Why I Am Prescribing Medication-Assisted Treatment for Substance Use Disorder (Even Though it Failed to Save Someone Close to Me)

On May 16th, 2023 I got the worst phone call possible about someone in my life: “He overdosed”. There was a pause on the line. I remember that pause as my brain rapidly flashed through everything that short phrase could mean, from a relapse but he is ok, to him being in the hospital, to worse. Then, after that pause, all ambiguity was broken. “He is gone”. I will spare you everything that followed after this. But to say this was the saddest day of my life doesn’t do justice to how much my heart shattered.

So when medication-assisted therapy (MAT) for substance use disorder (SUD) first came on my radar several months later, I was initially skeptical. First off, I was pretty sure the person that I cared about and loved from above was on MAT and it failed to save him. Also, as a physician, I would like to think I am immune to pop culture. But fresh off of seeing series like Dopesick and Painkiller, I was skeptical of big pharma being here to help those who struggle with SUDs. And since the medications that comprise MAT have a controlled substance component (see below), I was worried that those with SUDs were just swapping an illicit narcotic for a socially acceptable narcotic. But I still wanted to do my due diligence before dismissing MAT completely. So I decided to look into MAT more. But before I get into my journey investigating MAT, it is worth giving some background on MAT in general.

How Opioids Work and How They Lead to Overdose:

Opioids are opioid receptor “agonists”. An agonist is a molecule that binds to a receptor and triggers a specific action in the body, similar to how a key starts a car [1]. When an opioid binds to a corresponding opioid receptor, it can suppress pain. It also causes suppression of your respiratory system (your drive and ability to breathe). If used in a high enough dose, this corresponding respiratory suppression becomes too strong, and the amount of breathing drops to the point of becoming inadequate to support life.

What Are The Most Common MAT Components (and How They Work):

?1.) Naltrexone: is an opioid “antagonist” [2]. An antagonist, like an agonist, binds to a given molecule receptor. However, instead of triggering an effect, it just sits on the receptor without triggering the given effect [See Footnote] and blocks agonists from binding at the given receptor [1]. Continuing with our car key analogy, imagine someone placing a covering over the keyhole that prevented you from putting the key in the ignition and starting the car. So in this context, Naltrexone binds to opioid receptors, thereby preventing opioids from binding to these receptors, and having their intended (or unintended) effect. It is important to note that Naltrexone doesn’t reduce the cravings for opioids. Also, enough opioids can still “overpower” Naltrexone, or stay in the system and bind to opioid receptors after the Naltrexone wears off. ?

Footnote: Some antagonists work by not directly blocking the agonist receptor site, but by binding to a different location on the receptor. But for the sake of this article, assume antagonists bind directly to the receptor binding site. ?

2.) Suboxone: has two components: buprenorphine and naloxone. Buprenorphine is a partial opioid agonist [3], which means it activates the same receptors in the brain as other opioids but produces a weaker effect. This helps reduce cravings and withdrawal symptoms in people who are dependent on opioids. Naloxone, like Naltrexone, is an opioid antagonist [4]. It's included in Suboxone to discourage misuse of the medication. If Suboxone is taken as prescribed (under the tongue), the naloxone has little effect. However, if someone attempts to misuse Suboxone by injecting it, the naloxone will block the effects of the buprenorphine, preventing the user from experiencing the high they might seek from opioids [5].?

3.) Methadone: is an opioid agonist, which means it works by binding to the same brain receptors as other opioids, like heroin or prescription painkillers, but methadone exerts its effect more slowly and without producing the same high [6]. The theory is that this produces a steady-state concentration of opioid in the system. This in turn should help alleviate withdrawal symptoms and cravings, making it easier for individuals to break their addiction cycle. By providing a controlled level of opioid in the system, methadone also reduces the euphoric effects of other opioids, which is meant to discourage misuse and help patients to lead more stable lives. It is usually dispensed daily under supervision at clinics.

