Pathophysiology

• 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

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Acute Effects	Adaptations with Prolonged Use	Response to Cessation
Increased CNS inhibition through binding GABA-A and ↑ hyperpolarization of the nerve membrane	Down-regulation of GABA receptors through ↓ levels of GABA in the brain and reduced GABA-receptor sensitivity	Overall ↓ CNS inhibitory capacity
↓ excitation through antagonism at NMDA receptors	Up-regulation of glutamate to maintain homeostatic excitation	Overexcitation at NMDA receptors via up-regulation of glutamate

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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

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CIWA-Ar 

• 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

Objective	To assess the effect of an individualized treatment regimen on the intensity and duration of medication treatment for alcohol withdrawal.
Design	A randomized double-blind, controlled trial
Setting	An inpatient detoxification unit in a Veterans Affairs medical center.
Intervention Control	Fixed-schedule: Chlordiazepoxide four times daily +PRNs vs Symptom triggered therapy: Chlordiazepoxide only in response to signs and symptoms of alcohol withdrawal
Results	The 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.
Conclusion	Symptom-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.

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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