Binds to GABAA enhancing GABA activity (requires GABA to be present)
Increases the frequency of GABAA receptor channel opening
Common agents: lorazepam, chlordiazepoxide, diazepam
Dose
Depends on agent, higher doses than used for sedation
PK/PD
Onset: 2-10 minutes
Metabolism: Hepatic and substrate of CYP isoenzymes
Elimination: primary through urine as metabolites
Adverse Effects
Hypotensive
Respiratory depression
Agent
Equivalent Dose (mg)
Onset of Action
Duration
Active Metabolites
Chlordiazepoxide
10
Intermediate
Long
Yes
Clonazepam
0.25
Fast
Intermediate
Yes
Diazepam
5
Fast
Long
Yes
Lorazepam
1
Fast
Intermediate
No
Alprazolam
0.5
Fast
Short
Yes (Minimal)
Midazolam
1.25-1.7
Fast
Short
Yes
Oxazepam
15
Slow
Intermediate
No
Should we do symptom-triggered or fixed dosing of benzodiazepines?
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.
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
