Archive for the ‘Overdose deaths’ Category

Opioids and Gabapentin: A Potentially Dangerous Mixture

 

A Canadian study, published late last year, showed co-prescribing of gabapentin and opioids was associated with significantly increased risk of opioid-related death.

I’ve had a few of my patients on methadone or buprenorphine misuse gabapentin, and even had one patient end up in the emergency room with an overdose from a mixture of buprenorphine and gabapentin, but I thought it was because the patient took way too many of the gabapentin. In the past I’ve thought of gabapentin as a “junior” substance of abuse. I thought most people with opioid use disorder wouldn’t deign to be interested in such a low-powered drug. I thought it might fall in the category with trazadone, Seroquel, or Benadryl…something young people might experiment with, but not what people with established opioid use would want to mess with.

After reading this study, I’ve changed my mind. Gabapentin with opioids is associated with increased risk of death. This is serious.

The Canadian study by Gomes et al., says gabapentin is often prescribed for pain, and obviously opioids are as well, resulting in many patients who are prescribed both. The purpose of the study was to discover if co-prescribing gabapentin and opioids resulted in higher risk of death from accidental opioid-related reasons.

Before describing the study, let’s talk more about this medication, gabapentin, sometimes marketed and sold under the brand name Neurontin.

Gabapentin is a medication that is structurally similar to the neurotransmitter GABA, but gabapentin has no activity at the GABA receptor. Gabapentin appears to attach to calcium channels, but we don’t know the exact mechanism of action of its anti-seizure and anti-analgesic effects.

This medication isn’t changed into other compounds, meaning gabapentin is the active drug. It’s metabolized by the kidneys, and so the dose must be adjusted in patients with kidney failure.

This drug is odd because its bioavailability goes down as the dose goes up, which means that as the dose goes up, the amount available in the blood stream goes up too, but not by as much as one would expect, due to the decrease in bioavailability.

Its half-life is around 6 hours, and so it is dosed three times per day. It can be removed by hemodialysis.

Gabapentin can cause sedation and suppression of respiratory rate, both by itself and when combined with prescription opioids. In fact, the product’s monograph was changed in 2014 to emphasize the risk of suppression of respiratory rate when combined with opioids. This may be more important in patients with COPD, renal insufficiency, and older age.

Gabapentin can also cause dizziness, fatigue, and swelling of the lower legs. It is not categorized as a controlled substance because studies didn’t show it to be prone to misuse or addiction. In fact, it has been studied for use in alcohol and marijuana use disorders, with some evidence of benefit.

Gabapentin is prescribed for an assortment of reasons, and not all are FDA approved. Gabapentin is approved for the adjuvant treatment of partial seizures in kids and adults, which means it can be used as an add-on to main seizure treatment medications. It is also indicated for the treatment of pain after a bout of shingles, called post-herpetic neuralgia.

That’s it. There’s no FDA approval for the many other conditions for which it’s commonly prescribed, like fibromyalgia, anxiety, hot flashes of menopause, pain of diabetic neuropathy, or alcohol withdrawal symptoms, though there are studies that support its use for some of these conditions. There’s evidence gabapentin may help with restless legs syndrome and itching from kidney failure.

Use of gabapentin for other than FDA approved uses isn’t unusual and it isn’t necessarily bad medical practice. Many medications are used “off-label” which means they are used for purposes for which they don’t have FDA approval.

A newer version of gabapentin, called pregabalin, is marketed under the brand name Lyrica, and it is classified as a controlled substance because of its potential for addiction and misuse. It has FDA indication for treatment of neuropathic pain, post-herpetic neuralgia (pain from previous shingles outbreak), epilepsy, fibromyalgia, and diabetic peripheral neuropathy pain.

The article I’m describing today did not look at any data relating to pregabalin.

The study was a nested case-control study, which means each opioid user who died of opioid-related causes was matched with four control subjects, with age, sex, start date of opioids, and presence or absence of chronic kidney disease being similar for each index case and the controls.

This was a big study, with 1256 index cases and 4619 controls.

An analysis was conducted to see how many of the index cases, patients who died of opioid-related reasons, were also prescribed gabapentin within 120 days of the index date. The dose of gabapentin was further categorized as high, medium, or low dose.

The results showed that 12.3% of the people who died of opioid-related causes were prescribed gabapentin within 120days preceding death. Of the age and sex matched control patients who did not die, only 6.8% were prescribed gabapentin within 120 days.

