Naltrexone

Naltrexone works by blocking the receptors in your brain that opioids and alcohol activate to produce feelings of pleasure and reward:

For opioid use disorder: - Naltrexone sits on the opioid receptors in your brain like a lock, preventing opioid drugs from attaching and producing their effects. - If you take opioids while on naltrexone, you will not feel high. This removes the incentive to use. - This is different from methadone or buprenorphine, which partially activate these receptors. Naltrexone fully blocks them.

For alcohol use disorder: - Alcohol triggers the release of natural opioid-like chemicals (endorphins) in your brain, which create the pleasurable "buzz." - Naltrexone blocks these endorphin receptors, so drinking becomes less rewarding — you may find you simply don't enjoy drinking as much or don't crave it. - This "pharmacological extinction" gradually weakens the brain's association between drinking and pleasure.

Naltrexone is not addictive and does not cause withdrawal if stopped. It does not make you sick if you drink (unlike disulfiram/Antabuse).

Opioid use disorder: - Before starting: You must be completely opioid-free for 7-14 days before starting naltrexone to avoid precipitated withdrawal. A naloxone challenge test may be performed. - First dose: No euphoric or psychoactive effects. Some people experience mild nausea or headache. - Ongoing: You will not feel different day-to-day. The medication works by removing cravings and blocking the ability to get high if opioids are used.

Alcohol use disorder: - Week 1: Nausea is the most common early side effect (affects ~10-15%). Some people notice reduced cravings within days. - Weeks 2-4: Drinking episodes may become less satisfying. Many people find they drink less without having to "white-knuckle" it. - Months 1-3: Clinical trials show naltrexone reduces heavy drinking days by 25-30% and increases abstinent days ^{[3, 4]}. - Long-term: Benefits increase with continued use and are strongest when combined with counseling.

Vivitrol injection: - Monthly injection eliminates the need for daily pill adherence. Injection-site reactions (soreness, induration) are common but mild.

Food: Naltrexone can be taken with or without food. Taking it with food may reduce nausea ^[1].

Alcohol: Naltrexone does NOT cause a disulfiram-like reaction with alcohol (it will not make you violently ill if you drink). Instead, it reduces the pleasurable effects of alcohol. Some treatment protocols (the Sinclair Method) actually involve taking naltrexone specifically before planned drinking to leverage pharmacological extinction ^[3]. However, the FDA-approved approach for AUD is daily dosing combined with abstinence goals and counseling.

Opioid use disorder [1, 2]: - Oral: 50 mg once daily - Vivitrol injection: 380 mg IM (gluteal) every 4 weeks - CRITICAL: Patient must be opioid-free for minimum 7-14 days before starting. Verify with urine drug screen and/or naloxone challenge test.

Alcohol use disorder [1, 2]: - Oral: 50 mg once daily - Some clinicians start at 25 mg daily for the first week to reduce initial nausea - Vivitrol injection: 380 mg IM every 4 weeks

Important notes: - Naltrexone is NOT a controlled substance - No dose adjustment needed for mild-to-moderate renal impairment - Use with caution in hepatic impairment; contraindicated in acute hepatitis or liver failure - Patients should carry a medical alert card indicating they are on naltrexone, as opioid analgesics will be ineffective in emergencies

Generic oral naltrexone is very affordable. The Vivitrol injection is significantly more expensive but may be covered by insurance or assistance programs ^{[6, 7]}.

Pricing comparison: - Generic naltrexone 50 mg tablets: $25-60/month - Brand ReVia: rarely prescribed - Vivitrol 380 mg injection: $1,500-1,800/injection (monthly)

Cost-saving options for Vivitrol: - Manufacturer patient assistance program (Alkermes) - State substance abuse treatment programs often provide Vivitrol at no cost - Insurance coverage has improved significantly under mental health parity laws

Pregnancy: Naltrexone should be used during pregnancy only if the potential benefit justifies the risk ^[1].

- Animal studies at 100x human doses showed increased early fetal loss - Limited human data. No clear pattern of birth defects in small case series. - If a pregnant woman with OUD is on naltrexone and relapses, the lack of opioid tolerance (due to receptor blockade) significantly increases overdose and death risk - ACOG recommends methadone or buprenorphine as preferred MAT for OUD during pregnancy ^[5]

Breastfeeding: Naltrexone and its metabolite are excreted in breast milk. The clinical significance is unclear. The decision to breastfeed should weigh the benefits of breastfeeding and the mother's need for naltrexone treatment ^{[1, 5]}.

Generic oral naltrexone (50 mg tablets) is widely available and is the standard for daily oral therapy. The brand ReVia is no longer commonly stocked. Vivitrol is the only available extended-release injection formulation and has no generic equivalent. The choice between oral and injectable often comes down to adherence — patients who struggle with daily pill compliance may benefit from monthly Vivitrol injections.