Managing the Risk of Overdose in Medication-Assisted Treatment for Opioid Use Disorder (OUD)

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The opioid crisis in the United States, which began in the early 1990s, did not disappear during our most recent public health crisis, the coronavirus pandemic. In fact, it got worse. During the pandemic, rates of fatal overdose for all drugs increased. The percentage of opioid involved fatal overdose deaths increased as well.

At the beginning of the pandemic, mental health experts warned that worry about getting sick combined with the stress associated with public health measures such as business closures, shelter-in-place guidelines, social distancing, virtual school, virtual school, and other unforeseen consequences would cause an increase in psychological and emotional disorders such as depression and anxiety.

Evidence indicates they were right. In March 2022, the World Health Organization (WHO) reported a 25 percent increase in the prevalence of depression and anxiety worldwide.

Experts also warned that increase in these mental health issues – which are known risk factors for substance use and substance use disorder (SUD) – would cause an increased in SUD nationwide.

Evidence indicates they were right about that, too. According the National Institutes of Health (NIH), rates SUD increased during the pandemic, which impacted overdose rates.

Here’s the data on overall overdose and opioid related overdose for 2019-2021, as reported by the Centers for Disease Control (CDC):

  • 2019:
    • All drugs: 50.178
    • Opioid-related: 67,697
  • 2020:
    • All drugs: 69,061
    • Opioid-related: 78,056
  • 2021:
    • All drugs: 107,306
    • Opioid-related: 73, 453

We include 2019 and 2020 for context, and to identify the most recent trend in the opioid crisis. That trend – as the numbers show – is not good.

One thing that we can do to address this problem is increase access to and participation in the gold-standard treatment for opioid use disorder (OUD), which is medication-assisted treatment (MAT).

What is Medication-Assisted Treatment (MAT)?

To learn about MAT in detail, please navigate to this page on our website:

Medication-Assisted Treatment

We’ll summarize what you’ll learn on that page for you now, though, in case you don’t want to leave this article. Medication-assisted treatment, known as MAT, is a therapeutic modality most often used for people with opioid use disorder, and sometimes used for people with alcohol use disorder (AUD). For OUD, three FDA-approved medications – methadone, buprenorphine, and naltrexone – help to mitigate the symptoms of withdrawal, reduce opioid cravings, and stabilize people psychologically and physically, which allows them to initiate comprehensive treatment for OUD.

An MAT program always involves counseling, therapy, community support, and lifestyle change: it’s not just about the medication. Evidence shows the following benefits of MAT:

  • Reduced opioid use
  • Decreased overdose rates
  • Increased time-in-treatment
  • Decreased overall mortality (death)
  • Increased participation in work, family, school, and social life
  • Decreased involvement in the criminal justice system
  • Improved outcomes for pregnant women with OUD

Despite these benefits, stigma persists around the use of MAT for OUD. One problem many people cite as a drawback to MAT is the risk of overdose.

We won’t pull any punches: that risk is real.

It happens for two reasons. One is the diversion of the medications used in MAT. Since they’re opioid-based medications, they can be misused, which may result in overdose. However, evidence shows that while diversion is a problem, diverted medications result in a relatively small share of opioid overdose. The second reason is that when a person is on MAT, their tolerance to opioids decreases. Therefore, if they relapse, a typical, pre-MAT dosage of an illicit opioid may be dangerous and lead to overdose.

Since these issues are a real, a team of researchers in Canada conducted a study to determine what factors increase risk of overdose in people with OUD on MAT.

That study is the topic of this article.

MAT, OUD, and Overdose

We mention these issues are real: they are very real. And they’re a very real concern because MAT is the best treatment we have for OUD – and fear of overdose increases stigma around MAT. Stigma has a negative impact on public policy, public perception, individual perception, and individual willingness to initiate an MAT program.

That’s why researchers sought to learn more about the factors that may increase overdose risk for people with OUD on MAT.

Here’s how the lead researchers on the study describe their goals:

  1. Identify the lifetime prevalence of self-reported opioid overdoses among patients currently receiving MAT, and the past-year prevalence of self-reported overdose requiring care in the emergency department
  2. Explore factors associated with opioid overdoses during MAT
  3. Examine the association between length of time in MAT and opioid overdose

This information can help. In light of the ongoing opioid crisis, we need to know everything we can about MAT, which – as we state above – is the current gold-standard treatment for OUD.

