From the Guidelines
Lorazepam is the preferred treatment for alcohol withdrawal due to its efficacy, safety, and pharmacokinetic profile, and should be administered at 2-4 mg every 1-4 hours as needed for symptoms, with gradual tapering over 3-5 days as symptoms improve. According to the most recent and highest quality study 1, benzodiazepines are considered the 'gold standard' treatment for alcohol withdrawal syndrome (AWS), and lorazepam is a recommended option, particularly for patients with severe AWS, advanced age, or liver dysfunction. The advantages of lorazepam include a shorter half-life, more predictable absorption, and no active metabolites, making it a safer choice for patients with hepatic dysfunction or elderly patients 1.
Key Considerations
- Lorazepam has a shorter half-life (10-20 hours) compared to phenobarbital (80-120 hours), allowing for easier dose adjustments and less accumulation 1.
- Lorazepam can be given through multiple routes (oral, IV, IM), making it a more versatile option 1.
- Phenobarbital may be preferred in certain situations, such as patients with severe withdrawal at high risk for delirium tremens, those with benzodiazepine tolerance, or in resource-limited settings where frequent monitoring is challenging.
- The choice between lorazepam and phenobarbital should consider individual patient factors, including severity of withdrawal, comorbidities, previous withdrawal experiences, and the clinical setting's monitoring capabilities.
Treatment Approach
- Use a symptom-triggered regimen rather than a fixed dose schedule to prevent the accumulation of the drug 1.
- Monitor patients closely for signs of autonomic nervous system activation, such as high fever, tachycardia, hypertension, and sweating, as well as comorbidities such as dehydration, electrolyte imbalance, renal failure, head trauma, infection, gastrointestinal bleeding, pancreatitis, and liver failure 1.
- Consider thiamine supplementation (100-300 mg/day) for all patients with AWS to prevent diminished cognitive function due to thiamine deficiency 1.
From the FDA Drug Label
The lethal dose of a barbiturate is far less if alcohol is also ingested. The symptoms of barbiturate withdrawal can be severe and may cause death. Treatment of barbiturate dependence consists of cautious and gradual withdrawal of the drug Barbiturate-dependent patients can be withdrawn by using a number of different withdrawal regimens. One method involves substituting a 30 mg dose of phenobarbital for each 100 to 200 mg dose of barbiturate that the patient has been taking The total daily amount of phenobarbital is then administered in 3 to 4 divided doses, not to exceed 600 mg daily. After stabilization on phenobarbital, the total daily dose is decreased by 30 mg a day as long as withdrawal is proceeding smoothly.
Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the risk of drug-related mortality compared to use of opioids alone The continued use of benzodiazepines, including lorazepam, may lead to clinically significant physical dependence Abrupt discontinuation or rapid dosage reduction of lorazepam after continued use, or administration of flumazenil (a benzodiazepine antagonist) may precipitate acute withdrawal reactions, which can be life-threatening To reduce the risk of withdrawal reactions, use a gradual taper to discontinue lorazepam or reduce the dosage
Comparison of Phenobarbital and Lorazepam for Alcohol Withdrawal
- Both phenobarbital and lorazepam can be used for the treatment of alcohol withdrawal, but the FDA drug labels do not provide a direct comparison of the two.
- Phenobarbital is used for the treatment of barbiturate dependence, and the dosage is gradually decreased by 30 mg a day as long as withdrawal is proceeding smoothly 2.
- Lorazepam is used for the treatment of anxiety disorders, and the dosage should be gradually tapered to discontinue or reduce the dosage to minimize the risk of withdrawal reactions 3 3.
- No conclusion can be drawn about which is better for the treatment of alcohol withdrawal, as the FDA drug labels do not provide sufficient information for a direct comparison.
From the Research
Comparison of Phenobarbital and Lorazepam for Alcohol Withdrawal Treatment
- The studies 4, 5, 6, 7, 8 suggest that benzodiazepines are the primary treatment for alcohol withdrawal syndrome.
- Lorazepam is a commonly used benzodiazepine for this purpose, but the studies do not provide a direct comparison of lorazepam tapering dose with phenobarbital tapering dose.
- However, a study 6 found that a single dose of phenobarbital in addition to symptom-triggered lorazepam may be beneficial in the acute management of alcohol withdrawal syndrome, with more patients being discharged within three days.
Pharmacokinetics and Efficacy
- A study 4 suggests that diazepam, another benzodiazepine, has a favorable pharmacokinetic profile for the treatment of alcohol withdrawal, with a rapid onset of action and a gradual decrease in levels, resulting in a smoother withdrawal.
- The same study 4 notes that the fear of increased risk of over-sedation with diazepam is unfounded, and that diazepam is safe for use in patients with liver disease and elderly patients when administered using a symptom-based approach.
Treatment Guidelines
- The guidelines reviewed in a study 7 recommend benzodiazepines as the first-line treatment for alcohol withdrawal syndrome, with the association of other medications such as anticonvulsants, adrenergic alpha-2 agonists, betablockers, and antipsychotics recommended for symptom reduction in severe cases.
- A systematic review 8 found that benzodiazepines have the best evidence base for the treatment of alcohol withdrawal, followed by anticonvulsants, and that a symptom-monitored loading approach may be beneficial for severe withdrawals.