what would have been a better plan?  Buprenorphine induction is always more dangerous in patients with low opioid tolerance, so careful patient selection will mitigate that risk.  In patients with low tolerance, reducing the starting dose buprenorphine to low-milligram levels does little to reduce the risk of respiratory depression because of the ceiling effect, which reflects the minimal difference in strength between 2 or 16 mg of buprenorphine.   Much lower doses of buprenorphine, on the order of 0.5-1 mg, are required to reduce risk of respiratory depression and overdose in patients with inverse tolerance to mu opioid agonists.

A second option would be to continue naltrexone through the induction process, and afterward gradually reduce the dose of naltrexone over a week or two.  As the block from naltrexone decreases, buprenorphine bound to mu receptors would gradually increase, allowing opioid tolerance to grow more slowly.  Precipitated withdrawal would not be a problem, as PW occurs when bound agonist is suddenly displaced by buprenorphine—  not when antagonists are displaced by agonists or partial agonists like buprenorphine.

Thankfully, the patient is now doing well, with no lingering problems caused by his course of treatment.  But the incident also relates to another common problem, i.e. the erroneous blaming of symptoms on medication ‘allergies’.  In an era of electronic medical records, that mistake often removes, permanently, a patient’s access to medication that may someday be helpful—and in the case of buprenorphine, irreplaceable.

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.

Benzos and Buprenorphine

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

I’ve heard more and more from insurers, regulators, and well-meaning agencies about the dangers of combining buprenorphine and benzodiazepines.   Some insurers protest paying for buprenorphine if patients are taking benzodiazepines.  Medicaid recently sent a letter that described a ‘severe risk’ of using benzodiazepines in patients on buprenorphine.  And the state drug database contains a graph for each patient of the morphine-equivalent narcotic dose over time, and shades the data in red if benzodiazepines are also prescribed.

Readers of my blog know I’m no big fan of benzodiazepines (read this for example).  But in an era of ‘fake news’, I’m even less of a fan of incorrect statements by doctors.   The drug database also ignores the ceiling effect of buprenorphine, and extrapolates the morphine equivalency of low doses of buprenorphine as if the dose response ‘curve’ was a straight line.  That ridiculous calculation leads the graph of opioid use to show buprenorphine patients as taking the equivalence of 900 mg of morphine per day.  The harm is minor I suppose by limitations on access to the database, but the error leads to misperceptions among doctors, and could potentially lead to mistakes in treatment decisions.

Benzodiazepines are respiratory depressants, especially when added to opioids.  The combination is dangerous when patients take doses of either class of drug that are higher than their tolerance levels.  The ceiling effect of buprenorphine eliminates that risk in patients who are stable on addiction-level doses of the drug, i.e. doses above the ceiling threshold.  A patient taking a maximal amount of buprenorphine CANNOT take a dose of buprenorphine that will cause respiratory depression.  Note the word ‘maximal’, not ‘maximum’.   By maximal, I mean a dose above about 8 mg per day, beyond which further doses will have no increase in mu receptor activity.

It is very difficult, and rare, to die from buprenorphine.  A person who lacks tolerance to opioids can die from buprenorphine, but deaths in that case are rare unless a second respiratory depressant is added– usually a benzodiazepine.  The high safety of buprenorphine, except when combined with a benzodiazepine, has been twisted in comments about the drug (and in the minds of regulators) to buprenorphine being uniquely dangerous when combined with benzodiazepines, which is not true.  Benzodiazepines are much, much more dangerous when combined with opioid agonists.  That risk is almost completely mitigated by buprenorphine, providing the person is tolerant to buprenorphine.

Buprenorphine rarely causes overdose unless combined with benzodiazepines in patients who are not tolerant to opioids.  Valid questions over benzo use should not be confounded by fears over buprenorphine.

Below, I will paste a letter I recently sent to one insurer who refused to cover buprenorphine in a patient on benzodiazepines.  Comments, of course, are welcome– and encouraged.