This means that patients on opioids who were co-prescribed gabapentin had odds of an opioid-related death 49% higher than patients on opioids who were not prescribed gabapentin.

The authors also found a significantly increased risk with higher dose gabapentin than low or moderate dose.

The authors of the study used the same method looking at anti-inflammatory medication prescriptions, to see if those medications increased risk of opioid-related death, and found no difference in use of anti-inflammatories in patients who died compared to controls who did not die.

It’s important to note that patients with opioid use disorder who were being prescribed methadone were not included in this study. Patients with cancer diagnoses and who were in palliative care were also not included. The authors didn’t explicitly say why these patients were excluded, but patients in these groups may not represent general patient populations. Patients with cancer, getting end-of-life care, are likely to be prescribed much higher doses of opioids, due to a shifting of the focus of their care. At the end of life, comfort is of more importance that functioning.

As for patients on methadone, perhaps the authors thought patients with substance use disorders would be more likely to misuse their prescribed gabapentin. Maybe the authors thought including such patients would skew the data, and gabapentin would appear to be more dangerous than it is. This study was not done on people with substance use disorders; it was done on the general population.

This is a powerful study because it was so large, and it spanned sixteen years. Canada has a population similar to that of the U.S., so I think it’s safe to assume their data should be valid for patients in the U.S.

What does this mean for me and my patients? I don’t treat pain, I only treat opioid use disorders. But are my patients, for whom I prescribe buprenorphine and methadone, at increased danger if they are co-prescribed gabapentin by another doctor? Yes, by my interpretation of this data, they are at increased risk. For sure, if they take more gabapentin than prescribed, they are increased risk for death, but this study shows that even when taken as prescribed, this medication is associated with increased risk of death.

Association doesn’t always mean causation, but given what we know about how these medications who, a causal relationship is strongly suggested.

In the past, I had more of a “pick your battles” attitude. I was happy if my patients stopped drinking alcohol or using benzodiazepines. For the latter, we have good studies (for example, Park et al., 2015, BMJ, “Benzodiazepine prescribing patterns and deaths from drug overdose among US veterans receiving opioid analgesics”) that have shown a four-fold increase in the risk of overdose death when benzodiazepines are co-prescribed with opioids. Now I will add gabapentin and pregabalin to my list of medications that can harm my patients.

It’s tempting to issue a blanket policy against gabapentin. Blanket policies make life easier for the opioid treatment program, but such policies treat every patient the same.

For this issue, I think the best course is to talk to each patient, evaluate each patient, and ask them how much benefit they receive from gabapentin. I will advise them of the increased risks of this medication, and we will decide whether it’s best to stop or continue the gabapentin. Some patients may decide the benefit it worth the risk. Other patients may decide it’s better to stop taking gabapentin. Either way, I’ll document this in their charts, and re-visit the issue regularly.

I am grateful, as always, to the website sponsored by the North Carolina Governor’s Institute: http://addictionmedicineupdates.org/ for bringing this article to my attention. The tireless people at the GI support excellence in substance use treatment around the state.

  1. https://doi.org/10.1371.journal.pmed.1002396

 

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Avoiding Overdoses

August 31: Overdose Awareness Day

 

 

 

“I’m not gonna overdose. I know my limits.”

I really hate hearing these words. Usually patients say this in response to my concerns about their pattern of drug use while I’m prescribing methadone or buprenorphine. But many patients feel like they are the experts. They can’t imagine making a deadly mistake with their drug use. But I’ve heard this phrase, or something close to it, from at least five people who are now dead from overdoses.

I was reminded of this situation after reading an article in the latest issue of Journal of Addiction Medicine. Najman et al. wrote an article titled “When Knowledge and Experience Do Not Help: A Study of Nonfatal Drug Overdoses.”

The author of the study looked at nonfatal overdoses in Australia in 2013, where overdose deaths have risen steadily since 2007. In that country, unlike the U.S., heroin use is declining while pharmaceutical opioid misuse is rising.

This study looked at nonfatal overdoses in people who inject drugs. These people, identified by the needle and syringe exchange programs in Australia, were interviewed about the circumstances surrounding these overdoses, in order to get a better understanding of the risks. A total of 50 people were interviewed for this study.

Most of these people were male, middle-aged, single, and unemployed. Nearly all were smokers. Half had a diagnosis of liver disease and almost all reported a mental health diagnosis. Most injected pharmaceutical opioids, though some also injected heroin and methamphetamine. These were very experienced drug users, with an average of 21 years of intravenous drug use.

