Naltrexone: Definition, Mechanism of Action, Uses, Dosage, Side Effects, Alternatives

Naltrexone is used to treat opioid use disorder (OUD) and alcohol use disorder (AUD). As an opioid antagonist, Naltrexone blocks opioid receptors in the brain and reduces cravings for alcohol and opioids. By interfering with the brain’s reward system, Naltrexone prevents the euphoric effects associated with these substances, helping to cut relapse rates. The naltrexone market was valued at $21 billion in 2023 and is projected to grow at a compound annual growth rate (CAGR) of 3.6% through 2034, driven by its use in addiction treatment and emerging applications for autoimmune conditions, as provided by Transparent Market Research.

The standard dosage of Naltrexone is 50 mg daily for alcohol and opioid use, with injectable forms offering a longer-acting option at 380 mg per month. Naltrexone received approval from the US Food and Drug Administration (FDA) in December 1994. On average, addiction medicine physicians prescribed Naltrexone to 13% of their patients with alcoholism.

The primary reasons physicians did not prescribe the medication to more patients were patient refusal to take the medication or follow prescribing regimens (23%) and the cost of the medication (21%). Multivariate analysis revealed that physicians’ perceptions of Naltrexone’s effectiveness and safety were significantly linked to prescribing practices, as noted by Mark et al. 2003 in the study “Understanding US Addiction Physicians’ Low Rate of Naltrexone Prescription.”

Common side effects include nausea, headache, and fatigue, while moderate side effects involve injection site reactions and sleep disturbances. Serious risks are liver damage and allergic reactions, requiring liver function monitoring. In 2018, only 1.64% of admissions for AUD in substance use treatment centers involved naltrexone prescriptions, reflecting its underutilization despite its FDA approval and efficacy, as referenced by Quedan et al. 2021 in “Trends in the Use of Naltrexone for Addiction Treatment among Alcohol Use Disorder Admissions in U.S. Substance Use Treatment Facilities.”

For those with opioid use disorder, alternatives like Buprenorphine, Methadone, and Acamprosate are available. Alcohol dependence can also be managed with alternatives such as Disulfiram and Topiramate. In New Hampshire, opioid addiction remains a significant concern, with over 1,200 overdose deaths reported in 2020, emphasizing the importance of effective treatments like Naltrexone in addressing the opioid crisis.

What Is Naltrexone?

Naltrexone is an opioid antagonist primarily used in the treatment of alcohol dependence and opioid use disorder. It works by blocking the effects of opioids at the opioid receptors, reducing cravings and preventing the rewarding effects of alcohol and opioids. Well-known brand names for Naltrexone are ReVia and Vivitrol. As a non-addictive medication, Naltrexone does not precipitate dependence, making it a valuable option in medication-assisted treatment (MAT) for addiction. Naltrexone helps individuals maintain sobriety by supporting long-term recovery efforts without the risk of misuse or addiction.

In 2021, approximately 2.5 million adults in the U.S. experienced opioid use disorder (OUD) in the past year, yet only 22% of them received medications to treat it, according to a recent study. The research also highlighted substantial disparities in treatment access, with certain groups being notably less likely to receive medication for OUD, as revealed by Jones et al. 2023 in “Use of Medication for Opioid Use Disorder Among Adults With Past-Year Opioid Use Disorder in the US, 2021.”

What Is the Mechanism of Action of Naltrexone?

The mechanism of action of Naltrexone involves its role as an opioid receptor antagonist, where it competitively binds to mu-opioid receptors in the brain. This prevents opioids from activating these receptors, effectively blocking their euphoric and pain-relieving effects. By doing so, Naltrexone supports relapse prevention in individuals with opioid use disorder (OUD). Additionally, it plays a key role in neurotransmitter regulation, specifically affecting dopamine levels. This helps reduce the rewarding effects of substances like opioids and alcohol, which are associated with addiction. 

