What it is
Lorazepam is a high-potency benzodiazepine with an intermediate half-life (10–20 hours) and no relevant active metabolites. What sets it apart is its metabolism: it is eliminated by direct conjugation (glucuronidation), a pathway better preserved than oxidation in mild to moderate liver failure and in older people.
It is used in anxiety and short-term insomnia, with the same rules as the other benzodiazepines: short periods, the lowest dose and gradual withdrawal. Its risk of dependence is similar to alprazolam's.
Mechanism of action
It enhances:
- GABA-A receptor agonist, increasing the affinity for GABA
- Anxiolytic, sedative, muscle relaxant
- Effects similar to alprazolam, with a slightly longer half-life
At the counter
When to recommend it
- Acute anxiety
- Panic disorder while an SSRI takes effect
- Patients with mild to moderate liver failure or older people (metabolism by conjugation)
- Short-term insomnia linked to anxiety, on prescription
When not to
- History of substance misuse (caution)
- Pregnancy
- Sleep apnoea
- Long-term use (risk of dependence, like the other benzodiazepines)
Warnings
- Important Dependence: a risk similar to other benzodiazepines. Severe withdrawal.
- Important Disinhibition: risky behaviour, anterograde amnesia.
- Caution Drowsiness and unsteadiness.
- Caution Older people: higher risk of falls, confusion and hip fracture. Use the lowest dose and review whether it is needed.
Pharmacokinetics
- Absorption
- Rapid absorption, slightly less abrupt than alprazolam. Bioavailability of 90%. Peak at 1–2 hours.
- Distribution
- Wide distribution in the CNS. Fat-soluble. Protein binding of 85%. It crosses the placenta.
- Metabolism
- A peculiarity among benzodiazepines: direct conjugation (glucuronidation), with NO need for hepatic oxidation.
- Elimination
- Renal elimination of conjugates. Half-life of 10–20 hours. No significant active metabolites.
Lorazepam vs alprazolam
| Aspect | Lorazepam | Alprazolam |
|---|---|---|
| Speed of action | Fast (peak at 2 h) | Fast (peak at 1–2 h) |
| Potency | High | High |
| Hepatic metabolism | Direct conjugation (better in mild to moderate liver disease) | Oxidation via CYP3A4 (interactions) |
| Risk of dependence | High | High |
| Half-life | Intermediate (10–20 h) | Intermediate (11–16 h) |
Lorazepam is an alternative to alprazolam, especially in older patients or those with mild to moderate liver disease, and without the CYP3A4 interactions. Both only for short periods.
Self-assessment
Three questions. When you check your answers you will see the explanation for each one.
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Lorazepam does not need hepatic oxidation. It is conjugated directly. Better in cirrhosis or liver failure.
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In liver disease, lorazepam is preferable because conjugation is better preserved than oxidation, the pathway alprazolam uses.
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Like all benzodiazepines, there is a risk of dependence. It should not be used long term.
Training content. It does not replace the summary of product characteristics or clinical judgement.