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.

Sedatives

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

 

 

The Car Dosing Cart

Nurse Sylvia behind the Car Dose Cart

 

 

 

 

 

 

 

 

 

 

 

 

 

 

At our opioid treatment program, we’ve been dosing some patients in their cars, either because the patients have fragile health and we’re trying to keep them away from crowds, or because they have COVID infections, possible COVID infections, or have been exposed to someone with COVID infection.

In order to give more protection to our nurses while they deliver a dose to a patient in a car, one of our excellent employees, Jerry, created the Car Dosing Cart (Patent is pending.) as pictured above

As you can see, it’s made from a wheeled cart. Plexiglass sheets were attached to the front and sides of the cart, with a cut-out for a window just large enough to push a dose of methadone or buprenorphine toward the patient seated in the car. Just below the top level, there’s a second shelf where the patient can push their lock box onto the cart so that it can be filled with take home doses. The rest of the car is enclosed in plastic which is taped on three sides to the cart.

It’s genius.

The nurses feel protected while using it, and there’s enough surface area for everything they need. It’s wheeled, so it can be pushed easily out of the pharmacy, out our front door and to the curb outside. It’s the next best thing to a take-out window.

Per protocol, nurses never go by themselves to the parking lot to administer a dose. For security, another staff member accompanies him or her, both to discourage theft, and to provide a second set of eyes to vouch that the dose was given to the patient for whom it was intended. All of this is documented in the patient’s chart.

The idea for the Car Dosing Cart was born after a case staffing, when the staff asked me to allow car dosing for all our patients who work at a local poultry plant, after they had a large outbreak of COVID 19 infections.

I balked at this idea, feeling there were too many patients involved. I also worried the nurses would be more exposed to patients when dosing them in their cars. But as the number of cases at the poultry plant soared, I had second thoughts. I asked other doctors working at opioid treatment programs for advice. They recommended car dosing all poultry plant employees, who could unintentionally spread COVID infection. I backtracked my initial decision and we started to car dose many more patients.

That’s when Jerry invented the Car Dosing Cart.

Thus far, the cart is working very well. It’s stocked with everything the nurses might need, like cups, tissues, gloves, etc.

We will car dose patients for as long as the state allows, for as long as we have consistently elevated number of new cases of COVID 19 in our county and state.

I’m so grateful for the courage, compassion, and creativity of all our staff at our opioid treatment program.

Misuse of COVID 19 Extra Take Home Doses?

 

 

 

Opioid overdose deaths in North Carolina have risen recently, coinciding with the COVID 19 pandemic. Some state officials wonder if this increase is related to the increase in the number of take-home doses given by the state’s opioid treatment programs to our patients.

My own experience convinces me this increase is NOT related to opioid treatment programs take homes. When the toxicology results are known, I believe we’ll see the overdoses were due to fentanyl and its analogues, found in the heroin that’s currently being sold. I also think benzodiazepines will be a major contributing factor, possibly due to use fueled by anxiety brought by the changes the COVID 19 pandemic has brought to us.

We’re now three months into our COVID 19 response, so our OTP has given extra take home doses during this time. I’ve been pleasantly surprised at how few problems we’ve had. Thankfully, we’ve had no overdoses due to extra take home doses, and no deaths. Around half of our patients are on buprenorphine, and we were a little more liberal with extra take homes for those patients, given its better safety profile compared to methadone.

But we also gave many extra take homes to methadone patients, with no fatal outcomes, and so far, no overdoses.

Out of our present patient population of around five hundred and seventy-five people, only about a dozen have had problems with their take home doses. Of course, that’s probably the tip of the iceberg, since I’ll never know about most cases of medication diversion or misuse. But still, that’s much better than I expected. Other OTP providers report similar experiences.

In those dozen patients, most of came to my attention when they returned early to dose on site with us. Most returned a day or two early, saying they had no idea what happened to the doses for those days.

Why did I expect more medication misuse than we had? I worried because one of the hallmarks of addiction is loss of control. I worried that especially for patients relatively new to treatment, we could be setting them up to fail, by giving them more doses than they were used to managing. However, we had to weigh that risk against the risk of spreading COVID 19 to patients if we had a lobby full of patients dosing daily.

