When to discontinue high-dose Lorazepam (benzodiazepine) in a male patient with resolved catatonia, now presenting with delirium and elevated C-reactive protein (CRP), and fluctuating levels of sedation?

From the Guidelines

I would advise gradually tapering the lorazepam now while investigating the cause of the delirium and rising CRP, as the patient no longer shows signs of catatonia and may be experiencing benzodiazepine toxicity. Begin by reducing the dose by 25-50% every 24-48 hours while monitoring for return of catatonic symptoms or withdrawal. Complete discontinuation should occur over 3-7 days depending on the previous dose and duration of treatment. During this taper, implement a comprehensive workup for infectious, metabolic, or other causes of delirium, including blood cultures, chest imaging, urinalysis, and metabolic panels. The rising CRP suggests inflammation or infection that could be causing the delirium, and high-dose benzodiazepines can worsen confusion and sedation, especially in vulnerable patients 1. Consider alternative treatments for any recurring catatonia such as electroconvulsive therapy (ECT) or NMDA receptor antagonists like memantine. Maintain close monitoring of vital signs, mental status, and inflammatory markers throughout the tapering process to guide management decisions.

Some key points to consider during the tapering process include:

• Monitoring for signs of benzodiazepine withdrawal, such as rebound anxiety, hallucinations, seizures, delirium tremens, and in rare cases, death 1
• Considering alternative treatments for anxiety, such as evidence-based psychotherapies (e.g., CBT) and/or specific anti-depressants or other nonbenzodiazepine medications approved for anxiety 1
• Coordinating care with mental health professionals managing the patient to discuss the patient’s needs, prioritize patient goals, weigh risks of concurrent benzodiazepine and opioid exposure, and coordinate care 1

It's also important to note that benzodiazepines are not considered part of the initial strategy in delirium management, and their use should be limited to patients who have distressing delirium symptoms or if there are safety concerns where the patient is a potential risk to themselves or others 1. In this case, since the patient is experiencing delirium and the cause is unknown, it's crucial to investigate and address the underlying cause while tapering the lorazepam to minimize the risk of worsening the patient's condition.

From the FDA Drug Label

To reduce the risk of withdrawal reactions, use a gradual taper to discontinue lorazepam or reduce the dosage If a patient develops withdrawal reactions, consider pausing the taper or increasing the dosage to the previous tapered dosage level. Subsequently decrease the dosage more slowly

The patient is presenting with delirium and up trending CRP, and fluctuating sedation but no overt signs of catatonia, while on high dose lorazepam. Given the development of delirium, it is likely that the lorazepam is contributing to the patient's condition. Lorazepam should be gradually tapered to reduce the risk of withdrawal reactions. It is advised to stop the lorazepam by gradually tapering the dose, as the benefits of continuing the medication may be outweighed by the risks of delirium and potential withdrawal reactions 2.

From the Research

Stopping Lorazepam in a Patient with Delirium and Catatonia

• The patient is currently being managed for catatonia with high-dose lorazepam, but has now developed delirium and an up-trending CRP, with fluctuating sedation and no overt signs of catatonia.
• According to the study by 3, catatonia and delirium can be comorbid, and the therapeutic response to lorazepam may vary.
• The study by 4 suggests that lorazepam is highly effective in treating catatonia, but the optimal duration of treatment is unknown and requires further study.
• In terms of stopping lorazepam, there is no clear guidance in the provided studies, but it is likely that the decision to stop or continue lorazepam will depend on the patient's individual response to treatment and the underlying cause of their delirium and catatonia.
• The study by 5 recommends prompt administration of lorazepam for catatonia in medically ill patients, but also notes that electroconvulsive therapy may be necessary for patients who do not respond to benzodiazepines.
• The development of delirium in a patient being treated for catatonia with lorazepam may indicate a need to reassess the patient's treatment plan, as delirium can be a side effect of benzodiazepine treatment 6, 7.
• Further evaluation and monitoring of the patient's condition, including their CRP levels and sedation status, will be necessary to determine the best course of action regarding lorazepam treatment.