Surprisingly, more than half of the study subjects were in some form of treatment for substance use disorder. This finding is contrary to other studies, which have found being in treatment lowered the risk for overdose. Around 46% were in medication-assisted treatment with either methadone or buprenorphine. However, some of the overdoses happened on days that the person missed dosing for some reason, and substituted another opioid such as heroin or fentanyl. Thirty-two percent of study subjects dosed with either methadone or buprenorphine in the twenty-four hours prior to experiencing their overdose.

Most of these overdoses happened in private homes, and around half received some sort of folk remedy for overdose such as being slapped, put into cold water, or being shaken. Naloxone kits weren’t routinely being distributed at the time of this study.

When asked about the cause of their overdose, many the subjects said they were impaired by alcohol or benzodiazepines. Over half said they used benzodiazepines within twenty-four hours of their overdose. Of the 50 subjects, 64% said they had been prescribed anti-anxiety medications sometime in the year prior to overdose, and 38% said they’d been prescribed sleeping pills. Another 36% said they’d been prescribed some sort of tranquilizer in the year prior to overdose. I’m assuming many of the subjects were prescribed more than one of these groups of medications.

Alcohol was not as prominent as sedative medications as contributory cause of overdose; only 34% of subjects said they had some amount of alcohol in the twenty-four hours prior to their overdose.

Over a third of subjects had used fentanyl, a very powerful opioid, leading up to the overdose.

The authors of the study concluded that these experienced drug users were aware of common risks for overdose, yet drug intoxication from sedatives such as alcohol or benzodiazepines may have clouded the user’s thinking when injecting opioids. They also found that unexpected availability of drugs contributed to overdoses.

It’s an interesting study, and a little disturbing to me, particularly the data about overdoses in people who were enrolled in medication-assisted treatments. It does underline the importance of daily dosing of MAT, and the importance of avoiding alcohol and benzodiazepines in patients on MAT.

And if you didn’t know…August 31 is International Overdose Awareness Day.

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.

 

Naloxone in Action


At the recent American Society of Addiction Medicine (ASAM) conference, I read a poster describing a study entitled “Lives Saved with Take-home Naloxone for Patients in Medication Assisted Treatment.” The article, by Katzman et al., from the University of New Mexico School of Medicine, described the outcomes from providing naloxone overdose reversal kits to patients enrolling in medication-assisted treatment of opioid use disorders

The study subjects were admitted to medication-assisted treatment over three months in 2016. The poster didn’t say whether they started buprenorphine, naltrexone, or methadone, but I’m guessing the patients were admitted to methadone maintenance.

In the end, 244 subjects enrolled and had education about opioid overdose and how to use a naloxone auto injector kit.

Twenty-nine subjects were lost to follow up, leaving 215 subjects available for inclusion in the study. Of these 215 subjects, 184 didn’t witness or experience overdose.

That means 31 subjects either experienced or witnessed at least one opioid overdose episode.

The scientists conducting the study interviewed these 31 subjects, and discovered that 39 opioid overdoses had been reversed and all of those lives were saved. Thirty-eight people were saved with the naloxone kits distributed by the opioid treatment program, and one study subject was revived by EMS personnel.

When study authors looked at who was saved by these study subjects, they discovered 11% of people saved were acquaintances of the study subjects, 16% were family members, 58% were friends, 6% were the significant others of study subjects, and 13% were strangers.

The study authors concluded that “a significant number of lives can be saved by using take-home naloxone for patients treated in MAT [medication assisted treatment] programs.” The authors also felt the study showed that naloxone isn’t usually on the patient who entered treatment, but more frequently on friends, relatives, and acquaintances that the MAT patient encounters.

I was intrigued by this study because it mirrors what I’ve heard in the opioid treatment program where I work. We are fortunate to get naloxone kits from Project Lazarus to give to our patients. It’s rare that one of our patients enrolled in treatment needs naloxone for an overdose, but much more frequently, I hear our patients say they used their kit to save another person’s life.

If anyone doubted the abilities of people with opioid use disorders, and felt they couldn’t learn to give naloxone effectively, this study should put that idea to rest. If anyone mistaken thought people with opioid use disorders wouldn’t care enough about other people to put forth an effort to save another person, this study should put that idea to rest, too.

In fact, I’ve seen a real enthusiasm among our patients to make sure they have a kit, in case they get the opportunity to save a life. They are eager to help other people, and I find that to be an admirable attitude that’s nearly universal among the people we treat.

