Suboxone v. Methadone v. Naltrexone in Opioid Addiction Treatment

The medications most widely prescribed today in the treatment of opioid addiction are methadone, the combination-medicine of buprenorphine/naloxone (most commonly sold under the brand Suboxone®) and naltrexone. Here’s what you need to know about these medications, how they are administered and the effectiveness of medication-assisted treatment options for opioid addiction.

First, a quick note about terminology: The word opiate refers to natural substances that can be extracted from the flowering opium poppy plant, such as heroin, morphine and codeine. Opioid is a broader term used to describe these natural substances as well as man-made substances such as fentanyl and semi-synthetic substances such as oxycodone. All opiates are opioids, but not all opioids are opiates.

What Is Methadone?

Since the 1960s, methadone has been the primary medication to assist in opioid addiction treatment.

Methadone is a medication that—like morphine, oxycodone and heroin—works as an "opioid agonist," activating receptors in the brain and changing how the brain responds to pain. 

Available only through methadone maintenance clinics and opioid treatment programs certified by the Substance Abuse and Mental Health Services Administration (SAMHSA), methadone is ideally used in conjunction with other addiction treatment therapies and services. Its use is highly regulated, which provides a level of structure—daily dosing, for example—that is beneficial for some patients.

Taken as a tablet, injectable solution or oral solution, a single dose of methadone can last 24-36 hours, although it varies from person to person, depending on body weight and the severity of the opioid use disorder.

When taken daily, methadone can relieve opioid cravings, decrease withdrawal symptoms, promote abstinence from other substances and help people function in their daily lives. While safer than the other opioid agonists it helps people to stop using, methadone does come with some risks. As a Schedule II drug as defined by the U.S. Drug Enforcement Administration, methadone has a high risk of misuse. If methadone treatment is not carefully managed and the medication is not used exactly as prescribed in the treatment of heroin or other opioid addiction, it is possible for users to get intoxicated and overdose. Methadone also has considerable street value, along with a history of being diverted for nonprescription use.

The most common side effects of methadone include sleepiness, constipation, vomiting, headache, nausea and stomach pain.

What Is Buprenorphine/Naloxone?

In 2002, the U.S. Food and Drug Administration approved a buprenorphine monotherapy, Subutex® (no longer sold in the U.S., although generic versions exist), and a buprenorphine/naloxone combination product, Suboxone®, for treating opioid addiction. In the combination product, the buprenorphine works to keep opioid withdrawal symptoms at bay, and the naloxone discourages misuse of the medication. The combination product is generally considered to be safer than buprenorphine alone. It has been shown to be effective in reducing opioid cravings, reducing the risk of relapse and overdose, and improving retention and engagement in addiction treatment.

Buprenorphine belongs to a class of drugs called "partial opioid agonists"—substances that activate the brain’s opioid receptors but to a lesser degree than full agonists like methadone. At a certain level, buprenorphine provides comfort but reaches a plateau in terms of increasing intoxication. This ceiling effect helps protect against addictive euphoria and reduces the risk of misuse, dangerous side effects and overdose. Naloxone, the other drug in the combination product buprenorphine/naloxone, is an "opioid antagonist"—it blocks the activation of opioid receptors. Also known as Narcan®, naloxone is most commonly used as a stand-alone medication to reverse opioid overdoses. In buprenorphine/naloxone, the naloxone has no effect unless the medication is crushed or otherwise manipulated, which is why it serves to deter improper use.

As part of a medication-assisted treatment and recovery program, buprenorphine/naloxone is typically taken daily as a tablet or dissolvable film under the tongue.

The most common side effects associated with buprenorphine/naloxone are constipation, chills, diarrhea, dizziness, drowsiness, flushing, headache, insomnia, nausea, weakness and sweating.

A new medication, Sublocade®, is an extended-release form of buprenorphine designed to be injected monthly.

What Is Naltrexone?

Naltrexone is a non-addictive medication that, like naloxone, acts as an “opioid antagonist,” meaning it prevents the euphoric high that individuals normally experience when taking opioids. Given most often as an extended-release injection once a month and sold under the brand Vivitrol®, naltrexone has been shown to decrease opioid cravings, reduce the risk of relapse and overdose, and help people stay engaged in addiction treatment programming.

Methadone, buprenorphine/naloxone and naltrexone are life-saving medications. They also can interact with other medications and cause serious side effects. Talk with your physician about all medications you may be taking.

What Is Medication-Assisted Treatment?

Medication-assisted treatment (MAT) refers to the use of medications in the treatment of addiction and the general view that medications are most effective when combined with, or assisting, evidence-based psychosocial therapies. MAT is most typically used to describe treatment for opioid use disorders, for which there is substantial evidence to support the use of medications. Medicine is also sometimes used in the treatment of alcohol use disorder and other addictions. Alternative terms for MAT include pharmacotherapy and medication-assisted recovery.