I underestimated my patients. Recovery is about regaining control and learning to manage impulses to misuse medications. Most patients rose to the challenge and took the extra doses just like prescribed. These extra take homes helped keep patients from crowding at the opioid treatment program and gave them more freedom to dose at home and stay safe.

Repeatedly, patients have voiced appreciation to our staff for the extra take homes and the other safety precautions enacted at our opioid treatment program. I’ve had ten or twelve people tell me they appreciated that our opioid treatment program was able to act to quickly to issue extra take home doses. I tell all of them it wouldn’t be possible without cooperation from our governmental agencies. Our state opioid treatment authority (SOTA) held frequent teleconferences early on and throughout the last three months to answer questions and give advice for how best to help patients dosing at opioid treatment programs. Our state’s Department of Health and Human Services has been very supportive of actions necessary to allow patients more freedom to dose at home, where they are safer.

Curiously, some patients told me they expected our opioid treatment program might close during COVID and they would be” out of luck” regarding dosing on their medication. That hurt my feelings a little bit. I told them we are a medical facility and of course we would remain open. We have remained open for business as usual with no change in our hours through the past three months.

Of course, catastrophe can hit anywhere, but each OTP is required to have an emergency plan for continued care of patients to limit disruption of care. If, for example, our OTP disappears into a giant sinkhole, (This is a thing in North Wilkesboro. One Taco Bell was eaten by a sinkhole but that’s an oddity for another time.) we have plans to get our patients dosed at a nearby facility until we are open again.

Our county had an outbreak of COVID 19 at the local poultry plant. According to the newspapers, around one-fourth of the two or three thousand workers tested positive for COVID 19. Fortunately, many didn’t have symptoms, but others got plenty sick. Thankfully, by now most have recovered and are back at work. If we had not given extra take homes, we could have had a catastrophic COVID outbreak at our opioid treatment program.

We’re not out of the woods yet. In fact, in North Carolina, we are still in the first wave on infection. The total number of people with COVID infection has risen, of course, with the increased number of tests done. However, more critically, the number of patients hospitalized with COVID has risen to an all-time sustained high. Every day last week, we broke records for the number of hospitalized COVID patients. This is an important indication of the burden of serious COVID illness in the state.

We are all sick of COVID. I am sick of hearing about it, talking about it, thinking about it. I’m sick of wearing a stupid mask and I’m tired of wiping my keyboard, cell phone, and stethoscope over & over. My hands are chapped from washing and using hand sanitizer.

But now is not the time to stop taking precautions.  We can’t let up know, at least not in my area, with increasing cases. We need to continue all the common sense precautions like social distancing, mask wearing, hand washing, etc. And we must continue to give take home doses to patients so they can stay safer at home. As far as I know, there are no plans to revoke the exception that allowed the emergency take home doses.

At our opioid treatment program, we will continue to monitor patients as best we can. We will continue to balance the safer-at-home strategies behind the extra take home doses with safety concerns about medication misuse. We will keep a watchful eye, but I do not think these doses are behind the uptick in opioid overdose deaths. As I said above, once the toxicology reports are back, we’ll have more information.

COVID Scare

Cartoon style illustration of a sign or symbol that says ban, stop coronoavirus or COVID-19 being stamp out and prohibited on isolated white background.

 

 

 

I’ve had a rough week.

I’ve been so careful. I’ve worn an N95 mask every day at work, removing it only briefly when I need to eat or drink. I’ve wiped my office multiple times per day with cleaning wipes, not forgetting my cell phone, computer keyboard or door handles.

I haven’t gone anywhere, except once to the pharmacy for my blood pressure pills, and even then I used their drive- through. And I made several short trips for groceries, wearing my mask while inside.

That’s why I was so surprised when, shortly after going to bed one night early last week, I got a shaking chill more suitable to being on an icy Tibetan mountaintop rather than my snug bed.

It grew worse. I ached in every part of my body. I was too cold to get out of bed for more covers but eventually had to do so. While I was up, I went to the bathroom and ratted around trying to find a thermometer.

When I found one, my temp was 98.8. I laughed at myself. I am such a silly goose, imagining I’m ill when I’m not. But my symptoms continued with my chills and when I checked again a half hour later, the thermometer read 101.2.

My beloved fiancé was asleep in the bed next to me. I had to get some distance between us and moved to the upstairs guest room. I didn’t want to make him sick. I took some Tylenol and tried to get some sleep. But then the dry cough started, and later, some diarrhea.

