Author Archive

Stop Sharing Medication!

 

 

 

 

 

I read a tragic article in my local paper today. A young man pled guilty to involuntary manslaughter and received a sentence of four to seven years. The article said he gave another woman a prescription opioid pill, and she died after drinking alcohol after taking the pill. He was prosecuted for her death.

The article went on to say that if a person gives or sells another person an opioid pill (or any other controlled substance) and that person dies as a result of ingesting that medication, involuntary manslaughter or second-degree murder can be charged.

People don’t realize it’s illegal to share their prescribed controlled substance medication with other people. The law says it doesn’t matter if you sell it or just give it to someone else…it’s illegal.

I can’t tell you how many times I have a patient test positive on a drug test, and they tell me they were offered a Xanax at a funeral, or a Vicodin for muscular pain from a relative.

This is not OK.

I’ve had people tell me that once they pay for and fill their medication, it should be theirs to do with what they want. That’s not true. It is a felony to give or sell that medication to anyone besides for whom it was prescribed.

So that old Lortab pill you have in your medicine chest…don’t be tempted to give it to your brother when he has a migraine. You don’t know what other medication he’s on, and you can’t know if it is safe for him. And if he dies, you could be charged with a felony, on top of the guilt you would feel for contributing to his death.

Numerous studies have also shown young people who develop opiod use disorder often get their first opioids from friends or relatives. Parents spend energy worrying about their children being approached by drug dealers, but it’s far more likely that the first opioids used by their children will be obtained from someone’s medicine cabinet.

This means it’s important to change cultural attitudes about sharing medication and saving medication.

 

 

News You Can Use

 

 

 

 

 

 

 

 

New ACOG Recommendations:

The American College of Obstetrics and Gynecology (ACOG) just released an updated recommendation about the treatment of opioid use disorder in pregnant women: https://www.acog.org/Resources-And-Publications/Committee-Opinions/Committee-on-Obstetric-Practice/Opioid-Use-and-Opioid-Use-Disorder-in-Pregnancy

Their last statement was issued in 2012, in cooperation with the American Society of Addiction Medicine (ASAM). This newer statement was released earlier this month, also in cooperation with ASAM.

By my reading, this update is more direct about recommending medication-assisted treatment for pregnant women with opioid use disorder, and specifically discouraged medically supervised withdrawal from opioids during pregnancy.

This statement was in the update’s conclusions: “For pregnant women with an opioid use disorder, opioid agonist pharmacotherapy is the recommended therapy and is preferable to medically supervised withdrawal because withdrawal is associated with high relapse rates, which lead to worse outcomes. More research is needed to assess the safety (particularly regarding maternal relapse), efficacy, and long-term outcomes of medically supervised withdrawal.”

I suspect this released update may have been prompted by the actions of obstetricians in certain locations (Tennessee, for example), where medically supervised withdrawal is routinely recommended by obstetricians. As you recall in a blog earlier this summer, I showed you a letter written by OBs from TN, recommending “medically supervised withdrawal” for patients on medication-assisted treatment of opioid use disorders.

As the ACOG update emphasizes, there’s scant evidence to show medically supervised withdrawal provides any better outcomes for the baby, but certainly places the mother at risk for relapse.

I am pleased to see this update, and plan to mail it to a few obstetrics practices in my own area. Some OBs may be giving patients recommendations not supported by their own professional organization out of ignorance, in which case more information can help. Other OBs do it for ideological reasons, in which case I doubt any amount of information can help, but at least I’ll know I’ve tried to do something.

Screening for substance use disorders was also strongly emphasized in the new document, with specific recommendations about how this should be done. In other words, asking a pregnant patient, “You don’t take any drugs, do you?” is not considered to be adequate or recommended screening.

Increased Risk for Death in Patients with Opioid Use Disorder who Leave Buprenorphine Treatment

We have multiple studies, dating back decades, showing patients with opioid use disorder who leave treatment with methadone have higher risks of overdose deaths. We believe the same thing is true with buprenorphine treatment, but now we have more data to support that assumption.

A French study of 713 buprenorphine patients showed that being out of buprenorphine treatment was associated with a 30-fold increase in death, compared with patients who stay on buprenorphine treatment.

Now that’s impressive.

This was a study done in France, where most patients with opioid use disorder are treated by general practitioners in private practice. This would be roughly equivalent to what physicians do now in the U.S. in their office-based buprenorphine practices, often called OBOT treatment.

The study was published in the July/August 2017 issue of the Annals of Family Medicine, by Dupouy et al. It looked at new patients admitted onto buprenorphine treatment from early 2007 until the end of 2011, and covered over 3,000 person -years of treatment.

The authors say that the data showed, “…being out of treatment was associated with sharply elevated mortality risk.”

We already knew that people with opioid use disorder have an increased risk of death. Early in this article, the authors state that the accepted mortality rate of untreated heroin use disorder is around 2 people per 100 patient years. This means that if you follow 100 heroin users for a year, it is likely that 2 will be dead at the end of the year. An older study, by Hser et al., followed people with opioid use disorder over time, and found that around 50% were dead at 30 years.