Let’s take a look at that study.

New Research on MAT for OUD: How They Did It

Researchers recruited from 2,360 participants from an ongoing, long-range research effort called the Pharmacogenetics of Opioid Substitute Treatment Response (POST) study. To qualify for this secondary study, participants met the following criteria:

Treatment for OUD in Canada works differently than here in the U.S. Because Canada has a single-payer healthcare system, it’s possible to organize anyone in MAT and deliver care through a centralized system. Therefore, all patients in MAT programs engage in treatment managed by the Canadian Addiction Treatment Centers (CATC).

About CATC:

  • Serves over 15,000 patients
  • Administers methadone or buprenorphine + Naloxone, called Suboxone
  • Buprenorphine alone is not approved for MAT in the general population
  • Buprenorphine alone is approved for MAT for pregnant women diagnosed with OUD

But we digress: back to this specific study.

First, let’s look at the data they collected.

Overdose Risk: Critical Metrics

To establish baseline reference values for the study topics, researchers collected a wide range of information from each participant, including:

  • Demographic characteristics
  • Substance use characteristics
  • Substance use history
  • Medical history
  • Overdose history:
    • Any lifetime overdose
    • Past-year overdose requiring visit to hospital emergency department (ED)
  • OUD treatment history
  • MAT treatment history:
    • Dosage
    • Duration of treatment
  • Psychological and physical symptoms, using the Maudsley Addiction Profile (MAP)
    • Measured psychological symptoms included:
      • Anxiety
      • Tension
      • Fear
      • Anger/irritability
      • Anhedonia
      • Loneliness
      • Hopelessness
      • Suicidal ideation
    • Measures physical symptoms included:
      • Appetite
      • Fatigue
      • Muscle/joint pain
      • Respiratory problems
      • Digestive problems
      • Neurological/cognitive problems

Researchers needed information on all these subjects/metrics from each patient in order to clarify what factors increased risk of overdose for people with OUD on MAT, and what factors had no effect or potentially decreased overdose risk. The breadth of data collected combined with the size of the study group add weight to the experimental results.

Let’s take a look at those results now.

What Increases Overdose Risk for People with OUD on MAT?

Researchers divided the 2,360 participants – all people with OUD on MAT – into three groups: those with no reported overdose, those with any history of overdose, and those with a past year overdose that required a visit to a hospital emergency room (ER).

Here are the results for each of these groups.

No History of Overdose

Total: 1,619 (69%)

  • Demographics:
    • Average age: 40
    • 45% female/55% male
    • 29% high school graduates
    • 70% had children
    • 36% were employed
    • 51% received social assistance
  • Treatment:
    • Methadone: 1270 (79%)
    • Suboxone: 346 (21%)
    • Average time in treatment: 3 years
    • Previous treatment, non-MAT: 500 (31%)
    • Abstinent from opioid use at treatment initiation: 537 (33%)
  • Substance Use:
    • Average age of onset of OUD: 26
    • IV drug use in past 30 days: 164 (10%)
    • Alcohol use in past 30 days: 588 (36%)
    • Prescription benzodiazepine use in past 30 days: 242 (15%)
    • Non-prescription benzodiazepine use in past 30 days: 88 (5%)
    • Cannabis use in past 30 days: 846 (52%)
    • Had access to Naloxone: 1,210 (75%)
    • Knew how to use Naloxone: 1,263 (77%)
  • Psychological and Physical Symptoms:
    • Average psychological symptoms score on MAP: 11
    • Average physical symptoms score on MAP: 14
    • Presence of suicidal ideation: 298 (18%)

Next, let’s look at the results for people who reported at least one overdose during their lives.