Re: XXX XXXX

XXX XXXX is treated with Suboxone for opioid dependence, and with a combination of medication for depression and anxiety that includes clonazepam and a shorter-acting benzodiazepine, currently lorazepam.    He has a history of (a significant anxiety disorder that I won’t disclose here).

The issue of benzodiazepine use in combination with opioids is complex, but fairly predictable in people who use benzodiazepines correctly (e.g. at regular intervals, rather than taking a month’s supply in three days and then going without for several weeks).

I am experienced in the use of medications that have respiratory depressant properties.  I am Board Certified in Anesthesiology and also in Psychiatry, and I worked as an anesthesiologist for over ten years before training in psychiatry.  I also have a PhD in neurochemistry, and I teach the section on opioids at the Medical College of Wisconsin.  I will take some time to explain the interaction of benzodiazepines and buprenorphine—so I hope you will read my comments and take them seriously.

Buprenorphine has been known to be a very safe medication for the past 3 decades.  Review of the pharmacology literature will show that deaths from buprenorphine are rare. While over 30,000 Americans die from overdose each year, only about 40 of those deaths occur in people who have buprenorphine detected in the bloodstream.  Of those 40 deaths, almost all were from opioid agonists, with buprenorphine NOT acting as a contributor to the death—and in most cases the death would have been prevented had MORE buprenorphine been present in the bloodstream.

The few deaths attributable to buprenorphine each year in adults require 1. An absent or low opioid tolerance, AND 2. the presence of second respiratory depressant that the person also lacks tolerance to.  Because of the ceiling effect, which caps the CO2 response-shift from mu-receptor activation,  deaths from buprenorphine alone are rare in adults.   Death is possible in adults naïve to opioids–  but only if a second respiratory depressant is present.

The fact that death from buprenorphine can only occur in the presence of benzodiazepines has been misinterpreted at times, in warnings about opioids, as the idea that benzodiazepines and buprenorphine are uniquely dangerous when combined.   Understand that patients tolerant to buprenorphine have a partial-pressure of carbon dioxide equal to 40 mm mercury (the normal level).  Because of the ceiling effect, additional doses or amounts of buprenorphine cannot shift the carbon dioxide response curve.  For that reason, patients who have been maintained on buprenorphine doses above the ‘ceiling threshold’ for over a couple weeks have no respiratory depression from the drug.  Such patients have similar respiratory responses to benzodiazepines as those of normal patients.

Mr XXXX is fully tolerant to the cap effect of buprenorphine, so he is not at risk of respiratory depression from the drug.  Frankly, he is in a much safer position than other patients contemplating benzodiazepines, because if he used opioid agonists their effects on respiratory function would be blocked.

I am not a big fan of benzodiazepines, and for that reason have tried to taper Mr. XXXX off of them in the past.  But when we have attempted to taper them, the insomnia and anxiety symptoms become more severe, causing him to isolate from others and miss work.  I am fearful- for good reason—that attempts to reduce benzodiazepines at this point would result in another significant depressive episode, resulting in hospital admission.  My goal has been to avoid any further increase in his dosage—something we have been able to do over the past two years.

Understand that the risk of respiratory depression comes down to tolerance, for both opioids and benzodiazepines.  Mr. XXXX uses the same amount of each medication every 24 hours, and does not stockpile medications or use medications impulsively.  His tolerance to BOTH medications, along with the cap on opioid effects intrinsic to buprenorphine, provides a significant margin of safety.

Cannabinoid Hyperemesis: How Rare?

Marijuana might cause pain and vomiting in the people who value the drug the most. Doctors should learn more about cannabinoid hyperemesis syndrome.

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.

Make Sleep Meds Work For You

I’ve been busier than I like, and haven’t had as much time for posting.  But I spend a lot of time answering emails from my patients, and some of my responses may be useful for others.  Below I’ll share my answer to a patient who has been unable to get quality sleep.  Next week I’ll find another answer to share with readers.

