Treatment for Opioid Use Disorder: Finding the Most Effective Modality

Evidence collected over the past five decades shows that the most effective treatment for opioid use disorder (OUD) is medication-assisted treatment (MAT). This approach to treatment for opioid addiction involves therapy, counseling, and one of three medications approved by the Food and Drug Administration (FDA): methadone, buprenorphine, and Naltrexone.

Many people may be surprised we have close to 50 years of data on MAT – but it’s true. The first methadone clinics opened in New York City in the early 1970s, naltrexone received FDA approval in 1984, and buprenorphine received FDA approval in 2002.

Researchers have studied these drugs extensively during the time since the first methadone clinic opened, and with each new study, results indicate that MAT can lead to the following benefits:

• Reduced opioid use
• Reduced opioid overdose
• Improved time-in-treatment
• Improved daily functioning: home, school, work, social activity
• Reduced criminal activity
• Improved outcomes for pregnant women with OUD

However, one thing missing from the research on MAT is a large-scale, nationally representative study that compares treatment outcomes for people with OUD on MAT against other treatment modalities. That’s why an original investigation published by the Journal of the American Medical Association got our attention.

The name of the study reveals its relevance:

“Comparative Effectiveness of Different Treatment Pathways for Opioid Use Disorder”

This article will discuss the results of this research effort, which fills the void in the data we mention above. It’s a large-scale, nationally representative study that compares outcomes of various treatment modalities for people who meet criteria of opioid use disorder (OUD) as defined by the Diagnostic and Statistical Manual of Mental Disorders, Volume 5 (DSM-5).

We’ll describe the study, report the results, and end with a brief discussion of how these results can support and inform treatment for OUD moving forward, as we work to mitigate the ongoing harm caused by the opioid crisis in the United States.

Evidence-Based Treatment for Opioid Use Disorder: About the Study

Here’s how the study authors describe their investigation:

“This retrospective comparative effectiveness study was designed to inform treatment decisions made by policy makers, insurers, practitioners, and patients.”

That’s important work that meets a real, demonstrated need in the U.S. In 2021, over 100,000 people died of drug overdose, and over 70 percent of those overdose deaths involved opioids. That means this research – as over-the-top as this may sound – can literally save lives. Anything we can learn to help offer people the treatment they need will help.

To that end, researchers examined records from 40,885 individuals diagnosed with OUD with either commercial insurance or insurance through the Medicare Advantage (MA) system, in which private insurers contract with Medicare to provide a variety of insurance options. Records from insurers provided the primary data for analysis in this study.

Here are the reported baseline characteristics of the 40,855 person study group, called a cohort:

• Over age 16
• Diagnosis of OUD
• Commercially insured or MA insured

Here’s a list of relevant information on the cohort:

• Average age:
  • 47
  • 16-34: 28%
  • 35-64: 54%
  • 65+: 18%
• Gender:
  • 54% male
  • 46% female
• Insurance status:
  • 58% commercial insured
  • 42% MA insured
• Race/ethnicity:
  • 74% White
  • 2% Black
  • 3% Hispanic
  • 3% other or unknown
• Mental health status:
  • 45% diagnosed with co-occurring mental health disorder. Among those:
    • Anxiety: 26%
    • Depression: 24%
    • Bipolar disorder: 8%
    • Post-traumatic stress disorder (PTSD): 4%
    • Psychosis: 4%
    • ADHD: 4%
    • Other: 30%

Among these 40,000+ participants, researchers examined the outcomes of treatment for OUD for six mutually exclusive treatment pathways:

1. No treatment:

• • 5% of the cohort received no treatment

2. Inpatient detoxification or residential services:

• • 16% of the cohort participated in inpatient detox or residential treatment

3. Intensive behavioral health:

• • 5% of the cohort participated in intensive behavioral health treatment

4. Buprenorphine or methadone:

• • 12% of the cohort received medication-assisted treatment with buprenorphine or methadone

5. Naltrexone

• • 2% of the cohort received medication-assisted treatment with Naltrexone

6. Non-intensive behavioral health

• • 60% of the cohort received non-intensive behavioral health treatment

In most cases – with the exception of no treatment, these treatment modalities are delivered to patients in combination with other treatment modalities. However, in this study, individual records corresponded to participants that engaged in/received treatment from one pathway only, and did not combine treatment modalities.

To determine treatment effectiveness, researchers used the following metrics:

• Instances of opioid-related overdose:
  • At three months after treatment initiation
  • At 12 months after treatment initiation
• Instances of need for serious acute medical care related to opioid use:
  • At three months after treatment initiation
  • At 12 months after treatment initiation

That’s the information on the participants, the study method, and the metrics researchers used to determine the effectiveness of each of the six therapeutic approaches.