Sometimes I get into discussions with patients about what they think about the naloxone kits, and where they think the kits can do the most good. I’ve heard some good ideas. One patient said every fast food restaurant should have a naloxone kit, since she knew many people with opioid use disorder inject in the bathrooms of these facilities. Actually, I just an online article discussing something similar: http://www.wbur.org/commonhealth/2017/04/03/public-bathrooms-opioids  

This article expresses the problems that injection drug use has become for public restrooms, and makes a case for safe injection centers. This is presently illegal in the U.S.

Even Massachusetts General Hospital armed its security guards with naloxone kits, so they could give this life-saving medication to people they found who had overdosed in the hospital’s public bathrooms.

Another patient suggested giving naloxone kits to people living in trailer parks.

I know that feeds into a kind of stereotype of those who live in trailer parks, but apparently there is some basis for saying such residential areas have high density of people with opioid use disorders. It’s worth looking at.

Several patients said that all people receiving opioid prescriptions for chronic pain should also be prescribed naloxone kits, and I think that’s been recommended by many health organizations too.

Most communities have at least talked about arming law enforcement and first responders with naloxone kits, and hopefully that’s a trend that will continue to spread.

Naloxone isn’t a permanent solution for opioid use disorder, but it can keep the people alive until they can enter opioid use disorder treatment. Because dead addicts don’t recover.

 

The Good, the Bad, and the Ugly

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The Good

 Probuphine

Probuphine was approved by the FDA. I’ve written about this medication in several other blog posts. Probuphine is an implantable form of buprenorphine that lasts for six months. It will be suitable for buprenorphine patients who are stable at 8mg per day or less.

I think logistical problems will prevent this medication from becoming mainstream. I hear it must be implanted in a surgical suite, which makes little sense. Maybe it’s more involved than I realize, but I had been under the impression it could be done in an office setting, like Norplant.

I’ve also read that the physician must purchase and store the Probuphine implant, which adds financial risk and DEA scrutiny to a buprenorphine physician’s already crowded schedule.

As I’ve said before, I predict Probuphine will be administered at a few specialty centers, but isn’t likely to be done by most mainstream addiction medicine doctors. Still, it’s another option that hopefully will work well for patients on less than 8mg per day.

Watch your language

The field of Addiction Medicine is pushing for non-stigmatizing language to be used by treatment professionals. Words are important, and some words carry hidden and pejorative meaning in the general public.

For example, I’ve always cringed when I hear the term “dirty” or “clean” urine drug screen. I have to quash my desire to be sarcastic towards the speaker. The proper terms are “positive,” meaning a substance was found in the urine, or “negative,” meaning a given substance wasn’t found in the urine. Addiction Medicine gurus continue to emphasize the importance of using proper clinical terms. I enthusiastically agree with their efforts.

Now experts in the field want to get rid of the term “addict” and “opioid addiction.” They want to replace those words with terms such as “person with opioid use disorder,” and “opioid use disorder,” respectively.

I understand the reason behind these recommendations, and I agree with them, but it’s going to be tough to replace a two-syllable word with a ten-syllable phrase.

Besides, when I say the word “addict,” I suspect I mean something very different than the average person using the word. In my mind, the word “addict” has come to mean “person with the disease of addiction who is probably more likeable and interesting than an average person.”  But then, I chose to spend my career treating these people, so of course I think that way.

Contrast that to an average person in the community, to whom the word “addict” means a bum in the gutter with a needle hanging out of his arm. Most of the time, people are surprised when then encounter real addicts, or to use the new term, people with an opioid use disorder. Because since anyone can develop opioid use disorder, these people usually don’t look different from the rest of us.

Government Support for Addiction Treatment

When the President of the United States endorses medication-assisted therapies, we have arrived. That’s old news now, since he has been discussing MAT in some of his addresses since last year, as a way of addressing the opioid overdose epidemic. But now the promised money is starting to become available.

Available grant money fueled plans for new, collaborative opioid use disorder treatment programs in our state…

One primary care low-cost clinic just started working with their local opioid treatment center to provide needed primary care to patients in that OTP. Referrals should flow both ways, with the OTP sending patients to the medical clinic for needed healthcare, and the medical clinic will detect opioid use disorders in their patients, and refer them for treatment at the OTP.

An exciting initiative to connect people involved with the criminal justice system with appropriate medication-assisted treatment is in the planning phase. With this program, prisoners being released and people under parole and probation will be evaluated by addiction medicine doctors. Where appropriate, they will be offered methadone, buprenorphine, or naltrexone, to better treat their illness, and they will get increased counseling.

