An estimated 2.7 million people in the U.S. have opioid use disorder (OUD).[1] One of the primary ways to combat this complex, chronic disease is with Medication for Addiction Treatment (MAT) programs, which use a combination of medication and behavioral therapy.
Three primary medications are used in MAT:
- Methadone
- Naltrexone
- Buprenorphine
Although they all work with the opioid receptors in the brain, there are important differences to know before starting treatment. You’ll work with your addiction treatment team to determine the best choice for you.
Key Facts About Methadone Alternatives
Key Facts
- MAT significantly increases a person’s chances of sticking to a recovery plan and staying away from opioid misuse.[2]
- Some people switch from methadone to buprenorphine because they like the convenience of using their medication at home instead of in a clinic.[3]
- Naltrexone helps people stay abstinent and stay out of the criminal justice system.[4]
- When compared to abstinence alone, buprenorphine is much more likely to help people avoid opioid misuse.[5]
Methadone to Treat Opioid Use Disorder: First of Its Kind
Chemists first isolated methadone in the 1940s, but it wasn’t used to treat people with OUD until 14 years later.[6] Even then, researchers worried that people would misuse this drug rather than recognizing that it would save lives. That confusion persists today.
Methadone is an opioid agonist, meaning it’s capable of attaching to the same receptors used by heroin and prescription painkillers. But the attachment is comparatively weak, and people with OUD don’t use methadone to get high.
Misuse potential exists for people who use methadone without OUD. For this reason, it’s a Schedule II controlled medication.[7]
SAMHSA
Because methadone is so tightly controlled, people new to the medication must use it while supervised. They head to a clinic and take the medication while their doctors watch. Only later can they take the drug on their own at home.
Other, more recent alternatives to methadone have proven effective and are often more convenient.
How Many Methadone Alternatives Are There?
Quick Answer
The U.S. Food and Drug Administration (FDA) recognizes two methadone alternatives for MAT.[8] Those two medications are buprenorphine and naltrexone.
FDA-approved brand-name medications include the following:[8]
- Suboxone (buprenorphine and naloxone)
- Subutex (buprenorphine)
- Sublocade (buprenorphine)
- Zubsolv (buprenorphine and naloxone)
- Probuphine (buprenorphine)
- Cassipa (buprenorphine and naloxone)
- Bunavail (buprenorphine and naloxone)
- Vivitrol (naltrexone)
Comparing Methadone vs. Alternates
When you enroll in an MAT program for OUD, your doctor will ask questions about your health, lifestyle and addiction history. Your answers will guide your doctor in choosing the right medication for you.
The following chart can help you be an informed participant in these discussions about your medication.[7,9–14]
Comparison Chart: OUD Medications
| Methadone | Buprenorphine | Naltrexone | |
|---|---|---|---|
| How it works | As a long-acting opioid agonist, methadone binds to opioid receptors and reduces cravings | As a partial opioid agonist, buprenorphine partially binds to opioid receptors to eases cravings and withdrawal symptoms | As an opioid antagonist, naltrexone blocks other opioids from binding |
| Generic version? | Yes | Yes | Yes |
| Side effects | Restlessness, nausea, slow breathing, itchy skin, sweating, constipation, sexual problems | Constipation, headache, nausea, vomiting, dizziness, drowsiness, sweating, dry mouth, tooth decay, muscle aches, insomnia, fever, blurry vision, tremors | Nausea, vomiting, fatigue, headache, lightheadedness, reduced appetite, muscle cramps, joint pain, cold symptoms, insomnia, toothache |
| Pricing | From $15 (per tablet) to $366 (per injection) | From $18 (per tablet) to $55 (per transdermal film) | From about $2 (per tablet) to more than $1,500 (per injection) |
| Forms | Tablet, oral solution, injectable liquid | Tablet, dissolving film, injectable liquid | Tablet and injection for OUD |
| Dosages | Liquid or tablet doses typically range from 20 mg to 80 mg | 2 mg to 24 mg | 50 mg (in tablet form), or 380 mg (in injection form, given once every 4 weeks) |
| Drug class | Schedule II | Schedule III | None (not a controlled substance) |
| Convenience | Inconvenient, especially at first when in-clinic administration is required | Designed for at-home use | Designed for at-home use |
| Time to work | 30–45 minutes (oral dose) | About an hour | Immediate (in injection form) or about an hour (for tablets) |
Keep reading for more information about each type of medication listed within this table.
Naltrexone as a Methadone Alternative
Naltrexone is a prescription medication approved by the FDA to treat both OUD and alcohol use disorder. It’s available as a pill (for alcohol use disorder) or an injection (for OUD).[14]
Naltrexone is not an opioid, and it’s not addictive. Instead, it blocks the euphoric action of drugs like alcohol and opioids, making a relapse both less dangerous and less rewarding.
