Benzodiazepine Toxicity Treatment & Management

Updated: Apr 28, 2022
  • Author: J Michael Kowalski, DO; Chief Editor: Gil Z Shlamovitz, MD, FACEP  more...
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Approach Considerations

The cornerstone of treatment in benzodiazepine (BZD) overdoses is supportive care and monitoring. Death secondary to sedative-hypnotic overdose usually results from cardiorespiratory collapse. Therefore, the first step in management is an assessment of the patient's airway, breathing, and circulation, and these should be addressed rapidly as needed.

Gastrointestional (GI) decontamination, including single-dose activated charcoal and orogastric lavage, is not routinely recommended, as the risks far outweigh the benefits. BZD overdoses are rarely fatal, and altered mental status greatly increases the risk of aspiration. [8]

Flumazenil (Romazicon) is a specific antidote for BZD poisoning, but its use in acute BZD overdose is controversial and its risks usually outweigh any possible benefits. [9] In BZD-dependent patients, flumazenil may precipitate life-threatening withdrawal. Flumazenil use is also associated with seizures in patients with prior seizure history or a mixed overdose. [10] In patients taking BZDs for a medical condition, flumenazil may result in exacerbation of the underlying condition. The ideal indication for flumazenil is in isolated iatrogenic (eg, during conscious sedation) cases or BZD overdose in BZD-naive patients.

Disposition of patients is as follows:

  • Patients may be discharged if they remain asymptomatic at least 6 hours post ingestion.
  • Patients with mild toxicity may be observed in the emergency department until they recover.
  • Patients with intentional overdoses require psychiatric evaluation before discharge.
  • Admit patients with hemodynamic instability, coma, or respiratory depression to the intensive care unit (ICU). Respiratory depression may be treated with assisted ventilation.
  • Regional Poison Centers can be helpful in management and disposition of acute cases (1-800-222-1222)

The American Psychiatric Association and the National Institute of Clinical Excellence have treatment and diagnostic guidelines available for cases of substance abuse and self-harm. [23, 24]


Prehospital Care

Prehospital care for patients who have overdosed on benzodiazepines (BZDs) includes the following:

  • Cardiac monitoring
  • Supplemental oxygen and airway support
  • Intravenous (IV) access
  • Rapid glucose determination (finger stick) and administration of 50% dextrose solution (D50) if necessary

Naloxone can be administered at a very low dose (0.04 mg IV with a gradual increase if needed) if the diagnosis is unclear and an opioid co-ingestion is suspected (eg, if the patient has severe respiratory depression).

An important caveat is that although 0.4 mg IV naloxone will reverse respiratory depression in most patients with opioid overdoses, it will also cause severe withdrawal symptoms (nausea, vomiting) in those who are opioid dependent. This can result in aspiration of gastric contents in patients who are unable to protect their airway because of sedation from the BZD.



Flumazenil is a competitive BZD receptor antagonist and is the only available specific antidote for BZDs. Its use in acute BZD is controversial, however, and its risks usually outweigh any benefit. [9] Common adverse events with flumazenil include agitation and gastrointestinal symptoms, while serious adverse events include supraventricular arrhythmia and convulsions. [25]

Flumazenil does not consistently reverse central respiratory depression due to BZDs, and over half the patients in a large multicenter study experienced re-sedation after use. [26]

In benzodiazepine-dependent patients, flumazenil may precipitate life-threatening withdrawal. In patients taking BZDs for a medical condition, flumenazil may result in exacerbation of the condition. 

In addition to those patients with long-term BZD use, flumazenil should not be used in any patient at an increased risk of having a seizure, including those with a seizure history, head injury, co-ingestion of BZD and tricyclic antidepressant or other proconvulsant, or even a possible ingestion of a proconvulsant. [27]

The ideal consideration for flumazenil use is for isolated iatrogenic BZD overdose in BZD-naive patients (eg, during conscious sedation of a BZD-naive patient).