This patient asked whether her insurance would cover Lunesta.  She wrote at 2 AM that she is up most of the night tossing and turning. She now takes 10 mg of Ambien, and wrote that it ‘stopped working’.  She doesn’t think 20 mg of Ambien would be covered by insurance (although Ambien is very inexpensive when purchased for cash).  She takes gabapentin for a pain condition and wonders if increasing it would help with sleep.

My response:

Before getting into a discussion about insurance I want to make sure you have a good understanding about the issues you’re facing when you take sleep medications.  Most sleep medications are subject to tolerance, and some share ‘cross tolerance’.  Lunesta (s-zopiclone) and Ambien (zolpidem) act at the same receptor and have the same actions, so if a person is used to one, she is used to the other.  The situation is analogous to opioids, where a person tolerant to a significant dose of oxycodone will find little effect from morphine.

I have taken Lunesta but stopped it for the same reason you are unhappy with Ambien:  it just didn’t do much.  Lunesta also causes a very bitter taste in the mouth, not from the pill touching taste buds, but from the drug circulating in your bloodstream.  The taste is unpleasant but goes away aftef a few weeks in most people.  If you are not responding to Ambien, you won’t likely respond to Lunesta.

Some people change from an ‘ultrashort’ to a benzodiazepine, typically temazepam.  That change will often offer some benefit, but tolerance will eventually match the effects of temazepam just as with the shorter medications.  Patients often ‘chase’ tolerance higher until their doctor refuses to prescribe larger amounts.  The exercise only deepens the plight of the insomniac, making it harder and harder to sleep without medication.

What is your current dose of gabapentin?  Pain docs sometimes taper that drug up to a total of 3 grams per day, and higher doses cause some degree of sedation.  But again, step back and look at the big picture.  With any sedating substance, including gabapentin, you are only  addressing the short-term.  Your body will adjust to any dose of sedative, just as with opioids, and you will eventually need to address the same symptoms on even higher doses of sedatives.

I am willing to look at the gabapentin, but understand what you are up against.   Patients tend to focus on the short-term at 2 AM.  My job is to know that you will be around for years, even decades!  I often see new patients whose doctor prescribed benzodiazepines for years, repeatedly raising the dose.  At some point the patient ran out too early, prompting discharge.  At that point there is little to be done for such patients beyond helping them through several weeks of severe insomnia caused by benzodiasepine withdrawal.  Sometimes questiapine, clonidine, or hydroxyzine will help patients find some restless sleep while lowering their tolerance to benzodiazepines, but that sleep is usually poor in quality and associated with significant daytime sedation.

My best advice:  When taking sleep medications, the most important point is to NEVER ‘double up’.  If you take two tablets instead of one of any medication, you will never get the same benefit from taking one again.  You will only run out early, and the doctor, pharmacist, and state will all prevent early refills  The second point is that newer sleep meds will not just make a person fall asleep.  For the first few nights a new medication might feel more potent, but over time, the best thing a sleep med will do is HELP a person fall asleep.  Patients must do everything else correctly, including sleep hygiene measures such as using a dark, somewhat cool room, using white noise to help the mind avoid focusing on creaking boards or other noises, avoiding significant alcohol use, avoiding caffeine after noon, avoiding eating or smoking right before bed,  calming down at the end of the day (some people can’t  sleep if they exercise late in the day), dimming lights, avoiding watching football right before bedtime, etc.

If you do all those things, a sleep medication will help ease the transition to sleep.   But the shorter meds like Lunesta and Ambien work best when they take effect in people who are in bed already, working on getting to sleep.  People often make the mistake of taking a sleep medication and wating to go to bed until they feel sleepy.  The newer sleep meds don’t cause the sleepiness that came with the older drugs, and they don’t last near as long.  Waiting ‘until they work’ can also cause amnestic behaviors like sleep-eating, sleep-sexting, sleep-driving, and worse.

