What is the mechanism of action of lorazepam (Ativan) in the treatment of delirium tremens?

From the Guidelines

Lorazepam treats delirium tremens by enhancing the inhibitory effects of gamma-aminobutyric acid (GABA) in the central nervous system, and its typical dosing is 1-4 mg every 4-8 hours, as outlined in the management of alcohol withdrawal syndrome 1. The mechanism of action of lorazepam involves binding to GABA-A receptors, increasing chloride ion influx into neurons, which hyperpolarizes cell membranes and reduces neuronal excitability.

• This action directly counteracts the pathophysiology of alcohol withdrawal, where sudden removal of alcohol's GABA-enhancing effects leads to CNS hyperexcitability.
• As a benzodiazepine, lorazepam is effective in managing symptoms of delirium tremens, including agitation and seizures.
• The dosing of lorazepam can be adjusted based on the patient's response, with a typical range of 1-4 mg every 4-8 hours, as indicated in the guidelines for the management of alcohol withdrawal syndrome 1.
• It is essential to monitor patients for potential side effects, such as respiratory depression, excessive sedation, and paradoxical agitation, especially in elderly patients or those with respiratory compromise.
• Lorazepam is a preferred option in patients with liver dysfunction due to its lack of active metabolites and glucuronidation-based metabolism, as well as its medium-length half-life, which provides smoother control of withdrawal symptoms compared to shorter-acting benzodiazepines.

From the FDA Drug Label

CLINICAL PHARMACOLOGY Lorazepam interacts with the γ-aminobutyric acid (GABA)-benzodiazepine receptor complex, which is widespread in the brain of humans as well as other species. This interaction is presumed to be responsible for lorazepam's mechanism of action. The pharmacodynamic consequences of benzodiazepine agonist actions include antianxiety effects, sedation, and reduction of seizure activity.

The mechanism of action of lorazepam (Ativan) in the treatment of delirium tremens is through its interaction with the γ-aminobutyric acid (GABA)-benzodiazepine receptor complex, which leads to antianxiety effects, sedation, and reduction of seizure activity 2.

• The interaction with the GABA-benzodiazepine receptor complex is presumed to be responsible for lorazepam's mechanism of action.
• The pharmacodynamic consequences of benzodiazepine agonist actions include antianxiety effects, sedation, and reduction of seizure activity.

From the Research

Mechanism of Action of Lorazepam in Delirium Tremens

The mechanism of action of lorazepam (Ativan) in the treatment of delirium tremens is not explicitly described in the provided studies. However, the following points can be inferred:

• Delirium tremens is a severe complication of alcohol withdrawal syndrome, characterized by clouded consciousness, disorientation, and disturbed circadian rhythms 3, 4.
• Benzodiazepines, including lorazepam, are considered the gold standard treatment for delirium tremens due to their ability to suppress the symptoms of alcohol withdrawal 3, 4, 5.
• The use of benzodiazepines in the treatment of delirium tremens is thought to be related to their ability to enhance the activity of gamma-aminobutyric acid (GABA), a neurotransmitter that inhibits neuronal activity 3, 4.
• Lorazepam is often used in high doses to manage delirium tremens, and its effectiveness is thought to be due to its ability to rapidly achieve therapeutic levels and provide a calming effect on the patient 3, 4, 5.

Key Points

• Benzodiazepines, including lorazepam, are the mainstay of treatment for delirium tremens 3, 4, 5.
• The use of benzodiazepines in the treatment of delirium tremens is thought to be related to their ability to enhance the activity of GABA 3, 4.
• Lorazepam is often used in high doses to manage delirium tremens, and its effectiveness is thought to be due to its ability to rapidly achieve therapeutic levels and provide a calming effect on the patient 3, 4, 5.
• The treatment of delirium tremens should be managed at an ICU or wards ensuring vital signs monitoring 3.
• Supportive therapy is also of great importance in the treatment of delirium tremens 3.

Studies on Benzodiazepines in Delirium

• A study published in 2015 found that benzodiazepines, including lorazepam, are effective in managing delirium tremens 3.
• A study published in 2018 found that benzodiazepines, including lorazepam, are the mainstay of treatment for delirium tremens 4.
• A study published in 2020 found that there is limited evidence to support the use of benzodiazepines in the treatment of delirium in non-ICU settings 6.
• A study published in 2009 found that there is no evidence to support the use of benzodiazepines in the treatment of non-alcohol withdrawal related delirium 7.