We’ve had other studies that show being in treatment with buprenorphine or methadone decreases risk of death, but this may be the first study showing that getting help in a primary care setting reduces the risk of death so remarkably.

This was a very large study, so the data is more impressive to me All this data supports the conclusion that opioid use disorder is a serious and potentially fatal disease, and that being in medication-assisted treatment markedly reduces the risk of death.

 

Medicaid’s Limits for Non-compliance

 

The opioid treatment program where I work accepts Medicaid as payment, starting a few years ago. Overall, it’s been so beneficial for hundreds of our patients. However, when Medicaid patients have repeatedly positive drug screens, Medicaid overseers threaten to cut off their funding for treatment.

Our state’s Medicaid system is divided into counties, and these counties contract with agencies to provide oversight for the mental health and substance abuse treatment dollars. I’ve had several conversations with the doctors who do peer review for payment to our program.

We discuss patients’ progress, and whether more Medicaid money will be approved for their treatment. This agency says they have the right to cut off payment for treatment of Medicaid patients who don’t become drug-free within a reasonable period of time. So far, they haven’t cut off payment for any patients, but we have many patients at risk for this. If patients lose Medicaid coverage, they can remain in treatment with us, but have to pay out of their own pocket.

I feel torn about this issue.

On the one hand, I know my patients will do better if they are able to stay in treatment on MAT. If Medicaid quits paying for their treatment, many will leave treatment and go back to illicit drug use. I know from various studies that patients who leave MAT have high relapse rates. Relapses back to illicit opioid use can cost more to the Medicaid system than staying in treatment. Plus, patients who leave treatment are at greater risk of overdose death.

On the other hand, as a taxpayer, I understand why people object to using tax dollars, in the form of Medicaid, to pay for addiction treatment if the patient is still using illicit drugs. Some people may feel this is a government subsidy to continue drug use.

Most people feel we do have an obligation to the disabled and the poor to provide medical care. But should we apply different criteria for payment of substance use disorder compared to other chronic medical illnesses, which also have behavioral components?

The doctors who decide when to stop paying for MAT could use similar criteria to decide when to stop paying for other medical care of chronic illnesses.

Imagine this conversation:

“Hello, this is Dr. X. I am calling regarding approval of payment for the treatment of Mrs. Sweet, the diabetic you are seeing. I’ve authorized ninety days more of payment for her, but if her blood glucose readings and her hemoglobin A1C don’t improve, I will be recommending we stop paying for her treatment. She will have to pay for her diabetic medication and her medical care from her own pocket.”

“I don’t understand. I’ve been treating Mrs. Sweet for years…her diabetes is about as well-controlled now as it has been for years.”

“Our point exactly. She isn’t showing any improvement. You told her to follow a diabetic diet, lose weight, and exercise, and she hasn’t done any of these things. If she’s not willing to follow physician recommendations, Medicaid won’t approve payment for the medical care she needs for diabetes.”

Can you imagine the outrage at such a decision?

Let’s use an example of another chronic illness: heart disease. Let’s say I have a patient who has coronary artery disease. He had one heart attack and had to have a coronary stent placed. He has very high cholesterol, but despite dietary instructions, he continues to eat fatty foods and plenty of red meat. He also isn’t compliant taking his cholesterol medication.

He has another episode of chest pain, goes to the hospital, gets admitted with another heart attack, but the Medicaid overseers say his medical care will not be paid for, since he hasn’t made the changes recommended by his physician.

Are these scenarios starting to hit a little close to home?

Let’s be careful when we start deciding who deserves or doesn’t deserve to have their medical treatment paid for, if we use behavioral change as the yardstick for such decisions. Few of us with chronic illnesses do everything perfectly.

It’s part of human nature.

Book Review: “American Pain,” by John Temple

 

This nonfiction book, published in 2016, describes in amazing detail the rise and fall of one of the biggest of South Florida’s pill mills, named American Pain. The book reads as easily as a novel. It describes the casual criminality and greed that fueled one of our nation’s biggest drug overdose epidemics.

The book starts by describing how a felon, his twin brother, and a body-building buddy decide to open a pain clinic. They hire doctors to work there, but still manage clinic, in appallingly unprofessional ways. These owners and managers show a shocking lack of concern for human life and the suffering they saw daily. For example, they talk derisively of their customers as “druggies” and “zombies,” yet the owners were also drug users. Bribes were taken for all sorts of unethical activities, from advancing a patient through the line more quickly, falsifying drug screen results, or getting the patient seen by a doctor with a reputation for being a generous prescriber.

This pill mill saw mostly people from Appalachia – as the book points out, 43% of the clinic patients lived in Kentucky, 20% in Florida, 18% from Tennessee, and 11% from Ohio.