Naltrexone has a half-life of 4 to 6 hours when taken orally, while its injectable form, Vivitrol, offers a longer duration of receptor blockade, lasting up to 30 days. This extended release provides continuous support for those in recovery. The oral form has a bioavailability of about 5%, 5 to 40%, as cited by the National Institute of Health (NIH) while the injectable form allows for more consistent and higher absorption.

What Is Naltrexone Used for in Addiction Treatment?

Naltrexone is primarily used for relapse prevention in the treatment of opioid addiction and alcohol use disorder when combined with other psychological treatments like behavioral therapy and support groups to enhance recovery. 

In New Hampshire, the prevalence of substance use disorders has seen a notable increase, rising from 8.6% during 2016-2018 to 16.2% in recent years, as recounted by the American Civil Liberties Union of New Hampshire (ACLU-NH). This uptick highlights the critical need for effective treatment options like naltrexone. However, despite its proven efficacy, naltrexone remains underutilized. A 2003 study found that addiction medicine physicians prescribed naltrexone to only 13% of their patients with alcohol dependence. The primary reasons cited for this low prescription rate were patient non-compliance and cost-related issues. Addressing these barriers is essential to enhance the accessibility and utilization of naltrexone in treating opioid addiction and alcohol use disorder.

Alcohol Addiction Treatment

In the treatment of alcohol addiction and alcohol use disorder, Naltrexone has proven effective in reducing alcohol cravings and the likelihood of relapse. Studies indicate that individuals who take Naltrexone experience a significant reduction in the number of drinking days, and fewer report binge drinking episodes. Research has demonstrated that Naltrexone reduces the pleasurable effects of alcohol, assisting individuals in maintaining sobriety and managing alcohol addiction and dependence.

Naltrexone has been shown to increase abstinence rates and reduce heavy drinking days. In the COMBINE study, patients receiving naltrexone had an 80.6% abstinence rate compared to 75.1% for placebo, and a lower risk of heavy drinking days (66.2% vs. 73.1%), as explained by Anton R. 2009 in “Naltrexone for the Management of Alcohol Dependence.”

Opioid Addiction Treatment

For opioid addiction and opioid use disorder, Naltrexone acts by blocking the euphoric effects of opioids, thus curbing cravings. As part of medication-assisted treatment (MAT), Naltrexone is amalgamated with counseling and therapy to ameliorate overall recovery success. Completion rates for rapid opiate detoxification using Naltrexone and clonidine range from 75% to 81%, significantly higher than the 40% completion rate observed with methadone and clonidine alone, as detailed by Singh D. and Saadabadi A. in their 2023 StatPearls publication.

Supporting Relapse Prevention

Naltrexone supports relapse prevention by blocking the effects of alcohol and opioids, which can significantly reduce the chance of relapse during the critical early recovery period. The medication provides a safety net by mitigating the high-risk moments associated with craving or emotional stress.

Reducing Risk of Overdose When Used Correctly

When used correctly, Naltrexone also plays a role in reducing the risk of overdose, especially in those recovering from opioid use disorder. Blocking opioid receptors precludes a user from experiencing the typical euphoric effects of opioids, thus lowering the likelihood of overdose, particularly when in league with other recovery strategies.

How Is Naltrexone Administered?

Naltrexone is available in two primary forms: an oral tablet (ReVia) and an intramuscular injection (Vivitrol).

• Oral tablet: Taken daily, typically at a dose of 50 mg.
  
• Injectable form: Given as an intramuscular injection once a month at a dose of 380 mg. The injection form offers the benefit of fewer doses and more consistent medication levels.
  

Adherence to the prescribed dosage is crucial for the effectiveness of Naltrexone. Patients should also work with healthcare providers to ensure proper administration and avoid skipping doses, which can reduce its effectiveness in preventing relapse.

What Is the Standard Dose for Naltrexone?

The recommended dosage of Naltrexone is 50 mg per day for alcohol dependence and 50 mg daily for opioid use disorder. In cases of opioid use disorder, patients may also be prescribed a higher dose or a longer-acting injectable form for sustained release. The dosage may be adjusted based on individual response and side effects.

