What is the management for an overdose of Klonopin (clonazepam) and Trazodone in a patient?

Management of Clonazepam (Klonopin) and Trazodone Overdose

Prioritize aggressive airway management and supportive care over antidotal therapy, as flumazenil is contraindicated in this mixed overdose scenario due to the risk of seizures from trazodone co-ingestion. 1, 2

Immediate Stabilization

Airway and Breathing:

• Assess airway patency, breathing adequacy, and circulation immediately with continuous cardiorespiratory monitoring 1
• Provide bag-mask ventilation if respiratory rate falls below 8 breaths/min or respiratory depression is evident 1, 2
• Prepare for endotracheal intubation if Glasgow Coma Scale ≤8 or protective airway reflexes are lost 1, 2
• Obtain arterial or venous blood gas if respiratory depression is present to assess for hypoxemia and hypercarbia 1

Circulatory Support:

• Establish IV access immediately 1
• Monitor blood pressure continuously and treat hypotension with IV fluids 3, 4
• Consider vasopressors (levarterenol or metaraminol) if hypotension persists despite fluid resuscitation 3

Cardiac Monitoring:

• Obtain serial ECGs to detect QTc prolongation, conduction delays, or dysrhythmias that can occur with trazodone toxicity 1, 5
• Monitor continuously for wide complex tachycardia, ventricular tachycardia, and various degrees of heart block that may develop 12-24 hours post-ingestion 5
• Be aware that trazodone can cause QTc prolongation evolving into ventricular tachycardia and bundle branch blocks even when initial ECG appears normal 5

Critical Laboratory and Diagnostic Workup

• Perform bedside glucose testing immediately to rule out hypoglycemia as a cause of altered mental status 1
• Obtain comprehensive metabolic panel including electrolytes, renal function, and hepatic function 1
• Check complete blood count 1
• Perform urine drug screen to identify co-ingestants, particularly opioids, alcohol, or other CNS depressants 1
• Obtain serum acetaminophen and salicylate levels as part of standard overdose workup 1

Why Flumazenil Should NOT Be Used

Flumazenil is absolutely contraindicated in this mixed overdose scenario because:

• Trazodone lowers seizure threshold, and flumazenil reversal of benzodiazepine's anticonvulsant effects may precipitate seizures 6, 2
• The FDA label explicitly warns against flumazenil use in cyclic antidepressant overdose due to seizure risk 3
• Standard supportive care with airway management and mechanical ventilation is preferred over flumazenil in mixed overdoses 1, 2
• Even if flumazenil were considered, it would not reverse respiratory depression from trazodone 2

Specific Management Considerations

Gastrointestinal Decontamination:

• Consider gastric lavage if presentation is within 1-2 hours of ingestion 3, 7
• Administer activated charcoal if airway is protected 7, 8

Seizure Management:

• Monitor closely for generalized tonic-clonic seizures, which can occur 12-24 hours post-ingestion with trazodone 5
• Have antiepileptic medications readily available 5

Cardiovascular Complications:

• Be prepared for cardiogenic shock requiring norepinephrine and dopamine infusion 5
• Trazodone overdose can cause coma and hypotension as main concerns, successfully treated with fluid therapy and observation 4
• Unlike tricyclic antidepressants, trazodone is not typically associated with severe cardiac arrhythmias in most cases, though fatal arrhythmias can occur in severe overdoses 7, 5

Observation and Disposition

Monitoring Duration:

• Observe in healthcare setting for minimum 6-8 hours for benzodiazepine component, with longer periods if CNS depression persists 1
• Extend monitoring to at least 24-36 hours due to delayed cardiac toxicity from trazodone 5
• Monitor for at least 2 hours after any intervention to assess for recurrent toxicity 1

ICU Admission Criteria:

• Respiratory depression requiring mechanical ventilation 1
• Cardiac arrhythmias or conduction abnormalities 5
• Seizure activity 5
• Cardiogenic shock 5

Psychiatric Evaluation:

• Mandatory psychiatric evaluation before discharge to assess suicide risk 1

Common Pitfalls to Avoid

• Never administer flumazenil in this mixed overdose—the risk of precipitating seizures from trazodone far outweighs any potential benefit from benzodiazepine reversal 6, 1, 2, 3
• Do not assume initial normal ECG rules out cardiac toxicity—trazodone-induced arrhythmias can develop 12-24 hours after ingestion 5
• Avoid premature discharge after apparent clinical improvement—delayed cardiac complications and resedation can occur 1, 5
• Do not neglect respiratory support while focusing on pharmacological interventions 2
• Recognize that death from this combination overdose has occurred, particularly when other CNS depressants are involved 9