What are the recommended medications for managing ethanol (ETOH) withdrawal?

Medications for Managing Alcohol (ETOH) Withdrawal

Benzodiazepines are the first-line medications for managing alcohol withdrawal syndrome, with long-acting benzodiazepines such as chlordiazepoxide and diazepam being the preferred agents for most patients. 1

First-Line Pharmacological Treatment

• Long-acting benzodiazepines (chlordiazepoxide and diazepam) are recommended as front-line medications for alcohol withdrawal to alleviate discomfort, prevent seizures, and treat delirium through GABA activation 1
• Chlordiazepoxide dosing: 25-100 mg every 4-6 hours, tapered as symptoms resolve 1, 2
• Diazepam dosing: 10 mg, 3-4 times during the first 24 hours, reducing to 5 mg, 3-4 times daily as needed 3
• Symptom-triggered dosing (administering medication based on withdrawal symptoms) is preferred over fixed-schedule dosing as it results in lower total medication use and shorter treatment duration 4

Special Population Considerations

• Lorazepam (intermediate-acting benzodiazepine) is recommended for patients with:
  • Severe alcohol withdrawal syndrome
  • Advanced age
  • Recent head trauma
  • Liver failure or disease
  • Respiratory failure
  • Other serious medical comorbidities
  • Obesity 1, 2
• Lorazepam is typically started at 6-12 mg/day and tapered following symptom resolution 1
• Lorazepam and oxazepam are safer in patients with liver disease as they undergo only hepatic glucuronidation rather than oxidation, which is impaired in liver disease 5
• Lorazepam is preferred when intramuscular administration is required, as diazepam has erratic absorption via this route 5

Adjunctive Treatments

• Thiamine supplementation is essential for all patients with alcohol withdrawal:
  • Standard dosing: 100-300 mg/day orally for 2-3 months following withdrawal resolution 1
  • Higher risk patients (malnourished, severe withdrawal) or those with suspected Wernicke's encephalopathy should receive parenteral thiamine 1
  • Thiamine should be administered before any glucose-containing IV fluids to prevent precipitating acute thiamine deficiency 1
• Antipsychotic medications should not be used as stand-alone treatments for alcohol withdrawal 1
• Haloperidol (0.5-5 mg every 8-12 hours) may be used as an adjunct to benzodiazepines only for severe withdrawal delirium not responding to adequate benzodiazepine doses 1
• Anticonvulsants (like carbamazepine 200 mg every 6-8 hours) should not be used following an alcohol withdrawal seizure but may be an alternative to benzodiazepines for seizure prevention in some cases 1

Treatment Setting

• Inpatient management is recommended for patients with:
  • Risk of severe withdrawal
  • History of withdrawal seizures or delirium tremens
  • Concurrent serious physical or psychiatric disorders
  • Lack of adequate support
  • Failed outpatient treatment 1
• Conservative management should include fluids, electrolytes (especially magnesium), vitamins, and a comfortable environment 1

Monitoring and Duration

• Withdrawal symptoms should be monitored using validated tools like the CIWA-Ar scale 2
• Benzodiazepine treatment should be tapered following resolution of withdrawal symptoms 1
• Treatment duration should generally not exceed 10-14 days to avoid risk of benzodiazepine dependence 2
• Psychoactive medications used for withdrawal should be dispensed in small quantities or each dose supervised to reduce misuse risk 1

Post-Withdrawal Relapse Prevention

• After successful withdrawal management, medications to reduce relapse should be offered:
  • Acamprosate
  • Disulfiram
  • Naltrexone 1
• The choice among these medications should consider patient preferences, motivation, and availability 1
• Psychosocial support and referral to mutual help groups like Alcoholics Anonymous should be incorporated into the treatment plan 1

Common Pitfalls and Caveats

• Diazepam loading (giving larger initial doses followed by decreasing doses) can be an effective strategy that takes advantage of the drug's long half-life, providing a natural taper effect 6
• Psychiatric consultation is recommended for evaluation, acute management, and long-term abstinence planning 1
• Gabapentin may be considered for mild to moderate alcohol withdrawal, particularly in outpatient settings, though it is not first-line therapy 7
• The fear of increased risk of over-sedation with diazepam compared to other benzodiazepines is often unfounded when administered using a symptom-based approach 8