Addiction Medicine Conference

I usually blog about our North Carolina Addiction Medicine conferences after they take place, but today I wanted to do a little advance advertising, in case any addiction medicine professionals haven’t heard about the conference.

Our fall conference is this week, October 22 and 23, 2021, and you can read more about it here: https://addiction-medicine.org/fall-conference/The conference has some great speakers line up. On the first day we’re scheduled to hear updates on COVID 19, on state overdose data, and on both state and federal policies. Then Dr. Keith Humphreys, renowned author, will speak about the implications of the changing cannabis policies in the U.S. I’m particularly looking forward to hearing him because I’ve read his chapters in the ASAM Textbook of Addiction Medicine, among other things. He is a prolific writer in the field, with thoughtful insights.

Later in the day we have an assortment of workshops to chose from with everything from Addiction Medicine 101, for the basics, to harm reduction strategies. Then later in the afternoon Dr. Ed Salsitz is scheduled to talk about the fentanyl crisis.

Dr. Salsitz is a big part of why I decided to work in the field of opioid use disorder treatment. I first heard him speak at an ASAM conference just after I started working at an opioid treatment program for the first time. I was deeply conflicted about my work, coming from an abstinence-only, 12-step based background. Several people in my recovery meetings strongly criticized me because of my work. When I listened to Dr. Salsitz describe the evidence supporting the use of medication to treat opioid use disorder, I saw reason to feel good about working in this field. I appreciated his lectures against the stigma attached to both the disease and the treatment of opioid use disorder. I eventually decided it mattered more to me what the science showed than what people, with no real medical information, thought about me and my work. Thank you, Dr. Salsitz.

Then the second day, we have plenaries from several outstanding physicians: Dr. Ashwin Patkar will speak about abstinence versus moderation, and Dr. Steven Prakken will talk about psychiatric comorbidity in substance use disorders. Later, we will hear about reasonable screening for co-occurring physical comorbidity from Dr. Shuchin Shukla.

Then we have more workshops to pick from. I’m always conflicted about which one to attend, but I’m hoping since this is a virtual event, the sessions will be recorded so that I can listen later to all of them.

After that, one of the afternoon plenary sessions is about contingency management in the treatment of stimulant use disorder, presented by Dr. Dominick DePhilippis. I’m eager to hear this talk, because as I indicated in a recent blog, we have had many patients in treatment for their opioid use disorder who also have stimulant use disorder. I need some ideas to implement for treatment, and I know contingency management is one of the most heavily evidence-based treatments for this.

Then at the end of the day is a crowd favorite: “What’s New and Trending,” presented by Dr. Thomas Penders. He will talk about kratom, CBD, delta 8 and other things.

At each conference, we have special closed sessions for North Carolina medical providers who work at opioid treatment programs. This year, I was excited to see one of our topics was, “Advocating for patient care within an OTP corporate structure.”

This is great, I thought. Finally, maybe someone can tell me how to do this. I’ve struggled with the problem the twenty years I’ve worked at opioid treatment programs.

Then I was asked to be on the speaking panel for this topic. I felt a little panicky because what do I know? But as I’ve been contemplating the topic, I do have some experience to share, though sometimes it is what not to do.

I’ll let you know how it goes.

It’s not too late to register for this virtual conference, and you can get credit hours too.

Here’s the link again if you are interested: https://addiction-medicine.org/fall-conference/ There’s a physician and a non-physician link at that site.

Latest Obstacle to Treatment of Opioid Use Disorders: Pharmacies

Recent studies show some pharmacies refuse to stock buprenorphine products. This is a disappointment and a barrier to effective treatment of opioid use disorder. I’m not talking only of buprenorphine monoproduct; some pharmacists also refuse to stock or dispense buprenorphine combination products. Some do not stock naloxone kits for reversal of opioid overdoses.

Last week my husband tipped me off to an interesting podcast done by Jeffrey Bratberg, Pharm D, on an AMERSA podcast. AMERSA stands for The Association for Multidisciplinary Education and Research in Substance use and Addiction, a non-profit organization dedicated to promoting education and research into substance use disorders. You can read more about them at www.amersa.org

Dr. Bratberg had two researchers on his podcast, Dr. Lucas Hill, and Dr. Lindsey Loera, who described the outcome of a study they did on the availability of buprenorphine in community pharmacies. You can listen to the podcast here: https://attcniatx.blogspot.com/2021/09/amersa-people-passion-attc-network-podcast-barriers-treatment-opioid-use-disorder-buprenorphine.html.

During the podcase, both doctors talked about the study they did where they had a “secret shopper” protocol. They called 800 randomly selected pharmacies out of the 5078 pharmacies licensed by the state of Texas. Their first study was done only in Texas but later they made similar calls to all states, with similar results.

On their phone protocol, they asked to speak with the pharmacists, and asked about the availability of buprenorphine 8/2mg films. They selected this product and strength because addiction medicine physicians told them this was the most prescribed product. If the pharmacists said that medication was not in stock, they asked if the pharmacists were willing to stock it and if so, they asked how long it would take to get the medication ready to dispense. They also asked if the pharmacy had naloxone nasal spray kits in stock. [1]

This study was done from May of 2020 until June of 2020.

