What is the role of Naltrexone in treating opioid and alcohol dependence?

Role of Naltrexone in Treating Opioid and Alcohol Dependence

Naltrexone is an effective medication for treating both alcohol and opioid dependence, functioning as a competitive opioid receptor antagonist that blocks the euphoric effects of opioids and reduces alcohol cravings, with different formulations available for improved adherence. 1, 2

Mechanism of Action

• Naltrexone acts as a pure opioid antagonist that competitively binds to opioid receptors, blocking the effects of both exogenous opioids and potentially endogenous opioids involved in alcohol reward pathways 1, 2
• For alcohol dependence, naltrexone decreases dopamine concentration in the brain and dampens activation of the reward pathway by alcohol, thereby reducing excessive drinking and extending abstinence duration 3
• In opioid dependence, naltrexone prevents the euphoric effects of opioids, providing patients time to consider consequences of relapse and seek support 1

Available Formulations

• Oral naltrexone is available as 50-mg tablets taken daily or alternatively 100 mg on Mondays and Wednesdays, and 150 mg on Fridays 1
• Injectable naltrexone (Vivitrol) is administered as a 380-mg intramuscular injection once monthly, which may improve medication adherence compared to daily oral dosing 1, 4
• The injectable formulation provides reliable naltrexone release at therapeutic levels for at least one month 5

Efficacy in Alcohol Dependence

• Naltrexone has been shown to lower the risk of relapse in alcohol dependence with number needed to treat to prevent return to any drinking estimated at approximately 20 4, 3
• Clinical trials demonstrated that naltrexone is superior to placebo in measures including abstention rates (51% vs 23%), reduced number of drinking days, and lower relapse rates (31% vs 60%) 2
• The medication is most effective when combined with psychosocial support and behavioral interventions 2, 6

Efficacy in Opioid Dependence

• Naltrexone has been shown to produce complete blockade of the euphoric effects of opioids in both volunteer and addict populations 2
• It is most beneficial for highly motivated patients who cannot or do not wish to take continuous opioid agonist therapy 1
• Naltrexone is particularly effective in motivated populations such as healthcare professionals 1
• Unlike methadone or LAAM, naltrexone does not reinforce medication compliance and requires external conditions that support continued use 2

Clinical Considerations and Precautions

• Patients must be completely opioid-free before starting naltrexone to avoid precipitating withdrawal 1
• Naltrexone cannot be used in patients requiring opioids for pain control as it blocks pain relief from opioid agonists 1, 3
• Liver function tests should be performed at baseline and every 3-6 months due to potential hepatotoxicity, though this is uncommon at standard therapeutic doses 1, 4, 3
• Patients who discontinue naltrexone treatment have increased risk of opioid overdose and death due to decreased opioid tolerance 1
• For surgical patients, oral naltrexone should be held for 2-3 days prior to elective procedures if opioids are expected, while extended-release naltrexone should be held for 24-30 days after the last injection 1

Special Population Considerations

• Naltrexone has not been specifically studied in patients with alcoholic hepatitis or alcoholic cirrhosis 4
• For patients with evidence of alcohol-induced liver disease, acamprosate or baclofen may be safer alternatives 4, 3
• The American Academy of Pediatrics recommends considering medication-assisted treatment, including naltrexone, for adolescents with opioid use disorder 1

Common Side Effects

• The most common adverse effects reported with oral naltrexone at 50 mg/day include nausea and vomiting 6
• Discontinuation due to adverse events in clinical trials of injectable naltrexone occurred in 14.1% of patients receiving the 380-mg dose 7
• Naltrexone is generally well-tolerated with mild and transient side effects 5

Practical Implementation

• For alcohol dependence, the recommended dose is 50 mg once daily orally, or 380 mg monthly as an intramuscular injection 4
• Long-acting injectable naltrexone can significantly improve medication compliance in both opioid and alcohol dependence 5, 7
• Naltrexone should not be used as exclusive treatment but as an adjunct to comprehensive psychosocial treatment approaches 8