Webisodes: Resources for Providers Who Work at Opioid Treatment Programs

I’m pleased to announce new resources for providers who work at opioid treatment programs. The Governor’s Institute of North Carolina and our state’s Department of Health and Human Services sponsored this work, which is a series of webinars addressing various topics encountered at opioid treatment programs. These webinars can be found here: https://addiction-medicine.org/training/otp/

Here are the topics:

Webisode 1: Safe Standard Inductions

Webisode 2:  8-Point Take Home Criteria

Webisode 3: Exception Requests

Webisode 4: Split Dosing

Webisode 5: Effective use of the NC CSRS (North Carolina Controlled Substance Reporting System)

Webisode 6:  Benzodiazepines, Alcohol, and Opioids

Webisode 7: Reinstatements

Webisode 8: Drug Testing

Webisode 9:  Standing Orders and Scope of Practice Issues

Webisode 10:  Admission Criteria and Exceptions

Webisode 11: Pain Management for Patients on Methadone or Buprenorphine

Webisode 12: Methadone vs. Buprenorphine

Webisode 13: Duties of an OTP Medical Director

Webisode 14: Interpreting Drug Screens

Webisode 15: Methadone, EKG testing and the QT Interval

Webisode 16: Medical Conditions that may Mimic Opioid Withdrawal

Webisode 17: Hospitalized Patients Returning to an OTP

Webisode 18: Special Dosing Orders for Tapers

Webisode 19: Neurobiology of Opioid Use Disorder

These webisodes were written by Eric Morse, MD, Lisa Wheeler, PA, and…me. We picked topics and wrote brief essays that became the scripts that Dr. Morse read on the Webisodes. Each time after one of us completed an essay, we emailed it to others for critique and adherence to current evidence-based literature.

Did we agree on everything? No, but we only disagreed on fine points, not on the underlying principles of good patient care. I’m pleased with the final product, as it represents our best efforts.

A few of the webisodes are dated because they were written pre- COVID. We’ve had changes in our state, allowing many more take homes under COVID exception provisions, so Webisode 2 is a little dated.

Dr. Eric Morse did the recorded presentations. I am allergic to video presentations, so I am very grateful he was willing to do these. Dr. Eric Morse is a fellowship- trained addiction psychiatrist, with over eighteen years’ experience working in this field. Dr. Morse did a wonderful job on camera, and the graphics that accompany the verbal information were clear and simple. These are short and concise webisodes, lasting between five to eight minutes.

I wrote about half of the webisodes and was surprised that I still learned much as I was writing.  I would write a paragraph, then wonder if there was newer data available, and I’d go back to do an internet search just to make sure. Sometimes I did find new data to include, improving my essay.

Nearly twenty years ago, when I first started working at an opioid treatment program, I was woefully underprepared. I did get a facility tour and several hours of information from a physician who was medical director at the time, which was great so far as it went. I could have used a manual to help me, and webisodes such as these would have been a godsend.

These days, we have all sorts of informational media: SAMHSA has published books, downloadable for free from their website, containing the basic information needed. TIP 63 is the latest iteration of this data. ASAM (the American Society of Addiction Medicine) has published guidelines for treating opioid use disorder with medications.

There’s the PCSS forum, sponsored by APPP, where providers can get a mentor to help guide them when using medications to treat opioid use disorders.

These webisodes are the latest educational supports available for free to any OTP providers and need to be watched if you are new to the field. Maybe they need to be watched even if you are “old” to the field like me. Sometimes I think I know something, but what I remember turns out not to be quite accurate

I am grateful to the Governor’s Institute and the NC DHHS for identifying this educational need and their support to fill the need. I especially appreciate Dr. Morse’s willingness to do the on-camera work.

Check out these webisodes and let me know what you think!

Book Review: “Drug Dealer, MD” by Anna Lembke, MD

I hated the title but loved the book.

I imagine some marketing hack told the author she needed a title that would grab people, and this is what they came up with. The book doesn’t talk much about the few doctors who turned out to be drug dealers. Rather, the book tells the story of pain pill addiction in our country, about how it happened and the contributing factors. Most importantly, it discusses how to prevent opioid use disorder and how to treat the patients who developed opioid use disorder.

I like this book because it’s concise. The author succinctly presents data without getting wordy or going off on too many tangents. Even with so many other competing books on the market, this one stands out. Published by Johns Hopkins University Press, it only runs to 152 pages. But since it was published in 2016, it missed the last few years of our opioid epidemic and how patients have switched to heroin, now that pain pills are scarce.

The author uses some patients’ stories to underline points of information in the book but doesn’t overdo this. Her first chapter is about the nature of addiction, with descriptions of risk factors for initiation of substance use, and risk factors for the development of substance use disorders.

In Chapter Two, the author told about the overprescribing we saw in this country, beginning at the end of the twentieth century. She described how the internet functioned as a supplier, though most other experts say the internet wasn’t a prominent driver of the opioid epidemic in its early years.

By Chapter Three, the author, a well-known and respected Addiction Medicine specialist, expressed interesting ideas about the role of “illness narratives” in some patients. By this term, she means some people with physical and psychiatric differences get labelled as having an illness, rather than being accepted as normal human variations. She uses the example of back pain, which she says in the past might have been looked at as a normal part of human existence, which now is termed a chronic pain disorder. The implications of the illness narrative are that pain should be viewed as something dangerous that must be got rid of, rather than endured, exposing the afflicted person to the dangers of opioids and opioid use disorder.

As an example of psychiatric differences, she uses the normal human tendency to become distracted, which in an extreme form is now labeled as an illness: Attention Deficit Disorder. This label of illness, she says, implies the need to medicate the condition. This illness becomes part of the person’s identity and thus their “personal illness narrative.” She says it’s tempting for people to blame their illness as the cause for life’s failures and disappointments.

Later in the book, in Chapter Six, she describes the dilemma of people who have adapted an identity of an ill patient, calling them “professional patients.” She makes a case that people who have been granted disability benefits have a financial incentive to stay sick, in order to maintain their benefits. They may become so psychologically attached to their role as a sick person that the thought of recovery and wellness is frightening.

Most of all I enjoyed reading Chapter Four, titled, “Big Pharma Joins Big Medicine.” She did an excellent job of skewering Big Pharma’s great deception: marketing which masqueraded as education. Big Pharma identified physicians they could influence to parrot Pharma’s lies and coronated them “thought leaders.” These professionals were paid speakers’ fees to give talks to other prescribers, extolling the benefits and lack of risks of opioids.

What hard-working and underappreciated doctor wouldn’t be flattered to be called a “thought leader?” Along with hefty speaking fees, I can see how pharmaceutical companies seduced some physicians, encouraging them to present Big Pharma’s message about how safe opioids were for chronic pain treatment, even though there wasn’t data to support those claims.

In a few paragraphs, the author succinctly describes how the FDA failed to prevent drug companies from marketing opioids for the treatment of chronic pain, despite the lack of studies about safety. She also deftly describes a new study technique that’s bound to skew data about opioids, called “enriched enrollment.”

