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 2 of5
In Progress


Riszel January 14, 2022
  • Alcohol, or ethanol, is a psychoactive substance that produces electrical changes within the central nervous system (CNS)
  • Alcohol Withdrawal Syndrome (AWS) is the result of overexcitation in the CNS after abrupt reduction or abstinence from alcohol after prolonged use
    • Consequences: hyperthermia, arrhythmias, or seizures
  • The National Institute of Alcohol Abuse and Alcoholism reported that more than 14 million adults have alcohol use disorder (AUD)
  • More than half a million episodes of alcohol withdrawal require pharmacological treatment annually

Acute Effects
Adaptations with Prolonged UseResponse to Cessation
Increased CNS inhibition through binding GABA-A and ↑ hyperpolarization of the nerve membraneDown-regulation of GABA receptors through ↓ levels of GABA in the brain and reduced GABA-receptor sensitivityOverall ↓ CNS inhibitory capacity
↓ excitation through antagonism at NMDA receptorsUp-regulation of glutamate to maintain homeostatic excitationOverexcitation at NMDA receptors via up-regulation of glutamate
Pathophysiology of Alcohol Withdrawal

Stages of Withdrawal

•Categorized into 4 stages, which may not be sequential

DSM-5 Diagnostic Criteria for Alcohol Withdrawal

•DSM-5 is the standard diagnostic criteria for diagnosis AWS

  • A.Cessation of (or reduction in) alcohol use that has been heavy and prolonged
  • B.≥2 or more symptoms developing within several hours to a few days after Criterion A: autonomic hyperactivity, increased hand tremor, insomnia, N/V, hallucinations or illusions, psychomotor agitation, anxiety, generalized tonic-clonic seizures
Diagnostic and Statistical Manual of Mental Disorders (DSM-5) Diagnostic Criteria for Alcohol Withdrawal
A. Cessation of (or reduction in) alcohol use that has been heavy and prolonged
B. Two (or more) of the following, developing within several hours to a few days after criterion A:
1. Autonomic hyperactivity
2. Increased hand tremor
3. Insomnia
4. Nausea or vomiting
5. Transient visual, tactile, or auditory hallucinations or illusions
6. Psychomotor agitation
7. Anxiety
8. Generalized tonic-clonic seizures


  • The Clinical Institute Withdrawal Assessment for Alcohol scale in its revised version (CIWA-Ar) is the most widely used tool in US 
  • Used to determine the severity of the withdrawal symptoms as they are actively experienced
  • Validated 10-item Assessment tool
    • Examines: Agitation, anxiety, auditory disturbances, clouding of sensorium, headache, paroxysmal sweats, tactile disturbances, tremor, and visual impairment
  • Score 8-15 indicates mild alcohol withdrawal
  • Scores >20 indicate severe alcohol withdrawal

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