Medications: How They Work and Contraindications

Medications for Alcohol Use Disorder (AUD) work in different ways—some reduce cravings, some make drinking unpleasant, and others help stabilize brain chemistry. Here’s a clear breakdown of the main options, how they function, and key contraindications.

1. Naltrexone

How it works

  • Blocks opioid receptors involved in the brain’s reward system

  • Reduces the “high” and pleasure from alcohol → less urge to drink

  • Forms: oral (daily) or long-acting injection (monthly)

Contraindications/cautions

  • Current opioid use (can precipitate withdrawal)

  • Acute hepatitis or liver failure

  • Use cautiously in liver disease

Sources: SAMHSA – Naltrexone Overview | FDA – Vivitrol (Naltrexone) Information | SAMHSA – Medications for Substance Use Disorders

2. Acamprosate

How it works

  • Stabilizes glutamate and GABA balance disrupted by chronic alcohol use

  • Helps reduce post-acute withdrawal symptoms (anxiety, insomnia, cravings)

  • Best for maintaining abstinence

Contraindications/cautions

  • Severe kidney impairment (renal failure)

  • Requires dosing 3 times daily → adherence may be difficult

Sources: SAMHSA – Medication for the Treatment of Alcohol Use Disorder: A Brief Guide| SAMHSA Library – AUD Pocket Guide

3. Disulfiram

How it works

  • Blocks the breakdown of acetaldehyde when alcohol is consumed

  • Causes unpleasant reaction (flushing, nausea, palpitations) → deters drinking

Contraindications/cautions

  • Severe heart disease

  • Psychosis

  • Liver disease

  • Must avoid any alcohol exposure (including sauces, cough syrups, and some medications)

Sources:SAMHSA – Medication for the Treatment of Alcohol Use Disorder: A Brief Guide | SAMHSA Advisory – Prescribing Pharmacotherapies for AUD

4. Topiramate (off-label)

How it works

  • Enhances GABA activity and inhibits glutamate

  • Reduces cravings and heavy drinking

Contraindications/cautions

  • Cognitive side effects (“brain fog”)

  • Kidney stones

  • Teratogenic → avoid in pregnancy

Sources: SAMHSA Advisory – Prescribing Pharmacotherapies for AUD | SAMHSA – Medication for the Treatment of Alcohol Use Disorder: A Brief Guide

5. Gabapentin (off-label)

How it works

  • Modulates GABA activity

  • Helps with withdrawal symptoms, anxiety, insomnia, and cravings

Contraindications/cautions

  • Risk of sedation and misuse

  • Dose adjustment required in kidney disease

Sources: SAMHSA Advisory – Prescribing Pharmacotherapies for AUD | SAMHSA – Medication for the Treatment of Alcohol Use Disorder: A Brief Guide

Clinical Notes

  • First-line choices are usually Naltrexone or Acamprosate, depending on patient factors.

  • Disulfiram is most effective when adherence is supervised.

  • Off-label agents may help when first-line treatments fail or are not tolerated.

  • Medication is most effective when combined with behavioral therapy such as CBT or motivational interviewing.

General References: SAMHSA – Substance Use Disorder Treatment Options | SAMHSA – AUD Medication Guide | SAMHSA Library – TIP 49 Advisory