Then in Chapter Five, the author describes stereotypic behaviors of patients who try to manipulate doctors into prescribing the medications that they want. The author prefaces these behaviors with a sentence saying the terms aren’t meant to denigrate drug seeking patients, but that’s exactly what she proceeds to do.

For example, she describes patients who try to filibuster and talk past the allotted time for the appointment as “Senators.” She describes patients who flatter doctors by telling they are so much wiser/compassionate/competent than any other doctors as “Sycophants.” Other patients are described as “Exhibitionists,” who display dramatic emotions and physical scars to underscore dire need for opioid medication.

I recognize all these behaviors, both in patients I see with substance use disorders and in primary care patients; however, to place labels on the behaviors of people caught up in the desperation of active addiction is unseemly. The book would have been better if this section was omitted. However, in that same chapter, the author neatly summarizes the basic principles underlying the treatment of opioid use disorder with methadone and buprenorphine.

Chapter Eight was the most interesting. This chapter is titled, “Pill Mills and the Toyota-ization of Medicine.” In this chapter, the author talks about physicians who work at pill mills, who have long ago given up the illusion of working to help people. They are in a business to give pain pills to people who want them, no matter if it’s in the patients’ best interest, in order to make a lot of money for themselves.

But then she starts talking about how medicine has become a business, and that pill mills are only extreme examples of how medicine has changed into an industrial business. Physicians have less autonomy as their practices are bought by hospital corporations. Treatment options for all illnesses are more often determined by hospital administrators, insurance companies, and treatment guidelines promulgated by agencies like the Joint Commission (used to be called JCHCO).

Doctors are expected to meet productivity quotas and see ever more patients in a day. I’ve heard practice administrators use the euphemisms “practice maximization,” and “increased patient throughput.” The author of this book describes how she was given monthly feedback about whether she was hitting the billing targets that had been set for her. If she wasn’t meeting these targets, set by her employers, she had more to worry about than caring for her patients.

Giving patients what they want is the quickest way to get on to the next patient, further exacerbating overprescribing. It takes much less time to write a prescription than to talk to the patients about non-opioid ways to treat pain, and about the emotional issues that make pain worse. And this applies not only to opioids, but other medications. What physician hasn’t buckled at least once to the demands of a patient insisting that a Z-pack always gets rid of her viral illness? It’s easier to write the damned prescription than it is to have a conversation about how antibiotics don’t work for viral illness, and how inappropriate use of antibiotics causes antibiotic resistance.

I commiserate with the time pressures she describes.

On my 40th birthday, nearly two decades ago, I was told by a practice administrator that I was too slow. I was “only” averaging six patients per hour, and I’d have to pick up the pace if I wanted to keep working there.

Driving home that evening, I was shaking with anger and fear. I knew I couldn’t deliver quality care seeing more than thirty-six patients per day. I felt defective, like there must be something wrong with me because I couldn’t (or wouldn’t) keep up the pace of my colleagues.

I made up my mind that I needed to look for some other type of work in the medical field. I told my physician friends I was open to new ideas, and a few months later I was asked to fill in for a friend who was going on vacation. He was the medical director of an opioid treatment program. Deeply skeptical at first, I eventually found this to be my niche. It’s intensely satisfying to work with patients and see the tremendous life changes that I never saw while practicing primary care.

I feel sorry for doctors who never found their way out of the production line. I’m not saying opioid treatment programs never push providers to see more patients in less time, but I haven’t experienced near the pressure in OTPs that I have working in primary care.

The author then talks about another driver of the opioid epidemic: patient satisfaction scores. Many medical practices conduct surveys of patients after visits, to get feedback on what patients like and what they don’t like. They are asked about their physicians.

 Initially, these surveys were said to help providers pivot to a more patient-centered frame of mind, to sensitize them to patient concerns. Now, patient satisfaction scores are considered a “quality measure.” Providers with higher patient satisfaction scores are assumed to have provided better care, despite some evidence to the contrary. Physician pay is often linked to these satisfaction scores, giving doctors another reason to prescribe what the patient wants rather than take the time to have a difficult discussion about substance use disorders. Providers know giving patients what they want gives better satisfaction scores, and indirectly, better pay for themselves.

Then there’s the whole internet “Grade your doctor” websites. The author describes her trauma of reading a bad review online that was found by her son, and her angst in wondering who it could be who left such unkind remarks about her as a physician.

Back when there were one or two sites for physician grading, the internet could have been a factor that had an impact, but now there are at least twenty sites for this. I think this dilutes the effect of any one site, reducing the influence they have.

In Chapter Nine, titled, “Addiction, the Disease that Insurance Companies Still Won’t Pay Doctors to Treat,” the author describes the problem that persists in the U.S., despite passage of the Parity Law in 2008. The Parity Act, which said substance use disorders and mental health disorders must be covered by insurance companies to the same extent as other medical illnesses, has not assured equal coverage. This is a frustration that most providers of care to patients with substance use disorders face daily.

Though coverage for medical care of substance use disorders isn’t great, coverage for the medical complications of those disorders is much better. The complications of intravenous drug use, for example – endocarditis, osteomyelitis, cellulitis – are usually covered if the patient has medical insurance. Yet most medical insurers still don’t cover care delivered at opioid treatment programs or cover it poorly.

In the last chapter of the book, the author gives reasons to hope that our nation’s opioid problem may improve at some point. She points to better education of medical students, residents, and practicing providers about prescribing skills. More providers in training are being taught addiction medicine basics, and addiction medicine fellowship training programs have been started.

She hopes substance use disorders will be viewed as the chronic illness that it is, rather than a moral issue or a short-term medical problem. She says providers need to be allowed to spend more time with patients to give better care. She describes new models of care for patients with chronic pain, using both non-opioid medications and non-medication treatments, which have been successful.

I really wish she would have re-iterated the benefits of medications in the treatment of opioid use disorders in that last chapter. But at least this author did write three pages about the benefits of medications like methadone and buprenorphine in the middle of the book, and that’s more than most of the recent popular books about opioid use disorder have done. I thank her for that.

But then…she is an addiction medicine specialist, so maybe I’m justified to be a bit disappointed by this.

But this book is succinct, the data is accurate, the patient stories typical for many patients, and she does a wonderful job of documenting factors that merged to cause our present opioid problem.

For any person interested in opioid use disorders, I strongly recommend this book.

2020 Addiction Medicine Essentials Conference

I just had the pleasure of attending NC’s yearly fall Addiction Medicine Conference, which was held online this year, due to COVID.

My expectations weren’t extremely high; the Essentials conference is intended more for providers new to the field, compared to the yearly Spring conference, plus it was online. However, I’m glad I went because I learned a great deal that I can use, and the speakers were great.