Only 34% of pharmacies were willing and able to fill one week of buprenorphine/naloxone films and a naloxone kit right away. Of note, chain pharmacies were much more likely than independently owned pharmacies to stock these medications (45% versus 12%).

When looking only at the buprenorphine/naloxone medication without the nasal naloxone kit, 42% were able to fill the prescription. Of those who did not have the medication in stock, most (62%) were willing to order it. The average wait time for pharmacies needing to order it was two days. This is an unacceptably long time to wait for a patient in withdrawal, so that’s one kind of problem.

But their data showed that 38% of the pharmacies that didn’t stock this medication were unwilling to order it.

This is appalling. Of course, we could say yes but this is Texas and maybe there’s more stigma in that state than elsewhere, but the authors of the study say that results were similar when they called pharmacies in other states.

Why are pharmacists not willing to stock and dispense a medication that has been proven to save lives?

The study authors said they heard misconceptions from these pharmacists, such as overblown concerns about euphoria, misuse, or diversion of buprenorphine products. Of course, we know from studies that most people using illicit buprenorphine are trying to avoid withdrawal rather than trying to get high from it. And, as the authors pointed out on the podcast, all these pharmacies surely had oxycodone in stock, which is much more likely to cause euphoria, so that reasoning is fuzzy.

Some pharmacists said there were costs issues. If a pharmacy orders a supply of buprenorphine/naloxone films and no patients seek to fill that medication, the pharmacy could lose money. But isn’t that true of any medication the pharmacy stocks?

One of the study authors pointed to another possible reason pharmacists don’t stock buprenorphine products, based on a Kentucky study done by Cooper et al. [2]

This was a qualitative study done in 2020 of fourteen pharmacies in rural Kentucky. Some of these pharmacists said they would refuse to fill some, or all, buprenorphine product prescriptions written for opioid use disorder. When asked why, many of them said they feared increased scrutiny from the DEA and wholesalers.

To back up a bit, this opioid epidemic debacle we find ourselves in now had plenty of contributing factors. Among them, drug wholesalers were blamed for not reporting large orders of opioids to small communities, in violation of DEA law. The DEA faced some criticism that it didn’t detect and stop large shipments of opioids that were being overprescribed in some communities. And doctors at pill mills were blamed for overprescribing for financial incentive.

As all these failings are being addressed, pharmacies say they fear increased scrutiny from wholesalers and from the DEA, as the pendulum swings towards tighter regulation. They say they can’t accept new buprenorphine patients because they are being rationed by wholesalers.

However, there is no shortage of buprenorphine. There’s only the perception of increased risk to the pharmacy and pharmacists if they have too many patients on the medication, but nobody has defined how many is too many.

Some pharmacists are distrustful of buprenorphine prescribers and see them as bad doctors. That’s just an extension of the stigma that some people – including some pharmacists – still have toward people with substance use disorders. These pharmacists think there must be something wrong with a provider who wants to treat “those people.”

I’ve felt this when I’m on the phone with some pharmacists. One pharmacist told a patient of mine that he didn’t accept “out of town” prescriptions. I called to ask about this, since his pharmacy is twenty miles from my office, about the same distance as the next closest buprenorphine prescriber. Literally, my patient could not see a prescriber who was closer to this pharmacy. I felt his distain for me as we talked, and he didn’t budge. My patient had to go elsewhere to fill his buprenorphine/naloxone tablets prescription.

Electronic prescribing is more difficult when pharmacies don’t stock buprenorphine products. When I send a prescription to a patient’s preferred pharmacy, if they don’t have it, I must send a cancellation so that I can send it to a second pharmacy. That happens more with new patients, of course.  

The authors of the Hill study reasoned that efforts to increase buprenorphine prescribing must be matched by policy changes to encourage increased dispensing of buprenorphine medication. That conclusion is correct, of course. We can have the best treatment plans and the best warm hand-offs of new patients from the emergency department to prescribers, and it can all come undone at the pharmacy level when patients can’t fill their prescriptions.

1. Hill et al., Addiction, 2021 Jun;116(6):1505-1511.
2. Cooper et al., International Journal of Drug Policy, Vol. 85, November 2020.

Bad News

I knew overdose deaths were increasing since COVID started last year. But data from the Centers for Disease Control and Prevention (CDC) is worse than I’d thought.

You can look at several interesting maps filled with facts here: https://www.cdc.gov/nchs/nvss/vsrr/drug-overdose-data.htm

Overall, overdose deaths have increased 30.4 percent in the year from February 2020, the beginning of COVID, and February of 2021. At the end of February of this year, 95,133 people died from overdose over the preceding twelve months, compared to 73,344 who died over the twelve months prior to that. Opioids were involved in most of these deaths, though the total number includes deaths from all drugs.

That’s awful.

Some states are worse than others. Nearly all the Appalachian states had large percentage increases in overdose deaths. For example, Tennessee’s increase in overdose deaths was an astounding 51.1percent, while my home state of North Carolina went up by 40.5 percent. Kentucky’s deaths increased by 54.6 percent, and West Virginia increased by 55.2 percent.