The methods developed by the addicted patients and their handlers were astounding. Appalachian families who in the past may have distribute moonshine, marijuana, or methamphetamine used the same organizations to distribute these pain pills transported out of Florida. People called “sponsors” would arrange for a group of people to come to American Pain, located in Broward County, Florida, sometimes traveling hundreds in buses or vans or just carloads of people. Each of these people would be given money by the sponsor to be seen by the physician and to buy the pain pills and benzodiazepines dispensed on site. They gave a portion of these pills to their sponsor to be sold through the networks of drug dealers already established, or they could give all the pills to the sponsor in return for a tidy profit.

Some airlines offered cheap flights from the Appalachians to Florida. So many pain patients flew on one flight that it was called the “Oxy Express.”

MRI owners and operators profited because the pain clinic made every patient get an MRI, to maintain a veneer of medical respectability. Patients could bribe their way to the head of this long line, too. Pharmacies profited, as long as they didn’t ask too many questions. Many times, the pain clinics had their own pharmacies and dispensed on site, to make yet more money and to keep legitimate pharmacies from asking uncomfortable questions.

Flea markets in Kentucky sold urine in Mason jars to pain clinic patients who were required to pass a drug test. Dive motels in Florida rented rooms to “oxy-tourists,” and some overdosed and died in these places.

Between 2007 and 2009, Broward County went from having four pain clinics to having one hundred and fifteen. In one area, there were eighteen pain clinics within a two mile radius.

Everyone was happy; the people with addiction got more pain pills to inject or snort, the sponsors made money, the doctors made money, and the clinic owners made staggering amounts of money.

Of course, in the long run, irreparable harm was done. Patients of the clinics died, people who bought pills from American Pain patients died, and families suffered from the deaths of their loved ones. Many people were incarcerated, children were put into foster care, and medical costs of complications from addictions soared. The cost to taxpayers and U.S. social fabric can never be calculated.

Police routinely pulled over cars traveling north on the interstates if they had Kentucky, Tennessee, or West Virginia license plates and were filled with people. Usually, some crime could be detected. If one person had pill bottles from multiple doctors, this was the crime known as doctor shopping. If a pill bottle had too few pills remaining, the owner could be arrested for drug dealing. Many times, there would be drug paraphernalia in the vehicles. The driver could be impaired.

The book is painfully funny in places; the manager of the pain clinic describes what he calls “addict stunts,” like when an RV filled with three generations of a family from Appalachia rolled into their parking lot, spread an outdoor carpet on the asphalt, and set up folding chairs and a grill, planning to make a day of it at the pain clinic. It was a family outing, going to a Florida pain clinic to get pills to fuel one’s addiction.

Pain clinic patients would pee in the hedges, fornicate near other businesses, and shoot up in the parking lot, all of which appalled the owners, who were trying not to attract attention.

The owners even asked themselves, “How could this be legal?” But it was.

Apparently Florida didn’t have any corporate practice of medicine laws, which prevents non-physicians from owning any medical facility. I’ve derided these types of laws in the past, but here’s one situation which cried out for this kind of law.

Florida also had no prescription monitoring program, as I pointed out in my blog of March 8, 2011. Long after Florida’s pain clinic problem exploded, their governor inexplicably blocked development of a PMP. They have one now, but only after Purdue Pharma (manufacturer of OxyContin) offered money to the state to start one.

Florida also allowed physicians to sell pain pills and other medication directly, without involving a pharmacy. This allowed much of the mis-prescribing to go unnoticed.

Of course, things finally ended badly. The FBI got involved, and did investigations, undercover work, and eventually got wire taps to prove RICO indictments of all the main people. After they were arrested, the owners and operators, who talked big about how they would never turn on each other, all ratted on each other to get favorable plea deals.

The main owner got 14 years in prison for his part in the scheme that earned him 40 million dollars, and his twin was sentenced to 17 years in prison. Their friend, the manager of American Pain, was sentenced to 14 years.

All but two of the physicians took plea deals, and most lost their medical licenses and had various criminal penalties.

The two doctors who refused to take plea deals were both charged in the deaths of patients who had overdosed on medications these doctors prescribed. Both doctors said they had no idea they were working for a pill mill, and the juries acquitted both of them

However, they were both convicted of money laundering, under the premise that they would have to be willfully blind not to know the operations of this place weren’t legitimate medical care. Prosecutors said the doctors had to have known they were prescribing to people with addiction or people who intended to sell their pills. In one doctor’s case, she would see in excess of sixty patients per day, and was the largest prescriber in the nation for certain drugs.

She also made 1.2 million dollars in just the sixteen months she worked there. That last fact alone is so far out of line for what legitimate physicians make in that same time period that she had to have known she was committing crimes. She was sentenced to 6.5 years in prison.

The only other physician not to take a plea deal made around $160,000 for working at the pill mill, and was sentenced to 18 months in prison.

This is a fascinating book, about an incredible time in Florida’s history. Of course, as the book illustrates, Florida’s problem bled into other states, and poured gasoline of the raging fire of opioid use disorder that already existed in Appalachia.