On the first day, Dr. James Finch started with Basic Concepts of Addiction Medicine, but his talk was more than data. He exhorted his listeners to be more thoughtful and compassionate, and to look at the big picture of how and why we want to help our patients. And I was impressed that he gave his talk despite being hospitalized.  That truly is dedication. I pray you have a rapid return to health, Jim!

We had two speakers address racial inequities in Addiction Medicine, and about the explicit and implicit biases that exist in healthcare. Speakers presented some truly depressing data about racial health inequities, but also provided some action steps to address these health inequities. I also learned the new acronym: BIPOC, which stands for Black, Indigenous, and People of Color.

From the speakers, I got some ideas about how to assess our OTP for problem areas, as a prelude to making changes to reduce inequities, at least over issues we can control.

During a lecture on Update in Treating Tobacco Dependence in Mental Health Setting, I was in the “Amen!” corner. As the presenter said, we have data that shows people in recovery who stop smoking have lower rates of return to drug use, as well as better mental and physical health. Nicotine use disorder needs to be addressed in every patient.

At our OTP, about 95% of our patients smoke. Lately I’ve been talking to patients about participating in a free smoking cessation program at our local hospital, and I’ve been surprised at how many patients are receptive. This program offers free samples of patches, nicotine gum and lozenges, as an incentive for participation in group online counseling and support sessions.

At our OTP, we are NOT smoke-free, and we need to be. Our biggest problem may be addressing smoking cessation with our own employees, who often smoke outside on our front porch with the patients. I love our employees and would never hurt their feelings for anything, but I think that’s bad. They are setting a terrible example, besides putting themselves at risk for illness and premature deaths. That last part makes me sad.

We had an interesting session for opioid treatment program medical providers. Our presenter was a cardiologist who talked about the dangers of prolongation of the QT interval in patients treated with methadone. His recommendations about when to obtain an EKG on patients on methadone differed significantly from recommendations given by the American Society of Addiction Medicine. Listening to him speak, I perceived he focused on the dangers of methadone. As Addiction Medicine physicians, we also focus on the dangers of not prescribing methadone. We had good discussion about the topic, though not as many people attended as I would have hoped.

I learned much in a lecture about methamphetamine given by Dr. Richard Rawson of Vermont.

In the past, the methamphetamine found in our area was made by small-town “cooks” from over-the-counter decongestants. After laws were passed that restricted access to these raw materials, that type of manufacture decreased. Now, most of the methamphetamine used by people in our state comes from Mexican labs which make their product from the P2P method. This gives a more potent product which produces more severe complications.

Dr. Rawson said that since 2014, more methamphetamine and cocaine has been contaminated with fentanyl. In fact, in 2020, some areas of the country have found most of their cocaine to contain fentanyl as well.

This contaminated supply of stimulant drugs has caused a “fourth wave” of overdose deaths in the U.S.: first was opioid pain pills, then heroin, then fentanyl, and now stimulants contaminated with fentanyl.

This is not good news.

Dr. Rawson also mentioned a new drug, called “iso” for isotonitazene, a new drug found in overdose victims in the Midwest in June of 2020, who thought they were using cocaine. This was the first time I heard about this drug, which is a designer opioid, slightly more potent than fentanyl. This drug was just put on Schedule 1 by the DEA in the U.S.

The methamphetamine being used now is more potent and more dangerous. Dr. Rawson quoted studies indicating that people who use methamphetamine have more than a six-fold increase of risk of death compared to same-age controls.  Most deaths from methamphetamines are caused by cerebrovascular and cardiovascular disease. Even young patients have strokes, both hemorrhagic and ischemia, due to methamphetamine and other stimulant use.

The more potent methamphetamine being used now is toxic to the brain, causing cell death and brain dysfunction like that seen in patients with degenerative disease of the center nervous system. Even after active use of methamphetamine has ceased, studies show impaired verbal fluency, poor learning and comprehension, and slower processing of information. According to Dr. Rawson, more than two-thirds of users have cognitive impairment. This impairment is worse with intravenous use, older age, and higher quantity used.

As we would expect, patients who are in treatment for opioid use disorder who also use methamphetamine are at higher risk for leaving treatment.

Treatment of methamphetamine use disorder is challenging. Thus far, there are no FDA-approved medications that help with the treatment of methamphetamine use disorder, though there have been some promising trials using bupropion (brand name Wellbutrin) and mirtazapine (brand name Remeron). The mainstay of treatment remains counseling techniques, especially contingency management along with community reinforcement approach. Cognitive behavioral counseling and motivational enhancement counseling also may help.

Anyway, I learned a great deal during Dr. Rawson’s talk as well as others.

If you work in the substance use disorder field in any capacity, I highly recommend the Governor’s Institute’s fall and spring sessions. Our spring session this was truncated by the arrival of COVID 19, but we still had a small online conference.

Either in-person on online, these conferences are always worth the time.

Here’s a link to the Governors Institute website: https://governorsinstitute.org/

Writing a Blog: What I’ve Learned

I hereby return from my blog break. This year on my break I contemplated the future of my blog: do I want to continue the blog, or has it run its course? I decided I will continue writing blog posts for now, since people still seem to be reading them, and also because writing posts usually forces me to become better informed about my topics, ultimately benefitting me.

I started this blog ten and a half years ago, only for the purpose of promoting a book about opioid use disorder that I had written, titled “Pain Pill Addiction: Prescription for Hope.”

Against all odds, I was able to get an agent for my book. My agent tried hard to sell my book to publishers, but none were interested in an obscure topic like opioid addiction (in 2010 we were not yet using the term “opioid use disorder”). Eventually, I decided to self-publish.

My book did OK, for a self-published book, selling around 400 copies. I probably sold the majority of those myself, peddling them to independent bookstores to sell on consignment and giving copies to patients. A surprising number sold on Amazon. Then a few years ago, since the book was so out of date, I started sending an electronic copy to anyone who wanted it, for free.

I started the blog only to promote the book, a bit of advice I heard and read from many writers and would-be writers.  I started writing blog posts about opioid use disorder and its treatment with medication-assisted treatment.

The blog did much better than I expected, and I’ve enjoyed writing it more than I thought. I’m still amazed at the number of readers I’ve had over the years, and the variety of readers. I’ve been blessed by attracting the attention of knowledgeable people in this country, with reputations for brilliance. For example, I love every time Dr. Wartenberg writes a comment. He has so much experience and insight.

I’ve had over 1.6 million views of my blog, with over 5600 comments written. My blog traffic peaked a few years ago, when I still had the energy to write a blog each week. Now that I post every few weeks, I get 300-500 views per day. That’s still many more than I expected.

I’ve repeated some blog entries, such as those dealing with a specific topic like drug interactions, or specific drugs like kratom, but for the most part, my blog posts are original. Some posts that I’ve tried to re-cycle from ten years ago had to be re-written because the language has changed – or I have changed. I no longer use the words “addict” or ‘addiction” or at least don’t use them very often, because I’ve become more sensitized to people’s feelings.