As I lie in bed, feeling like I was wearing a jumpsuit of muscle aches, I thought, “This is it. I’ve got The COVID.” (That’s the way we say it here, “The COVID,” not COVID 19 or Coronavirus.)

I didn’t sleep any that night, and the next morning told my fiancé to stay away, I was sick. I sent emails to work supervisors telling them of my condition and that I could not come to work. My fiancé arranged COVID testing for the next day.

My fever jumped between 100.4 and 101.9 even with generous amounts of Tylenol and Advil.

But then the diarrhea got worse. My sweetie said, “Maybe you just have one of those 24 hour stomach flus.” I pooh-poohed him. I felt too bad for this to be a mere GI virus. Besides, the fever was lasting much too long for that and I had no nausea.

Then, about 48 hours after it started, I felt better. My fever started to come down, though the diarrhea grew ferocious. The cough never developed into anything. I took my COVID test and two days later, got the results: NEGATIVE

All I suffered from was  probably viral enteritis and a vivid imagination.

It’s easy to get carried away with any illness in the middle of the COVID 19 pandemic, especially if it’s accompanied by fever. At one point, I wrote my last will and testament. I laugh about it now, but I felt so bad, and my pessimism seemed to rise with my fever.

At least I got a chance to see what wonderful people are in my life.  At work, I was told not to worry about anything, and arrangements were made for another physician to do admissions for our OTP. I still handled the minor things by phone. My co-workers sent me encouraging emails and prayed for my wellness. My fiancé took great care of me – at a distance of course – and friends and family brought food and sent funny emails.

Right now, I feel very, very grateful. I’m now in my usual state of good health, which is wonderful. I’ll be able to get back to work this week, at a job I enjoy, with people I love. I have fantastic friends and family, and my life partner, the love of my life, didn’t get sick because of me.

And I don’t have The COVID.

Methadone Induction: Be Careful

Graphic illustrating how methadone blood level rises over five days with no dose change

 

 

 

This blog is written with gratitude to Thomas Payte M.D., a leader in the field of Addiction Medicine, who passed away in 2019.  Many years ago, I listened to an ASAM (American Society of Addiction Medicine) lecture by Dr. Payte (on cassette tape, which shows how long ago this was) that changed the way I did methadone induction.

At the time I started working at an opioid treatment program, I felt much empathy for the patients suffering opioid withdrawal when I admitted them to treatment. With the best intentions, I wanted to help them get out of withdrawal as quickly as possible, so I started them at doses higher than I probably should have and increased their doses daily. The other physicians I worked with practiced in a similar way, so I thought that was the way it should be done.

We had patient induction deaths. I learned some things the hard way, but also started going to ASAM conferences and listening to ASAM lectures, which was when I had the good fortune to hear Tom Payte.

Decades later, I can’t be sure exactly what he said, but this is what I remember:

He cautioned that induction deaths were relatively rare but devastating. If we start every patient on 30mg, eventually a patient will die during induction. That shook me up, because not only was I starting patients on 30mg, quite often I was dividing their dose on Day 1 to get a total of 40mg. He said patients inherently metabolize methadone at very different rates, and sooner or later a slow metabolizer would arrive for induction, and rapid increases in dosing during induction would be fatal.

Dr. Payte wasn’t unsympathetic to patient misery in opioid withdrawal. He just reminded me that we must temper compassion with science.

Today, induction guidelines look very different from the way I was practicing back when I started. I have changed my induction practices a great deal over the years as I’ve learned more.

Physicians who work at opioid treatment programs have so much more information available now than when I started in this field. It’s so easy to get colleague input about problems: at a national level, there’s the PCSS system, which stands for Providers Clinical Support System, a system for providing information and even mentors for providers who would like them (https://pcssnow.org/)

At our state level, the North Carolina Governor’s Institute has contracted with me and with Dr. Eric Morse, so that we can be available for questions from providers at any opioid treatment program in the state at any time.

Recently, at an organizational level, our Acadia programs in North Carolina arranged for a monthly phone call for physicians and physician extenders to discuss problems and concerns on a monthly phone call.

ASAM has all sorts of guidelines and position statements (asam.org). SAMHSA has publications to help physicians (https://store.samhsa.gov/)

Because of all this help that’s available, there’s no reason for any provider working at an opioid treatment program in the U.S. to be ignorant of current methadone induction recommendations.