Lifetime History of Overdose

Total: 562 (24%)

  • Demographics:
    • Average age: 39
    • 44% female/56% male
    • 27% high school graduates
    • 65% had children
    • 28% were employed
    • 62% received social assistance
  • Treatment:
    • Methadone: 456 (81%)
    • Suboxone: 105 (19%)
    • Average time in treatment: 2.4 years
    • Previous treatment, non-MAT: 217 (39%)
    • Abstinent from opioid use at treatment initiation: 166 (30%)
  • Substance Use:
    • Average age of onset of OUD: 23
    • IV drug use in past 30 days: 127 (23%)
    • Alcohol use in past 30 days: 208 (37%)
    • Prescription benzodiazepine use in past 30 days: 103 (18%)
    • Non-prescription benzodiazepine use in past 30 days: 64 (11%)
    • Cannabis use in past 30 days: 310 (54%)
    • Had access to Naloxone: 472 (84%)
    • Knew how to use Naloxone: 493 (88%)
  • Psychological and Physical Symptoms:
    • Average psychological symptoms score on MAP: 15
    • Average physical symptoms score on MAP: 13
    • Presence of suicidal ideation: 134 (24%)

We can see trends emerging here, the most notable being time-in-treatment use of non-prescription use of benzodiazepines. Let’s track those metrics as we review this next set of results, which are for people who reported an overdose in the last month that required them to got to a hospital emergency room.

Past Year, ED-Involved Overdose

Total: 179 (8%)

  • Demographics:
    • Average age: 35
    • 41% female/59% male
    • 24% high school graduates
    • 65% had children
    • 17% were employed
    • 67% received social assistance
  • Treatment:
    • Methadone: 142 (79%)
    • Suboxone: 37 (21%)
    • Average time in treatment: 6 months
    • Previous treatment, non-MAT: 87 (49%)
    • Abstinent from opioid use at treatment initiation: 29 (16%)
  • Substance Use:
    • Average age of onset of OUD: 22
    • IV drug use in past 30 days: 84 (47%)
    • Alcohol use in past 30 days: 74 (42%)
    • Prescription benzodiazepine use in past 30 days: 24 (13%)
    • Non-prescription benzodiazepine use in past 30 days: 28 (16%)
    • Cannabis use in past 30 days: 110 (68%)
    • Had access to Naloxone: 158 (88%)
    • Knew how to use Naloxone: 171 (95%)
  • Psychological and Physical Symptoms:
    • Average psychological symptoms score on MAP: 15
    • Average physical symptoms score on MAP: 16
    • Presence of suicidal ideation: 57 (32%)

We were right to track those two metrics. They increased for people who reported an ER-involved overdose in the past thirty days.

Now we’re ready to compare the results from these three study groups and identify which factors correlated with increased risk of overdose, and which did not.

Factors That Increase Overdose Risk: Demographics, Treatment, Substance Use, Mental and Physical Symptoms

This is the most relevant section of this study. The purpose of the research effort was to identify factors that increased risk for overdose in four areas: demographics, treatment, substance use, and psychological/physical symptoms. We’ll report those associations now, starting with demographics.

Demographic Factors: What Increases Overdose Risk?

  • Employment:
    • No overdose: 34% employed
    • Lifetime overdose: 28% employed
    • Past year ED-involved overdose: 17%
Individuals with no overdose history were employed at twice the rate as individuals with past month ED-involved overdose.
  • Use of Social Services:
    • No overdose: 51% reported use of social services
    • Lifetime overdose: 62% reported use of social services
    • Past year ED-involved overdose: 68% reported use of social services
Individuals with lifetime and past-month ED-involved overdose reported use of social services at significantly higher rates than those with no overdose history.
  • Age:
    • Average age in no overdose group: 40
    • Average age in lifetime overdose group: 39
    • Average age in past month ED-involved overdose: 35
Younger age is associated with increased risk of overdose.

Among the measured demographic characteristics, gender, education, marital status, and parental status were unrelated to increased overdose risk.

Now let’s look at the relationship between treatment factors and overdose risk.

Treatment Factors: What Increases Overdose Risk?

  • Time-in-treatment:
    • No overdose: 3 years
    • Lifetime overdose: 2.5 years
    • Past year ED-involved overdose: 0.5 years
Less time-in-treatment correlates significantly with increased overdose risk.
  • Previous treatment:
    • No overdose: 31% reported previous treatment
    • Lifetime overdose: 39% reported previous treatment
    • Past year ED-involved overdose: 49% reported previous treatment
Individuals who engaged in previous treatment for OUD reported higher rates of past year ED-involved overdoses.
  • Abstinence from opioids at initiation of MAT:
    • No overdose: 33%
    • Lifetime overdose: 30%
    • Past year ED-involved overdose: 16%
Non-abstinence at initiation of MAT correlates significantly with increased risk of overdose.

