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Naltrexone vs. Suboxone: Comparing MAT Medications

Naltrexone and Suboxone are both medications that can be effective in treating opioid use disorder (OUD). These forms of medication-assisted treatment (MAT) help people to stop abusing both prescription and illicit opioids and successfully transition into ongoing recovery.[1,2]

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The medications work a little bit differently. While both Suboxone and naltrexone may be a good fit for someone in recovery, each medication will be more effective at different points based on the person’s stage in recovery and their challenges in staying sober. 

Do not attempt to take naltrexone or Suboxone on your own without the support and guidance of a medical professional. Your treatment team will assess your situation and goals to help you determine the best choice for you. Discuss this with your team if you are currently taking either medication and interested in switching to the other one. 

Understanding Naltrexone & Suboxone

Naltrexone and Suboxone can both be exceptionally effective medications in the treatment of opioid addiction. Each has a different mechanism of action that makes it effective at different times in the treatment process. 

Learning how each medication works and how their differences can impact your recovery is a critical piece of the puzzle when trying to create an effective treatment strategy. 

How Does Naltrexone Work?

Naltrexone is an opioid antagonist, which means that it blocks opioid receptors in the brain.[3] This action prevents all opioids from binding to the opioid receptors, which can stop someone in recovery from relapsing. Essentially, if someone were to relapse while on naltrexone, the opioids they take wouldn’t work. There would be no high, and the person would be thrown into precipitated withdrawal.[4]

Unlike other medications that are or contain agonists or partial opioid agonists (like Suboxone), naltrexone does not bind to or activate the opioid receptors. This means that it does not create a high of its own, nor does it help in any way to manage pain.

In most cases, naltrexone is used when the person is no longer physically dependent on opioids of any kind (even those that contain partial opioid agonists like Suboxone) but would still like the psychological support that comes with knowing that any relapse on opioids would be futile. 

Everyone is different, but naltrexone can only be taken after the person has had no opioids in their system for at least a week to 10 days at a minimum in order to avoid precipitated withdrawal. Most people will start with a dose of 25 mg per day and potentially work up to 50 mg per day if needed.[3]

How Does Suboxone Work?

Suboxone combines two active ingredients: buprenorphine (a partial opioid agonist) and naloxone (an opioid antagonist).[5]

Buprenorphine’s partial agonist activity at opioid receptors helps to reduce cravings and withdrawal symptoms by partially stimulating opioid receptors. Naloxone is included to deter misuse (injecting the medication), as it can precipitate withdrawal symptoms when injected but is inactive when Suboxone is taken as prescribed sublingually.[6]

Comparing Naltrexone & Suboxone 

This chart breaks down how naltrexone and Suboxone compare at a glance:[3,5,7-11]

CriteriaNaltrexoneSuboxone
UsePreventing relapse for those in recovery from opioid addiction and alcohol addictionTreatment and relapse prevention for those in recovery from opioid use disorder to reduce withdrawal symptoms and cravings
Schedule DrugNo schedule, not a controlled substanceSchedule III substance
FormsOral tablets, extended-release injectionSublingual films and tablets
How They Are UsedOral tablets daily or extended-release injections once a monthSublingual administration once a day
Common Side EffectsNausea, headache, dizziness, fatigue, and injection site reactions (for injection form)Nausea, constipation, headache, and sweating
Addiction PotentialNone, because it does not activate opioid receptorsLow, due to the ceiling effect of buprenorphine and the presence of naloxone
CostGenerally lower, but may vary based on formulation and insuranceMay be higher, especially for brand-name versions but generic versions are available
Insurance CoverageWidely covered, including the injection version, but specific coverage may varyBroadly covered, including Medicaid for many patients, but coverage specifics vary
Efficacy & SafetyEffective in reducing opioid and alcohol misuse; favorable safety profile with low risk of side effectsHighly effective in treating OUD; good safety profile, including low risk of overdose and respiratory depression

Key Differences Between Naltrexone & Suboxone

Both naltrexone and Suboxone offer a unique approach to managing and treating opioid addiction, allowing people to individualize their treatment plan to their needs and preferences. Here are some of the differences between these two forms of MAT:

Method of Administration

Naltrexone 

Naltrexone can be taken as an oral tablet taken one time per day or as an injection given by the doctor once per month.[1] The daily tablet is easy to take at home while the injection option offers a unique opportunity to “forget” about taking a medication except for once a month when it’s time to go to the doctor for the next shot. 

