What is the role of naltrexone (opioid receptor antagonist) in treating opioid or alcohol dependence?

From the Guidelines

Naltrexone is a highly effective medication for treating opioid and alcohol dependence, and its use should be prioritized in clinical practice due to its ability to block opioid receptors in the brain and reduce the reinforcing properties of opioids and alcohol. For opioid dependence, naltrexone (typically 50 mg daily oral tablet or 380 mg monthly extended-release injection) prevents the euphoric effects of opioids, reducing their reinforcing properties and helping prevent relapse, as shown in a study published in the American Family Physician 1. The medication should only be started after complete opioid detoxification (7-10 days opioid-free) to avoid precipitating withdrawal. For alcohol dependence, naltrexone (50 mg daily oral or 380 mg monthly injection) reduces alcohol cravings and the pleasurable effects of drinking, helping patients maintain abstinence or reduce heavy drinking, as supported by a Cochrane systematic review 1.

Some key points to consider when prescribing naltrexone include:

• Starting the medication after complete opioid detoxification to avoid precipitating withdrawal
• Monitoring liver function due to the risk of liver enzyme elevations
• Avoiding use in patients with acute hepatitis or liver failure
• Warning patients that they will be unable to obtain pain relief from opioid medications while taking naltrexone
• Considering the use of naltrexone in combination with other medications, such as bupropion, for weight loss and smoking cessation, as suggested by a study published in Gastroenterology 1

It is essential to weigh the benefits and risks of naltrexone treatment, including its potential side effects, such as nausea, headache, and dizziness, and to closely monitor patients during treatment. Overall, naltrexone is a valuable treatment option for opioid and alcohol dependence, and its use should be considered in clinical practice to improve patient outcomes and reduce morbidity and mortality.

From the FDA Drug Label

Naltrexone hydrochloride is a pure opioid antagonist. It markedly attenuates or completely blocks, reversibly, the subjective effects of intravenously administered opioids. Naltrexone hydrochloride blocks the effects of opioids by competitive binding (i.e., analogous to competitive inhibition of enzymes) at opioid receptors. The mechanism of action of naltrexone hydrochloride in alcoholism is not understood; however, involvement of the endogenous opioid system is suggested by preclinical data. Naltrexone hydrochloride, an opioid receptor antagonist, competitively binds to such receptors and may block the effects of endogenous opioids Naltrexone hydrochloride tablets USP 50 mg is indicated in the treatment of alcohol dependence and for the blockade of the effects of exogenously administered opioids.

The role of naltrexone in treating opioid or alcohol dependence is to block the effects of opioids by competitive binding at opioid receptors, and to reduce alcohol consumption by blocking the effects of endogenous opioids.

• Key benefits:
  • Blocks the subjective effects of intravenously administered opioids
  • Reduces alcohol consumption
  • Does not lead to physical or psychological dependence
• Main uses:
  • Treatment of alcohol dependence
  • Blockade of the effects of exogenously administered opioids 2, 2

From the Research

Role of Naltrexone in Treating Opioid or Alcohol Dependence

• Naltrexone, a broad opioid-receptor antagonist, has been approved by the United States of America Food and Drug Administration for the treatment of alcohol dependence 3.
• Studies have shown that naltrexone is effective in reducing relapse to heavy drinking, but less effective in enhancing abstinence, with a modest effect size of .15 to .2 3.
• Naltrexone has been found to be safe and effective in preventing alcohol relapse, particularly in patients who drink any alcohol while attending outpatient treatment 4.
• In the treatment of opioid dependence, naltrexone may be administered on a chronic basis to block any future effects of opioids, and appears to have some limited benefit in helping formerly opioid-dependent individuals to remain abstinent 5.

Efficacy of Naltrexone in Preventing Relapse

• A meta-analysis of seven randomized controlled trials found that naltrexone was significantly more effective than placebo in reducing the risk of drug abuse, with a pooled relative risk of 0.72 5.
• However, another study found that naltrexone was not effective in preventing alcohol relapse, with no significant differences between the naltrexone and placebo groups in terms of time to first heavy drinking or secondary effectiveness measures 6.
• The efficacy of naltrexone in preventing relapse may depend on various factors, including the population being studied, the dosage and duration of treatment, and the presence of other interventions or therapies 7, 5.

Safety and Tolerability of Naltrexone

• Naltrexone has been found to be generally safe and well-tolerated, with the most common side effect being nausea 3, 4.
• However, hepatotoxicity has been reported at higher doses of naltrexone, and monitoring of liver function is recommended 3.
• The safety and efficacy of naltrexone in combination with other medications, such as memantine, have also been studied, with mixed results 7.