Some readers send appalling comments that I won’t approve to appear on my blog, either because they demean people with opioid use disorders or demean people trying to provide care to them. Occasionally I’ll post an offensive comment, to serve as an example of outdated attitudes still held by some people about the nature of substance use disorders and their treatments.

I had one interesting commenter say that I was sinning by having this blog, and that I’d go to hell for it. I’m still not sure what my sin was, aside from dangling a participle or two. Thankfully most commenters are more intelligent and focus on content rather than attacking me as a person.

By far, the most accessed of my blog posts are the ones related to injecting buprenorphine. My site stats tell me that out of the past 408,000 blog views, 151,000 of those views were of my blogs about injecting buprenorphine and complications related to it. I’m not sure what to make of this. It could be a good thing, if people injecting or contemplating injecting buprenorphine are concerned and want to know of possible adverse effects of this practice.

The next most frequently viewed post was about switching from methadone to buprenorphine, at 54,000. The next most popular posts were about overdose with opioids and benzodiazepines, urine drug screening, and getting a commercial drivers license while on buprenorphine.

Often I’ll write a fluffy little post that I regard as a throw away, just something to put on the blog until I get something of substance to post, and I’ll get a big response that I didn’t expect. For example, my post recently about how I got a fever and viral gastroenteritis during COVID and thought I was dying got a lot of responses. Most were in sympathy, acknowledging how jumpy we all are with any sign of illness that could be COVID.

In the blog posts where I complain about difficulties with pharmacies, I get many responses from patients but even more from other medical providers. They tell me their stories of frustration with pharmacy practices and attitudes, and my own frustrations feel validated.

I have intelligent readers who are in treatment for opioid use disorders. They’ve helped me understand more about patients’ feelings, and how they view things. For example, I regarded the reduction of a patient’s take home level for positive urine drug screens as enforcement of state regulations, kind of mechanical and temporary. However, I’ve learned patients take the revocation of take home doses very personally. They take revocation as a slap in the face, like I am telling them I’ve lost faith in them and their recovery.

I don’t write as much about 12-step recovery now as I did ten years ago. Referral to 12-step groups is evidence-based, but most patients aren’t interested in going. I also feel that these 12-step groups have missed opportunities to reach people with opioid use disorder. My patients on medications to treat opioid use disorder aren’t always treated well at meetings.

I know that these groups can work well. In some prior posts, I’ve hinted that I’m in recovery, so today I’ll say it outright – I’ve been blessed with over twenty-two years of recovery mostly through the power of 12-step groups. I’ve gone to two or three thousand meetings over the past few decades. But this form of recovery is not the only way people recover, and some people don’t want to go to such groups.

A few years ago, four of us in recovery founded a Narcotics Anonymous meeting in our little town, with the express purpose of welcoming people in medication-assisted treatment to our NA meeting. We attracted a dozen or so people to come irregularly, but for the most part, only the four founding members regularly attended our meeting. After a few years, COVID hit, and we changed to online meetings for some months. Now, after one member moved away and another had a change in work schedule, we let the meeting close due to lack of interest. I must admit I was relieved.

These days I see how important it is to fact check everything that I write. In these days of misinformation, and dis-information, and outright lies, truth is ever more important. If I write a blog post stating that this or that conclusion is supported by research, I’ll double – check before posting.

Of course, blogs are more than recitations of fact. When I state an opinion, I’ll make it clear that it is only an opinion. I have many of these opinions, and they are subject to change, as new information is revealed. When I read posts from ten years ago, some of them embarrass me a little, because I no longer feel exactly the same. But that’s OK, because – hopefully – it means I’m still capable of change and growth as a person.

Having a blog is a fun way to vent. I try not to be grouchy in my real life, but on the blog…I can spew about my frustrations regarding various work irritations. I can give anonymous voice to my patients who are treated badly by this medical system because they are in medication-assisted treatment. I can call out pharmacists who seem to give my patients a hard time only because they have opioid use disorder.

It’s fun.

So for now, I’m going to keep my blog going.

Revision of SAMHSA’s 42 CFR Part 2: Better Coordination of Care Balanced with Patient Privacy

The federal law holds providers of services to patients with mental health and substance use disorders to a higher standard of privacy than ordinary medical providers. While other providers must obey HIPPA privacy laws, physicians in our field have always had to meet the more stringent 42 CFR standards.

This year, long-standing rules guarding the confidentiality of patients in treatment for substance use disorders were revised, with the intent of allowing better coordination of care for these patients.

Last week, a group of medical providers who work in North Carolina’s opioid treatment programs met on a teleconference when this issue was discussed. (Pre-COVID we held a conference once a month; now we meet once a week). It was obvious that most of us, including me, didn’t know the exact changes made in the revision. Out of curiosity, I decided to dive deeper into this issue and thought I’d pass it along on my blog.

SAMHSA has a great Fact Sheet that describes all of these changes at this website: https://www.hhs.gov/about/news/2020/07/13/fact-sheet-samhsa-42-cfr-part-2-revised-rule.html

The major changes boil down to a few items. Chief among them is that non-opioid treatment program providers can query a central registry of patients receiving care at opioid treatment programs, in order to prevent double enrollment and (hopefully) prevent adverse drug interactions. In the past, providers who didn’t work at opioid treatment programs didn’t have access to this sensitive information.

On the plus side, advocates of this change say that patients being prescribed methadone or buprenorphine at opioid treatment programs will get better care, because their non-OTP doctors will see which of their patients are receiving methadone or buprenorphine from opioid treatment programs, and won’t prescribe medications which may interact.

On the negative side, we worry patients on methadone or buprenorphine could face discrimination and judgmental attitudes from providers who don’t know any better.

I don’t think this revision will change anything at all. It’s difficult enough getting physicians and other providers to check our state’s prescription monitoring program. I doubt any providers will be savvy enough to know they can get access to our state’s central registry of patients in opioid treatment programs, let alone have the enthusiasm to access this registry.

And speaking of prescription monitoring programs…under the revision, opioid treatment programs are now permitted to report the medications they dispense (nearly always methadone or buprenorphine) to their state’s prescription monitoring program.

Again, proponents of this new rule say it will allow for better coordination of care and will prevent medication interactions. Opponents say, as mentioned for the other change outlined above, that it could lead to discrimination against patients getting treatment for opioid use disorder with medications.

Of course, the wording of the revised CFR 42 says the OTP “may” report prescribing data, not that they “must” report. For now, it’s up to the OTP to decide. At present, I don’t think a system is in place to receive this data anyway. During our latest teleconference here in NC, none of the providers said their OTP was reporting to the state’s PMP.

My opinion – and why have a blog in the first place if I can’t blather about my views – is that this new rule is a mistake. I am opposed to OTPs reporting their dispensing data to the prescription monitoring program.

