Mortality in Opioid Treatment Programs

By Ukrainian artist Maksym Kisilov

I came across an excellent article about mortality in Norwegian opioid treatment programs. [1]

Unlike the U.S., Norwegians have an organized healthcare system, making it easier to do studies on groups of citizens. The researchers who wrote the article wanted to study mortality among patients enrolled in their Norwegian Opioid Treatment Programs, so they looked at data from the Norwegian Cause of Death Registry and the Norwegian Patient Registry and studied those patients.

We already know that people who use illicit opioids have  up to fifteen times the risk of premature death as compared with the general population, and we know from multiple studies that MOUD reduces mortality for these people. Studies like this one help us find common causes of death for patients in treatment which may help us provide interventions to improve the quality and length of life for patients on MOUD (medications for opioid use disorder).

In this study, out of the 7622 patients enrolled in treatment, 38% were dosing on methadone and 59% on buprenorphine, either as monoproduct or in combination with naloxone. The article doesn’t mention what the other 3% were taking but I suspect it was naltrexone.

The researchers looked all patients who died in a two-year period from early 2014 until the end of 2015. To be included in the study, these patients had to have died no more than 5 days after their last dose of medication. Two-hundred patients died during that time, which gave a rate of 1.4% per year, out of all patients enrolled in treatment.

That’s a little higher than what has been found in other studies. A recent systematic review with meta-analysis of all-cause mortality in patients enrolled in opioid treatment programs showed a rate of .93 people out of 100 over a one-year period. [2]

Again, I want to emphasize this rate is between two to eight times lower than patients with opioid use disorder who aren’t on MOUD.

Causes of death in the Norwegian study fell into broad categories: somatic disease accounted for 45% of the deaths; drug-induced deaths made up 42% of the deaths, and 12% were categorized as violent deaths, leaving 1% as uncategorized. The mean age of death was 49 years old, and 74% of the decedents were male. Autopsies were done on 63% of the decedents, a relatively large percentage.

Somatic deaths were due mostly to cancer, cardiovascular deaths, pulmonary illnesses, and liver diseases. A full 30% of cancer deaths were due to lung cancer. Bacterial infections accounted for 15% of the somatic deaths.

Homicides, suicides and auto accidents accounted for most of the violent deaths, with half due to suicides.

Among the drug-induced deaths, none occurred during induction, though induction has been found to be the most dangerous time in other studies. More patients (55%) of the decedents died while taking methadone than buprenorphine. In fact, the mortality rate was double in methadone patients compared to buprenorphine patients. The average dose of methadone for those patients who died was 90mg, and for buprenorphine was 16mg.

 In Norway, MOUD is started by either specialists or general practitioners, and 68% of the decedents had their medication prescribed by general practitioners.

Nearly 30% of the patients who died from drug-induced deaths had a non-fatal overdose within the past five years, and 43% had filled at least one sedative prescription in the year before death. The median duration of treatment among these deceased patients was eight years.

Out of the 84 drug-induced deaths, methadone was reported as the main cause of death in 37%. Heroin was blamed in 20%, and buprenorphine was reported as the main intoxicant in around 18%.

 In the discussion section of this study, the authors say both age and lifestyle factors influence the causes of somatic disease seen in these patients.

Norway has one of the oldest opioid treatment patients in Europe, with a mean age of forty-five. With aging treatment programs come aging patients, which may account for the large number of deaths from somatic diseases. Nearly all countries face this situation, including the U.S. Also, nearly all patients with opioid use disorder smoke cigarettes, and this contributes to cancer risk, COPD, and cardiovascular diseases.

And why were there significantly more deaths among the methadone patients than among the buprenorphine patients? Again, the study’s authors wonder if increasing age and co-occurring medical disorders make methadone more dangerous. They wondered if patients taking more medications for these medical disorders might cause QT prolongation in these methadone patients.

So how does this data help providers of treatment in U.S. opioid treatment programs?

After reading this study, I’ve decided to spend more time talking to my patients about smoking cessation. I need to encourage those who wish to quit smoking and we need to put that as a goal in their treatment plans. We need to consider some stop-smoking groups at our OTP, and perhaps find funding for smoking cessation medications.