How Long Does Naltrexone Stay in Your System?

Naltrexone typically stays in the system for up to 5 to 10 days, depending on the form of administration. The oral tablet has a half-life of approximately 4 to 6 hours, while the injectable form remains in the system much longer, with a half-life of 5 to 10 days.

Naltrexone can be detected in urine tests for up to 4-5 days and in blood tests for up to a week. The detection window varies depending on the type of test and the individual’s metabolism.

What Are the Side Effects of Naltrexone?

Common Side Effects

• Nausea (15-30%)
  
• Headache (5-20%)
  
• Fatigue (5-15%)
  

Moderate Side Effects

• Injection site reactions (for injectable Naltrexone)
  
• Sleep disturbances (insomnia, vivid dreams)
  

Serious Side Effects

• Liver damage (monitor liver function regularly)
  
• Allergic reactions (rash, difficulty breathing)
  

Does Naltrexone Cause Withdrawal Symptoms?

Naltrexone does not cause withdrawal symptoms. However, if opioids are still in the system when starting Naltrexone, it may trigger precipitated withdrawal, which can be severe and uncomfortable.

Can You Use Naltrexone Long-Term?

Yes, Naltrexone is generally safe for long-term use. However, regular liver function monitoring is recommended as prolonged use may cause liver damage in some individuals.

What Happens If You Stop Taking Naltrexone Cold Turkey?

Stopping Naltrexone abruptly does not cause withdrawal symptoms, but it significantly increases the risk of relapse. Medical guidance is recommended to gradually taper off Naltrexone when discontinuing the medication.

What Are the Alternatives to Naltrexone for Addiction?

There are several alternatives to Naltrexone for treating addiction:

• Buprenorphine: A partial opioid agonist used to treat opioid addiction.
  
• Methadone: A full opioid agonist, often used in opioid maintenance therapy.
  
• Acamprosate: Used to treat alcohol dependence by helping reduce alcohol cravings.
  
• Disulfiram: An alcohol-aversion medication that causes unpleasant effects when alcohol is consumed.
  
• Topiramate: Used to reduce alcohol cravings and reduce relapse.
  
• Gabapentin: A medication that helps with alcohol cravings and withdrawal symptoms.
  

Who Should Not Take Naltrexone?

Naltrexone is contraindicated for individuals with liver disease, active opioid use, and pregnancy. Always consult a healthcare provider before beginning treatment.

How Does Naltrexone Interact with Opioids?

Naltrexone blocks the effects of opioids and can cause precipitated withdrawal if opioids are still in the system. Patients should complete an opioid detoxification process before starting Naltrexone treatment.

What Happens if You Drink Alcohol While on Naltrexone?

Naltrexone reduces the pleasurable effects of alcohol, making it easier to control cravings. However, it does not cause physical illness when alcohol is consumed, unlike medications like disulfiram.

Can You Get Naltrexone Over the Counter?

No, Naltrexone requires a prescription from a healthcare provider.

Is Naltrexone Covered by Insurance?

Yes, Naltrexone is covered by most private insurance plans, Medicaid, and Medicare. For those without insurance, the out-of-pocket cost can range from $200 to $900 per month.

Is Naltrexone the Same as Naloxone?

No, Naltrexone and Naloxone are different medications. Naltrexone is used for long-term addiction treatment, while Naloxone is an emergency medication for opioid overdose.

How Effective Is Naltrexone in Preventing Relapse?

Naltrexone is highly effective in relapse prevention, with studies showing a significant reduction in opioid and alcohol relapse rates when combined with behavioral therapy and support groups.

Is Naltrexone Addictive?

No, Naltrexone is non-addictive and does not cause dependence.

Will Naltrexone Show Up on a Drug Test?

Naltrexone will not show up on a routine drug test, but specialized tests can detect its presence in urine or blood.