Give these issues some thought and tell me the amount of gabapentin you take.  Beyond the controlled substances, consider trazodone or clonidine, two medications that work differently than benzodiazepine and Ambien.

The best sleep, of course, is found in the unmedicated condition desiged by evolution.  Evolution is not fast enough to keep up with changes in communication and the social media phenomenon, so it is often useful to think about the sleep environment of our ancestors, 40,000 years ago.  If I knew how to use twitter, I’d hashtag ‘sleep like a caveman.’

Congress Acts on Opioid Dependence (ugh)

I won’t weigh in on the upcoming election, for fear of being barraged with insulting tweets by one candidate or ‘offed’ by the other.  But the current opioid dependence crisis provides a great chance to learn whether you stand on the side of ‘limited government’ or the alternative.

The TREAT Act takes 5 minutes to read, that would have increased the cap on buprenorphine patients.  President Obama undermined the TREAT Act by announcing his own plans to raise the cap soon after the TREAT Act was presented in the Senate.  After 7 years without mentioning heroin or opioid addiction, it’s hard to believe Obama’s actions were a coincidence.   Only a master politician can ignore 200,000 deaths, and then claim to solve the problem single-handedly despite a do-nothing Congress!

As I wrote earlier, few doctors will make use of Obama’s lousy offer.  Today Congress approved a bipartisan bill that will reportedly signed ‘begrudgingly’  by President Obama– who complained that the Bill ‘doesn’t go far enough.’  I wonder how many pages HIS Bill would be.

I invite readers to check out the language of the TREAT Act in regard to the buprenorphine cap– and then read the language of the ‘Comprehensive Addiction and Recovery Act of 2016‘.  And then, please, tell me how many patients doctors will be able to treat with buprenorphine.  The new law will provide treatment authority for nurse practitioners and physician assistants– I think.  How?  When?  How many?  I see a number of details that are left to the HHS Secretary–  a post that changes a couple times during a 4-year Presidential term.

How do we set up practices based on rules that change every couple years?!

I’m no political scientist, so I’m just reading the Bill and trying to figure it out– and I encourage you to do the same.  Myself, I prefer the language of the TREAT Act, but hopefully the attorneys will get this new thing figured out and let us know how many people we get to help with 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.

Obama’s Lousy Suboxone Offer

I was reading more about Obama’s executive order over at Dr. Burson’s blog.  I guess she is a ‘competitor’ in the blogging world, but I have to admit that her blog has a lot more detail about the issue than I do.  If you haven’t been there yet, check it out.  Keep coming back here too of course!

She wrote recently about the rules that would be required by the Feds, in order for them t o allow us the ‘right’ to treat people with buprenorphine.   I wrote to Dr. Burson after reading her post that she is providing the facts, and I can’t help but provide the emotion.  And after reading the baggage tied up with the ‘right’ to treat heroin addicts, I am.. ‘pissed’!  I realize that isn’t a word that doctors should use.  But honestly… I just don’t have another one!

Dr. Burson wrote that according to the current proposal, Doctors begging the Federal Government to treat another 100 addiction patients must 1. Use electronic medical records; 2. Accept insurance for the treatment; and 3. Require counseling of patients treated with buprenorphine products.  There were other requirements as well, but these were the three that I remember for irritating me the most.

Dr. Burson goes through her reactions to the requirements, and mine are mostly the same.  As a solo psychiatrist, I don’t see the value of electronic records.  Many of my patients don’t WANT their addiction treatment in a database. They know the stigma that they face already every time they go to the pharmacy.  Some of them work for employers who would discriminate against people once-addicted to opioids.  Some of them know they would be accused of ‘impairment’ for taking buprenorphine.  Those of us who prescribe buprenorphine know that they are not impaired– and that they’ve worked at jobs for years with no problems should speak volumes.  BUT IT WON’T.  We all know that ‘impairment’ can be in the eye of the beholder– and once someone thinks it is there, it IS there.  Once accused, how do you prove you’re not impaired?