Vermont saw the biggest percentage increase, at 74 percent.  New Hampshire, right next to Vermont, was one of the few states that had a reduction in overdose deaths.

Vermont has an innovative hub-and-spoke model, which other states try to emulate, to provide care for people with opioid use disorder. Yet New Hampshire has been lukewarm in its response to treatment of opioid use disorder, so initially this data puzzled me. But the data I’m talking about from the CDC reports the percentage change in overdose deaths. When I look at the actual total of deaths for the last reported 12-month period, they had 194. New Hampshire, however, had 381 over the same time.

But these raw numbers aren’t controlled for the population density. Vermont has, very roughly, about a third of the population that New Hampshire has.

Why have overdose death rates gone up? What’s driving this? The answer, in a word, is fentanyl.

This very potent opioid far surpassed heroin and prescription opioids a few years ago. When I started working at the OTP in my small town in the foothills of the Appalachian Mountains, all my patients were using prescription pain pills. Starting a year or so ago, heroin entered our area, but it wasn’t really heroin. It was the much cheaper and more potent fentanyl and its analogues.

Lately our patients tell us fentanyl is being added to stimulants like cocaine and methamphetamine. It’s also been pressed into pills that look like Xanax and other prescription medications. We had a few people tell us they bought Xanax or knew someone who bought Xanax that turned out to be fentanyl.

Stimulants are also killing people, but usually in combination with an opioid. According to NIHCM (National Institutes of Health Care Management), 63% of stimulant overdose deaths also involved an opioid in 2019, the last year that data is available. Cocaine overdose deaths haven’t increased as much as methamphetamine overdose deaths, which were climbing even before the pandemic. [2]

What are we to do?

First, we don’t give up. We can’t. This issue is too important, and the well-being of people affected by substance use disorders is too important. For workers in the field, it feels like we are trying to empty a swimming pool one teaspoon at a time. It feels overwhelming at times, yet even a teaspoon is something.

Second, use science to guide what we do. Use evidence-based methods to prevent new cases of substance use disorders. Implement the evidence-based methods of harm reduction to help people with substance use disorders. We need to demand funding for treatments that work and stop funding treatments that don’t work. For example, let’s stop cycling patients with opioid use disorder through short-term detox admissions that have little chance of producing real change. Or if patients are sent to detox units, let’s make sure they leave those places on one of the three medications that treat opioid use disorder. Inpatient detox is a great place to start depot naltrexone, for example.

Let’s demand more funding for research into all aspects of substance use disorders. And then, let’s use the data. Let’s refuse to be led by ideology with no evidence.

Third, let’s train new people to work in this field of substance use disorders, and let’s pay them an attractive wage. And let’s voice appreciation to the people working in the field now.

Today is National Addiction Professional Day, so celebrate by telling someone you know who works in the field how much you appreciate them!

1. Ahmad FB, Rossen LM, Sutton P. Provisional drug overdose death counts. National Center for Health Statistics. 2021.
2. https://nihcm.org/publications/stimulant-deaths-on-the-rise-compounded-by-rise-in-synthetic-opioids

Lack of Knowledge, Lack Of Understanding

“…Poor management & security. No patients are held accountable for their misuse & the doctor allows patients to use other drugs over & over when getting treatment.”

I was tooling around on the internet. Somewhere between looking at recycled textile art on Etsy and viewing lists of the best audiobooks for 2021, I looked at job satisfaction reports on Indeed and found the above comment. It was written by a nurse who had worked at my facility. She was talking about me!

Before COVID, this nation faced significant nursing and other healthcare personnel shortages. COVD made this worse. Our opioid treatment program has had problems hiring and retaining nurses (and other personnel) just as other healthcare facilities have had. Most OTPs have early hours and lower pay than hospitals and other facilities, making it more difficult.

I wanted to get on Indeed to read about what nurses are saying about their job situations, hoping to find comments from nurses working at OTPs. I never dreamed I’d read a comment from a nurse who had worked at the same facility as me.

I felt angry and hurt when I read the comment, but then I felt sad. I didn’t do a good enough job educating her about the nature of addiction and the purpose of treatment programs. I missed an opportunity.

I can’t emphasize this enough: I can’t keep anyone from using drugs if that’s what they want to do. I don’t have that kind of power. No one does. Even placing people in prison doesn’t always stop people from using drugs.

Since I don’t “allow” or “disallow” anyone’s drug use, what good am I?

First, I can prescribe medication that keeps most opioid users off illicit opioids and on much safer and longer-acting medications. This allows them freedom from chasing opioids several times per day, and freedom from committing crimes to get money to get these illicit opioids. It usually improves their quality of life and here’s the big thing: It reduces their risk of dying. Since they are alive, they have a chance of participating in counseling.

Second, the chronic nature of opioid use disorder and other substance use disorders means we rarely see patients enter treatment and never use another drug. This disease doesn’t work like that. However, we can use evidence-based counseling techniques to assess patients’ willingness to change drug use behavior. We can use those techniques to help them decide what kind of action they’d like to take to change drug use habits.