Now let’s take a look at the results.

Which Approach to OUD Treatment Was Most Effective?

To measure treatment effectiveness, researchers analyzed records at three months and 12 months after the initiation of treatment to identify the relative risk of overdose and the need for acute medical care associated with each treatment method.

Here’s what they found.

Comparing Treatments for OUD: Three-Month Follow Up

Overdose:

• 707 participants (1.7%) reported at least one opioid overdose within three months of initiating treatment

Risk Of Overdose by Treatment Method:

Note: in this study, researchers assigned a hazard ratio to each treatment method, with the no treatment group assigned a reference value of (1). In this study, hazard ratio values over 1 indicate increased risk of overdose, while hazard ratio values under (1) indicate decreased risk of overdose. For instance, with regards to overdose at three months, a hazard ratio of 0.5 means that for that treatment method, an individual is 50% – half – as likely to overdose at three months, compared to an individual who received no treatment at all. The first number you read is the average hazard for that method, while the numbers in parentheses represent the range for that method. Only methods with a range under (1) indicate statistically significant decreased risk of overdose.

Here’s the data:

• No treatment:
  • Hazard ratio: 1
• Inpatient detoxification or residential services:
  • Hazard ratio: 0.82 (0.57-1.19)
    • Patients who participated in inpatient detoxification or residential services were 82% as likely to overdose as patients who received no treatment.
• Intensive behavioral health:
  • Hazard ratio: 0.81 (0.5-1.32)
    • Patients who participated in intensive behavioral health programs were 81% as likely to overdose as patients who received no treatment.
• Buprenorphine or methadone:
  • Hazard ratio: 0.24 (0.14-0.41)
    • Patients who participated in buprenorphine or methadone programs were 24% as likely to overdose as patients who received no treatment.
• Naltrexone:
  • Hazard ratio: 0.59 (0.29-1.20)
    • Patients who received Naltrexone were 59% as likely to overdose as patients who received no treatment
• Non-intensive behavioral health
  • Hazard ratio: 0.92 (0.67-1.27)
    • Patients who received non-intensive behavioral health treatment were 92% as likely to overdose as patients who received no treatment

Serious Acute Medical Care Related to Opioid Use:

• 773 (1.9%) reported the need for acute care related to opioid use within 3 months of initiating treatment

Serious Acute Medical Care Related to Opioid Use by Treatment Method:

• No treatment:
  • Hazard ratio: 1
• Inpatient detoxification or residential services:
  • Hazard ratio: 1.05 (0.76-1.45)
    • Patients who participated in inpatient detoxification or residential services were 5% more likely to need acute opioid-related medical care as patients who received no treatment.
• Intensive behavioral health:
  • Hazard ratio: 0.84 (0.54-1.30)
    • Patients who participated in intensive behavioral health programs were 84% as likely to need acute opioid-related medical care as patients who received no treatment.
• Buprenorphine or methadone:
  • Hazard ratio: 0.68 (0.47-0.99)
    • Patients who participated in buprenorphine or methadone programs were 62% as likely to need acute opioid-related medical care as patients who received no treatment.
• Naltrexone:
  • Hazard ratio: 1.15
    • Patients who received Naltrexone were 15% more likely to need acute opioid-related medical care as patients who received no treatment
• Non-intensive behavioral health
  • Hazard ratio: 0.59 (0.44-0.80)
    • Patients who received non-intensive behavioral health treatment were 59% as likely to need acute opioid-related medical care as patients who received no treatment

Summary of Results of Three-Month Follow-Up:

• Treatment with buprenorphine or methadone was the only treatment method associated with a reduced risk of overdose at the three-month follow-up. At three months, patients on buprenorphine or methadone had 76 percent reduced likelihood of overdose.
• Treatment with buprenorphine or methadone was also the only treatment method associated with reduced need for acute opioid-related medical care at three-month follow up. At three months patients on buprenorphine or methadone had 32 percent reduced likelihood of need for acute opioid-related medical care.

That’s a lot of information – and we’re only half-way through. The reason this data is relevant to us, as treatment providers, and to our readers, as concerned family members, people seeking treatment, or people in treatment, is that this study is the only recent nationally representative study that compares outcomes for treatment methods for people with OUD. In light of the ongoing, and worsening, opioid crisis, this information may help people make an informed decision about what type of treatment to pursue.

With that reminder, let’s look at the data from the 12-month follow up.

Comparing Treatments for OUD: 12-Month Follow Up

Overdose:

• 1,432 participants (3.5%) reported at least one opioid overdose within 12 months of initiating treatment.