I realize that at first glance, accepting insurance sounds like a good deal.  But now, I am able to see at most 2 patients per hour.  I have accepted insurance in the past, and that’s a completely different business.  Insurance companies reimburse psychiatrists at a rate that anticipates seeing 4-5 patients per hour.  Medicaid reimburses far below that, expecting doctors to make up the difference through commercially insured patients.  But that doesn’t work when treating addiction, where the large majority of patients are on Medicaid.  The only way it works is if the doctor works for a network where knee replacements and MRI scans subsidize addiction treatment, or where care is ‘mass produced’ by a team that minimizes the time doctors spend with patients.

I LIKE seeing two patients per hour.  The Obama team says if that is the case, I can’t see more than 100 patients, no matter how much my home town needs my services..  How ironic… if I spend less time per patient, I can have MORE patients.

I’ve written about the counseling issue before.  The requirement is a nod toward the huge counseling/rehab industry that has tried to block medication-assisted treatment at every turn.  Shouldn’t something as personal as counseling be decided by each individual patient?  Is there any other illness that requires counseling in order for patients to receive medication?  Of course diabetics would benefit from nutritional counseling– but would we consider withholding insulin without it?!

Who will decide, by the way, if the counseling is adequate?  Will the doctor stop your medication if you miss too many sessions?  What if you have nothing to talk about– so you still have to go? How many times? What type of ‘counseling’ counts?  Can a person get a massage and call it ‘counseling’?  If I get my ears candled, is that good enough? Group therapy?  Music therapy?  I saw recently that Madison WI has practices offering ‘float therapy’– is that OK? What about equine therapy?

I think you get my point.

As I mentioned in an earlier post, the TREAT Act would have increased the cap and allowed doctors to decide the best course of action for each patient.  The doctor remained in charge of patient care– sort of like ‘if you like your health insurance, you can keep it.‘  President Obama stepped in front of the TREAT Act to offer something different.  I can almost hear him saying with a Bronx accent… ‘how can you turn down dis’ deal?’

With all the heroin deaths, he’s putting forward ‘an offer you can’t refuse’.   No thanks…. I’ll stay at 100.

Obama and the TREAT Act

I just read an article in the Daily Beast that reads like a better version of something I would write about the value of medication-assisted treatment of opioid dependence.  I appreciate Christopher Moraff telling a story that has been untold far too long, and I hope the story raises questions across the country.

But I have something else on my mind that deserves a story of its own.  I am just a small-town psychiatrist in the Midwest, of course, and so I could be missing something.  I watch Veep and House of Cards, but I assume that the political games in those shows are grossly exaggerated.  I’ll offer a bit of background… but if you already understand why people opposed to increasing the buprenorphine cap are idiots, just skip the next few paragraphs.

The Recover Enhancement for Addiction Treatment Act, a.k.a. TREAT Act, is a Bill with bipartisan support written in response to the epidemic of opioid dependence in the US.  If enacted into law, the TREAT Act (among other things) would increase number of patients that a physician can treat with buprenorphine from 100 to 500 and allow nurse practitioners and other ‘mid-level prescribers’ to treat opioid dependence with buprenorphine medications. For newcomers, treatment professionals debate the wisdom of raising the cap on the number of patients treated by each practioner.  Some people argue against medication treatment entirely and claim that abstinence is the only legitimate goal when treating addiction, despite the fact that abstinence-based treatments rarely work.  ‘Rarely’ is in the eye of the beholder, I guess– but even the most optimistic promoters of abstinence-based treatments claim they fail only 70% of the time– within ONE YEAR.   Other addiction docs advocate using medications that dramatically cut death rates, in concert with counseling.  They demand the counseling despite no evidence– none– that counseling improves outcomes in medication-assisted treatments.  But arguing against counseling is like arguing against… milk, I guess.  Who can argue against milk?