Back to My Journey Researching MAT – The Literature:

Now that we have a lay of the land of the most common MAT agents, back to me looking into MAT. I started my investigation with Uptodate. This is a doctor’s go to source when determining what the mainstream accepted standard of care is for a given disease or condition. Uptodate can be hit or miss as a resource. But in most cases they do a good job of offering high-level guidance, and are a good starting point. And in this case they provided helpful data and recommendations. These were my takeaways from Uptodate and the supporting literature Uptodate referenced [7]:

·????? In a meta-analysis including 30 observational studies and over 562,000 individuals with Opioid Use Disorder (OUD), treatment with opioid agonists was associated with a greater than 50% reduction in all-cause mortality compared with no opioid agonist treatment. For those that are MDs/Dos/PhDs, or have a background in statistics, the relative risk was 0.47, and the corresponding confidence interval was 0.42-0.53 [8].

·????? Uptodate favors Naltrexone in patients with substance use disorders with a mild substance use disorder. Uptodate favors Suboxone in patients with a moderate to severe substance use disorder. The severity of the substance use disorder is as defined by the DSM-5 [9].

·????? Uptodate had a preference for Suboxone in most cases over Methdaone. However, this recommendation was not absolute, and was more based on the availability of Suboxone and moderately increased risk of adverse effects of methadone over Suboxone, rather than the effectiveness of methadone versus Suboxone [10].

I also wanted to get a sense of the risk of harm to patients when using MAT. The biggest danger of MAT seems to be if the patient uses other respiratory suppressants when using MAT with an opioid agonist component. Overall, Suboxone carries less of a risk of this than Methadone. However, even with Suboxone, there is still a significant risk of death if a patient uses other respiratory suppressants. Of note, the increased risk of death while using respiratory suppressants was not limited to illicit drug use. In a retrospective study looking at 63,389 patients on Suboxone, of the 183 deaths, 31% happened when the patient was using benzodiazepines like Xanax [11]. On a separate note, with Methadone, the therapeutic dose exceeds what would be a lethal dose in an opioid na?ve person. So if someone abstains from both Methadone and illicit drug use for an extended period, and then goes back on Methadone, there is a risk of death and/or other adverse events [12].

My Conversations with Healthcare Professionals:

I didn’t just want to stop at the literature. I also wanted to directly talk with experts in the field.

I had two conversations with physicians who specialize in addiction medicine. Of note, one of the physicians had an important disclosure as being the chief medical officer of a telehealth provider of MAT. I also had a conversation with an intake counselor for an addiction treatment/rehabilitation center. I asked each of them the same set of questions.

My questions included: even though MAT is part of the accepted standard of care, is MAT actually effective, or is it just the best we can offer? Overall, what has your experience been like prescribing MAT and/or working with patients on MAT? What ways, if any, can this medication be abused? What best practices should I be aware of when prescribing MAT?

By the time I was conducting interviews, I was focusing on Suboxone. Both physicians were bullish on the use of Suboxone. They felt that it was a compassionate use of a pharmaceutical agent, and that Suboxone helped prevent illicit drug use. In terms of abuse, my first concern was whether the drug could be altered to change the pharmacokinetics and enhance abuse potential. Both physicians felt if the drug were to be abused, it would most likely be due to patients simply taking more than any type of manipulation of the drug. But both doctors ultimately felt if a patient wanted to abuse drugs, there are easier options out there due to the Naloxone subcomponent in Suboxone. Both physicians agreed that Suboxone should be part of a comprehensive plan that includes psychotherapy.? ?

The counselor had a more bearish opinion. She opened with this: she grew up in a time in which people were expected to quit without the use of pharmaceutical aids. So she admitted that this biased her opinion. However she felt the best results came without the use of MAT. She also noted that, “many [patients] told me they had an easier time quitting heroin than quitting Suboxone”. She also felt that many patients were using MAT to get a “buzz”.

