Naltrexone for Opioid and Alcohol Dependence
Direct Recommendation
Naltrexone is FDA-approved and effective for both alcohol dependence and opioid dependence, but patients must be completely opioid-free for 7-10 days (short-acting opioids) or up to 2 weeks (buprenorphine/methadone) before initiation to avoid precipitated withdrawal, and it works best in highly motivated patients as part of comprehensive treatment including psychosocial support. 1, 2
Clinical Indications
Alcohol Dependence
- Naltrexone reduces alcohol craving and consumption by blocking opioid receptors, thereby dampening the reward pathway activation by alcohol. 2, 3
- Moderate-quality evidence supports effectiveness in reducing relapse to heavy drinking and increasing abstinence duration. 3
- The 50 mg daily oral dose or 380 mg monthly injectable (Vivitrol) are both FDA-approved for alcohol dependence. 1, 2
Opioid Dependence
- Naltrexone is most beneficial for highly motivated patients who cannot or do not wish to take continuous opioid agonist therapy (buprenorphine/methadone). 2, 4
- It provides complete blockade of exogenously administered opioids at 50 mg daily dosing. 1
- Healthcare professionals and criminal justice populations show particularly good outcomes. 2
- Buprenorphine and methadone remain first-line treatments with stronger evidence for preventing relapse; naltrexone is an alternative for motivated patients preferring opioid-free treatment. 4, 2
Dosing Protocols
Oral Naltrexone
- Standard dose: 50 mg once daily 1, 2
- Alternative supervised dosing schedules: 1
- 100 mg on Monday and Wednesday, 150 mg on Friday
- 100 mg every other day
- 150 mg every third day
- Initiate with 25 mg test dose for opioid dependence; if no withdrawal occurs, advance to 50 mg daily. 1
Injectable Naltrexone (Vivitrol)
- 380 mg intramuscular injection monthly 2
- Provides reliable therapeutic levels for 1 month and significantly improves medication compliance compared to daily oral dosing. 3, 5
Dose Adjustments
- Moderate-to-severe renal impairment: Reduce dose to 25 mg daily 2
- Moderate-to-severe hepatic impairment: Do not exceed 25 mg daily 2
Critical Pre-Treatment Requirements
Opioid-Free Period (MANDATORY)
- Minimum 7-10 days opioid-free for short-acting opioids (heroin, morphine IR, oxycodone) 1, 2
- Minimum 10-14 days for extended-release formulations 1
- Up to 2 weeks for patients transitioning from buprenorphine or methadone 1, 4
- Failure to observe adequate opioid-free period will precipitate severe, potentially life-threatening withdrawal. 1, 6
Naloxone Challenge Test
- Perform if any question of occult opioid dependence exists 1
- Do NOT perform if patient shows clinical withdrawal signs or has opioids in urine. 1
- Intravenous protocol: 0.2 mg naloxone, observe 30 seconds; if no withdrawal, give 0.6 mg and observe 20 minutes 1
- Subcutaneous protocol: 0.8 mg naloxone, observe 20 minutes 1
- If withdrawal signs appear (agitation, nausea, vomiting, sweating, dilated pupils, tachycardia, abdominal pain), test is positive—do NOT start naltrexone. 1, 6
Baseline Screening
- Obtain liver function tests at baseline and repeat every 3-6 months due to hepatotoxicity risk at supratherapeutic doses 2, 7
- Screen for depression, anxiety, and insomnia before initiation, as naltrexone may worsen these conditions. 2
- Assess for acute hepatitis or liver failure (absolute contraindications). 2
Absolute Contraindications
- Current opioid use or dependence without adequate opioid-free period 1
- Acute hepatitis or decompensated cirrhosis 2
- Patients requiring opioid analgesics for pain control 2, 1
- Pregnancy (for opioid dependence)—use buprenorphine or methadone instead 2
Management of Precipitated Withdrawal
Agitation is the most prominent and difficult symptom to manage in naltrexone-precipitated withdrawal. 6
Common Withdrawal Symptoms
- Severe agitation (96% of cases), altered consciousness, nausea, vomiting, abdominal pain, diarrhea, bone/muscle pain, tachycardia, dilated pupils 6
Treatment Approach
- Use α2-adrenergic agonists (clonidine) for withdrawal symptom management 4, 2
- NSAIDs or acetaminophen for muscle aches and pain 2
- Do NOT administer opioid agonists, as naltrexone will block their effects 1
- Supportive care with close monitoring until symptoms resolve 6
Perioperative Management
Oral Naltrexone
Injectable Naltrexone (Vivitrol)
- Hold for 24-30 days after last injection before elective procedures 2, 3
- Plan surgeries accordingly or use non-opioid analgesics (regional anesthesia, NSAIDs, acetaminophen). 2
Critical Safety Warnings
Overdose Risk After Discontinuation
- Patients who discontinue naltrexone have markedly decreased opioid tolerance and face increased risk of fatal overdose if they return to previous opioid doses. 2, 3
- Provide opioid overdose education and prescribe naloxone to all patients discontinuing naltrexone. 2
Hepatotoxicity
- Higher risk with single doses above 50 mg 1
- Monitor liver function tests every 3-6 months during treatment. 2, 7
Depression and Suicidality
- Naltrexone may cause or worsen depression; screen and monitor closely. 2
Essential Treatment Context
Naltrexone is NOT a standalone treatment and will fail without comprehensive psychosocial support. 1
Required Components
- Individual counseling 2
- Group therapy 2
- Community-based support groups (AA, NA) 1
- Compliance-enhancing techniques for medication adherence 1
- Treatment of comorbid psychiatric conditions 1
Treatment Duration
- Placebo-controlled trials demonstrating efficacy used 12 weeks of treatment for alcohol dependence 1
- Longer durations may be needed based on individual response and relapse risk. 1
Response Assessment
- Assess treatment response after 12 weeks on maintenance dose 2
- For alcohol dependence: Monitor drinking days, heavy drinking episodes, and craving levels 3
- For opioid dependence: Monitor abstinence, urine drug screens, and treatment retention 2
Prescribing Access
Both oral naltrexone and injectable Vivitrol can be prescribed from office-based practices without specialized clinic enrollment or DEA X-waiver, unlike methadone. 2 This makes naltrexone more accessible for motivated patients in outpatient settings. 8
Common Clinical Pitfalls
- Starting naltrexone before adequate opioid-free period—this causes severe precipitated withdrawal 1, 6
- Failing to perform naloxone challenge when opioid-free status is uncertain 1
- Using naltrexone as monotherapy without psychosocial support 1
- Not educating patients about overdose risk after discontinuation 2
- Prescribing to patients who need opioid analgesics for pain 2, 1
- Inadequate monitoring of liver function tests 2
- Not screening for or addressing comorbid depression before initiation 2