Chlordiazepoxide (Librium)
Chlordiazepoxide was the first benzodiazepine, introduced in 1960, and is licensed for anxiety and, prominently, for managing alcohol withdrawal. Its long half-life and active metabolites give smooth coverage, but it retains the class dependence, tolerance, and withdrawal liability.
01 Overview
Chlordiazepoxide potentiates GABA at the GABA-A receptor and has a long duration of action from active metabolites, making it a mainstay of alcohol withdrawal management where a smooth, self-tapering profile is valued. It is also used for short-term anxiety.
Despite its therapeutic role in withdrawal, chlordiazepoxide itself produces tolerance and dependence with sustained use, and abrupt cessation after regular use can precipitate withdrawal including seizures. Co-use with opioids or alcohol adds respiratory depression, and it causes dose-dependent sedation and cognitive impairment.
02 Mechanism
Positive allosteric modulator of the GABA-A receptor with long-acting active metabolites; enhances GABAergic inhibition producing anxiolysis and sedation.
03 Dosing
| Tier | Dose | Route | Notes |
|---|---|---|---|
| Light | 5–10 mg | Oral | Lower dose for mild anxiety. |
| Common | 10–25 mg | Oral | Typical anxiolytic per-dose range. |
| Therapeutic (alcohol withdrawal) | 25–100 mg | Oral | Higher tapered doses used in supervised alcohol withdrawal regimens. |
04 Effects
| Effect | Magnitude | Evidence | |
|---|---|---|---|
| AnxiolysisReliable reduction of anxiety and agitation. | Clinical | ||
| Alcohol withdrawal symptom controlReduces tremor, agitation and seizure risk during managed alcohol withdrawal. | Clinical | ||
| SedationDose-dependent drowsiness and calm. | Clinical |
05 Side effects
| Effect | Severity | Frequency | Evidence | Countermeasures |
|---|---|---|---|---|
| Dependence and withdrawalTolerance and dependence; abrupt cessation can cause rebound anxiety, insomnia and seizures. | Severe | Common with regular use | Clinical | |
| Respiratory depressionAdditive respiratory and CNS depression with opioids or alcohol. | Life-threatening | Uncommon alone, higher with CNS depressants | Clinical | |
| Sedation and cognitive impairmentDrowsiness, psychomotor slowing and memory impairment. | Moderate | Common | Clinical |