Diazepam (Valium)
Diazepam is a long-acting benzodiazepine licensed since 1963 for anxiety, alcohol withdrawal, muscle spasm, and seizures. It has decades of clinical use and produces anxiolysis, sedation, and muscle relaxation, but carries substantial dependence, tolerance, and withdrawal liability.
01 Overview
Diazepam potentiates the inhibitory neurotransmitter GABA at the GABA-A receptor, producing anxiolytic, sedative, muscle-relaxant, and anticonvulsant effects. Its long half-life and active metabolites (notably desmethyldiazepam) give a smooth, prolonged action that historically made it a first-line agent for alcohol withdrawal and acute anxiety.
With regular use, tolerance develops and physical dependence can form within weeks. Abrupt cessation after sustained dosing risks a withdrawal syndrome that can include rebound anxiety, insomnia, and seizures. Combined with opioids or alcohol, diazepam produces additive CNS and respiratory depression that can be fatal.
02 Mechanism
Positive allosteric modulator of the GABA-A receptor, enhancing chloride conductance and neuronal inhibition, which produces anxiolysis, sedation, muscle relaxation, and raised seizure threshold.
03 Dosing
| Tier | Dose | Route | Notes |
|---|---|---|---|
| Light | 2–5 mg | Oral | Lower end for anxiety or elderly patients. |
| Therapeutic (daily) | 4–40 mg/day | Oral | Total daily range across licensed indications; alcohol withdrawal may use higher tapered regimens. |
| Common | 5–10 mg | Oral | Typical anxiolytic or muscle-relaxant dose. |
04 Effects
| Effect | Magnitude | Evidence | |
|---|---|---|---|
| AnxiolysisReliable reduction in acute anxiety and agitation. | Onset 30-60 min oral | Clinical | |
| Muscle relaxationReduces skeletal muscle spasticity and spasm. | Clinical | ||
| SedationDose-dependent drowsiness; desired for sleep, unwanted during daytime use. | Clinical |
05 Side effects
| Effect | Severity | Frequency | Evidence | Countermeasures |
|---|---|---|---|---|
| Dependence and withdrawalPhysical and psychological dependence with tolerance; abrupt cessation can cause rebound anxiety, insomnia and seizures. | Severe | Common with regular use | Clinical | |
| Respiratory depressionAdditive respiratory and CNS depression, markedly increased when combined with opioids or alcohol. | Life-threatening | Uncommon alone, higher with CNS depressants | Clinical | |
| Anterograde amnesia and cognitive impairmentImpaired memory formation, psychomotor slowing and reduced concentration. | Moderate | Common | Clinical |