What are the effects of benzodiazepine (Benz) overdose?

From the Guidelines

I'd advise against the use of flumazenil as a first-line treatment for benzodiazepine overdose due to its potential to precipitate refractory benzodiazepine withdrawal and seizures. Benzodiazepines are commonly used sedative-hypnotics that can cause CNS depression, respiratory compromise, and even death when overdosed, usually in combination with other CNS depressants like opioids or alcohol 1. The management of benzodiazepine poisoning typically involves standard life support measures, including establishing an open airway, providing bag-mask ventilation, and endotracheal intubation when necessary. Some key points to consider when managing benzodiazepine overdose include:

• The potential for mixed overdoses, which may require the administration of naloxone if opioid overdose is suspected 1
• The importance of careful patient assessment and monitoring for signs of respiratory depression, cardiac dysrhythmias, and seizure activity
• The need for a gradual tapering schedule when discontinuing benzodiazepine use to avoid withdrawal symptoms, which can be dangerous and include rebound anxiety, insomnia, tremors, and seizures 1. Given the potential risks associated with flumazenil administration, it is generally recommended to prioritize supportive care and monitoring over the use of this medication, except in cases where the benefits of flumazenil use outweigh the risks, such as in patients with severe respiratory depression or cardiac arrest 1.

From the FDA Drug Label

OVERDOSAGE Clinical Experience Manifestations of alprazolam overdosage include somnolence, confusion, impaired coordination, diminished reflexes and coma. Flumazenil, a specific benzodiazepine receptor antagonist, is indicated for the complete or partial reversal of the sedative effects of benzodiazepines and may be used in situations when an overdose with a benzodiazepine is known or suspected.

The treatment for an overdose of alprazolam (a benzodiazepine) includes:

• General supportive measures
• Immediate gastric lavage
• Intravenous fluids
• Maintenance of an adequate airway
• Use of vasopressors if hypotension occurs
• Flumazenil may be used for the reversal of sedative effects, but with caution due to the risk of seizure, particularly in long-term benzodiazepine users 2. Key considerations:
• Monitoring for re-sedation, respiratory depression, and other residual benzodiazepine effects
• Awareness of the risk of seizure in association with flumazenil treatment

From the Research

Benzodiazepine Use and Discontinuation

• Benzodiazepines are highly effective for treating insomnia and anxiety, but long-term use poses a risk-benefit dilemma due to addiction, withdrawal symptoms, and potential side effects 3.
• Only 5% of patients can discontinue benzodiazepine use on their own, and with the help of a general practitioner, this rate does not exceed 25-30% of patients, with approximately 7% remaining drug-free in the long term 3.
• Cognitive Behavioral Therapies (CBT) have been shown to increase abstinence success to 70-80%, offering a crucial solution to the problem of benzodiazepine discontinuation 3.

Risks and Benefits of Benzodiazepines

• Benzodiazepines are linked to a variety of adverse effects, whether used long-term, short-term, or as needed, and many patients take them without receiving evidence-based first-line treatments 4.
• The risks and benefits of benzodiazepines, as well as alternatives to their use, have been discussed in the literature, highlighting the need for evidence-based indications and contraindications 4, 5.
• Benzodiazepines may have significant adverse effects, increasing the risk of overdose and death, and their use has been increasing, with a growing number of unregulated novel psychoactive substances 6.

Alternative Treatments

• Cognitive behavioral therapy has shown the most benefit in terms of behavioral treatments for benzodiazepine discontinuation, and CBT for insomnia (CBT-i) is now commonly recommended as first-line treatment for chronic insomnia 6, 7.
• CBT-i has been shown to be an effective treatment for adults with chronic insomnia, with clinically meaningful effect sizes, and approaches to CBT-i often incorporate cognitive therapy, stimulus control, sleep restriction, sleep hygiene, and relaxation 7.