In my county, patients are sometimes treated differently by medical personnel after they reveal they have opioid use disorder and are in treatment with us. And by differently, I don’t mean they are congratulated on their recovery and offered words of encouragement. Instead, they are told something like, “I hope you aren’t here to ask for any pain medication because I’m not going to prescribe it,” even if they are at a routine office visit for treatment of hypertension.

In some cases, patients are told they can’t be accepted as a new patient because the doctor isn’t comfortable treating them. These providers pretend that the patient’s issues are just so complicated that they don’t have the medical expertise. This is an excuse meant to hide an attitude of judgment and contempt for our patient who have the disease of opioid use disorder, and who are viewed as “difficult” patients.

I don’t think patients know about this recent change to privacy law, and I worry they won’t be happy about it. I hope it won’t deter people from entering treatment at opioid treatment programs. Before these changes become operational, we should tell our OTP patients, so they won’t be caught off guard. Of course, patients receiving buprenorphine products at doctors’ offices (so-called office-based practices) already have their data reported to the state’s prescription monitoring program, so it won’t be any change for them.

This revision also said that natural disasters which disrupt treatment facilities should be considered medical emergencies, allowing for patient information to be disclosed without patient consent. I interpret that to mean that if our facility is swallowed by a giant sink hole (not an unreasonable fear in our little town), we could send patient data to another OTP so that our patients could be dosed, without waiting for individual consent forms to be signed. This would streamline care and be more practical. We could also give patient data to hospital emergency departments or other facilities helping those patients during emergencies.

The revision document takes pains to declare that many things have not changed under this revised rule. For example, the document clearly states that law enforcement is still prohibited from obtaining substance use disorder treatment records without a court order. In other words, random police officers can’t come into the OTP and ask if an individual is a patient. We are still prohibited from releasing this information.

This is how things are at the federal level. At state levels, there are different laws about who can access prescription monitoring programs.

In North Carolina, the law changed in 2018, with the HOPE (Heroin and Opioid Prevention and Enforcement) Act. Prior to this, law enforcement had to have a court order to look at a subject’s data on the prescription monitoring program. After HOPE was passed, law enforcement officers can access PMP data if they have a “reasonable, good-faith belief based on specific facts and circumstances,” to access the data. The law has a few safeguards in place; the officer has to a “certified diversion investigator” before given access to the PMP.

I don’t know how this law slipped past me. I don’t like it. It makes me uneasy. With the previous court-ordered access, at least there was a judge who balanced (thoughtfully, one would hope) patient privacy against legitimate law enforcement goals. Now it appears to be left to the judgment of law enforcement officers who may be predisposed to believe their goal is justified.

I remember all the caution that abounded in 2007, when the NC prescription monitoring program first became operational. There was argument about whether the NC PMP could be accessed without patient consent (it could). I was told not to store the printed record of a patient’s PMP report with the rest of the chart, least it inadvertently be forwarded with any request to send records to other providers. The prescription monitoring program was hush-hush private, only for doctors’ eyes, and only to be used to provide better healthcare.

Now, law enforcement doesn’t even need a court order to access it.

I worry law enforcement officers won’t be able to interpret the data they find on the prescription monitoring program. For example, if they look at one of my patients being prescribe buprenorphine/naloxone films, will they look at the “overdose score” that is usually very high for patients on buprenorphine products? Despite warnings from the American Society of Addiction Medicine and other experts, who say it’s not possible to assign an MME (morphine milligram equivalent) to buprenorphine…our prescription monitoring program does just that, thereby implying a patient on sixteen milligrams of buprenorphine is more likely to overdose than a patient on oxycodone and a benzodiazepine. Ridiculous.

I’d like to hear from readers about how you feel about the changes to privacy laws. I don’t think patients, at least in North Carolina, know about the HOPE law that passed in 2018.

COVID and Opioid Overdose Deaths





People in the U.S. are dying from more than just COVID. Opioid-related deaths have increased in nearly forty states this year, coinciding with the COVID pandemic. According to a recent New York Times article, opioid overdose deaths showed a slight drop in 2018, went up again somewhat in 2019, but in 2020 they have risen by around 13%. [3]

The article says the drop in opioid-related overdose death in 2018 reflected fewer prescription opioid pills available for misuse by people with opioid use disorder. Then by 2019 fentanyl was found at ever-increasing frequency and purity in heroin, causing the increase in overdose deaths.

An article by the AMA (American Medical Association) was released just last week, reporting similar findings nationwide. The AMA article says that at least forty states are reporting increases in opioid-related mortality, mostly due to fentanyl-containing drugs. [4]

My state of North Carolina has seen a jump in drug overdoses since March of this year, compared to last year.  According to our state’s Department of Health and Human Services, overdose visits to emergency departments from potentially addicting drugs increased to 1,454 in the month of June in 2020 statewide. This compares with 1,145 in June of 2019 [1]

Other states report similar news.  In a blog last month by Margaret Williams, M.D. says that in Franklin County, home to the state’s capitol of Columbus and to The Ohio State University (my medical school alma mater), during the first four months of 2020, overdose deaths were up by 50% compared to 2019. That’s a big jump. [2]

Why is this happening? In Dr. Williams’ blog, she cites some possible causes: increased financial stress from job loss during COVID and increased stress from social isolation could be a trigger for increased drug use. Boredom and loneliness could also be triggers for use. Then there’s the fearful stress of contracting the COVID virus. Since usual social networks have been interrupted, more people may be using drugs alone, with no one available to call for help or administer Narcan if they overdose.

I agree with Dr. Williams. When people with substance use disorders of all types experience stress, they tend to seek a chemical solution to alleviate that stress. More alcohol has been consumed in this country since the COVD pandemic hit, and so it makes sense that people who prefer opioids would seek to use more opioids when stressed.

It’s not just drug use that people use to alleviate stress. Think of the extra weight many people have gained, eating because they are bored, fearful, or lonely. We humans use drugs, food, sex, gambling, or other things to make us feel better when we have bad feelings. The COVID pandemic has exaggerated ordinary stress for most people.

Conversely, people with substance use disorders are often at higher risk for contracting COVID 19. If they are homeless, they may lack simple things like soap and water. Incarcerated people, the majority of whom have substance use disorders, are subjected to crowding and may lack personal protective gear.

People with substance use disorders may have higher rates of other chronic illnesses, like HIV and Hep C. Most people with substance use disorders smoke cigarettes, a risk factor for contracting COVID and for having more severe illness from COVID.

People with substance use disorders may have even more difficulty that usual accessing treatment services during the COVID pandemic. Despite the push for substance use disorder treatment facilities to remain open, some closed their doors to people at higher risk for COVID infection. For example, some have refused to take new patients directly from jail or prison, due to the increased risk of those patients for COVID>

During COVID, the AMA is asking state governors and state legislatures to remove barriers to treatment of opioid use disorder, specifically by allowing telemedicine to be used for admission and prescribing of life-saving medications. They also ask that other barriers such as prior authorizations for insurance coverage be removed. They ask states to remove barriers for patients with pain, such as dose caps, quantity limits, and refill restrictions. They advocate harm reduction strategies be implemented and supported, such as needle exchanges.