Behavioral changes don’t happen quickly. Anyone who has tried to lose weight, exercise more, stop smoking or other things can probably relate to the difficulties of changing behavioral patterns. Sometimes we try things that don’t work, but we gain information about what may work for us in the future.

In the old days, I did taper people off their treatment medication (methadone or buprenorphine) if they continued to use illicit drugs. I’ve changed my approach, after learning more about how to support patients and help them in their recovery. These days, especially with fentanyl prowling around the drug scene, patients die when out of treatment. Accepted best practices show patients have best outcomes when we retain them in treatment and keep talking to them.

Obviously, the nurse who wrote the complaint wasn’t educated about this fact. I am one of several people who should have educated her about this.

I do lower doses if there’s another medical condition that makes methadone or buprenorphine dangerous, or if patients’ use of sedative drugs make dosing methadone or buprenorphine too dangerous. Even with these conditions, we try to talk the patient into going to an inpatient program for more intense counseling and help.

In fact, continued use of opioids is an indication to increase methadone/buprenorphine, not to decrease it.

Perhaps the writer of the complaint felt we should have stopped giving any take home doses to patients using illicit drugs. The comment was written after COVID started and we’ve been more liberal with take homes. State and federal regulations around take-home doses were relaxed so patients could dose at home and avoid crowds. We agreed this seemed appropriate to do. For the most part, our patients did well with these extra home doses.

Since I read the comment, I’m more careful to remind nurses and counselors during case staffing that we always must think about the risk/reward of treatment. In very few situations does excluding patients from treatment make sense. On the other hand, we don’t ignore drug use; every positive urine drug screen result must be addressed in counseling. But addressing drug use does NOT mean dismissing patients from treatment.

We recently had a nurse who worked only one day before she decided the job wasn’t for her. I hope she’s the one who wrote the comment. She didn’t have enough time to learn about what we do at the OTP. She didn’t work long enough to see all the miracles we see at OTPs.

I’ve said this many times before: I see more positive changes in people enrolled in opioid treatment programs than I ever saw back when I worked in primary care.

That’s the main reason why I love working at the OTP.  I’m sorry our nurse didn’t get a chance to see this for herself.

The Heartbreak of Methamphetamine

Reference at the end of this blog

Like so many places in the U.S., my area has struggled not only with heroin/fentanyl use, but also with methamphetamine use. We’ve seen a sharp increase in the numbers of patients at the opioid treatment program who also used methamphetamine.

However, sometimes prospective patients show up for admission to our opioid treatment program who have no opioid use at al. They have great expectations that the medication we use to treat opioid use disorder will also help them stop using methamphetamines. They say that if they could take a drug of some kind to “take the edge off” they would no longer crave and use methamphetamine.

Some of these patients have dabbled with opioids, using them with an assortment of drugs, but they have never become physically dependent and aren’t using opioids regularly when they come for help at our opioid treatment program.

I meet with these patients and talk to them myself, to make sure I get an accurate history of their drug use. But then I must tell them that they are not appropriate for admission to our program. I hasten to tell them that they certainly do need treatment, and we can direct them to the most appropriate provider. But these people are terribly disappointed and often vent a great deal of anger towards me.

Of course, thus far there are no medications approved by the FDA to treat methamphetamine use. Many medications have been studied, and some have shown some promise, only to fail to show benefit in later studies. Neither buprenorphine nor methadone have benefit for methamphetamine use disorder.

I tell these people that if I were to start them on buprenorphine or methadone, they would then develop a physical dependence on that medication, adding to their problems rather than helping. They don’t care. They often say things like we really helped their uncle, who used to use drugs and now is doing well, and why can’t we make an exception because they are so desperate for help?

It’s sad because I’d love to be able to help everyone. The other options in our community don’t look attractive to these people. They include a short-term detox unit and outpatient group and individual counseling. Inpatient detox followed by rehabilitation is available for people with substance disorders at a state-funded program several hours from us.

Behavioral therapies are still the most heavily evidence-based treatment for stimulant use disorder. Contingency management is the most effective intervention that we have (see my blog of June 6, 2021). Other techniques include groups that use the Matrix Model, and individual therapies such as cognitive behavior therapy, motivation enhancement, and 12-step facilitation.

There are no FDA-approved medications that treat stimulant use disorder.

We have long lists of medications that were tried and failed to provide benefit for stimulant use disorders. We also have some tantalizing data about drugs and combinations of drugs that might be proven to work after more study, such as the combination of naltrexone and bupropion. The size of benefit from this combination of medication isn’t great, but anything that can help would be a bonus for desperate patients. Transcranial magnetic stimulation is another intriguing technique that is still undergoing study.

As usual with difficult-to-treat illnesses and desperate patients, many sham treatments have been peddled over the years. Anyone remember Prometa (also known as Gabasync), the proprietary combination of flumazenil, gabapentin, and hydroxyzine? This combination of drugs was peddled as a cure for methamphetamine addiction with a hefty price tag of up to $15,000 per patient. As is so often the case with snake oil vendors, salesmanship outpaced science. Eventually, after proper clinical trials were performed, Prometa was found to be no more effective than placebo. We should expect to see more methamphetamine “cures” peddled as problems with methamphetamine climb.