The book illustrated the mindset of people who operate such pill mills, their derision towards the people who are making them all this money, and their disregard to the human misery caused by addiction.

One of the most poignant scenes in the book is when the mother of a young man who dies of an opioid and benzodiazepine overdose goes to talk to the doctor who prescribed him the pills. This mother left the hills of Kentucky and drove to Florida for the confrontation. But the doctor said nothing, only looked downward to the floor. For what could she say? Under the best light, she was guilty of willful blindness, and under the worst, something much more sinister.

The events in this book took place not even ten years ago, and we were about ten years into the opioid epidemic when American Pain opened its first clinic. The owners and operators and doctors weren’t the only ones at fault. Why did it take Florida so long to get an operational prescription monitoring program? Why did their governor, Rick Scott, block efforts to establish this important program? Where was the state’s medical board, and why didn’t they investigate the doctors’ actions at American Pain?

I highly recommend this book to anyone interested in the opioid use disorder situation in the U.S., to get better insight into how it started and how it was perpetuated

 

Mismanagement of Opioid Use Disorder

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I’m going to give an overview of what happened to one patient with opioid use disorder, changing enough details to keep people from recognizing the person. I’ve changed non-essential data, but not the medical facts as I learned them from the patient. The facts were confirmed by medical records that I obtained from two local hospitals, a local cardiologist, and a teaching hospital. I could not get records from the mental health clinic that is mentioned because none were made. All of this happened a few years ago.

This 31 year-old man had years of opioid use disorder which progressed to intravenous use for a little over a year before he started feeling ill. He went to his local hospital and was correctly diagnosed with endocarditis, which is a serious and life-threatening infection of the delicate valves of the heart. He was transferred to a teaching hospital, had a surgical repair of a heart alve, given six weeks of antibiotics, and sent home.

He says no one mentioned any sort of addiction treatment, but he admits he probably would not have agreed to treatment anyway. He also admits it’s possible he just doesn’t remember and treatment was discussed. His records contain no mention of substance use treatment referral upon his discharge from the hospital.

About a year later, he was re-admitted to our local hospital with fever and suspected endocarditis. His attending physician in the hospital started treatment with appropriate antibiotics but correctly identified he needed to be seen by a specialist too. As his medical record reveals, two teaching hospitals refused to accept this patient in transfer because he had no insurance, no money, and because he didn’t quit using drugs after the first illness. The physicians that could have accepted the patient in transfer said they don’t want to waste resources treating him again.

His admitting physician explained all of this to the patient. Since it appeared he would die without surgery, Hospice care was arranged to ease his remaining days. He was sent home to die. Somehow, qualifying for Hospice care also got him approved for Medicaid.

After his Medicaid came through and he’d been on antibiotics waiting to die for some weeks, he started wondering what would happen if he arranged an appointment with a cardiologist on his own. Since he now had Medicaid, he was able to make an appointment with a local cardiologist. Though he hadn’t died yet, he was very sick, with fluid building in his lungs and backing up into his feet and legs.

I got the cardiologists’ records, and between the lines I could sense he had been as puzzled as I was now– why was this man turned down for medical care? The cardiologist correctly suspected the patient didn’t have a severe endocarditis, since he probably wouldn’t still be alive at that point. He arranged a referral to a cardiologist friend of his at the local teaching hospital, and a more sophisticated evaluation was done. It showed a hole in the patient’s heart. Blood was flowing in the wrong direction, causing heart failure and severe shortness of breath.

The patient was admitted to the hospital and had a procedure to patch this hole. As it turned out, this procedure could be done without open-heart surgery.

All is well, right? Nope. The original problem, opioid use disorder, has still not been comprehensively treated, although this teaching hospital did at least give this patient a few days of buprenorphine during his short hospitalization. He was told to follow up with a Suboxone doctor in his area.

He tried. He called several office-based buprenorphine physicians in his area. But he had Medicaid, and couldn’t find a doctor to accept this form of payment, or else the few that did accept Medicaid didn’t have appointments for many weeks.

He relapsed to intravenous opioid use, and became sick with fever, had trouble breathing, and went to his local hospital’s emergency department. He was given some fluids, some antibiotics for “pneumonia,” and told to go home.

Before he left, he asked if he could be referred for treatment of his addiction, and was told he would have to go to the local mental health provider that contracts with Medicaid in his county.

He went in person to that facility the next day, and asked the receptionist if he could be referred to the local methadone clinic. He was told they didn’t make referrals to the methadone clinic, so he left, discouraged. He never imagined it could be so hard to get treatment for his addiction.

He continued to feel very bad, with fevers, cough, and then developed severe back pain. He went to another local hospital’s emergency department, was again told he had pneumonia, and that he needed different antibiotics. He was sent home from the emergency department, but went back a few days later, when his back pain worsened.

He says he got the feeling the hospital personnel felt he was drug seeking for pain medication. He admits he did want pain medication, but mainly because of severe back pain. He was told to be patient, and give the antibiotics time to work.