This is all commonsense stuff, not too different from what the addiction treatment field has been asking for years.

Except now, it’s more urgent.

Most providers I know have used telehealth to communicate with their patients. Even though I personally don’t like it as much as in-person visits, it has been a godsend. The technology isn’t perfect, and patients with poor connectivity have a harder time connecting with providers.

For the opioid treatment program, relaxation of the formerly strict take home regulations probably helped the most. We reduced crowding in our waiting room dramatically because of this. It also reduced wait times for patients when they do come in. We still are giving these extra take homes, which I expect will continue until the governor revokes the status of “State of emergency.” Most patients have been helped with the extra take homes, though a few weren’t able to manage their medication as well as we’d hoped. So far as I know, we haven’t had any deaths due to extra take homes, nor have I heard of this from any practitioners working in NC opioid treatment programs.

In other words, I don’t see any evidence that extra take home doses from opioid treatment programs are fueling the rise in opioid overdose deaths. I believe the increase is due to overall stress in the lives of people who use opioids who are not in treatment.

  1. https://www.injuryfreenc.ncdhhs.gov/DataSurveillance/StatewideOverdoseSurveillanceReports/OpioidOverdoseEDVisitsMonthlyReports/MedDrugOverdosewithPotentialforDependency-EDVisits-June2020.pdf
  2. https://wexnermedical.osu.edu/blog/why-are-overdose-deaths-surging-amid-covid-19
  3. https://www.nytimes.com/interactive/2020/07/15/upshot/drug-overdose-deaths.html?smid=em-share
  4. https://www.ama-assn.org/system/files/2020-08/issue-brief-increases-in-opioid-related-overdose.pdf


Update on COVID 19 at the Opioid Treatment Program





Yeah I’ve got nothing new. Same old stuff. Social distancing, extra take homes for patients, everyone wear masks, wash hands every two minutes, wipe down facility periodically…

We’ve had a few COVID positive patients, but not as many recently as a month or so ago. We car-dose anyone who is medically fragile or who has any symptoms of COVID. Confirmed cases are usually given two weeks of take homes, unless they are terribly unstable.

Financial stress on patients has been worse. Our state grants for treatment that are administrated by area LMEs (local management entities, a frustratingly vague term) dried up at the end of June. More money from the State Opioid Response (SOR) grants has become available, but prospective grant recipients must qualify for them. In order to qualify for this grant money that pays for treatment, the patients must first apply for, and be turned down for, Medicaid coverage.

In the past, patients could go to our local department of social services, be interviewed, and get a letter saying they didn’t qualify for Medicaid within a day or two. Now, for some reason, our local department of social services says it will take at least a month to process applications for Medicaid.

I hate red tape.

Many of our patients, out of work due to COVID, have no money to pay for treatment. They have great difficulty hanging on for a week, let alone for a month. As a result, we’ve had a higher-than-normal number of patients drop out of treatment last month, mostly because their grant that paid for treatment ended. Our OTP, owned by a for-profit company, has allowed people to charge, especially for extra take home doses, for the last four months and that’s been great. But there’s an end to all charity in such companies, and now our clerical personnel have been instructed to ask for payment on balances.

Lest any person think our for-profit company is unfeeling for asking to be paid, allow me to remind readers that in our country, healthcare is not a right. It is a privilege. People with no money and no insurance are denied medical care every day of the week, in all areas of medicine. If you don’t like that arrangement, be sure you vote this fall. I know I will.

Some readers will surely point out that prospective patients spend more each day for illicit drugs than they would for treatment, but it’s different. When using drugs, people often resort to illegal activities to finance their addiction, and in treatment of course we don’t want them to do this.

Overall, I sense a downward slide in the overall wellness of our patients. More patients have tested positive for benzodiazepines, and judging from my conversation with these patients, it appears driven by the stress and uncertainly of present-day life.

Patients with school-age children must decide how to manage the every-other-day schedule our local school system announced. The schools are doing this to reduce the number of children in school at the same time, to promote distancing. But parents, if they work, have to find child care on the off days from school, adding to their anxiety burden.

Many more patients are testing positive for methamphetamines. From what I hear from other doctors, this seems to be a statewide trend. It’s a cheap and widely available drug, with effects that last for days.

At first, this liking for methamphetamine puzzled me. If a patient prefers sedating effects of opioids, why would he like the speedy effects of methamphetamine? But I was thinking too simplistically. Some patients with opioid use disorder say they like the energy it temporarily brings, or they enjoy feeling different for a short time, to forget about their problems.

We have no medication that’s been proven to help treat stimulant use disorder, so counseling is the mainstay of treatment. Often it must be provided in an inpatient setting, where the patient is removed from the source of methamphetamine, before patients make progress in recovery.

I used to taper patients on methadone or buprenorphine out of treatment for intractable methamphetamine use. Now, with overdose deaths from fentanyl rising in our state, I keep these patients in treatment while we try to increase their “dose” of counseling, either with us or to go to inpatient treatment at a facility where they can stay on their methadone or buprenorphine.

Overall, it feels like our opioid treatment program is in limbo, waiting for the end of COVID, waiting for more grant money for patients with no means to pay for treatment.

Yet some patients have thrived over the past months. Unexpectedly, some patients are making progress in their recovery despite difficult and stressful times. Some people are like that – fires that burn brighter against the wind. Watching those patients, I remember how resilient people can be. Many, if not most of our patients are survivors of one disaster or another: suboptimal parenting, physical/sexual/emotional trauma, terrible auto accidents, major health issues at a young age, or other calamities.

These are the people who inspire me to remain positive. It’s easy to give in to pessimism and cynicism, but watching these patients reminds me there’s another way, a better way to conduct myself in the world. I lean on these people for inspiration and hope I can reflect it back to others.


Pregnant Women with Opioid Use Disorder: Treatment with Combination Buprenorphine/naloxone versus Buprenorphine Monoproduct









Browsing through my copy of the May/June 2020 issue of the Journal of Addiction Medicine, I started reading an article titled, “Buprenorphine and Naloxone Versus Buprenorphine for Opioid Use Disorder in Pregnancy: A Cohort Study.” Then I happened to read the authors’ names and discovered it was written by physicians and scientists from Asheville, NC. I was pleased to see a submission in this major journal by people I knew in my state and read it with interest.

In their introduction, the authors of this article gave some basic facts about opioid use disorder and pregnancy. They quoted statistics from the 2017 NSDUH report, saying 8.5% of pregnant women reported that they had used an illicit substance within the past month, and 1.4% reported the use of some sort of opioid, either heroin or prescription opioid pain medications.

In our nation, opioid use disorder during pregnancy quadrupled between 1999 and 2014, at a rate of 6.5 per 1000 pregnant women. In North Carolina, our rate was 7.8 per 1000 pregnant women. Along with this increased use of opioids, the U.S. has seen a five-fold increase in neonatal abstinence syndrome between 2009 and 2012.