Prescription Monitoring Programs Work!

I had a few spare hours last week, and was able to look at around 125 of my 450 OTP patients. I discovered only one patient with some questionable findings, and she’s scheduled to talk with me this week.

What a change from 2007, when over 20% of all my OTP patients had serious prescriptions for opioids, benzodiazepines, and/or stimulants. These were prescriptions about which I knew nothing. Patients had filled prescriptions and there was no way for me to know about it, until our prescription monitoring program came online in mid-2007.By the time I got access late in the year, I found data indicating over a fifth of our patients were filling prescriptions that could harm them with the methadone I was prescribing.

Over the last nine years, our system has improved, making it ever easier and more accurate.

The Bad

All Use of Methadone is Toxic?

Perhaps in response to my blog post that was critical of the medical examiners in North Carolina, a medical examiner called me.

My complaint in the June 5, 2016 blog is that any patient who dies while on methadone maintenance is said to have died from methadone toxicity, regardless of clinical information.

This doctor and I had a cordial yet frustrating conversation. The physician introduced himself and said he was calling me because he had promised to do so after I spoke with him last year about a patient of mine who had died. When we last spoke, the toxicology results had just been sent off. He called yesterday to tell me that the level of methadone in this patient was toxic, and that along with the cocaine found in her system, he was reporting cause of death as “Methadone toxicity, cocaine toxicity.” I already knew this from reading incident report data, but I didn’t interrupt him. I was hoping he would give me additional information, but he didn’t.

When he was done, I informed him, again, that she had dosed at 130mg of methadone for months in the several years prior to her death. At her request, we started a slow taper. She came down on her dose by 5mg every couple of weeks, and she had been dosing at 60mg for several weeks prior to her death. I asked him how, with that information, could he still say she died from methadone toxicity?

He didn’t have an answer, and just repeatedly said her methadone level was “toxic.” He read the level to me, and I told him that I have patients with trough levels  higher than that.  I told him toxic for an opioid-naïve patient may be just what one of my patients needs for stabilization.

I don’t think he ever heard what I was saying. He never got off the topic of drug levels, and implied perhaps she could have obtained methadone from another source.

I suppose this is possible, but unlikely. For this patient to have overdosed on methadone, she would have had to gotten a supply of the medication from another source. I know she didn’t get a prescription for it, since I checked the state prescription monitoring database. And why would she buy illicit methadone off the street when she could just ask to go back up on her dose if she were in withdrawal?

I appreciate that this doctor took the time to call me. He didn’t have to do that, and it probably wasn’t an easy conversation for him. I don’t doubt he’s conscientious at his job.

I only wish he could have heard what I was saying.

What I heard him was saying was more of the same: the medical examiners will base their decision about cause of death on the methadone level, and will not consider any clinical information from me, or presumably from any another other opioid treatment program physician, if a patient dies under my care.

This increases the risk of being a doctor at an opioid treatment program. Because no matter how cautious we are, we treat a group of people who die at higher rates than age-matched controls. Nearly all of our patients smoke cigarettes. Of course they can die from methadone overdose, but they also die at higher rates from cancer, heart disease, liver failure, and other medical problems created from a life time of drug use, including nicotine.

But we now know in advance that methadone will be blamed no matter what. And that’s bad news

The Ugly

Heroin Comes to Town

Last week, several people who should know and have no reason to lie told me heroin can be bought in Wilkes County. I am really sad to hear this.

Heroin has already invaded many small communities. It crept in after black market prescription opioids pain pills became scarce. Indeed, at my state’s yearly Addiction Medicine conference, most OTP doctors said they’ve been treating heroin use disorder for several years.

For some reason, the people I admitted to our opioid treatment program have thus far been around 98% pain pill addicts. Last week, more than half of the new patients were using heroin. One patient came to treatment because the first time he used heroin, he overdosed, nearly died, and woke up in the ambulance. That scared him enough to propel him into substance use disorder treatment.

You may question if heroin addiction is that much worse than pain pill addiction. I think it is, though I could be wrong about this. With pharmaceutical grade pain pills, the user has an idea, usually, of how strong the product is. There’s not much variation from one pill to another. But with heroin, the batch one day could have only a few percent of pure heroin, or 100% pure heroin. There’s no way to know. There’s no way to gauge how strong it is, unless the user dose a “tester shot.” This is when the user uses a small amount of the purchased heroin to see how strong it is. This tester shot is recommended by Harm Reduction Coalition as a way to reduce overdose risk.