Vivitrol is the OUD injectable form of naltrexone. The shot doesn’t block withdrawal symptoms, but it can offer protection from euphoria caused by a relapse. With repeated use, this shot could help break the connection between getting high and feeling good.
Learn more: What is Vivitrol?
Should You Use Naltrexone as a Substitute for Methadone?
Naltrexone could be a good option for you if you meet some or all of the following criteria:
- You aren’t physically dependent on opioids.
- You struggle with daily pill options because you forget or your willpower slips.
- You can’t get to a clinic to take methadone or another medication regularly.
- Other medications didn’t work well for you and you’re looking for an alternative.
Buprenorphine as a Methadone Alternative
Buprenorphine is a prescription medication designed to help people with OUD. Buprenorphine works as a partial opioid agonist, linking to the same receptors used by drugs like heroin and oxycodone. Its loose attachment means it doesn’t deliver a high for people with OUD.
Once buprenorphine enters the brain, it latches to opioid receptors. It can treat withdrawal symptoms (like nausea or diarrhea) and reduce drug cravings. Buprenorphine has low misuse potential, so people can use the drug at home instead of in a clinic.
Multiple forms of buprenorphine exist, including the following:
Suboxone
Suboxone combines buprenorphine with naloxone. This medication can ease OUD symptoms while providing overdose and misuse protection.
This is a good fit for people with the following characteristics:
- Medication compliant: You must take Suboxone every day, as doses wear off within about 24 hours.
- Responsible: People without OUD can get high when they misuse this drug. It must be stored safely. If you have OUD, you are not opioid naïve, so you will not likely experience euphoria from this medication.
- Not sensitive to unusual tastes: Suboxone strips can taste unusual or unpleasant to some people. Most people get used to this sensation within a couple weeks.
Learn more: What is Suboxone?
Subutex
Subutex is a prescription medication containing buprenorphine in a dissolving pill format. This option can ease OUD withdrawals and cravings, but it doesn’t contain overdose or misuse protections like Suboxone.
Subutex is a good fit for people with the following characteristics:
- Allergies to naloxone: Some people can’t use naloxone and need a pure form of buprenorphine instead.
- Pregnant women: Some doctors recommend that women use monotherapies like Subutex until their babies are born.
- Medication compliant: You must use this medication every day, as doses wear off.
Subutex is not available in the U.S. as of 2011. You can still get it in its generic form, but Suboxone is a much more popular buprenorphine option due to its abuse-deterrent form.
Learn More: What is Subutex?
Sublocade
Sublocade is an injectable form of buprenorphine designed to help people with OUD. Once per month, you’ll visit your doctor for an injection of this medication.
Sublocade is a good fit for people with the following characteristics:
- Noncompliant: If you’ve used pills and strips and keep skipping doses, an injection may be better for you. You also don’t have to worry about forgetting your dose.
- Unsafe housing: If your roommates or neighbors steal your pills and strips, an injection might be a good choice for your medication.
- Remote living: If going to a clinic or pharmacy is tough for you, a once-a-month visit might be easier to schedule and maintain. Mail-order prescriptions are another option in this situation.
Learn More: What is Sublocade?
Zubsolv
Zubsolv is a prescription medication that combines buprenorphine and naloxone. It’s essentially the same therapy as Suboxone, but it’s provided in pill form, not strips.
Zubsolv is a good option for people who dislike the taste of Suboxone strips, but it can be much more expensive. If you can afford the extra fees, it could be a good choice for you.
Learn More: What is Zubsolv?
Should You Use Buprenorphine as a Substitute for Methadone?
It’s reasonable to consider switching from methadone to buprenorphine if you meet some or all of the following characteristics:
- You’re physically dependent on opioids.
- You’re struggling with methadone side effects.
- Your OUD isn’t well controlled on methadone.
- You don’t want to go to a methadone clinic every day for therapy.
New & Emerging Medications for OUD Treatment
While methadone, buprenorphine and naloxone are effective therapies for people with OUD, researchers believe more can be done to ease symptoms. New medications are in development that could be good options for you in the future.
New and emerging medications: Probuphine & Lofexidine
Those newer options include the buprenorphine implant Probuphine. While this formulation was proven effective, it was too expensive to produce and was pulled from the U.S. market as a result.
Learn more: What is the buprenorphine implant?
Lofexidine (also known as Lucemyra) is also sometimes mentioned as a methadone alternative. This blood pressure medication can ease opioid withdrawal symptoms, but it isn’t a long-term option for managing OUD cravings. It’s not considered a good option for people who are no longer in withdrawal.