The authors point out that medication (methadone and buprenorphine products) for stabilization of opioid use disorder during pregnancy is the recommended standard of care, endorsed by the World Health Organization, The American College of Obstetrics and Gynecology, the American Society of Addiction Medicine, and the Substance Abuse and Mental Health Services Administration.

Prior to DATA 2000, these pregnant women could only get this treatment at opioid treatment programs, with methadone. Since DATA 2000, these patients also can get treatment with buprenorphine products at office-based practices as well as at opioid treatment programs. All of the patients in this study received buprenorphine product prescriptions from office-based practices, either at the community-based OB/GYN residency program or community-based providers.

Past studies (MOTHER trial, 2010, Jones et al –  another great scientist from North Carolina, at University of North Carolina) showed buprenorphine worked as well as methadone for pregnant patients with opioid use disorders, and over the past ten years, more moms-to-be have chosen buprenorphine over methadone.

This present study was done in order to compare outcomes of moms (and their babies) treated with buprenorphine monoproduct compared to those treated with the combination product, buprenorphine/naloxone.

In the past, pregnant women were usually treated with buprenorphine monoproduct because of fears the fetus could be exposed to naloxone if the combination product was used. However, over the past ten years, more physicians have prescribed the combination product for pregnant women, after some small studies reported no adverse effects. Prescribers were hesitant to prescribe the monoproduct buprenorphine because it is more often misused, and can be injected. The monoproduct has a higher street value than the combination product in most areas, underlining its popularity on the black market.

This retrospective cohort study looked at pregnant patients with opioid use disorder treated from January of 2014 to July 2018. Of the 226 women who met criteria for the study, 108  women taking the buprenorphine monoproduct delivered locally and could be included in the study. Eighty-five women taking the combination product delivered locally and were able to be included in the study.

At the end of the study, the women who had taken the combination product, buprenorphine/naloxone, had outcomes that were not worse than those of the women who had taken the monoproduct. Therefore, this article reassures providers that they can treat pregnant women safely with the combination product.

But hold on…there’s another interesting finding…

The incidence of neonatal abstinence syndrome (NAS) was significantly lower in babies born to moms on the combination product as compared to the monoproduct.

Thirty-five percent of the babies born to moms on the combination product had neonatal abstinence syndrome severe enough to need treatment. However, 55% of babies born to moms on the monoproduct buprenorphine had NAS severe enough to need treatment. That difference was found to be statistically significant.

There were some other differences between the two groups of women that didn’t meet statistical significance, such as age, race, insurance type, presence of chronic pain diagnoses, mental health diagnoses, buprenorphine dose prescribed, and other physical health problems. Interestingly, prescribers working at the residency program were more likely to prescribe the combination buprenorphine/naloxone product than community prescribers.

Intriguing though this finding is, this present study can’t show cause and effect. That is, the most we can say is that the combination buprenorphine is associated with lower neonatal abstinence rates in the babies, but not that the combination buprenorphine product causes lower neonatal abstinence rates. To determine a causal relationship, a different kind of study must be done.

The authors have some ideas about possible factors that could explain these findings. For one thing, there may have been selection bias in which medication was started. This was not the type of study where patients were randomly assigned the monoproduct versus combo product. Selection bias means that perhaps some unknown factor made the study subjects or their prescribers pick one form of medication over the other, and this factor is responsible for the difference in NAS rates.

The authors also suggested that there’s been a trend toward lower NAS rates in recent years compared to earlier years, and that coincided with the trend towards prescribing the combination product instead of the monoproduct. Maybe since both of those things happened at the same same time, it made it appear that the combination product was associated with lower NAS rates.

However, is it possible that the mothers on the combination product actually do absorb more naloxone that we have thought in the past? Is it possible that there’s enough naloxone in those moms’ bloodstream to affect the risk of withdrawal in the newborns?

We know some patients (not necessarily pregnant) complain of low-grade withdrawal symptoms when they take combination products of buprenorphine/naloxone. Some patients report headaches, persistent nausea, and body aches when taking the combination buprenorphine/naloxone sublingual products. These patients’ symptoms resolve on the monoproduct.

Many providers assume such patients are lying, trying to scam them to get monoproduct buprenorphine for some illicit intent. But perhaps sublingual naloxone in the combination product is more active physiologically than we think, causing withdrawal symptoms in susceptible patients, and causing less opioid effect in utero, and reduction of the risk of withdrawal in the newborn.

This issue desperately needs more study, both for pregnant patients with opioid use disorder, and for the patients who describe withdrawal symptoms with the combination product buprenorphine/naloxone.


Medication Interactions with Methadone and Buprenorphine






Patients being treated for opioid use disorder with methadone or buprenorphine often need other medications to treat chronic and acute medical conditions. When our opioid treatment program patients fill other prescriptions at retail pharmacies, the pharmacist might not know that the patient is on methadone or buprenorphine. Due to privacy laws, OTPs don’t report patient data to state prescription monitoring programs. That puts the burden on opioid treatment providers to watch for potential drug interactions.

I take that burden seriously.

Methadone, for various reasons, is more likely to have drug interactions than buprenorphine. Buprenorphine’s various pharmacologic properties reduce the risk of drug interactions. It has a high affinity for the opioid receptor, which means it’s not easily displaced off the receptor. Also, buprenorphine has a ceiling effect, so fluctuations in blood levels are less likely to cause sedation than methadone. Drug interactions can still occur, but not with the frequency or severity as with methadone.

Many medications interact with methadone, too many for me to reliably remember. I use a smart phone app to supplement my aging memory with up-to-date data. And if I can use these smart phone apps, believe me…anyone can. I prefer the Medscape app, though it’s only one of many. Other providers like Epocrates or others. If you work at an opioid treatment program and make dose decisions, I strongly recommend you get one of these apps, because there’s no way to remember or keep up with all new data.

Here are some of the main ways methadone interacts with other medications.


Any sedative medication can have an increased sedative effect when it is administered to a patient on methadone, or any other opioid, for that matter. Sedatives affect that ancient part of our brain that tells us to breath while we sleep. Opioids also affect that brain center, so when opioids and other sedatives are mixed, patients can fall asleep and stop breathing, which is how overdose deaths occur.

By far, the most commonly consumed sedative that my patients use, by prescription or illicitly, are benzodiazepines. However, other sedatives are just as deadly, and alcohol is a sedative drug too. Recently we’ve had more patients prescribe gabapentin (Neurontin) or its mirror-image molecule, pregabalin (Lyrica). These medications are commonly prescribed by primary care providers for just about any complaint of pain, anxiety, or anything else. When misused, or when taken with methadone, it can lead to impairment and even overdose.

I’ve railed against the inappropriate use of benzodiazepines so many times that even I get tired of hearing myself, so I’ll refer to reader to past blog entries. But let me just say that many patients being treated for opioid use disorder with methadone have been harmed by also taking benzos, prescribed or not prescribed. It’s a hazard that should be avoided if possible.