Of course, patients at the opioid treatment program who are being treated with methadone or buprenorphine also can have or develop stimulant use disorder. Over the past several years, we’ve seen the number of methamphetamine-positive urine drug screens climb.

Our patients’ use patterns vary considerably. Some inject methamphetamine nearly daily. Others smoke or snort it several times a week, and others use in a binge pattern, for several days at a time with long stretches of abstinence between episodes. These patterns of use determine the degree of damage caused to our patients.

Nearly all have some problems caused by methamphetamine. We see financial problems, shattered relationships, decline in physical health, and worsening of mental health problems.

We try to increase patients’ “dose” of counseling, or even refer to inpatient care, but that’s difficult. There’s only one facility in our part of the state that will accept our patients and maintain them on their usual methadone or buprenorphine while treating the methamphetamine use disorder.

Even though the below-referenced article for the National Institute on Drug Abuse was published earlier this year, data from 2020-2021 is expected to be even worse. Stress makes everything worse, and COVID stressors have affected all of us.

1. https://www.drugabuse.gov/news-events/news-releases/2021/01/methamphetamine-overdose-deaths-rise-sharply-nationwide

Oops…I Goofed

One of my astute readers point out an error in my previous post.

Practitioners are no longer required to get eight hours of training if they only want to treat thirty or fewer patients. These prescribers can still prescribe buprenorphine products for their patients with opioid use disorder, but they still to submit Notice of Intent to SAMHSA under established protocols. Then once SAMHSA approves the practitioner’s request, the DEA is notified, and the practitioner is issued an X DEA number to be used for those patients’ buprenorphine prescriptions.

https://www.federalregister.gov/documents/2021/04/28/2021-08961/practice-guidelines-for-the-administration-of-buprenorphine-for-treating-opioid-use-disorder

Using High-dose Buprenorphine Induction in the Emergency Department for Patients with Opioid Use Disorder

In my last blog post, I talked about the new idea of micro dosing buprenorphine in patients who have not yet stopped using full opioids, to switch them to buprenorphine products without going through a time of opioid withdrawal.

I was surprised at the response to that blog. I now feel about micro dosing buprenorphine like I did about sex in high school: everybody but me seems to be doing it and they are having a great time. I’m envious.

In this blog post, I’m going to review a study of “high dose” buprenorphine induction done in an emergency department setting. This study was done on patients already in withdrawal, in contrast to the micro dosing studies.

This recent article, by Herring et al., describes the outcomes of patients with untreated opioid use disorder who were started on doses of buprenorphine that were higher than 12mg sublingual per day while in the emergency department. [1]

This study described 366 encounters of patients with opioid use disorder in the emergency department of one large urban hospital in Oakland, California. The study was done because the authors suspected that the usual buprenorphine induction, which takes several days, could discourage the most fragile patients. They felt an accelerated induction process that could achieve therapeutic buprenorphine blood levels within four hours, and that a quicker process could be more likely to engage patients in further treatment. They hoped to increase both the magnitude of withdrawal suppression as well as the duration.

As a side note, it’s important for emergency departments to provide treatment for opioid use disorder. We know that ED-initiated buprenorphine treatment is lifesaving and cost effective. All the following organizations have recommended ED initiation for opioid use disorders: the American College of Emergency Physicians, the U.S. Surgeon General, the National Institute of Drug Abuse (NIDA), and the Substance Abuse and Mental Health Services Administration (SAMHSA). Now that there is no requirement for an “X” number (as of April 2021), any physician with a DEA number can legally prescribe for patients. Some ER providers protest that they don’t have anywhere to refer these patients. However, many Emergency Departments with many referral options still don’t prescribe, as it is in my little town.

Of the patients in this study, 23% were homeless and 41% had co-occurring psychiatric diagnoses. Around 44% were black, and 15% Hispanic, and 54% of all the patients had no prior formal treatment for their opioid use disorder. The type of study was a retrospective chart review.

The patients were excluded from the study for certain criteria: those with recent methadone use, impending surgery, current intoxication with alcohol, benzodiazepines or other sedatives, post-overdose reversals, serious acute medical issues including kidney failure or respiratory distress.

Those not excluded were asked about time since last use. Patients had to be at least 12 hours from last use of heroin or fentanyl, 24 hours from last use of long-acting opioids, and 72 hours from last use of methadone. These patients were given a COWS (Clinical Opioid Withdrawal Scale) score and those scoring less than 8 were not dosed but were re-checked in 1-2 hours. Those scoring above 8 were given a first dose of 4-8mg of buprenorphine sublingually and re-assessed about 30-60 minutes.

Then patients either underwent standard induction or high-dose induction.

For patients who had improvement in their withdrawal symptoms and no barriers to same-day dispensed buprenorphine were given a total of 8-12mg in the emergency department and a prescription for 16mg SL per day until they could get a follow-up appointment. These were the standard dose patients.

