Do you need to stop drinking before starting naltrexone (Naltrexone hydrochloride)?

Naltrexone Initiation and Alcohol Use

No, you do not need to stop drinking alcohol before starting naltrexone for alcohol use disorder, but you must be completely opioid-free for at least 7-10 days to avoid precipitating severe, potentially life-threatening opioid withdrawal. 1

Critical Pre-Treatment Requirements

Opioid-Free Status (Mandatory)

• Patients must be off all opioids, including opioid-containing medicines, for a minimum of 7-10 days before starting naltrexone to avoid precipitation of opioid withdrawal. 1
• Patients transitioning from buprenorphine or methadone may be vulnerable to precipitation of withdrawal symptoms for as long as two weeks. 1
• Precipitated opioid withdrawal can be severe enough to require hospitalization and intensive care unit management, with symptoms including confusion, somnolence, visual hallucinations, and significant fluid losses from vomiting and diarrhea. 1
• Even patients with negative urine toxicology screens or those who tolerate a naloxone challenge test may still experience precipitated withdrawal, particularly when transitioning from buprenorphine. 1

Alcohol Use Status (Not a Barrier)

• Naltrexone can be initiated while a patient is still drinking alcohol—there is no requirement for alcohol abstinence before starting treatment. 2, 3
• Trials not requiring lead-in abstinence from alcohol reported larger reductions in heavy drinking days per month (WMD -2.0,95% CI = -3.52, -0.48). 3
• Naltrexone works by blocking opioid receptors and dampening activation of the reward pathway by alcohol, thereby decreasing excessive drinking and increasing abstinence duration. 2

Liver Function Assessment (Essential)

• Baseline liver function tests must be performed before initiating naltrexone, as the medication can cause hepatocellular injury, particularly at higher doses. 2, 4, 1
• Naltrexone is contraindicated in patients with acute hepatitis or decompensated liver disease. 4, 1
• Liver function tests should be monitored every 3-6 months during treatment. 2, 4
• Naltrexone exposure increases approximately 5-fold in compensated cirrhosis and 10-fold in decompensated cirrhosis compared to normal liver function. 1

Key Distinction: Alcohol vs. Opioid Dependence

For Alcohol Use Disorder

• Patients can start naltrexone while actively drinking—no alcohol-free period is required. 2, 3
• The medication is designed to reduce cravings and drinking behavior in patients who are still consuming alcohol. 2, 5
• Extended-release naltrexone reduces drinking days by 2 days per month and heavy drinking days by 1.2 days per month compared to placebo. 3

For Opioid Use Disorder

• Patients must be completely opioid-free for 7-10 days (or up to 2 weeks for buprenorphine/methadone) before starting naltrexone. 1
• This requirement applies even to patients being treated primarily for alcohol dependence who may have concurrent opioid use. 1

Assessment Protocol Before Initiation

Screen All Patients for Opioid Use

• All patients, including those with alcohol dependence, must be assessed for underlying opioid dependence and any recent opioid use prior to initiation. 1
• Precipitated opioid withdrawal has been observed in alcohol-dependent patients when prescribers were unaware of additional opioid use or co-dependence. 1
• Patients should be encouraged to give an accurate account of last opioid use, as there is no completely reliable method for determining adequate opioid-free period. 1

Verify Absence of Opioid Withdrawal Symptoms

• Patients should not take naltrexone if they have any symptoms of opioid withdrawal. 1
• Symptoms of withdrawal precipitated by naltrexone typically appear within 5 minutes of ingestion and can last up to 48 hours. 1

Treatment Considerations

Duration and Efficacy

• Naltrexone's suppressant effects on drinking are most pronounced in the first 3 months of treatment. 6
• Trials lasting longer than 3 months reported larger reductions in heavy drinking days per month (WMD -1.9,95% CI = -3.2, -0.5). 3
• Many clinicians recommend one year of treatment, though optimal duration has not been well established. 5

Combination with Psychosocial Support

• Naltrexone must always be combined with psychosocial interventions such as cognitive behavioral therapy or motivational enhancement therapy for maximum efficacy. 2, 7, 1
• The medication has been shown to be effective only when used as part of a comprehensive treatment program that includes counseling and support. 1

Common Pitfalls to Avoid

• Never initiate naltrexone without thoroughly screening for recent opioid use, even in patients presenting solely for alcohol treatment. 1
• Do not assume a negative urine drug screen guarantees safety—some patients have experienced precipitated withdrawal despite negative screens. 1
• Avoid using naltrexone in patients with acute hepatitis, decompensated cirrhosis, or significantly elevated baseline transaminases. 4, 1
• Do not fail to warn patients that they will not experience effects from opioid-containing medications (analgesics, antidiarrheals, antitussives) while on naltrexone. 1
• Remember that patients who discontinue naltrexone have increased risk of opioid overdose due to decreased tolerance. 2, 1