What is the management approach for an adult patient with a history of depression, anxiety, or chronic pain who has overdosed on amitriptyline (tricyclic antidepressant)?

Management of Amitriptyline Overdose

All patients with suspected amitriptyline overdose require immediate ECG monitoring and assessment for cardiac dysrhythmias, severe hypotension, convulsions, and CNS depression, as these are the critical life-threatening manifestations that develop rapidly and require hospital monitoring as soon as possible 1.

Immediate Assessment and Monitoring

Critical ECG Findings

• QRS duration ≥0.10 seconds (100 ms) is the best indicator of overdose severity and predicts risk of life-threatening complications 1.
• Look specifically for: rightward axis shift in terminal QRS complex, prolonged QT interval, sinus tachycardia, prolonged PR interval, ST-T wave changes, ventricular tachycardia, and ventricular fibrillation 2, 1.
• Sinus tachycardia occurs in approximately 66% of cases and is the most common cardiac finding 3.
• Establish continuous cardiac monitoring for a minimum of 6 hours; if any signs of toxicity appear, extended monitoring is mandatory as fatal dysrhythmias can occur late after overdose 1.

Neurologic Assessment

• Altered mental status occurs in approximately 78% of cases 3.
• Assess for: impaired consciousness (Glasgow Coma Score), seizures, confusion, agitation, hyperactive reflexes, visual hallucinations, dilated pupils, and disorders of ocular motility 1, 3.
• Symptoms typically develop within 30 minutes of ingestion and peak between 2-6 hours 3.

Cardiovascular Assessment

• Hypotension occurs in approximately 7-8% of cases 3.
• Assess for impaired myocardial contractility and signs of cardiovascular instability 1.

Airway and Respiratory Management

• Protect the airway immediately and secure it prior to gastric lavage if consciousness is impaired 1.
• Early intubation is advised in patients with CNS depression due to potential for abrupt deterioration 1.
• Mechanical ventilatory support is required in approximately 9% of cases 3.
• Establish intravenous access immediately 1.

Gastrointestinal Decontamination

All patients with suspected tricyclic antidepressant overdose should receive gastrointestinal decontamination with large volume gastric lavage followed by activated charcoal 1.

• EMESIS IS CONTRAINDICATED 1.
• Activated charcoal should be administered after gastric lavage 1, 4.
• Some cases may benefit from whole bowel irrigation in addition to activated charcoal 5.

Cardiac Management

Sodium Bicarbonate Therapy

Intravenous sodium bicarbonate is the primary treatment for cardiac toxicity and should be used to maintain serum pH between 7.45-7.55 1.

• Sodium bicarbonate is indicated for QRS widening and cardiac dysrhythmias 1, 4.
• If pH response is inadequate, hyperventilation may be added with extreme caution and frequent pH monitoring 1.
• Avoid pH >7.60 or pCO₂ <20 mmHg as these are undesirable 1.

Antiarrhythmic Management

• For dysrhythmias unresponsive to sodium bicarbonate/hyperventilation, consider: lidocaine, bretylium, or phenytoin 1.
• Type 1A and 1C antiarrhythmics (quinidine, disopyramide, procainamide) are generally contraindicated 1.
• In rare instances of acute refractory cardiovascular instability, hemoperfusion may be beneficial, though hemodialysis, peritoneal dialysis, exchange transfusions, and forced diuresis are generally ineffective 1.

Seizure Management

Seizures should be controlled with benzodiazepines as first-line therapy 1.

• If benzodiazepines are ineffective, use other anticonvulsants such as phenobarbital or phenytoin 1.
• Physostigmine is NOT recommended except to treat life-threatening symptoms unresponsive to other therapies, and only in consultation with a poison control center 1.

Adjunctive Therapies

Naloxone

• While not standard therapy, there is case report evidence that naloxone (2 mg IV) may have a beneficial role in severe amitriptyline poisoning, possibly due to amitriptyline's effects on opioid receptors 4.
• In one case, spontaneous respiration returned 20 minutes after naloxone administration as part of a coma cocktail (naloxone 2 mg, 50% dextrose 25g, thiamine 100 mg) 4.

Lipid Emulsion Therapy

• Intravenous lipid emulsion (20% lipid emulsion: 150 mL bolus followed by infusion at 16 mL/h) is an emerging therapy for lipophilic drug toxicity 5.
• Evidence in amitriptyline overdose is limited to case reports with mixed results; one case showed possible reduction in frequency of wide-complex tachycardia but no dramatic hemodynamic improvement 5.
• Consider only in refractory cases unresponsive to conventional therapy 5.

Disposition and Follow-up

• Most patients (69%) can be managed in the emergency department, with 54% discharged within 24 hours if they remain asymptomatic 3.
• Patients with clinical evidence of significant poisoning require extended monitoring beyond 6 hours 1.
• Plasma drug levels should not guide acute management 1.
• Therapeutic amitriptyline/nortriptyline levels are 50-300 ng/mL; levels >1600 ng/mL have been associated with status epilepticus and significant cardiac conduction abnormalities 6.

Critical Pitfalls to Avoid

• Do not assume low doses are safe: 500-1000 mg (approximately 1-week supply) can be life-threatening, with 50% of such overdoses being potentially fatal 7.
• Do not discharge patients early; fatal dysrhythmias can occur late after overdose in patients who had inadequate gastrointestinal decontamination 1.
• Do not use Type 1A or 1C antiarrhythmics as they can worsen toxicity 1.
• Do not rely on absence of ECG findings to exclude toxicity, though their presence is highly specific 2, 1.

Psychiatric Follow-up

Since overdose is often deliberate, psychiatric referral is appropriate as patients may attempt suicide by other means during recovery 1.

• Suicide attempts by amitriptyline overdose are most common in young single women 3.
• Contact poison control center for current treatment recommendations and pediatric-specific management 1.