High-dose induction patients were re-assessed 30-60 minutes after their first 4-8mg of buprenorphine, but then were given an additional 8-24mg every 30 minutes until relief of withdrawal or 32mg total. This protocol was done for patients with heavy opioid tolerance, scores of more than 8 after the re-assessment, and for patients who couldn’t reliably fill a buprenorphine prescription, whatever their reason might be. They were also sent home with a prescription for sublingual buprenorphine at a dose of 16mg per day until a follow-up appointment.

Precipitated withdrawal occurred in only .8% of these patients, a very low incidence. Nearly all those cases occurred within the first 8mg of buprenorphine given. Precipitated withdrawal was unrelated to high-dose buprenorphine. Median stay in the emergency department was only 2.4 hours, showing opioid withdrawal can be treated relatively quickly even under trying circumstances. None of the patients needed Narcan rescues, and there was no significant reduction of respiratory rate at doses higher then 28mg.

Three of the study patients had serious adverse events. One patient had diabetic ketoacidosis, and another patient returned to the ED in opioid withdrawal and had to be hospitalized for acute heart attack. None of these three events were felt to be due to buprenorphine, but I would have liked more information about whether that second patient could have had precipitated withdrawal. Some of the study patients were admitted to the hospital for treatment of medical illnesses that included infections such as abscesses and cellulitis, exacerbation of COPD (chronic obstructive pulmonary disease) and other conditions.

Between 10-18% of study patients did return to the ED if they were unsuccessful at accessing follow-up treatment with buprenorphine. I think that’s a remarkably low percentage. This shows this team of providers did a great job at referring patients.

The authors concluded that present dosing guidelines requiring multi-day buprenorphine inductions are unduly burdensome, particularly for patients who are homeless or have few financial resources to access treatment.

They felt the high-dose protocol was shown to be safe, at least for patients without serious illness or sedation from other drugs. The patients’ opioid withdrawal was addressed quickly and didn’t take much time to achieve, with an average stay of 2.4 hours in the ED. They felt this method of accelerated dosing helped removed barriers to treatment and that a higher dose lasted longer and extended the duration of action of buprenorphine.

I wish all ED providers could read this study. They might become convinced opioid use disorder can be treated without extreme burden on their time, with significant rewards.

I did have a few thoughts about the study.

I wish the authors would have told use what the primary opioids of use were in these patients. I suspect it was mostly heroin or fentanyl or both, but that data wasn’t included. If the primary opioid patients had been using was oxycodone or some other short-acting opioid, it could make a difference in the results.

Many patients were excluded from the high-dose option, so the degree of safety shown in this study may not apply to the type of patients that were excluded. For example, patients who received Narcan after an overdose were not included, and neither were patients who were using alcohol or benzodiazepines. The patients who are revived from an overdose may be the most important ones to get into treatment the quickest, since a history of opioid overdose is the leading predictor of future fatal overdose. This study doesn’t help us with this set of patients.

I’m appreciative of the study authors and I think this is an important study that supports induction of buprenorphine in selected patients who come to the Emergency Department for care.

1. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2781956

Micro dosing of Buprenorphine: Is it an Option Yet?

We all know fentanyl has taken over as the main opioid of use for patients with opioid use disorder. We have three medications that treat opioid use disorder, but some practitioners feel buprenorphine induction has become problematic for some fentanyl users. Even after waiting until patients are in moderate withdrawal, with a COWS (Clinical Opioid Withdrawal Score) of 12 or above, some of these patients have precipitated withdrawal symptoms after their first dose of buprenorphine, with either the mono- or combo product.

Why is this?

Since fentanyl has a relatively short duration of action, we might expect that if we wait until patients have at least moderate withdrawal, starting buprenorphine would be OK. But experts say that fentanyl is lipophilic, meaning it gets distributed into peripheral tissues in a non-dose-dependent fashion. For patients who have been using fentanyl long and hard, the drug has a large volume of distribution and may dissipate slowly, thus causing precipitated withdrawal after administration of the less potent buprenorphine, even if the patient feels a moderate or higher degree of withdrawal.

What can be done about this?

Some physicians ask patients using fentanyl to wait 24 to 48 hours after their last use of fentanyl to take that first dose of buprenorphine. This approach reduces the risk of precipitated withdrawal… but is extremely difficult for patients. No one likes to be sick, and enduring opioid withdrawal for nearly two days is too much for some patients.

At the opioid treatment program, I’ve had only a few cases of precipitated withdrawal in such patients. Patients I treat usually know how long they must wait to take buprenorphine, from prior experience using buprenorphine illicitly for their opioid withdrawal. I can use their knowledge. I do shared decision-making with the patient for the best outcome. Some patients, having had precipitated withdrawal from buprenorphine products in the past, want no part of this medication, and want to start methadone.

That’s fine with me. Methadone has been around for decades and works very well to treat opioid use disorder. It’s a more complicated medication, but is as good as buprenorphine, and studies show methadone retains patients in treatment longer. But office-based practitioners can’t prescribe methadone to treat opioid use disorder. That’s illegal.