While new medications and therapies will continue to emerge, Suboxone is currently considered the best methadone alternative for most patients.
Additional Resources for OUD Medications
These helpful resources can assist you in learning more about your medication options, so you can be an active participant in discussions with your doctor:
How Bicycle Health Can Help With Opioid Use Disorder
At Bicycle Health, we know buprenorphine medications can be lifesavers for people with OUD. We also know that far too many people can’t find doctors able to administer MAT programs. We can help.
Our telemedicine approach gives you access to the following elements:
- An accessible care team
- Online appointments
- Online support groups
- Prescription refills
Your healthcare information is always protected. You can preserve your privacy and your health at the same time by working with Bicycle Health.
When you work with us, you’ll have easy access to the medication you need and support at every step of your recovery journey. Find out more about our treatment model.
Learn more: How Bicycle Health Treatment Works
Reviewed By Peter Manza, PhD
Peter Manza, PhD received his BA in Psychology and Biology from the University of Rochester and his PhD in Integrative Neuroscience at Stony Brook University. He is currently working as a research scientist in Washington, DC. His research focuses on the role ... Read More
- Opioid Use Disorder. Centers for Disease Control and Prevention. https://www.cdc.gov/dotw/opioid-use-disorder/index.html. August 2022. Accessed March 2023.
- Medication-Assisted Treatment Improves Outcomes for Patients with Opioid Use Disorder. Pew. https://www.pewtrusts.org/en/research-and-analysis/fact-sheets/2016/11/medication-assisted-treatment-improves-outcomes-for-patients-with-opioid-use-disorder. November 2016. Accessed March 2023.
- “I Wanted Something That Was More Flexible;” A Qualitative Study of Patient Preferences on Choosing Buprenorphine Over Methadone in a Large, Safety-Net Hospital Opioid Treatment Program. Substance Abuse. https://www.tandfonline.com/doi/abs/10.1080/08897077.2021.2010251. February 2022. Accessed March 2023.
- Acceptability and Efficacy of Naltrexone for Criminal Justice-Involved Individuals With Opioid Use Disorder: A Systematic Review and Meta Analysis. Addiction. https://onlinelibrary.wiley.com/doi/abs/10.1111/add.14946. December 2019. Accessed March 2023.
- Efficacy and Safety of a Monthly Buprenorphine Depot Injection for Opioid Use Disorder: A Multicentre, Randomised, Double-Blind, Placebo-Controlled, Phase 3 Trial. The Lancet. https://www.sciencedirect.com/science/article/abs/pii/S0140673618322591. March 2019. Accessed March 2023.
- A Brief History of Methadone in the Treatment of Opioid Dependence: A Personal Perspective. Journal of Psychoactive Drugs. https://pubmed.ncbi.nlm.nih.gov/1765883/. June 1991. Accessed March 2023.
- Methadone. Substance Abuse and Mental Health Services Administration. https://www.samhsa.gov/medications-substance-use-disorders/medications-counseling-related-conditions/methadone. January 2023. Accessed March 2023.
- Information About Medication-Assisted Treatment (MAT). U.S. Food and Drug Administration. https://www.fda.gov/drugs/information-drug-class/information-about-medication-assisted-treatment-mat. February 2019. Accessed March 2023.
- Methadone. Drug Enforcement Administration. https://www.dea.gov/sites/default/files/2020-06/Methadone-2020.pdf. April 2020. Accessed March 2023.
- Methadone Maintenance. Providers Clinical Support System. https://pcssnow.org/wp-content/uploads/2018/01/Methadone-Maintenance.pdf. January 2018. Accessed March 2023.
- Buprenorphine. Substance Abuse and Mental Health Services Administration. https://www.samhsa.gov/medications-substance-use-disorders/medications-counseling-related-conditions/buprenorphine. January 2023. Accessed March 2023.
- Buprenorphine. Drug Enforcement Administration. https://www.deadiversion.usdoj.gov/drug_chem_info/buprenorphine.pdf. May 2022. Accessed March 2023.
- Clinical Use of Extended-Release Injectable Naltrexone in the Treatment of Opioid Use Disorder: A Brief Guide. Substance Abuse and Mental Health Services Administration. https://store.samhsa.gov/sites/default/files/d7/priv/sma14-4892r.pdf. February 2015. Accessed March 2023.
- Naltrexone. Substance Abuse and Mental Health Services Administration. https://www.samhsa.gov/medications-substance-use-disorders/medications-counseling-related-conditions/naltrexone. January 2023. Accessed March 2023.
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