I recently blogged about ASAM’s newly updated guidelines for the treatment of opioid use disorders. In those guidelines, initial dose of methadone, “ranges from 10 to 30mg, with reassessment as clinically indicated (typically in 2 to 4 hours)…” and then goes on to say, “methadone…generally should not be increased every day.” The guidelines recommend methadone be increased no more than 10mg approximately every 5 days.

If you are a provider who is starting every patient at 30mg and then increasing the dose daily, stop it. You are going to have an overdose sooner or later.

And although these guidelines did say that benzodiazepine use should not be a reason to suspend or withhold treatment with methadone or buprenorphine, they did make it clear that use of sedative-hypnotics with these medications increases the risk of serious side effects.

In other words, we shouldn’t deny treatment to patients with a co-occurring benzodiazepine use disorder, but we can’t admit them and carry on like their risk is the same as other patients who aren’t on benzodiazepines. Consider lower methadone starting doses and consider slower rates of induction for these more fragile patients. Consider closer observation and more frequent drug screening

The provider has a lot more work to do when a patient is using benzodiazepines. First, that provider needs to figure out, if possible, how extensive that patient’s use is, and decide the appropriate setting for methadone induction. That may need to be at an inpatient facility.

Second, since benzodiazepine prescribing guidelines recommend these medications not be prescribed for longer than three months, except for end-of-life care, an ongoing prescription must be explained. The prescribers of benzodiazepines must be talked to. In my area, most of the benzodiazepines are prescribed by a handful of practitioners.  When I talk to these prescribers, they say the patient complains of anxiety, indicating they think this justifies ongoing benzodiazepines.

That’s not good enough. Benzodiazepines aren’t first-line medications for anxiety disorders. Like opioids did for pain, it appears benzodiazepines make people more anxious when they are used long-term. Benzodiazepines make post-traumatic stress disorder worse, and they complicate ordinary grief reactions. Yet many patients are prescribed benzodiazepines for these reasons.

Third, a plan must be formulated to reduce the risk for the patient. In most cases, this means a reduction in benzodiazepine use by some method. If the patient can control their use of benzos, their prescriber can gradually lower their dose. Most of the time the patient can come off benzodiazepines, or at least get by with much less of these medications. In the meantime, a more appropriate medication for anxiety can be started for better treatment of anxiety.

In many cases, the patient needs trauma-focused therapy to address old issues. Many, perhaps most, of our patients have experienced serious physical, sexual, or emotional trauma in their lives. Appropriate counseling and medication can be just as life-changing for patients as can treatment for their opioid use disorder.

Since alcohol is as big a risk as benzodiazepines, the same cautions during methadone induction need to be taken for patients with alcohol use disorders. Start with lower doses and increase more slowly.

More cautious induction must be considered for medically fragile patients: those with underlying pulmonary disease, lower body weight, those on multiple medications, and the “elderly” over fifty years old. And be sure to ask about opioid use over the preceding week. If a patient was admitted to a detoxification unit, or just got out of jail or a hospital, their opioid tolerance will be lower, and the patient needs a lower methadone starting dose.

If their admission drug screen is negative for opioids, stop for a moment to consider what this means. Does the patient really have opioid use disorder? Has the patient taken an opioid recently that doesn’t show on your drug screen? Or has the patient been unable to use opioids for the last several days? If the latter is true, consider a lower starting dose.

Don’t do cookie-cutter inductions. Carefully evaluate each new patient and gather all the data that you can, including history and physical, old records, the prescription monitoring program, and other treating physicians to help you make the best decisions possible. There will always be that pull…trying to get the patient out of opioid withdrawal so they can stop using dangerous illicit opioids….while trying to provide safe methadone induction.

I’ve written mostly about methadone induction because it’s much trickier than buprenorphine. Methadone is much less forgiving during induction than buprenorphine. With buprenorphine induction, just make sure you don’t start too soon and make your patient sick. At times I wish all my patients could do well on buprenorphine, but that’s not possible. We will never have one medication that works well for everyone. Many patients never feel right on buprenorphine, or it isn’t strong enough to treat their opioid use disorder.

I’m more cautious with methadone induction prescribing now than when I started many years ago. This is from a combination of experience and learning from experts. I strongly recommend the latter form of learning; it’s much less painful.