15.3 Alcohol Use Disorder Drugs

Alcohol Use Disorder

Alcohol use disorder (AUD) is a chronic condition where repeated alcohol exposure changes brain chemistry, leading to tolerance, dependence, and compulsive drinking. Three FDA-approved medications target different aspects of the disorder: disulfiram discourages use through aversive effects, naltrexone reduces cravings by blocking reward pathways, and acamprosate stabilizes neurotransmitter balance to support abstinence. Pharmacotherapy combined with behavioral therapy gives patients the best outcomes.

Biological Mechanisms of Alcohol Addiction

Chronic alcohol use disrupts several neurotransmitter systems, and understanding these changes helps explain why the medications work the way they do.

• Dopamine release increases in the nucleus accumbens (the brain's reward center), which reinforces alcohol-seeking behavior. Over time, the brain starts to depend on alcohol to trigger dopamine release.
• GABA, the brain's main inhibitory neurotransmitter, is enhanced by alcohol at first. With chronic use, GABA receptor sensitivity decreases, so the brain becomes less able to self-regulate.
• Glutamate, the main excitatory neurotransmitter, is suppressed by alcohol. The brain compensates by upregulating glutamate receptors. When alcohol is suddenly removed, this glutamate overactivity drives withdrawal symptoms like tremors, anxiety, and seizures.

These neuroadaptations produce tolerance (needing more alcohol for the same effect) and physical dependence (withdrawal symptoms when alcohol is stopped).

Signs and Symptoms of Alcohol Addiction

Behavioral changes:

• Drinking larger amounts or for longer periods than intended
• Repeated unsuccessful attempts to cut down despite wanting to stop
• Neglecting work, school, or relationship responsibilities because of drinking

Physical symptoms:

• Tolerance: needing progressively more alcohol to feel the same effects
• Withdrawal: tremors, sweating, nausea, tachycardia, and anxiety within hours of the last drink; severe cases can include seizures and delirium tremens

Psychological symptoms:

• Persistent cravings or strong urges to drink
• Continued use despite clear negative consequences (legal problems, liver disease, damaged relationships)

Pharmacology of Alcohol Addiction Treatments

Each of the three medications targets a different mechanism, so knowing how they work helps you understand when to use them.

Disulfiram (Antabuse) uses aversion therapy. It irreversibly inhibits aldehyde dehydrogenase, the enzyme that breaks down acetaldehyde (a toxic byproduct of alcohol metabolism). If a patient drinks while taking disulfiram, acetaldehyde accumulates rapidly, causing intense flushing, throbbing headache, nausea, vomiting, and hypotension. The unpleasant experience is meant to deter drinking. The patient must be fully informed and motivated, because the drug only works if they take it consistently.

Naltrexone (ReVia, Vivitrol) is an opioid receptor antagonist that blocks mu-opioid receptors. Alcohol normally triggers endorphin release, which contributes to its pleasurable effects. By blocking these receptors, naltrexone reduces the "reward" from drinking, which lowers cravings and decreases the likelihood of relapse. It's available as a daily oral tablet or a once-monthly intramuscular injection (Vivitrol).

Acamprosate (Campral) modulates the balance between GABA and glutamate. It partially restores normal neurotransmitter activity by acting on NMDA glutamate receptors, reducing the hyperexcitability that persists after a person stops drinking. This helps ease protracted withdrawal symptoms like insomnia, anxiety, and restlessness, making it easier to maintain abstinence.

Side Effects of Addiction Medications

Nursing Considerations for Addiction Treatments

• Before starting therapy, assess for contraindications: check liver function (especially for disulfiram and naltrexone), renal function (for acamprosate), pregnancy status, and current opioid use (for naltrexone).
• During therapy, monitor for side effects and adverse reactions. With disulfiram, watch for signs of hepatotoxicity (jaundice, dark urine, elevated liver enzymes). With naltrexone, monitor liver function tests periodically.
• Support adherence by educating patients on why consistent dosing matters. Missed doses of disulfiram remove the aversive "safety net." For naltrexone, the monthly injection (Vivitrol) can help patients who struggle with daily pills.
• Coordinate care by referring patients to counseling, cognitive-behavioral therapy, and support groups like Alcoholics Anonymous. Medication alone is rarely sufficient.

Patient Education for Addiction Medications

For all patients:

• Explain how the specific medication works in plain language. Patients who understand why they're taking a drug are more likely to stay on it.
• Discuss common side effects and practical management strategies (e.g., taking naltrexone with food to reduce nausea).

Disulfiram-specific teaching:

• The patient must avoid all sources of alcohol, not just beverages. This includes alcohol-containing mouthwash, cough syrups, vinegar-based sauces, and topical products like aftershave. A disulfiram-alcohol reaction can begin within 10 minutes and last several hours.
• Patients should carry an identification card stating they are taking disulfiram, in case of emergency.

Naltrexone-specific teaching:

• Patients must be opioid-free for at least 7 to 10 days before starting naltrexone, or it can trigger acute opioid withdrawal.
• Naltrexone also blocks opioid pain medications. Patients should inform all healthcare providers and wear a medical alert bracelet.

Acamprosate-specific teaching:

• This medication works best when started early in abstinence (ideally within the first 5 to 7 days after the last drink).
• It's taken three times daily, which can be a challenge. Encourage patients to use reminders or pill organizers.

Encourage open communication with providers about how treatment is going, and connect patients with counseling and peer support resources.

Effectiveness of Pharmacological Approaches

• Disulfiram works best in highly motivated patients, particularly when dosing is supervised (by a spouse, clinic, or treatment program). Its effectiveness drops significantly if patients simply stop taking it. Requires regular liver function monitoring due to hepatotoxicity risk.
• Naltrexone has strong evidence for reducing heavy drinking days and relapse rates, especially when paired with behavioral therapies like CBT or motivational interviewing. The injectable form (Vivitrol) improves adherence.
• Acamprosate is most effective for maintaining abstinence rather than reducing drinking in active users. It's a good option for patients with liver disease who can't take naltrexone or disulfiram, as long as renal function is adequate.
• Combination therapy (e.g., naltrexone + acamprosate) may benefit some patients, though evidence is mixed. Medication choice should be tailored to the individual based on motivation level, comorbidities, organ function, and concurrent medication use.

Comprehensive Approach to Alcohol Use Disorder Treatment

Medication is one piece of a larger treatment plan:

• Detoxification is often the first step for patients with physical dependence. Medically supervised withdrawal typically uses benzodiazepines (not the AUD maintenance drugs above) to prevent seizures and manage symptoms safely.
• Abstinence is the primary treatment goal. Complete cessation prevents further organ damage and allows the brain to begin recovering normal neurotransmitter function.
• Relapse prevention requires identifying personal triggers, building coping skills, and maintaining ongoing support through therapy and peer groups. Relapse is common and should be treated as a setback to learn from, not a treatment failure.