What is the role of Naltrexone in the treatment of alcoholism?

From the Guidelines

Naltrexone is a recommended medication for treating alcoholism, but its use should be carefully considered due to potential liver damage and other side effects. According to the most recent and highest quality study, a 2020 systematic review and network meta-analysis published in the BMJ 1, naltrexone was found to be a promising intervention for maintaining abstinence from alcohol, although the evidence was not sufficient to make a strong recommendation. The study suggested that naltrexone could be used in combination with other interventions, such as counseling or behavioral therapy, to improve treatment outcomes.

The mechanism of action of naltrexone involves blocking opioid receptors in the brain, which reduces the pleasurable effects of alcohol and decreases cravings. The standard dosage is 50 mg once daily, though some patients may start with 25 mg to minimize side effects. Naltrexone is typically prescribed for 3-12 months, but some patients benefit from longer treatment. However, a 2013 study published in Clinical and Molecular Hepatology 1 noted that naltrexone is not recommended in patients with alcoholic liver disease (ALD) due to the risk of toxic liver injury.

Before starting naltrexone, patients must be alcohol-free for at least 3-7 days and should undergo liver function tests to minimize the risk of liver damage. Common side effects include nausea, headache, dizziness, and fatigue, which usually diminish over time. Naltrexone is contraindicated in patients taking opioid medications or with acute hepatitis or liver failure. The medication reduces relapse rates by about 30-50% and is most effective when taken consistently. Patients should carry medical identification indicating they are taking naltrexone, as it blocks the effects of opioid pain medications that might be needed in emergency situations.

Key considerations for the use of naltrexone in treating alcoholism include:

• Careful patient selection to minimize the risk of liver damage and other side effects
• Combination with counseling or behavioral therapy to improve treatment outcomes
• Close monitoring of liver function and other potential side effects
• Patient education on the potential risks and benefits of naltrexone treatment.

From the FDA Drug Label

To reduce the risk of precipitated withdrawal in patients dependent on opioids, or exacerbation of a preexisting subclinical withdrawal syndrome, opioid-dependent patients, including those being treated for alcohol dependence, should be opioid-free (including tramadol) before starting naltrexone hydrochloride treatment The placebo-controlled studies that demonstrated the efficacy of naltrexone hydrochloride as an adjunctive treatment of alcoholism used a dose regimen of naltrexone hydrochloride 50 mg once daily for up to 12 weeks. Naltrexone hydrochloride should be considered as only one of many factors determining the success of treatment of alcoholism. A dose of 50 mg once daily is recommended for most patients

• Naltrexone and Alcoholism: Naltrexone hydrochloride is used as an adjunctive treatment for alcoholism.
• Dosing: The recommended dose is 50 mg once daily for most patients.
• Important Consideration: Patients should be opioid-free before starting naltrexone hydrochloride treatment to reduce the risk of precipitated withdrawal.
• Efficacy: Naltrexone hydrochloride has been shown to support abstinence, prevent relapse, and decrease alcohol consumption in clinical studies 2.
• Key Factors for Success: The success of treatment depends on various factors, including the type, intensity, and duration of treatment, management of comorbid conditions, use of community-based support groups, and good medication compliance 2.

From the Research

Naltrexone and Alcoholism

• Naltrexone is an opioid receptor antagonist that has been shown to be effective in reducing heavy drinking in individuals with alcohol dependence 3.
• Studies have demonstrated that naltrexone is more effective in reducing heavy drinking than in increasing abstinence, with 19 out of 27 clinical trials showing an advantage for naltrexone over placebo in reducing heavy drinking 3.
• The mechanism of action of naltrexone is thought to be related to its ability to decrease the reward associated with drinking alcohol, thereby reducing excessive drinking 3.
• Naltrexone has been compared to other medications, such as acamprosate, in the treatment of alcohol dependence, with some studies suggesting that naltrexone may be more effective in reducing relapse rates 4.
• The clinical efficacy of naltrexone is limited by compliance with taking the medication, and it is recommended that naltrexone be used in conjunction with psychosocial therapies to address the psychosocial complications of chronic alcohol dependence 5.

Efficacy of Naltrexone

• A systematic review of 29 randomized placebo-controlled trials of naltrexone for the treatment of alcohol dependence found that 19 trials demonstrated an advantage for naltrexone over placebo in reducing heavy drinking 3.
• A study comparing naltrexone to acamprosate found that naltrexone was more effective in reducing relapse rates and heavy drinking days 4.
• Another study found that naltrexone reduced rates of alcohol relapse, number of drinking days, and alcohol craving in individuals with alcohol dependence 5.

Mechanism of Action

• Naltrexone is thought to work by blocking the opioid receptors in the brain, which are involved in the rewarding effects of alcohol 3.
• The opioid system is thought to play a role in the reinforcing effects of alcohol, and naltrexone's ability to block this system may contribute to its efficacy in reducing heavy drinking 5.
• The exact mechanisms of action of naltrexone are not fully understood, but it is thought to involve the modulation of dopamine and other neurotransmitters involved in reward and motivation 6.