Heroin manufacturers usually don’t care about quality control. The heroin could be cut with God knows what else. Some of these substances cause special problems, since they weren’t meant to be injected into the human body.

Quinine, for example, has been found as a contaminant. I’m not sure why it’s used to dilute heroin, but it is. Quinine can cause kidney damage, bleeding disorders, and severe allergic reactions. Some experts believe many heroin overdoses are really fatal allergic reactions to products used to cut the heroin. In the street parlance, adding substances to a drug is called “stepping on it,” meaning diluting it so it can go farther and make the seller more money.

Other regular heroin contaminants include caffeine, talcum powder, powdered milk, chalk, or flour.

Recently there’s been a tendency to include fentanyl in the heroin product, making it an even stronger opioid. This has caused many overdose deaths, particularly in the Northeast. I strongly suspect that’s what my patient with the near-fatal overdose injected.

 

 

 

 

 

 

 

 

 

Action by the North Carolina Medical Board

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Last month, the North Carolina Medical Board (NCMB) announced they will query our state’s prescription monitoring program and investigate physicians identified as having worrisome prescribing habits. In order to help combat the prescription opioid overdose death crisis, this is part of an action that the NCMB is calling the Safe Opioid Prescribing Initiative.

Announced last month, the initiative will focus on three groups of physicians. This is taken directly from the NCMB’s website:

  1. The prescriber falls within the top one percent of those prescribing 100 milligrams of morphine equivalents (MME) per patient per day.
  2. The prescriber falls within the top one percent of those prescribing 100 MMEs per patient per day in combination with any benzodiazepine and is within the top one percent of all controlled substance prescribers by volume.
  3. The prescriber has had two or more patient deaths in the preceding twelve months due to opioid poisoning. (The initial group of prescribers under investigations were reviewed for the period beginning July 2014 and ending June 2015.)

The NCMB also says letters were issued to the first 72 prescribers (physicians and physician assistants) in April, most of whom were identified under the third criteria. Since nurse practitioners are also allowed to prescribe controlled substances, they will be scrutinized by the North Carolina Board of Nursing.

Responses to this new NCMB initiative have been mostly supportive. In my local newspaper, an editorial applauded the board’s actions, and advocated more such actions, to reverse the crisis of opioid overdose deaths in the state. The Charlotte Observer carried an article that said the NC General Assembly criticized the NCMB for not doing enough to combat prescription opioid overdose deaths

I’m probably not the NCMB’s biggest fan, but I don’t think it’s fair to blame that board for not doing more about the prescription overdose death crisis. The medical board wasn’t even allowed to access the prescription monitoring program’s data until the law changed last year to allow them to do so. Before that, they had no authority to do what the Safe Prescribing initiative outlines. In the past, they could investigate a physician only if they received a complaint about him or her.

Members of any state medical board have a thankless job. They are asked to make perfect judgments about medical professionals who may present a danger to the public. If they appear to be too lenient, they are criticized by the public for “protecting their own.” (This isn’t accurate anyway, since at least in my state, over one-third of board members aren’t physicians.) If they take strongly punitive stances, they are criticized for overstepping their authority and ruining the livelihoods of the professionals they license.

The professionals on my state’s medical board spend hours evaluating cases, for little or no pay. I think they may be paid nominal reimbursements for travel expenses, but I’m certain it doesn’t come close to making up for the time these people lose from their own businesses and practices.

Contrary to public opinion, state medical boards exist to protect the public, not to advocate for the doctors they license.

The NCMB initiative won’t be easy to implement, either. Just because a physician prescribes a whole lot of opioids doesn’t necessarily mean he’s a bad doctor. For example, a physician working with hospice patients, doing end of life care, should be expected to prescribe large amounts of opioids, and have frequent patient deaths.

Peer review of physicians will be essential. The NCMB will send charts of doctors identified by the three criteria above to be reviewed by other doctors in the same subspecialty. That means, hopefully, that doctors will be judged by other doctors in the same field of medicine.

This is important. This means that good pain management doctors may have to be evaluated and judged by other pain management doctors, through the NCMB. That will no doubt be unnerving, but the outcome should ultimately be positive, if the doctors are taking appropriate precautions.

Only doctors failing to meet accepted standards will have action taken on them by the NCMB, and only those actions will become public.