Then there are the extremists like me who argue that addiction is an illness that should be treated like any other illnesses and managed with medications, sometimes over the course of a person’s life.  Maybe counseling is indicated, and maybe not– but the need for counseling should not stand in the way of obtaining a life-sustaining medication.  After all, do we withhold insulin from diabetics who don’t receive nutritional counseling?  We extremists point out that there is no ‘cap’ on patients who are prescribed opioid agonists– the type of practice that started this epidemic in the first place.  We point out that literally no deaths have been caused by buprenorphine in patients who were prescribed the medication.  In all of medicine, THAT is the medication that needs a ‘cap’?  Doctors can treat unlimited numbers of patients with cancers, pain disorders, or complicated surgical procedures, but can’t handle more than 100 of THESE patients?!

I don’t see the point of the other groups, so I won’t try to explain their thought processes– accept one example.  Some docs are Boarded in Addiction Medicine– a secondary certification that can be obtained after certification in primary care or psychiatry.  Full disclosure– I am not Board Certified in Addiction Medicine.  I am Board Certified in Anesthesiology and in Psychiatry, and I worked with narcotics as a pain physician and anesthesiologist for ten years.  And I have a PhD in neurochemistry.  From my perspective, I have enough things on the wall. But the docs who DID get boarded in addiction medicine are angry that they get nothing special for their efforts.  The law that created buprenorphine treatment was intended to increase addiction treatment by primary care practitioners.  But that’s sour grapes to the addiction docs, who want the sole right to treat more than 100 patients.  Never mind that 30,000 people die from overdose each year, and buprenorphine could save many of them.  The addiction-boarded docs are angry that they aren’t given special privileges.  Isn’t THAT a problem!

What does all of this have to do with President Obama?  A bipartisan group of members of Congress of worked on the Treat Act over the past 8 months.  Professional societies have come to compromises over the Bill.  According to Schoolhouse Rock, Congress creates laws and then if passed, the President signs them into law.  The President often pulls opposing factions together, encouraging them to get a Bill to his/her desk.  For most of President Obama’s term, about 20,000-30,000 young Americans have died each year– far more than the total number of Americans killed by war, terrorism, hurricanes, and other natural disasters combined.    Until a month ago, I’ve heard absolutely nothing from the US President– no calls to action, no pressure on lawmakers, no requests to call our congresspersons.  But as the TREAT Act was introduced in the Senate, President Obama announced that he will raise the cap by Executive Order.  A supporter of the President would say (I know, because I’ve heard them) that the important thing is that it got done– so who cares how it happened?

Readers of this blog know that I pretty-much dislike everybody… so it is no surprise that I’m not happy.  We have the TREAT Act sitting in Congress, needing a simple majority to be sent to the President’s desk and signed into law.  During an epidemic of overdose deaths, the support would not be difficult to find for most Presidents, even with an ‘obstructionist Congress’, as our President likes to call them.  A change in the law would be relatively PERMANENT, unlike an Executive order– which can be changed with a new President, or with a new set of political calculations by the same President.   And an Executive Order to change rules at HHS requires hearings for citizen comments, which take more time– time when more patients will die.  Shouldn’t President Obama have used the operations that other Presidents used for far-more controversial issues, and changed the law?  This temporary, delayed Presidential action will get kudos from articles like the one in the Daily Beast.  And Obama gets TV time and headlines to describe how he addressed the opioid epidemic, on his own– in spite of a ‘obstructionist Congress.’

What irks me the most, though, is that an Executive Order didn’t need to take seven years.  By 2010 the overdose epidemic was well-underway, and had already killed a couple hundred thousand young people.  Did President Obama need to wait until the TREAT Act was almost at his doorstep before taking ANY action to stem the surge in overdose deaths?  From the sidelines it looks like the deaths themselves didn’t provoke a response.  But the threat of bipartisan action during an election year?  I guess that’s another story!