Back to Course

Phenobarbital for Alcohol Withdrawal Masterclass

0% Complete
0/0 Steps
  1. Pathophysiology and Assessment of Acute Alcohol Withdrawal Syndrome
  2. Pathophysiology
  3. Pharmacology and Pharmacokinetics of Common Medications
  4. Phenobarbital Pharmacology
  5. Clinical Literature
Lesson 3 of 5
In Progress


Riszel January 14, 2022

Mode of Action

  • Binds to GABAA enhancing GABA activity (requires GABA to be present) 
    • Increases the frequency of GABAA receptor channel opening
  • Common agents: lorazepam, chlordiazepoxide, diazepam


  • Depends on agent, higher doses than used for sedation


  • Onset: 2-10 minutes
  • Metabolism: Hepatic and substrate of CYP isoenzymes
  • Elimination: primary through urine as metabolites 

Adverse Effects

  • Hypotensive 
  • Respiratory depression

AgentEquivalent Dose (mg)Onset of ActionDuration Active Metabolites
Chlordiazepoxide10Intermediate LongYes
Alprazolam0.5FastShortYes (Minimal)

Should we do symptom-triggered or fixed dosing of benzodiazepines?

Saitz et al. Individualized Treatment for Alcohol Withdrawal: A Randomized Double-blind Controlled Trial

ObjectiveTo assess the effect of an individualized treatment regimen on the intensity and duration of medication treatment for alcohol withdrawal.
DesignA randomized double-blind, controlled trial
SettingAn inpatient detoxification unit in a Veterans Affairs medical center.
Intervention ControlFixed-schedule: Chlordiazepoxide four times daily +PRNs vs Symptom triggered therapy: Chlordiazepoxide only in response to signs and symptoms of alcohol withdrawal
ResultsThe median duration of treatment in fixed-schedule 68 hr vs 9 hr in symptom-triggered group (P<.001)Mean dose 425 mg vs 100 mg (P<.001)No significant differences in the severity of withdrawal, the incidence of seizures, or delirium tremens.
ConclusionSymptom-triggered therapy individualizes treatment, decreases both treatment duration and the amount of benzodiazepine used, and is as efficacious as standard fixed-schedule therapy for alcohol withdrawal.

American Society of Addiction Medicine

  • Sedative hypnotic drugs are recommended as the primary agents for managing AWD (grade A recommendation)
    • There isn’t evidence that one sedative-hypnotic agent that is superior to others or that switching from one to another is helpful.
  • Dose agents to achieve light sedation (grade C recommendation).
    • The patient is awake but tends to fall asleep unless stimulated
  • Adrenergic antagonists may be considered as adjunction (grade C recommendation)
    • For control of persistent hypertension or tachycardia