Putting The Pieces Together:

Overall I have become much more in favor of MAT the more learned. This is based both on the reduction in all-cause mortality noted in the literature, as well as my conversations with fellow physicians. I would be lying if I said my conversation with the intake counselor didn’t give me pause. However, I felt her perspective, while valuable, did not outweigh both the research findings and conservations I had with other healthcare providers. So I have decided to give prescribing MAT a try. This will be my initial approach:

1.) Start with a small pilot group of patients.

2.) Only prescribe Suboxone to patients that meet the DSM-5 criteria of moderate to severe SUD. I know the DMS criteria is far from perfect. And I never want to deny compassionate use of medication to those who truly need it. But keep in mind that most MAT patients are recommended to be on MAT for life. So I want to start with a conservative approach and refer patients to Naltrexone and therapy if it is possible they could thrive with those treatments alone. I understand this is controversial.

3.) Work towards a combination approach of therapy and MAT. I actually really like a group therapy approach. However, the reality is this requires a larger base of patients before I can offer this service. So initially I will prescribe MAT and strongly encourage patients to seek therapy. However, I am actively searching to hire a therapist and will make therapy part of my MAT program.

4.) I think I will pass on Methadone prescriptions for now. I feel there is a place for methadone in substance use disorder treatment. However, this is best handled with methadone clinics that specialize in this. So I will strive to make partnerships with methadone clinics, so I can refer patients to these clinics. But I will not directly prescribe methadone.

Closings Thoughts:

In terms of the person from the story I opened with, I hope I am doing right by this person. One way to look at his passing is that MAT failed to save him. However, it is entirely possible that the time we did have together, both in terms of total time and quality time, was in part made possible by MAT. And if that is the case, I am grateful for any contribution that MAT may have made to make that possible.?

References:?

1.???????? Agonist / Antagonist [https://www.drugsandalcohol.ie/glossary/info/agonist#:~:text=Agonist%3A%20A%20chemical%20substance%20that,examples%20of%20opioid%20receptor%20agonists.]

2.???????? What Is Naltrexone? [https://psychiatry.uams.edu/clinical-care/cast/what-is-naltrexone/]

3.???????? Virk MS, Arttamangkul S, Birdsong WT, Williams JT: Buprenorphine is a weak partial agonist that inhibits opioid receptor desensitization. J Neurosci 2009, 29(22):7341-7348.

4.???????? Naloxone [https://www.samhsa.gov/medications-substance-use-disorders/medications-counseling-related-conditions/naloxone#:~:text=Naloxone%20is%20a%20medication%20approved,heroin%2C%20morphine%2C%20and%20oxycodone.]

5.???????? Sivils A, Lyell P, Wang JQ, Chu XP: Suboxone: History, controversy, and open questions. Front Psychiatry 2022, 13:1046648.

6.???????? How do medications to treat opioid use disorder work? NIDA 2021.

7.???????? Eric Strain MMP, PhD, MAC: Opioid use disorder: Treatment overview.

8.???????? Santo T, Jr., Clark B, Hickman M, Grebely J, Campbell G, Sordo L, Chen A, Tran LT, Bharat C, Padmanathan P et al: Association of Opioid Agonist Treatment With All-Cause Mortality and Specific Causes of Death Among People With Opioid Dependence: A Systematic Review and Meta-analysis. JAMA Psychiatry 2021, 78(9):979-993.

9.???????? DSM-5 diagnostic criteria for opioid use disorder [https://www.mcstap.com/docs/DSM%20Checklist.pdf]

10.?????? Bell JR, Butler B, Lawrance A, Batey R, Salmelainen P: Comparing overdose mortality associated with methadone and buprenorphine treatment. Drug Alcohol Depend 2009, 104(1-2):73-77.

11.?????? Park TW, Larochelle MR, Saitz R, Wang N, Bernson D, Walley AY: Associations between prescribed benzodiazepines, overdose death and buprenorphine discontinuation among people receiving buprenorphine. Addiction 2020, 115(5):924-932.

12.?????? Luty J, O'Gara C, Sessay M: Is methadone too dangerous for opiate addiction? Bmj 2005, 331(7529):1352-1353.

?