The day before he came to our opioid treatment center, he went back to the first local hospital with fever, back pain, and trouble breathing. He was told for a fourth time that he had pneumonia, and was sent home with new antibiotics.

He got the address of our opioid treatment program from one of his friends, and came in person to see if we could help him. Since I wasn’t there that day, we set him up with an intake appointment for the next day, and he arrived bright and early to start the intake process.

When I first laid eyes on this patient, my impression was that he was seriously ill and not stable enough to start treatment with us that day. He looked bad. However, I listened with fascination to his entire story, which he told in short bursts of conversation between gasping breaths.

I didn’t want to start treatment. I wanted to get him to a teaching hospital as quickly as possible. He was sweaty, breathless, wincing in pain and clutching his back, and running a low-grade fever. He did have sounds in his lungs consistent with pneumonia, but at this point he’d been on antibiotics for over a week. Clearly something more than pneumonia was going on.

But I knew I could not turn him away without doing something for him. More as a gesture than as a real treatment, I gave him an induction dose of buprenorphine and sent him to the teaching hospital, located about an hour from us.

I got a call back later that day from the resident physician who admitted this patient. The severe back pain that my patient had reported at four hospital emergency department visits turned out to be osteomyelitis, which is a bacterial bone infection needing antibiotic treatment for several months. He also had an abscess on the spine nearby the infected bone. The bacteria they finally cultured was methicillin-resistant Staph aureus, also known as MRSA.

He spent months in several hospitals. He had to undergo a debridement of the bone to get rid of infected and dead material, and had to be on very heavy intravenous antibiotics for a prolonged time.

Because he had been started on buprenorphine at our opioid treatment program, I convince the residents they could continue that medication, and gave some suggestions for increasing it a little bit.

Finally, he was healthy enough to leave the acute care hospital to go to a physical rehabilitation hospital, where he stayed for about six weeks. Thankfully, since he had already been started on buprenorphine, these providers were also willing to continue his medication. He was re-admitted to our opioid treatment program the day after he was discharged from the physical rehab hospital so that we could continue his treatment.

He had to have strong opioids early in his hospitalization but by the time he came back to our OTP, he was only on buprenorphine 8mg sublingually per day. I did have to increase his dose a little for fine-tuning, and he’s been healthy ever since, with no positive UDS, no illicit drug use.

He looks fantastic. He’s healthy, energetic, and works every day. He’s usually smiling, and he makes me smile too. I don’t think he’s using any illicit opioids for many months.

He asked me a difficult question. He wanted to know how his medical treatment could have been better. I told him that I had the luxury of hindsight and the pile of his medical records, but I did see some mismanagement of his care. I told him these were the things that bothered me about his treatment:

  1. He was turned down for medical care when he came to his local hospital for what they thought was endocarditis. It turned out to be something different, but the small hospital didn’t have the technology to diagnose and manage the problem. They did the right thing by attempting to transfer him to another hospital, but were refused. I don’t know what recourse a physician at a small hospital has if teaching hospitals refuse to accept a patient, and I’m sure this patient was refused because he had drug addiction, and judged as a person not worthy of care.
  2. There was an appalling lack of attention to his underlying medical disease that fueled all of his medical problems. He should have been told about buprenorphine and methadone as treatments for his problem, and referrals should have been made. Ideally, he should have been referred after his endocarditis infection, or by any of the half-dozen doctors who saw him after that. Then even when he specifically asked for referral for that sort of treatment, the mental health facility missed an opportunity to help this man, saying they didn’t refer to the methadone clinic.

Believe me, we notified people who supervise this mental health facility about their failure to act, and what we thought of this failure. We have been assured this will never happen again.

3.This patient sensed an attitude of distain in his caregivers, and I also sensed it in the wording of the documents from the hospital. The emergency department records are sketchy, with little documentation of the medical reasoning of the attending physician. I worry that the physician saw the patient as a bad person seeking drugs, rather than a sick person with a treatable illness. I know I’m sensitized to this issue, so it’s possible I’m jumping to the wrong conclusion.

I’ve tried my best to talk to local physicians. In a few enjoyable exceptions, I’ve had great responses and cooperation. In other cases, I’ve had rude responses. Most responses are neutral, neither rude nor friendly, and I sense a disinterest in the topic.

I wish all of the doctors who treated this patient when he was sick with opioid use disorder could see him now. He’s a happy and productive member of society, and yes, he does plan to stay on buprenorphine indefinitely. I support that decision.

This patient, and hundreds like him, are why I love my job.

Tidbits

 

 

 

 

 

 

As I promised several weeks ago, in this blog I’m writing about some of the studies published in the latest issue of the Journal of Addiction Medicine, the journal published by ASAM (American Society of Addiction Medicine). All of the following articles were in the last issue, May/June of 2017.

The opioid situation in the U.S. has temporarily claimed a big chunk of our attention, but elsewhere in the world, amphetamine and methamphetamine use disorders are more common than heroin and cocaine use disorders combined. In fact, amphetamine and methamphetamine are second only to marijuana worldwide as the most commonly used illicit drug.