The NCMB has a big job ahead. They will need to separate the sheep of the doctor world from the goats, and decide appropriate actions to take. I do not envy them this task.

The NCMB has already taken action against many of the pill-mill type doctors, starting over a decade ago. If the board received a complaint, investigated a prescriber, and found him or her to be engaging in worrisome prescribing practices, that practitioner either lost the license to practice medicine, or was prevented from prescribing controlled substances, or was asked to take educational courses in proper opioid (or other controlled substance) prescribing.

I have other concerns about the third criteria of the NCMB’s Safe Prescribing Initiative.

First of all, how will the NCMB know if a prescriber has had two or more patient deaths in the preceding twelve months? I suspect the only cases examined by the NCMB will be those found to be opioid poisoning per the North Carolina Office of the Chief Medical Examiner (NC OCME).

Deciding if a prescribed opioid caused a patient death can be tricky. It depends to a large degree on the tolerance of the decedent, which needs to be determined by patient history. A dose of opioids that would kill one person won’t even make another person drowsy, if they have tolerance.

That factor is particularly important with methadone. My colleagues and I bemoan the fact that when our patients die, it WILL be blamed on methadone, no matter what. One doctor grimly remarked that if one of his methadone patients got shot in the head, the cause of death would still be listed as methadone toxicity. I think he’s exaggerating, but only by a little

The problem is that the North Carolina Office of the Medical Examiner has no standard case definition of what constitutes a methadone overdose death, which inevitably leads to mistakes about cause of death. According to information on their website and what I’ve learned by speaking with them, the decision is made by the blood level of methadone in the deceased.

I’ve felt the sting of being unfairly accused of killing patients. On several occasions, I’ve called the OCME about one of my patients who died while on methadone. I wanted to provide information about the patient’s dosing history before they determined the cause of death. I felt I had important information that could help them…but it did no good.

In one case, my patient had dosed on methadone 130mg for about a year, and then started a slow and steady taper. One year later she was dosing at 60mg per day when she died suddenly and unexpectedly. At autopsy, she had cocaine in her system, and she had a history of heart trouble. I suspected a fatal cardiac arrhythmia caused by cocaine, but the OCME announced the cause of death was: “Methadone toxicity, cocaine toxicity.”

Apparently they based their decision on post-mortem blood levels, known to be inaccurate. After death, the methadone stored in the liver can leak back into the blood vessels, causing elevated readings on which their determination was made, regardless of the history I gave them about her dose.

Five or so years before, another patient of mine died of what I thought was a severe asthma attack. In fact, she called 911 herself, saying she was having an asthma attack. Sadly, by the time EMS arrived, she had stopped breathing and couldn’t be resuscitated. I called the OCME to see what they found at her autopsy. The physician who did the autopsy said he found mucus plugging and bronchial casts, classic findings of status asthmaticus, which is a severe and sustained asthma attack. I was sad about her death, and told him I had treated her for many months for opioid addiction, and that she had dosed daily on methadone 75mg for at least two months.

When the death certificate was issued months later, after the toxicology report was available, I was surprised to see the cause of death listed as “methadone toxicity.” I called the medical examiner again and asked why this was listed, and the answer was that it was based on the drug level of methadone in her system.

Thankfully those types of cases are relatively rare.

I worry much more about all the people who die from opioid overdose who are never identified as a coroner’s case. That’s a bigger issue.

Consider the ways in which a deceased person becomes a coroner’s case. Of course, all instances where foul play is suspected require autopsies. Young people with no known medical issues should be investigated. Sometimes, deaths that occur in hospitals or nursing facilities require autopsy, if unexpected. Deaths that occur in police custody always require an autopsy..

In the community, if a person dies unexpectedly, a coroner is called to come to the scene to look for foul play. If there is none, the coroner calls the person’s doctor, to see if there’s an obvious cause of death like cancer or heart disease.

If you are a doctor freely prescribing opioids and/or benzos, what would you say to a coroner? Possibly, you’d say the decedent was ill with various problems and that the death was expected. It could be convenient to describe as “cardiac arrest.” (Technically, all deaths are ultimately due to cardiac arrest, but that doesn’t tell us the cause of death) This would be less upsetting for the family, keep the doctor out of trouble, and save the cost of an autopsy to the state.

Besides, no doctor wants to think the medications he prescribed killed a patient, or even contributed to the person’s death, so that inevitably biases judgment about cause of death by the prescriber.

I wonder how many overdose deaths slip through unnoticed and unexamined. Current data shows a very high incidence of prescription opioid overdose deaths, but I fear it is even higher.