Cardiac Effects: prolonged QT interval

Methadone can prolong the QT interval in the heart. In the interest of not getting overly technical, let’s just say that the QT interval has to do with how the beats are conducted through the electrical system of the heart. If the QT interval lengthens past a critical point, it puts the patient at risk for a potentially fatal heart rhythm.

Many opioids can cause this, but methadone is probably the most well-known. Other opioids, like tramadol and oxycodone, carry some risk of QT prolongation, but usually not to a clinically significant degree. Some sources say buprenorphine can theoretically cause QT prolongation, but most experts don’t feel it’s clinically significant. In fact, if a patient on methadone develops QT prolongation issues, that patient is often recommended to switch to buprenorphine.

While methadone alone infrequently causes clinically significant QT interval prolongation, other factors can increase patient risk. For example, some patients with certain types of underlying heart problems may already be prone to QT prolongation and starting methadone could make this situation worse.

Many other medications also can cause QT prolongation. When these medications are started in a patient on methadone, the combination can cause significant QT interval prolongation.

For a recent list, go here: https://crediblemeds.org/pdftemp/pdf/CombinedList.pdf

As you will see, many common medications are listed. Common antibiotics, like cipro and erythromycin, cause prolonged QT interval and these are often prescribed to our patients. Many commonly prescribed mental health medications can prolong the QT interval.

What should opioid treatment providers do when a patient on methadone gets a new prescription for a medication which could critically prolong the QT interval? I’ve searched the internet and can’t find exact evidence-based solutions. But that’s not uncommon. Physicians often need to weigh decisions of risks and benefits of medications and act based on this.

First, I inform patients if there might be a problem. Next, I decide if the risk presented by the medication is so high that I need to ask the prescriber to change it. Or, if the patient is young and healthy, I might decide to check an EKG to monitor the QT interval. Lowering the dose of methadone can help reduce the QT interval, but at the risk of de-stabilizing the patient, so that’s rarely the best course of action.

Opioid treatment programs vary widely in their abilities to get and interpret ECGs. Thankfully, I’m trained in Internal Medicine and feel comfortable getting my ECG calipers to calculate the QT interval and yes, of course I correct for heart rate too.

Here are two examples of how I handled potential QT situations.

The first patient was young and healthy, and dosing with methadone at 95mg per day. He was started on ciprofloxacin for two weeks for an infection. The other prescriber had done a culture of the infectious situation and cipro was one of few antibiotics that the bacteria was sensitive to, so antibiotic choices were limited. I decided to check an ECG after my patient had been taking cipro for a few days, and the QT was fine. He was able to remain on the cipro until the infection cleared, with no problems

The second patient was older, nearly 50, with several chronic medical conditions including severe mental health diagnoses. A new psychiatrist changed his medication and started him on ziprasidone (Geodon), a medication infamous for causing QT prolongation. My patient was dosing at 115mg per day, and extremely fearful about any dose change. I did an ECG as soon as I knew he was on Geodon, and his QT interval was significantly lengthened. I called his new psychiatrist and explained the problem and she immediately switched him to a lower-risk medication. A repeat ECG done a few days after the switch showed his QT was back to normal, and he did well on this second medication, with good resolution of his mental health symptoms.

Drug affected methadone metabolism by the Cytochrome P450 System

Other drugs and substances affect methadone blood concentrations by influencing the rate of methadone metabolism. Methadone is an active opioid, while its first metabolite, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (called EDDP for short), is not pharmacologically active. That metabolic process is done in the liver via the cytochrome P450 (CYP450 for short) system. Many other medications affect this system.

Some medications that affect the CYP 450 system slow methadone metabolism and are called inhibitors. They can increase methadone blood levels and the opioid effect it has. Conversely, medications called inducers speed metabolism of methadone into its inactive metabolite, and thus can reduce methadone’s blood level and effect.

Of course, rising or falling methadone blood levels affects patient stability.

To add to the complexity, there are different types of cytochrome P450 enzymes. Several are involved with methadone metabolism, named CYP 3A4, CYP 2D6, CYP2B6, and CYP 2C29. And each enzyme’s activity is further determined by what genes we’ve inherited. Other medications that are metabolized by CYP3A4 are thought to be particularly prone to affect methadone metabolism and regarded with more caution.

So…it’s complicated. But as if that complication weren’tt enough, some scientists now say that though in the past we thought methadone was mainly metabolized by CYP 3A4, that’s old data, and now, we should be looking at drugs metabolized by CYP 2B6. In fact, in a recent article I read, “It has now been unequivocally established that CYP2B6, not CYP3A4, is the principle determinant of methadone metabolism, clearance, elimination, and plasma concentrations in humans.”  [1]

Also, some medications act as inhibitors of inducers of methadone in a test tube but not in real life.

What’s a doctor to do?

Again, I’ve searched the internet for evidence-based recommendations. Should we increase the patient’s methadone dose if he’s started on a medication that induces methadone’s metabolism? Or should we wait to see if the patient has symptoms before we change the dose? Conversely, should we decrease a patient’s methadone dose if she is started on a medication that inhibits methadone’s metabolism, in case her blood levels are going to rise? Or should we just prohibit the use of any medication that can affect methadone blood levels?

That last option, though it would make my life easier, isn’t possible. For example, nearly all mental health medications interact with methadone in some way or another. There’s no way for a patient to get treatment without using medications with the potential to affect methadone metabolism.

Same as with the QT interval problem, the degree of risk must be assessed for each patient. The degree of risk varies with patient medical history,  and the known risk of the inducers or inhibitors. For example, patients newly started on phenytoin nearly always have a clinically significant drop in methadone blood level. For those patients, I’ll make sure I have an order in place to increase their methadone dose with any symptoms of opioid withdrawal.

Most other cases aren’t so clear-cut. I’ll inform patients of potential risks and ask that they communicate with us regularly.

Almost all medications that treat HIV influence methadone metabolism, making it essential for the opioid treatment provider to communicate directly with the provider prescribing HIV medications.

In fact, good communication is essential with other prescribers and I try to cultivate a cooperative attitude with them, so far as it is possible with me.

Our opioid treatment program patients, particularly as they age, will be prescribed medication with possible interactions with their methadone. For their safety, each OTP must have a system in place that: 1. Gets patients to report new prescriptions as soon as possible 2. Gets that information to the program medical provider in order to make decisions about safety and monitoring 3. Informs patients of potential risks 4.  Arranges follow up meeting with medical providers when appropriate 5. Opioid treatment providers must collaborate with other prescribers when necessary

Each OTP needs a system that works for their facility, and methods can differ widely between OTPs. It doesn’t matter how we get the job done, just that it gets done.

Our patients’ safety depends upon this.

  1. Kharasch, “Current Concepts in methadone metabolism and Transport,” Clinical Pharmacology in Drug Devopment, 2019