Now there may be a new option for buprenorphine induction, called micro dosing. With this technique, patients don’t have to stop using opioids and wait for moderate withdrawal. Micro dosing eliminates the uncomfortable wait time and thus is more attractive to potential patients.

I’ve been scouring the internet for information about micro dosing protocols and have found several. An article from scientists in British Columbia from last year described their technique of micro-dosing buprenorphine. For this method, the patient can continue to use illicit opioids during the induction of buprenorphine, which is started in very low doses, compared to what we usually use. Then once the patient reaches 12mg of buprenorphine per day, the patient hopefully can stop using illicit opioids, without going into withdrawal. [1]

The article describes the following recipe:

• Day 1: 0.5 mg once a day
• Day 2: 0.5 mg twice a day
• Day 3: 1 mg twice a day
• Day 4: 2 mg twice a day
• Day 5: 3 mg twice a day
• Day 6: 4 mg twice a day
• Day 7: 12 mg (stop other opioids)

Since new patients don’t have to stop using illicit opioids or experience withdrawal with this method, it may make treatment with buprenorphine products more attractive.

How do you dose patients at half a milligram since the lowest tablet and film on the market is a 2/.5mg dose? Even though drug manufacturers have not done studies to assure the active medication is evenly distributed over the film or throughout the tablet, patients have been cutting tablets and films for years. Right now, I have seven office-based patients doing a slow taper who are cutting their 2/.5mg film into multiple pieces, to take much lower doses as they ease off the last bit of medication.

I had one patient who said she could cut a 2mg film into sixteen pieces, with sharp scissors. Then she took one of the sixteenths every other day. I prescribed her one 2mg film per month for many months, until she forgot to take a dose, had no withdrawal, and stopped buprenorphine/naloxone altogether.

My point is that with sharp scissors, a 2/.5mg film can easily be cut into quarters, equaling a half milligram each, roughly.

The original method, called the “Bernese method,” called for starting at .2mg per day and gradually increasing to 12mg over nine days. There are case reports dating back to 2010 that give positive results for induction with this method.

Micro dosing has also been suggested for a quicker and less painful method to transition from methadone to buprenorphine. It’s difficult for some patients to tolerate methadone withdrawal symptoms for long enough to get started on buprenorphine in the traditional manner.

Patients who wish to switch from methadone to buprenorphine currently need to gradually lower their dose of methadone to 40mg or less, then miss several days of dosing before starting buprenorphine under our present protocols. It’s hard for patients to tolerate a slow taper, particularly if they are at doses above methadone 100mg. I usually recommend they lower by 5mg per week, so it takes many weeks to get the dose low enough to make the switch. Some patients get frustrated and chose to remain on methadone. Others get frustrated and drop out of treatment, incurring the risk of overdose death that we see in untreated opioid use disorder.

This micro dose method could help patients make the transition much more quickly and easily… if it works.

It’s an intriguing idea, giving us more options to treat patients. But after my internet search, I haven’t found any large studies of these micro dosing protocols, only a few case reports here and there. Before I try micro dosing, I’ll need more objective information and more expert opinion. Ideally, I’d like to read about results from many patients, transitioned from fentanyl or methadone in a controlled manner.

I also question the reason who people want patients to transition from methadone, which works well as a treatment for opioid use disorder. True, it doesn’t work for everyone, because no medication works for everyone. But it’s a good and acceptable treatment and if a patient is doing well, what is hoped to be achieved by the transition to buprenorphine? If it’s what the patient wants, that’s a great reason. Perhaps the biggest reason patients want to switch is the convenience of office-based treatment available with buprenorphine products. If the patient has side effects or medication interactions with methadone, those are great reasons to switch.

But in one case study, a woman was transitioned from methadone to buprenorphine because she was hospitalized and due to her medical illnesses, needed to live in a nursing home. No nursing home would accept her on methadone, but they would accept her on buprenorphine. That’s why she was switched. [2]

That is not a good reason. It’s an arbitrary reason that reveals the same old bias against methadone we’ve fought for years.

So yes, I agree with transitioning from methadone to buprenorphine if there’s reason to do so, but let’s not agree to do this if the decision is based on stigma.

In other news, at the other extreme, some emergency department practitioners are using high-dose buprenorphine induction to alleviate withdrawal symptoms more quickly. They feel a higher dose provides longer relief of withdrawal, until the patient can access dependable medication treatment for opioid use disorder. I will describe a new study that suggests this can be done safely and without much risk of precipitated withdrawal in my next blog post.

1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6970598/
2. Terasaki et al, “Transitioning Hospitalized Patients with Opioid Use Disorder from Methadone to Buprenorphine without a Period of Abstinence Using a Microdosing Protocol,” Pharmacotherapy, July 26, 2019.

Taking A blogging break…back soon…

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Education of New Physicians

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I read an interesting study in the May/June issue of the Journal of Addiction Medicine. This article, by Shuey et al, described Internal Medicine residents’ knowledge and attitudes towards treatment of opioid use disorder with buprenorphine.

This study reports on results of survey questionnaires sent to Internal Medicine residents in Florida residency programs.