Among the measured treatment characteristics, the type of medication is unrelated to increased overdose risk.

Next, we’ll look at the between substance use factors and overdose risk.

Substance Use Factors: What Increases Overdose Risk?

  • Average age at diagnosis of OUD:
    • No overdose: 26
    • Lifetime overdose: 23
    • Past month ED-involved overdose: 22
Younger age at diagnosis of OUD correlates mildly with increased overdose risk.
  • Past 30-day IV drug use:
    • No overdose: 10% reported past 30-day IV drug use
    • Lifetime overdose: 23% reported past 30-day IV drug use
    • Past month ED-involved overdose: 47% reported past 30-day IV drug use
Past 30-day IV drug use correlates strongly with increased overdose risk.
  • Past 30-day non-prescription benzodiazepine use:
    • No overdose: 5% reported past 30-day non-prescription benzodiazepine use
    • Lifetime overdose: 11% reported past 30-day non-prescription benzodiazepine use
    • Past month ED-involved overdose: 16% reported past 30-day non-prescription benzodiazepine use
Individuals with lifetime history of overdose used non-prescription benzodiazepines a twice the rate as those with no overdose, while individuals who reported an ED-involved overdose in the past 30 days used non-prescription benzodiazepines at three times the rate of those with no overdose.
Non-prescription benzodiazepine use correlates strongly with increase overdose risk.

Among the measured substance use characteristics, alcohol use, cannabis use, and prescription benzodiazepine use do not correlate strongly with increased risk of overdose. However, it’s interesting to note that access to Naloxone and knowing how to use Naloxone do significantly correlate with increased overdose risk: individuals in the past 30-day ED-involved overdose group reported higher rates of access to Naloxone, and also reported higher rates of familiarity with Naloxone administration.

Now we’re ready to offer our last set of data: the relationship between psychological and physical symptoms and overdose risk.

Psychological and Physical Factors: What Increases Overdose Risk?

  • Psychological Factors:
    • No overdose: average score of 8 on the MAP assessment
    • Lifetime overdose: average score of 13 on the MAP assessment
    • Past month ED-involved overdose: average score of 15 on the MAP assessment

Higher scores on the psychological MAP assessment appear to correlate weakly with increased risk of overdose. However, after researcher controlled for sociodemographic and other clinical factors, those correlations disappeared. On a related note, individuals with a lifetime and 30-day history of overdose reported more physical symptoms, compared to individuals with no history of overdose.

  • Suicidal Ideation:
    • No overdose: 18% reported suicidal ideation
    • Lifetime overdose: 24% reported suicidal ideation
    • Past month ED-involved overdose: 32% reported suicidal ideation
Higher rates of suicidal ideation correlate with increased risk of overdose for individuals with past-month ED-involved overdose.

Those are the results. Evidence shows that younger age, employment status, use of social services, misuse of non-prescription benzodiazepines, non-abstinence at treatment initiation, and IV drug use are all associated with increased risk of overdose, while gender, education, marital status, alcohol use, and cannabis use were not associated with increased risk of overdose for people with OUD on MAT.

How This Research Helps

We support people with OUD in MAT programs every day of the week. Their ongoing health and overall wellbeing is our primary goal and overall mission. That’s why we take overdose prevention in MAT programs seriously. We follow federal guidelines to monitor dosage, increase treatment adherence, and prevent diversion.

Now, with the results from this study, we have a new group of factors to screen for when determining overall risk of overdose, which informs the details of how we create an individualized treatment plan for an individual with OUD. We now know – with evidence to support this knowledge – what factors most substantially increase overdose risk for people on MAT: non-abstinence at initiation of treatment, use of non-prescription benzodiazepines, and younger age at diagnosis of OUD.

Based on this evidence – with enhanced screening for these specific risk factors – we can improve outcomes for people with OUD on MAT, beginning with the most important goal of all: prevention of opioid overdose.