Many scientists have been working to find a medication that will help in the treatment of patients with this disorder. Thus far, only psychosocial treatments have been helpful, including individual and group therapies using motivational interviewing, cognitive behavioral therapy, 12-step therapy, relapse prevention, and contingency management strategies. These treatments do improve outcomes, but are at best only moderately effective.

In Runarsdottir et al., extended-release injectable naltrexone was studied in 100 subjects with amphetamine use disorder in a randomized, placebo-controlled study done in Iceland.

This authors of this study postulated that the opioid blocker naltrexone could block the opioid receptors and thus the pleasurable effects on any endorphin-mediated dopamine release resulting from methamphetamine use. Preliminary studies in rats, primates, and healthy human volunteers suggested naltrexone could be effective, so this study on human subjects with methamphetamine use disorders was undertaken.

Subjects in one arm of the study were randomized to the usual psychosocial treatments plus placebo injection, and the other arm got the same psychosocial treatments plus active extended-release naltrexone injections.

Unfortunately, in this study, extended-release naltrexone did not show any statistically significant benefit over placebo. Both groups had high rates of drop-out at around 50%, which hampered the study results. However, the study’s authors postulated that their selection criteria for the study may have pre-chosen subjects with more severe use disorders.

This study’s results were disappointing. We would love to have a new and effective was treatment for amphetamine and methamphetamine use disorders, but this study didn’t show benefit from extended-release naltrexone for use in this disorder.

 

Another article was about a newer product containing buprenorphine: the rapidly-dissolving buprenorphine/naloxone sublingual tablet (brand name Zubsolv). It’s been on the market for a few years, and previous studies showed it works as well as other sublingual buprenorphine products on the market.

This study took patients from the previous studies and extended their treatment with this product for twenty-four more weeks, to evaluate the safety of longer-term treatment. As a secondary goal, study subjects were evaluated for their quality of life, opioid cravings, and their addiction severity.

Of the 665 patients who entered this second-stage study, only 44% completed the 24 week extension study. So that’s not great – we would like to see patients retained in treatment. The authors say patients withdrew due to being lost to follow-up, patient nonadherence to medication, and patient request for discontinuation.

But of the 44% of patients who finished the 24 week extension study, improvements were seen in their addiction severity, in their quality of life, in their employment status, and other measures. This means that the rapidly-dissolving buprenorphine tablet was found to be as safe as other similar products on the market, and the benefits of continued treatment persisted throughout this prolonged study period.

The high rate of discontinuation is concerning, but certainly not unusual. In fact, this drop- out rate was similar to studies done on other sublingual buprenorphine products.

I see this at my work. We use both buprenorphine and methadone at the OTP where I work, and drop-out rates are higher for patients on buprenorphine. They tend to bounce in & out of treatment more often than methadone patients do. I believe, but can’t prove, that the milder withdrawal gives patients less incentive to make sure they dose daily.

Patient drop-out is undesirable for all concerned. When a patient drops out of treatment at an MAT, relapse rates are very high, and risk of death may increase as much as eight-fold.

From that point of view, I might be tempted to regard methadone as a superior treatment. However, I know some of our buprenorphine patients would never consider starting methadone, often citing the difficulty of tapering off methadone as the reason. So offering buprenorphine attracts patients who may not enter treatment otherwise.

 

 

Another article in this copy of the journal, titled, “Methadone-Induced Hyperhidrosis Treated with Oxybutynin, by Hong et al., was a case study of a patient with pronounced sweating caused by methadone.

Pronounced sweating from any cause is termed “hyperhidrosis.” All opioids can cause this, including methadone. As the author points out, we think this may be caused by muscarinic receptor activity in the part of the brain that controls body temperature.

This case study is of a patient who stabilized on methadone 100mg for the treatment of his opioid use disorder, but had severe sweating, to the point he had to change clothes multiple times per day. This patient went to his internist, who prescribed oxybutynin, a medication also known under the brand name Ditropan. It’s used for overactive bladder disorders, and works through its anti-muscarinic activity.

The patient had resolution of his excessive sweating within two days, so the treatment was a success in this case.

I think I will start recommending to my patients with excessive sweating see their primary care providers for a trial of oxybutynin.

There are some pitfalls…it can lead to urinary retention, of course, and that’s always vexing when we ask patients to give urine drug screens.

 

 

What’s a Doctor To Do?

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Above, you will see two documents which illustrate the problem.

The second is a letter sent to North Carolina opioid treatment program (OTP) physicians from the preeminent OB/GYN group at the University of Tennessee. The first is a letter sent last month to obstetrical providers and opioid use disorder treatment providers from the Center for Substance Abuse Treatment, an arm of SAMHSA (Substance Abuse and Mental Health Services Administration).

You will note they recommend polar opposite approaches to the management of opioid use disorder in pregnant women. The obstetricians at University of Tennessee recommend that pregnant women with “chronic narcotic use” be offered the option of taper from opioids, to avoid neonatal abstinence syndrome and to avoid microcephaly.