Why Doesn't Hazelden Betty Ford Use Methadone to Treat Opioid Use Disorders?

We found that buprenorphine and extended-release naltrexone were better, safer options for our patients, who typically seek long-term recovery from all problematic substance use. While methadone is effective and useful for certain populations, people in methadone maintenance programs don't typically have an abstinence orientation, which can result in continued use of other drugs such as benzodiazepines, cocaine, alcohol or marijuana. In addition, the regulatory limitations with methadone treatment are onerous, which makes buprenorphine/naltrexone a more convenient option for those of our patients who, in consultation with their care team, choose to use medication.

Doesn't Medication-Assisted Treatment Just Replace One Drug for Another?

No, that would be a stigmatizing and harmful characterization. There are differences between substances used to get high and medications used under a physician's care to get well. The medically supervised use of buprenorphine/naloxone or naltrexone, for example, can aid in detox, encourage engagement in treatment, support long-term recovery and save lives. At the Hazelden Betty Ford Foundation, we maximize the impact of medications by also providing patients with robust, evidence-based psychosocial therapies and peer support. We also try to engage our patients in care for as long as it takes to help them comfortably transition from clinical management of their disease to community-supported self-management of their recovery. If our patients are using medication as prescribed and not using other substances, then they are abstinent and in recovery. At the same time, if patients decide at some point—sooner or later—that they no longer wish to use medications, we help them pursue that goal safely. We know medications help many but also that long-term recovery is possible without them in many cases. All such decisions are made collaboratively between the patient and his or her care team.

Current research does not provide information to indicate who requires medication for opioid use disorder and who does not. As a result, we recommend medications to the vast majority of our patients who have opioid use disorder, due to the higher risk of overdose death associated with the disorder. In addition, we generally recommend use of these medications long term—especially until the patient is in good, solid recovery. We also recognize medication decisions are up to the individual and will provide addiction treatment services with or without use of these lifesaving medications.

Who Can Provide Medication-Assisted Treatment for Opioid Addiction?

Unlike methadone, which must be dispensed through a clinic, buprenorphine/naloxone and naltrexone are prescribed by qualified physicians and mid-level practitioners in doctor's offices, community hospitals and health departments—making them more convenient options for patients. As with all medications used in medication-assisted treatment, buprenorphine/naloxone and naltrexone should be prescribed as part of a comprehensive treatment plan for substance use disorder.

Should a Patient Stop Taking Methadone or Buprenorphine/Naloxone without Seeing a Medical Professional?

No. If you need or wish to stop taking methadone or buprenorphine/naloxone, the dosage should be slowly adjusted over time to prevent opioid withdrawal symptoms. Ideally, addiction counseling, behavioral therapy and peer support should be utilized throughout the process as well. Do not stop taking the medication on your own. The process must be carefully regulated. Always consult medical professionals.

Is It Possible to Overdose on Methadone?

Yes. The most dangerous symptom is respiratory distress—the medication can slow or stop your breathing. Consuming alcohol while taking buprenorphine or methadone can also increase the risk of breathing difficulties. 

Other signs of overdose can include:

• Drowsiness
• Slowed or shallow breathing
• Low blood pressure, leading to fainting
• Cold, clammy skin
• Muscle weakness
• Stomach pain
• Slow pulse
• Extreme sedation, leading to coma

If you suspect an overdose, call 911 immediately. If you or a loved one is at risk for overdosing, please also consider keeping the medication naloxone (commonly sold under the brand name Narcan®) on hand. Naloxone is a life-saver that can reverse the effects of an overdose.

How Effective Is Hazelden Betty Ford’s Medication-Assisted Treatment Approach?

Our clinicians developed the Comprehensive Opioid Response with the Twelve Steps (COR-12®) program to innovatively integrate the use of medications with evidence-based psychosocial therapies and peer support, while engaging patients in care for longer periods of time at decreasing levels of intensity, and providing opioid-specific education and group therapy.

In a peer-reviewed addiction study published in the September 2019 issue of the Journal of Substance Abuse Treatment, our COR-12® framework was shown to result in high rates of medication compliance, high engagement in other aspects of treatment and recovery support, and high rates of continuous abstinence in the first six months after initiating recovery.

At Hazelden Betty Ford, treatment for opioid use disorder addresses all facets of recovery through science-based assessments, medication-assisted treatment and other evidence-based practices, including ongoing recovery support. We offer programming to address mental, emotional and spiritual health. Integrated care focuses on healing the body, mind and spirit. Mental health professionals work in tandem with addiction counselors and medical professionals to address co-occurring mental health conditions such as anxiety, depression, trauma, bi-polar disorder and other conditions.