Smoking causes or worsens cardiovascular diseases like strokes and heart attacks and causes most cases of COPD (Chronic obstructive pulmonary disease). We know it causes or contributes to many kinds of cancers.

If we want our patients, who have survived opioid use disorder and found recovery from it, to lead longer and happier lives, we must address nicotine use disorder. It’s another drug and just as deadly as opioids, though it kills more slowly and thus less dramatically.

Our patients must be connected to quality primary care. In the OTP where I work, owned by a nationwide corporation, providers are permitted to prescribe only the methadone, buprenorphine products, and naltrexone used to treat opioid use disorder. This means all primary care management of chronic health conditions is done outside of our OTP, and we must refer patients for care.

This is a rural area, and we don’t have enough primary care providers. Our patients often get turned down by these providers. I suspect it’s because of stigma in some cases, against people with substance use disorders. Also, most of our patients don’t have any health insurance. I’d estimate that around half our patients have no way to pay for medical care. There is a free clinic in town that’s open one day per month, but the amount of care provided is limited. There are FQHCs (Federally Qualified Heath Centers) in neighboring towns, but transportation is difficult.

I don’t know how to fix this in our broken healthcare system. It’s frustrating.

I was unpleasantly surprised that so many of the Norwegian patients died from overdose deaths. From the data, a large percentage filled a sedative in the year prior to death, underlining – once again – how dangerous these medications are when mixed with methadone or buprenorphine.

A depressing number of the overdoses were attributed to methadone alone. However, I wonder if Norway has the same issue we have in some states: there’s no standard case definition of what constitutes methadone overdose death. In North Carolina, it appears that if methadone is found in the decedent, it will be named as the cause of death.

The large number of suicides by patients in the violent deaths group was surprising and makes me wonder if we are doing all we should be doing at the OTP to screen for patients with serious mental health issues. We do have the local mental health clinic where we refer our patients, and their quality of care has improved in the past years. Perhaps we can start screening for depression more often, for example, by using the PHQ9 form that patients can complete.

According to the data in this Norwegian study, aging patients on multiple medications could benefit from being followed more closely than I’ve been doing. All patients must see me once per year at a minimum for a yearly assessment, but I’d like to see older patients on methadone every three months. I’ll be looking for potential medication interactions and adequacy of their dose.

 I’ll particularly be asking patients about gabapentin. I’m convinced this medication has been at least partially responsible for some episodes of impairment and overdose among patients, and it is prescribed way too freely by providers in my county.

In fact, in my more paranoid moments I think I’m the only person in the county who isn’t prescribed gabapentin.  I think there may be traffic checkpoints at the county lines: “Ma’am we’re just making sure you have a prescription for gabapentin. No? Ok, then we must issue you a prescription for it. Here’s your script for gabapentin 1800mg three times per day.”

Once a patient tells us he’s just been prescribed gabapentin for the ever-present “nerve pain,” I call the provider and explain the dangers of mixing gabapentin with methadone. Even if that provider reduces or stops the medication there’s always another provider eager to take over prescribing. Since it isn’t reported on our state’s prescription monitoring program, I don’t know who is getting a prescription unless the patient tells us. On at least two occasions, providers prescribed both pregabalin and gabapentin for the same patient. One provider said she didn’t realize she was prescribing both and the other was intentionally prescribing both medications because the patient asked for both. And yes, both patients had swollen legs.

This interesting article gave data that I can discuss with our clinic leaders with the goal of improving care and along with it, the quality and length of life of our patients.

  1. Bech et al., “Mortality and causes of death among patients with opioid use disorder receiving opioid agonist treatment: a national register study,” BMC Health Services Research 2019 Jul 2;19(1):440. Doi: 10.1186/s12913-019-4282-z. PMID: 31266495; PMCID: PMC6604272.  
  2. Ma et al., “Effects of medication-assisted treatment on mortality among opioid users: a systematic review and meta-analysis,” 2018, Molecular Psychiatry,

11 responses to this post.