The study showed that Internal Medicine residents cared for patients with opioid use disorder frequently: 73% of the survey respondents said they cared for such patients more than once per month. But only 82% reported having substance use disorder educational curricula. Specifically, 75% said their program didn’t provide training in the treatment of opioid use disorder with buprenorphine.

Respondents’ answers to questions about buprenorphine as used to treat opioid use disorder were uneven. While 88% correctly answered that buprenorphine was a partial opioid agonist, only 16% knew that buprenorphine has a higher affinity for opioid receptors than methadone, morphine, and naloxone. Seventy-six percent were aware of the dangers of precipitated withdrawal, and 69% knew that methadone cannot be prescribed from an office-based setting for the purpose of treating opioid use disorder.

However, only 17% knew that weeklong tapers of buprenorphine are not supported by medical evidence, and 56%, more than half, mistakenly thought resident physicians can’t prescribe buprenorphine.

Residents who indicated an interest in treating patients with buprenorphine scored better than those not interested in getting a buprenorphine waiver to prescribe.

Of the Internal Medicine residents who answered the study, only 2% already had waivers to prescribe buprenorphine. However, the vast majority, at 89%, felt deregulation of buprenorphine to allow any physician with a DEA license to prescribe buprenorphine was a good idea. (This study was done prior to the change in rules earlier this year that allows just that.)

The surveyed residents were also asked about their attitudes towards barriers to prescribing buprenorphine. When asked if they were willing to get trained and prescribe buprenorphine if it was offered by their hospital, 82% agreed. When asked if they felt they had been adequately educated about treatment of opioid use disorder, only 19% said they had, and 48% said they didn’t feel educated, while 33% felt neutral about the question. When the residents were asked if they agreed that opioid misuse and addiction was a serious national crisis, over 80% strongly agreed.

When the respondents were asked about obstacles to the prescribing of buprenorphine, by far the most common response was limited knowledge about diagnosing and managing opioid use disorder. Other answers were a lack of awareness of medication, laws preventing residents from prescribing buprenorphine, and limited understanding of the legal process to obtain a buprenorphine waiver. Less than 5% of survey respondents said they lacked interest in prescribing buprenorphine, around the same percentage who feared legal action against residents who prescribe buprenorphine.

Let’s talk about some interesting things about the study. For example, only around sixteen percent of the residents who were sent this survey responded. That’s a low rate of participation. However, the Internal Medicine (IM) residents who did responded to this survey were relatively diverse. More than half were female, and evenly divided over the three years of residency. Ethnicity was 42% white, 24 % Hispanic or Latino, 23% Asian, and 7% Black or African American.

That’s more diverse than my Internal Medicine residency, way back in 1987. We were 28% female and 85% white, with 15% black, with no Asian or Hispanic residents. And we were the most diverse class to date. The IM residents in the two years prior to mine were 100% white and 7% female. I’m glad residents are more diverse now.

Were minority residents more likely to respond to the survey for some reason? And were residents already interested in treating patients with opioid use disorder more likely to answer the survey? There’s no way to know.

This study indicated IM residents are not getting valuable information about treatment of opioid use disorder. We are now several decades into the opioid epidemic. It’s been over two decades since DATA 2000 was passed, allowing patients to be treated with buprenorphine in office-based settings. That’s a whole generation of physicians.

Why have medical schools and residencies been so slow to teach young doctors about opioid use disorder and its treatments? I used to think it was only because treatment with buprenorphine was so new, but it’s not new anymore.

I’m proud of North Carolina’s efforts to change this. We are fortunate to have the Governors Institute of Substance Abuse, a non-profit foundation that seeks to prevent, identify, and treat substance use disorders. Starting four years ago, they helped to convince and encourage our state’s medical schools and primary care residency programs to teach about opioid use disorder and its treatments. As a result, four (UNC at Chapel Hill, Wake Forest, East Carolina, and Campbell University) of our state’s medical schools already offer eight hours of training on opioid use disorder. Nurse practitioner training programs in NC now mandate a 24- hour training course on opioid use disorder.

This present study of survey responses by IM residents points to significant gaps in the education of young physicians, even twenty years into the opioid epidemic. That’s disappointing. Usually I’m not a fan of governmental mandates in education, but it’s starting to look like some states will need that to change. It’s important. The lives or many people depend on this.

Imagine a chronic illness that causes disability and death. Now imagine there’s a new drug developed that reduced the risk of dying by three-fold. Not by three percent, but it reduces the risk of death three times over.

Now imagine a patient who dies from this chronic illness. Imagine that this unfortunate patient was never offered the life-saving medication. In fact, this patient’s physicians never even told the patient about this l medication, which had been approved twenty years earlier.

It would be a travesty. Malpractice lawyers would salivate to get such an easy case. The negligent physician would be called to account for his actions and possibly investigated by the medical board. There would be consequences.

That’s where we are now, except the chronic illness is opioid use disorder, and there are no lawyers, no consequences for all the missed opportunities to treat this deadly illness.

Why do we allow this to happen, this many years into the opioid epidemic?