In contrast, the letter to providers from CSAT division of SAMHSA recommends, “Pregnant women with opioid use disorder should be advised that medically supervised withdrawal from opioids is associated with high rates of relapse and is not the recommended course of treatment during pregnancy.”

That mention of microcephaly in the U of T letter baffles me. The resources cited in their letter referred to one study of head circumference in babies with neonatal abstinence syndrome (NAS). There’s no mention whether the moms are on illicit opioids or MAT. The second study looked at head circumference in babies born to moms with polysubstance use. None of the studies looked at head circumference of infants born to moms on MAT and compared them with controls. Using microcephaly as an argument against MAT is a misuse of data.

Why on earth would Tennessee obstetricians send their letter to NC opioid treatment program providers? Because, as I have ranted about so often in the past, there are no opioid treatment programs in Eastern Tennessee. Because that portion of Tennessee still has no methadone programs, patients are forced to drive across the border to get the gold standard of treatment for opioid use disorder. True, there are some buprenorphine prescribers in that area, and that’s a great thing as far as it goes, but as we know, not all patients do well with buprenorphine, and we have around six decades worth of data about methadone in pregnancy.

So not only does Tennessee refuse to allow the most evidence-based treatment for opioid use disorder to exist in that part of their state, but their physicians seek to control the actions of opioid treatment physicians in North Carolina, and ask us to adopt treatment approaches discouraged by all other expert organizations.

The study touted by Dr. Towers in their above letter was published by Bell, Towers, et al. in September 2016 issue of the American Journal of Obstetrics and Gynecology: http://www.ajog.org/article/S0002-9378(16)00477-4/abstract

After reading this study in some detail, I’m surprised by the authors’ conclusions. I find their conclusions to be based on some very thin evidence.

This study was a retrospective analysis of four groups of pregnant women with opioid use disorder. The first group consisted of incarcerated women, allowed to go through opioid withdrawal without the standard of care, buprenorphine or methadone. How this is even legal is beyond me.

The study says that jail programs in east Tennessee have “no ability to provide opiates to prevent or perform an opiate-assisted withdrawal medical withdrawal.” It went on to say that the jail doctor can treat symptoms with anti-nausea meds, clonidine, and anti-diarrheal meds. They also lack the ability to perform fetal monitoring while incarcerated.

Of the 108 women in group 1, two suffered intrauterine fetal death, one at 34 weeks and one at 18 weeks. The authors don’t say what the expected rate of fetal death would be, and I don’t know either. Apparently the authors didn’t consider these two deaths to be outside the range of normal.

Group 2 consisted of 23 pregnant women with opioid use disorder who were sent to inpatient opioid detoxification followed by long-term follow-up behavioral health programs. These women did well, with only 17% relapsing while in treatment. This group had a 17% rate of neonatal abstinence syndrome in the newborns.

I guess that means all of the four women who relapsed had babies with NAS. That’s 100%, much higher than the 50% rate nationwide. That seems odd to me.

Group 3 did the worst. These 77 women had inpatient detoxification but then did not have the long-term treatment that group 2 were given. Of the infants born to these women, 22% needed admission to the neonatal intensive care unit. Of these 77 women, 74% relapsed, and NAS was present in 70% of those infants. Again, this gives a NAS rate of 95%, which is a great deal higher than most other studies of NAS in babies born to moms using opioids of any kind. Even with methadone, studies give estimates of 50% to 80% at the highest.

Group 4 consisted of 93 women on buprenorphine prescribed by office-based physicians who agreed to taper the women’s doses during pregnancy. The rate of relapse in this group was noted to be 22%, and 17% of all the babies had NAS. Again, this gives a relatively higher NAS rate than has been found in other studies. In this Bell study, NAS occurred in 76% of the women who relapsed, up from 50% of women on buprenorphine in the MOTHER trial who were not tapered.

A little sentence in the articles table of demographics and outcomes gives the clue to why their NAS rates were so high. The way this study determined relapse was by drug screen at the time of admission to the hospital for delivery, or an admission by the pregnant woman, or positive meconium screen, or treatment of NAS in the newborn.

I think relapses could have gone undetected very easily, so that only the women with a relapse close enough to the time of delivery were detected to have used opioids.

Other problems with this study have been pointed out by much smarter people than me. Dr. Hendree Jones, author of the landmark MOTHER trial comparing methadone and buprenorphine during pregnancy, commented in the Journal of Addiction Medicine in the March/April 2017 issue: Her conclusions after a review of the Bell article plus a handful of other similar studies is: “Evidence of fetal safety to support the equivalence of medically assisted withdrawal to opioid agonist pharmacotherapy is insufficient.”

Of course, pregnant patients have one big concern: “What can I do to keep my baby from having withdrawal?” and that’s what they focus on. They are willing to do anything, including coming off methadone or buprenorphine or other opioids, if it will keep their baby from withdrawal. As Doctor Jones cogently points out in the above referenced article, there’s lack of data to show medically-supervised withdrawal from opioids results in less risk of NAS.