  1. Posted by Alan Wartenberg MD on July 4, 2022 at 2:32 pm

    Very interesting commentary. I particularly like that you drew from it the importance of a greater focus on tobacco cessation, or at least harm reduction approaches. One problem is the large number of treatment staff who are smokers. At our program at Faulkner Hospital, where we became the first program in the city to ban smoking (long before it was banned in hospitals in general), we first worked on smoking cessation in our staff, and we were far more successful than we thought we would be (75% quit rate). It is hard for staff who are still smoking to have a realistic or effective strategy for smoking cessation in their patients.

    Reply

    • Thank you as always, Dr. Wartenberg. You are so right. Today after treatment team I asked staff about how they would feel about a stop smoking group for patients and staff and the response was tepid at best. It hurts my heart when I see staff – or patients – smoking, knowing all the health risks. It’s going to be a challenge.

      Reply

      • I doubt there’s anyone alive who doesn’t realize that smoking is bad for their health. However I’d imagine that people struggling full time with opioid addiction would consider themselves lucky if their biggest health concern was the fact they smoked cigarettes. Hard to imagine myself after allegedly making an illicit narcotics purchase and suddenly realize that my nicotine addiction should be a priority. Regardless of how much damage I knew it was causing my body. Honestly it’s one of the most difficult aspects of attending most rehabs. They fully expect patients to tackle all of their drug issues at once, including nicotine. The upside was that I was usually too sick to care about cigarettes any longer. Quiting smoking pales in comparison to heroin withdraw. Nicotine isn’t just challenging on a behavioral mental health level. It’s physically difficult to resist the urge. No matter how personally disgusted someone might be with it themselves. The compulsion is extremely strong. I know folks who have quit for ten years and occasionally still fight the urge to light up. And vaping appears to not be any different. Possibly worse. People prone to addictions would probably require a whole new approach if they honestly wish to stop. I’d imagine it’s back to the drawing board in regards to programs that offer incentives and practical coping skills.
        Actually just thinking about this makes me wanna light up! Lol

      • Plus I’ll kindly remind people that reverse psychology truly works! Once I’m not supposed to do something, I’ll definitely have it on my to do list by dawn!

  2. Posted by Kim Smith on July 4, 2022 at 5:48 pm

    Excellent article. I’m on methadone for pain but attend a clinic. I was prescribed gabapentin by my neurologist. I took 1 dose of it and started reading about it. It made me feel drunk and I didn’t want to be addicted to another drug.

    Reply

  3. Posted by Lilley Toole on July 5, 2022 at 4:36 am

    Gabapentin… hmmmm 🤔

    Once I found myself outside and without any methadone maintenance I was was forced to buy/accept any available opiate to deal with my withdraw symptoms.one thing I made a mental note about was the other homeless folks who seemed to seek out gabapentin in combination with opiates. Evidently there’s a possibility of getting “high”. Since I wasn’t concerned about getting high, only stable. I didn’t see the point in wasting cash on gabs. But now that you mention it plenty of methadone clients we’re seeking out gabs. So I’m wondering how does any clinic test for this drug? I’ve also witnessed plenty of overdoses first hand. I’d estimate almost half of those folks were obsessed with gabapentin.(??)) Guess I got LUCKY. I’m still here

    Reply

    • Interesting information, thank you!

      Reply

    • Posted by Kim on July 6, 2022 at 1:42 am

      Hi most clinics don’t test for it because it’s not deemed a controlled substance in their state. In Ohio they changed the schedule on it so it’s considered a controlled substance and is checked for at Ohio clinics. Many people in drug withdrawals have said it helps allot that’s why addicts look for it. Not so much to get high but to help. Hope that gives you an explanation

      Reply

  4. Posted by Ashley on July 5, 2022 at 10:47 am

    You commented that North Carolina seems to report cause of death as methadone toxicity in all cases where methadone is found in the autopsy… do you know why that is? Is there a regulation in place that guides coroner’s to list it as cause of death regardless?

    Reply

    • No, no regulation but it seems to happen that way over & over. OTP providers have tried to ask why this happens but I haven’t heard a good explanation other than, “The methadone level was high.” However, post-mortem blood samples give a higher reading that in a living patient since the methadone leaches out of the liver after death. And I’ve had cases where the level wasn’t high and still the ME said it was methadone overdose.

      Reply

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