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

Naltrexone for Treating Opioid and Alcohol Dependence

Naltrexone is FDA-approved for the treatment of both alcohol dependence and opioid dependence, functioning as a competitive opioid receptor antagonist that blocks the euphoric effects of opioids and reduces alcohol cravings. 1, 2

Mechanism of Action

• Naltrexone works by competitively antagonizing mu, kappa, and delta opioid receptors, preventing the reinforcing effects of opioids and reducing alcohol consumption and craving 2, 3
• By blocking opioid receptors, naltrexone prevents impulsive substance use, providing patients time to consider consequences of relapse and seek support 2
• For alcohol dependence, naltrexone dampens activation of the reward pathway triggered by alcohol, thereby decreasing excessive drinking and increasing abstinence duration 2, 4

Formulations and Dosing

• Oral naltrexone is available as 50-mg tablets typically taken once daily for most patients 1, 2
• Alternative oral dosing regimens include 100 mg on Mondays and Wednesdays, and 150 mg on Fridays 2
• Injectable naltrexone (Vivitrol) is a 380-mg monthly injection approved for both alcohol and opioid dependence 2
• For opioid dependence, treatment should be initiated with 25 mg orally, and if no withdrawal signs occur, increased to 50 mg daily 1

Efficacy

For Alcohol Dependence:

• 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%) 1
• Naltrexone is particularly effective in patients who suffer from high alcohol craving 4
• Treatment with naltrexone supports abstinence, prevents relapse, and decreases alcohol consumption when used as part of a comprehensive treatment program 1

For Opioid Dependence:

• Naltrexone produces complete blockade of the euphoric effects of opioids in both volunteer and addict populations 1
• Most beneficial for highly motivated patients who cannot or do not wish to take continuous opioid agonist therapy (e.g., methadone, buprenorphine) 5, 2
• Most effective when administered under conditions that enforce compliance 1

Important Clinical Considerations

• Patients must be completely opioid-free before starting naltrexone to avoid precipitated withdrawal 1, 2
• An opioid-free interval of minimum 7-10 days is recommended for patients previously dependent on short-acting opioids 1
• Patients transitioning from buprenorphine or methadone may be vulnerable to withdrawal symptoms for up to 2 weeks 1
• Naltrexone cannot be used in patients requiring opioids for pain control as it blocks pain relief from opioid agonists 5, 3
• Liver function tests should be performed at baseline and every 3-6 months due to potential hepatotoxicity at supratherapeutic doses 5, 2
• Patients who discontinue naltrexone treatment have increased risk of opioid overdose due to decreased tolerance 2, 3

Patient Selection

• For alcohol dependence: Most effective when combined with psychosocial support and as part of a comprehensive treatment program 1, 6
• For opioid dependence: Best results seen in highly motivated patients with good prognosis who take naltrexone as part of a comprehensive occupational rehabilitative program or behavioral contract 1
• Limited compliance with oral naltrexone is a known drawback; injectable depot formulations can significantly improve medication adherence 7
• Genetic factors may influence treatment response - allelic variation in the mu opioid receptor gene predicts response to naltrexone 4

Potential Adverse Effects

• Common side effects include headache, dizziness, fatigue, nausea, and gastrointestinal symptoms 2
• Serious side effects are uncommon 1
• One lesser-known issue is that a metabolite of naltrexone (noroxymorphone) can cause false-positive oxycodone urine drug screens 8

Clinical Pearls

• Naltrexone should be considered as only one component of a comprehensive treatment program for substance use disorders 1, 6
• Unlike methadone or buprenorphine, naltrexone does not reinforce medication compliance on its own and requires external conditions that support continued use 1
• Extended-release injectable naltrexone may be particularly valuable for patients with adherence challenges 7, 9
• For surgical patients on naltrexone, oral formulations 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 3