In other words, if prevention of NAS is our only goal, there’s not enough evidence to show that reducing opioids during pregnancy will achieve this. In part, that’s due to the high risk of relapse in the mother, and in part due to other factors.

This is the state of the situation right now. Things could change in the future. We do need new studies, done with closer attention to fetal monitoring and drug testing throughout pregnancy to help us determine the ideal treatment of pregnant women with opioid use disorder.

But for right now, maintenance on buprenorphine or methadone is still the treatment of choice.

It’s not only SAMHSA that’s recommending MAT as the treatment of choice for pregnant patients with opioid use disorder. Even the American College of Obstetrics & Gynecology (ACOG), the professional organization of OB/GYNs in the U.S., in a position statement from 2012, says:

  • “The current standard of care for pregnant women with opioid dependence is referral for opioid-assisted therapy with methadone, but emerging evidence suggests that buprenorphine also should be considered.”
  • “Medically supervised tapered doses of opioids during pregnancy often result in relapse to former use.”
  • “The rationale for opioid-assisted therapy during pregnancy is to prevent complications of illicit opioid use and narcotic withdrawal, encourage prenatal care and drug treatment, reduce criminal activity, and avoid risks to the patient of associating with a drug culture.”

The World Health Organization says, in its guidelines from 2014:

  • “Pregnant women dependent on opioids should be encouraged to use opioid maintenance treatment whenever available rather than to attempt opioid detoxification. Opioid maintenance treatment in this context refers to either methadone maintenance treatment or buprenorphine maintenance treatment.”

A new statement from the American Society of Addiction Medicine earlier this year, titled, “Substance Use, Misuse, and Use Disorders During and Following Pregnancy, with an Emphasis on Opioids” said:

  • “For pregnant women with opioid use disorder, opioid agonist pharmacotherapy is the standard of care; the ASAM National Practice Guideline for the Use of Medications in the Treatment of Addiction Involving Opioid Use recommends that pregnant women who are physically dependent on opioids receive treatment using methadone or buprenorphine monoproduct rather than withdrawal management to abstinence.

So the experts agree. Medication-assisted treatment is the gold standard for pregnant women with opioid use disorder.

Why are some OB/GYNs in Tennessee and other areas recommending the opposite, based on evidence that most of us consider preliminary at best, and flimsy at worst?

I don’t know for sure, but I think these physicians suffer from the same biases as other non-medical people. I would like for these physicians to base their actions on the best scientific data, but that’s not happening in some areas. I believe these doctors, with the best of intentions, have been swayed by the political climates of their areas. Rather than challenge long-held beliefs about medication-assisted therapies that have been based on ideology rather than fact, they have stayed inside the comfort zone of believing pregnant women shouldn’t be on methadone or buprenorphine.

This leaves addiction medicine physicians in the middle. We know what the standard of care is, but our patients are told we are wrong, and that they should taper off maintenance medication, or not start it in the first place.

I’ve tried, one OB at a time, to educate gently about what I see as the standard of care. I’ve sent studies and position papers and other data to the OBs with whom I share patients. I’ve blogged about the negative experiences I’ve had. In short, many of these obstetricians say something to the effect of: “Who are you to tell me how to care for this pregnant patient?” After all, I’m not an obstetrician. But I do read, and I do keep my fund of knowledge up to date in the field of addiction medicine, which overlaps with obstetrics at times.

I’m terribly frustrated by the situation, and I know my colleagues at other opioid treatment programs feel the same way. I’m fortunate that there is one group of OBs who are somewhat supportive of my pregnant patients on MAT, and I appreciate that. But often these pregnant ladies using opioids are already going to one of the anti-MAT OBs, and that creates real problems.

If it’s difficult for physicians, just think how the pregnant patients feel. They are given polar opposite recommendations by their OB and their physician at the OTP. They sought help in order to do the best thing for their babies, wanting to be good mothers. In most situations, they have tried desperately to quit opioid on their own, and couldn’t. Now the OB is telling them they must taper off their medication during pregnancy, and the OTP physician is recommending they stay on it, even recommending they increase their dose if needed.

At a difficult time in their lives, these mothers-to-be aren’t sure if they are doing the right thing by being in treatment with MAT or not. They second guess themselves, and their families also recommend, with the best of intentions, that they follow the OB’s directions.

I think this won’t change unless professional organizations like ACOG reach out more directly to obstetricians in the field. Perhaps SAMHSA can organize educational lectures, given by obstetricians who know the data and know the best practice recommendations. Perhaps state medical societies or state medical boards can contact these obstetricians with statements of best practices, if more are needed. With WHO, ACOG, SAMHSA, and ASAM all recommending MAT for opioid-dependent pregnant women, you wouldn’t think further statements of best practice would be needed…yet they are.

All I know is that I don’t seem to be making any headway at all. I need help, and my patients need help.