What is the management for a zopiclone (non-benzodiazepine hypnotic) overdose?

Management of Zopiclone Overdose

The management of zopiclone overdose should focus on supportive care with airway management and ventilatory support as the primary interventions, while flumazenil should be avoided in most cases due to risk of seizures and other adverse effects. 1, 2

Initial Assessment and Management

• Establish and maintain an open airway as the first priority, providing bag-mask ventilation for respiratory depression, followed by endotracheal intubation when appropriate 1
• Contact a regional poison center (1-800-222-1222 in the US) for expert guidance in management 1
• Perform immediate gastric lavage where appropriate, especially if presentation is soon after ingestion 2
• Administer intravenous fluids as needed to maintain adequate blood pressure 2
• Monitor vital signs, including respiration, pulse, blood pressure, and oxygen saturation 2

Supportive Care

• Provide respiratory support as needed, which is the cornerstone of management for zopiclone overdose 1
• Monitor for hypoxemia and hypercarbia, as they are the primary causes of tissue injury and death in sedative-hypnotic overdose 1
• Treat hypotension with IV fluids and vasopressors if necessary 2
• Consider the possibility of methemoglobinemia in patients with persistent hypoxemia despite oxygen therapy, especially if there's a saturation gap or chocolate-brown appearance of blood 3

Antidotal Therapy Considerations

• Flumazenil (a competitive antagonist at the benzodiazepine binding site on the GABA-A receptor) should generally be avoided in zopiclone overdose due to risk of precipitating seizures, especially in patients with:

  • History of benzodiazepine dependence 1, 4
  • Preexisting seizure disorders 1
  • Suspected co-ingestion of tricyclic antidepressants 1, 4
  • Co-ingestion of other seizure-threshold lowering drugs 4
  • Hypoxia 4

• If flumazenil is deemed necessary in select cases (pure zopiclone overdose with severe respiratory depression and no contraindications), the initial adult dose is 0.2 mg IV, titrated up to 1 mg 1, 4

Special Considerations

• Always consider the possibility of multiple drug ingestion, as it is common in overdose scenarios 1, 2
• If combined opioid and zopiclone poisoning is suspected, administer naloxone for respiratory depression before considering other antidotes 1
• Monitor for resedation after initial improvement, as the duration of action of any reversal agent may be shorter than that of zopiclone 4
• Fatal outcomes with zopiclone overdose are rare but have been reported, especially when combined with other CNS depressants 2, 5
• In patients on serotonergic medications who develop methemoglobinemia from zopiclone overdose, consider ascorbic acid instead of methylene blue to avoid serotonin syndrome 3

Common Pitfalls to Avoid

• Failing to recognize mixed overdoses, especially with opioids or alcohol, can lead to inadequate treatment 1, 4
• Administering flumazenil to patients with zopiclone dependence can precipitate withdrawal symptoms including seizures 1, 4, 6
• Assuming that zopiclone is safer than traditional benzodiazepines; it can still cause significant CNS and respiratory depression 7
• Neglecting to provide adequate respiratory support while focusing on pharmacological interventions can result in poor patient outcomes 1
• Underestimating the potential for zopiclone dependence and withdrawal symptoms in chronic users 6, 7