Suboxone

Suboxone, on the other hand, is prescribed in the form of a sublingual film or sublingual tablet that is taken daily.[2] Both forms are taken by placing them under the tongue until they dissolve. This method ensures that the medication is absorbed directly into the bloodstream, making the time of onset of effect much more rapid than swallowing and digesting a pill.

Dosing Ranges

Naltrexone 

Depending on the form prescribed, naltrexone doses vary. Oral tablets are typically prescribed starting at 25 mg per day and then increased to 50 mg per day for most patients, while the injection option is administered as a 380 mg dose once per month.[3]

Suboxone

Suboxone dosing is much more flexible, making it easier to match the needs of patients based on where they are in the treatment process. The buprenorphine component ranges from 2 mg to 12 mg, combined with naloxone in a 4:1 ratio.[11] The exact dose is tailored to the individual, taking into account their level of opioid dependence and response to treatment.

Key Differences in Action

Naltrexone

Naltrexone acts as a full opioid antagonist, which means that it blocks opioid receptors in the brain and prevents any opioids from giving the person a high. Additionally, it does not activate the opioid receptors, so it carries no risk of abuse or dependence.

Suboxone

Suboxone has both buprenorphine (a partial opioid agonist) and naloxone (an opioid antagonist) in it. As a partial agonist, buprenorphine does bind to opioid receptors and activates them to a degree, but only enough to reduce cravings and diminish withdrawal symptoms.[12] 

Buprenorphine would typically only induce any potential euphoria in someone who is opioid naïve. Since those taking Suboxone to treat OUD are not opioid naïve, it doesn’t trigger euphoria or a high.

Naloxone is included to stop people from misusing the drug by trying to inject it. This ingredient remains inactive when Suboxone is taken as directed, but it will trigger extreme withdrawal symptoms if the medication is abused.[13]

Choosing the Right Medication for Opioid Use Disorder

MAT can be one of the most effective tools available to help someone manage an opioid addiction. However, the right medication at the right time is key to a successful experience. Medication is also only one of the tools needed to achieve and maintain recovery. Behavioral therapy, such as cognitive behavioral therapy, is part of a comprehensive treatment plan and the core of effecting change long-term.

If you are interested in learning more about whether naltrexone or Suboxone is the better choice for you, reach out for more information. 

Updated April 6, 2024
Resources
  1. Naltrexone is alternative treatment for opioid addiction. University of Pennsylvania Penn Medicine. Accessed March 26, 2024.
  2. Grinspoon P. 5 myths about using Suboxone to treat opiate addiction. Harvard Health Blog. Published March 20, 2018. Accessed March 26, 2024.
  3. Singh D, Saadabadi A. Naltrexone. StatPearls. Published 2020. Accessed March 26, 2024.
  4. Hassanian-Moghaddam H, Afzali S, Pooya A. Withdrawal syndrome caused by naltrexone in opioid abusers. Human & Experimental Toxicology. 2014;33(6):561-567.
  5. Sivils A, Lyell P, Wang JQ, Chu XP. Suboxone: History, controversy, and open questions. Frontiers in Psychiatry. 2022;13.
  6. Dunn KE, H. Elizabeth Bird, Bergeria CL, Ware OD, Strain EC, Huhn AS. Operational definition of precipitated opioid withdrawal. Frontiers in Psychiatry. 2023;14.
  7. Buprenorphine (Trade names: Buprenex®, Suboxone®, Subutex®). DEA Office of Diversion Control. Published 2013. Accessed March 26, 2024.
  8. Naltrexone. MedlinePlus Drug Information. Accessed March 26, 2024.
  9. Buprenorphine sublingual and buccal (opioid dependence): MedlinePlus drug information. U.S. National Library of Medicine. Published October 2019. Accessed March 26, 2024.
  10. Medicaid coverage of medication-assisted treatment for alcohol and opioid use disorders and of medication for the reversal of opioid overdose. Substance Abuse and Mental Health Services Administration. Accessed March 26, 2024.
  11. Highlights of prescribing information. Suboxone. Revised December, 2023. Accessed March 26, 2024.
  12. Kleber HD. Pharmacologic treatments for opioid dependence: detoxification and maintenance options. Dialogues in Clinical Neuroscience. 2007;9(4):455-470.
  13. Yokell MA, Zaller ND, Green TC, Rich JD. Buprenorphine and buprenorphine/naloxone diversion, misuse, and illicit use: An international review. Current Drug Abuse Reviews. 2011;4(1):28-41.
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