Risk Of Need for Overdose by Treatment Method:

• No treatment:
  • Hazard ratio: 1
• Inpatient detoxification or residential services:
  • Hazard ratio: 1 (0.79-1.25)
    • Patients who participated in inpatient detoxification or residential services were as likely to overdose as patients who received no treatment.
• Intensive behavioral health:
  • Hazard ratio: 0.75 (0.56-1.02)
    • Patients who participated in intensive behavioral health programs were 75% as likely to overdose as patients who received no treatment.
• Buprenorphine or methadone:
  • Hazard ratio: 0.41 (0.31-0.55)
    • Patients who participated in buprenorphine or methadone programs were 41% as likely to overdose as patients who received no treatment.
• Naltrexone:
  • Hazard ratio: 0.73 (0.48-1.11)
    • Patients who received Naltrexone were 73% as likely to overdose as patients who received no treatment
• Non-intensive behavioral health
  • Hazard ratio: 0.69 (0.56-0.85)
    • Patients who received Naltrexone were 69% as likely to overdose as patients who received no treatment

Serious Acute Medical Care Related to Opioid Use:

• 1,554 participants (3.8%) reported the need for acute care related to opioid use.

Serious Acute Medical Care Related to Opioid Use By Treatment Method:

• No treatment:
  • Hazard ratio: 1
• Inpatient detoxification or residential services:
  • Hazard ratio: 1.2 (0.96-1.50)
    • Patients who participated in inpatient detoxification or residential services were 2% more likely to need acute opioid-related medical care as patients who received no treatment.
• Intensive behavioral health:
  • Hazard ratio: 0.9 (0.67-1.20)
    • Patients who participated in intensive behavioral health programs were 90% as likely to need acute opioid-related medical care as patients who received no treatment.
• Buprenorphine or methadone:
  • Hazard ratio: 0.74 (0.58-0.95)
    • Patients who participated in buprenorphine or methadone programs were 74% as likely to need acute opioid-related medical care as patients who received no treatment.
• Naltrexone:
  • Hazard ratio: 1.07 (0.75-1.54)
    • Patients who received Naltrexone were 7% more likely to need acute opioid-related medical care as patients who received no treatment
• Non-intensive behavioral health
  • Hazard ratio: 0.60 (0.48-0.74)
    • Patients who received non-intensive behavioral health treatment were 60% as likely to need acute opioid-related medical care as patients who received no treatment

Summary of Results of 12-Month Follow-Up:

• Treatment with buprenorphine or methadone was the only treatment method associated with a significant reduced risk of overdose at the three-month follow-up. At 12 months, patients on buprenorphine or methadone had 59 percent reduced likelihood of overdose.
• Treatment with buprenorphine or methadone was also the only treatment method associated with reduced need for acute opioid-related medical care at 12-month follow up. At 12 months patients on buprenorphine or methadone had 26 percent reduced likelihood of need for acute opioid-related medical care.
• Of note is that patients who received non-intensive behavioral health treatments, at 12-month follow-up, had 40 percent reduced likelihood of need for acute opioid-related medical care. We’ll discuss that result in a moment.

The most significant information in the results we list above is buried toward the beginning. We know MAT is effective because we see it work every day. People on MAT stabilize, enter treatment, and in many cases, change their lives completely and for the better. We know MAT works, and in combination with other treatment modalities, such as therapy, counseling, and lifestyle changes, MAT brings positive change to individuals, families, and communities.

What surprised us is this fact:

Only 12 percent of the people in this study engaged in MAT.

Out of 40,885 people, that’s less than 5,000. Unfortunately, that aligns with the latest information on the treatment gap for OUD nationwide, as reported in the National Survey on Drug Use and Health (NSDUH).

How This Research Helps

First, it confirms the effectiveness of MAT compared to no treatment at all, and compared to the most common, non-MAT approaches to OUD treatment, which are inpatient detoxification, psychotherapy, and behavioral counseling.

Second, it confirms what we know about the treatment gap: it’s far too wide, and we need to work to close the gap and provide evidence-based treatment to anyone who needs it.

Third, it validates our commitment to the counseling and therapy components of MAT. At 12-month follow-up, participants in non-intensive behavioral therapy showed a 31 percent reduced likelihood of overdose, and 40 percent reduced likelihood of the need for acute, opioid-related medical care.

Finally, the big-picture takeaway is that MAT is, in fact, as effective as we thought. Compared to the other modalities, it’s the most effective for reducing overdose and reducing the need for acute medical care. When we combine that knowledge with the fact that behavioral counseling can also contribute to reduced overdose risk, we know that offering MAT in the integrated, whole person context – which is what we do every day – is a safe, effective, lifesaving approach to treating people with OUD.