 

After the Overdose

aaaaaaaaaaaaaaaaaaaaaaaaaaapic

 

 

 

 

 
I just read an astounding and completely believable study in a recent issue of the Annals of Internal Medicine. [1]

This study, done by Dr. Larochelle and associates at Boston University Medical Center, did a retrospective study of prescription opioid overdoses. They looked at patients who were being prescribed opioids long-term for non-cancer pain who had a non-fatal overdose. The study lasted from May 2000 until December 2012, and included over twenty-eight hundred patients. All of these patients had commercial insurance, and were between 18 to 65 years old.

This study found that after having a non-fatal overdose, 91% of these patients resumed getting prescription opioids, and that 70% got them from the same doctor.

The lead author said he was shocked to find so many survivors continue to be prescribed opioids after having an overdose from these very opioids. He had hoped after a near-fatal experience, prescribers would do something different to address pain, in order to prevent future overdose.(https://hereandnow.wbur.org/2016/01/13/opioid-prescriptions-after-overdosing)

From other studies, we know that the best predictor of a future overdose is a past overdose, which is why I ask every patient entering the opioid treatment program (OTP) if he has ever had an overdose.

The author of this study postulated that with our fragmented healthcare system, the prescribers may not have known the patient had an overdose. Not knowing about any problems, the doctor continued to prescribe opioids.

I have no problem envisioning how this happens.

Not long ago, one of my opioid treatment program (OTP) patients missed two days of dosing. Per our protocol, her counselor called her on the first day she missed dosing. The patient told her counselor that she had been admitted to the hospital for trouble breathing, and was being treated for asthma.

Also per out protocol, we request hospital records for every patient of ours who gets admitted to the hospital, and our patient gave permission for this.

When I got the records four days later, imagine my surprise when I read that she had respiratory failure due to an overdose. Her drug screen at the hospital was positive for methadone and also benzodiazepines, and indeed she was now positive for benzos at the OTP too. This information lead to a drastic change in this patient’s treatment plan.

If we had not called to see where our patient was, she could have returned in several days and not told us about her hospital admission.

Our local hospital did not call our OTP to tell us our patient was hospitalized with an overdose. Indeed, they didn’t call to tell us she was in the hospital. To my patient’s credit, she did tell them she was a patient of ours, since it was recorded in her hospital record.

When our patients are admitted to the hospital for medical reasons, the admitting doctors continue to prescribe the usual dose of methadone, and I am happy about that, but they don’t call us to confirm the dose. They take the patient’s word for what the dose has been, instead of making a quick phone call. I worry that someday, one of our patients, in a misguided effort to feel an opioid effect, will tell his hospital doctor he’s been dosing at a higher dose than he actually is, and catastrophe could ensue.

In contrast, the big teaching hospital an hour away, which is where our patients go when they are really sick, routinely calls to confirm each patient’s dose.

The Larochelle study seems to indicate there’s a lack of communication in other medical communities as well. Emergency department physicians may administer Narcan and revive a patient, but no one thinks to take the next essential step: call that patient’s prescriber about the drug overdose.

We can’t assume the patient, now revived from a near-death experience, will tell her doctor about what happened. If that patient has an addiction, she might keep quiet about prescription mishaps, fearing her supply of opioids may be cut off.

Family members might tell the prescribers, and that’s very helpful, but often patients are told the doctor can’t release any information. That is true, but the family can certainly give information to the doctor.

I know hospitals and emergency departments are busy. Healthcare professionals are all busy. We are being asked to do more and more in less and less time. But this is a communication issue, and it need not be a physician- to- physician communication. A nurse or even a social worker from the hospital could call or fax valuable information quickly. Privacy laws can be blamed for some lack of communication, but there are exceptions in life-threatening situations.

And please, let’s make medical records readable. Even when I finally get local emergency department records about one of my patients, I have a hard time deciphering them. I’ll admit to being a bit of a Luddite when it comes to electronic medical records, but partly because most electronic records are not all that helpful.

For example, on our local emergency department records, I quickly can find the results for Ebola screening (it’s on the first page, at the top), but often I am left scratching my head about what the doctor’s final diagnosis and treatment plan was for the patient.

We’ve got to fix this communication problem. It’s great when an overdose is treated and prevented. But let’s do just a little more, and communicate to the prescriber of the overdose medications.

It is life and death.

  1. Ann Intern Med. 2016;164(1):1-9. doi:10.7326/M15-0038