• Overdose may cause severe toxicity including coma, seizures, hypotension and cardiac dysrhythmias.
• Consult BC Drug and Poison Information Centre 604-682-5050, or 1-800-567-8911.

• Mild to moderate symptoms include lethargy, delirium, sinus tachycardia, ileus, tremors, and myoclonus.
• Seizures are usually brief but may be associated with abrupt cardiovascular deterioration.
• Deaths are primarily due to cardiovascular toxicity.

• Symptom onset is usually within 4-6 hours.
• In massive overdose, symptoms may occur within 1 hour.

• “Quinidine-like” effects are due to inhibition of myocardial sodium channels causing delayed atrioventricular conduction.
• Direct myocardial depressant effects (decreased contractility).
• Anticholinergic effects.
• α Blocking effects.

• Acute ingestion of > 5 mg/kg of most tricyclics may result in toxicity.
• > 2.5 mg/kg with nortriptyline or trimipramine.
• Death may be seen following ingestion of 10-20 mg/kg.

• ECG should be obtained on presentation and used as a screening tool for the presence of TCAs.
• Classic ECG changes include:
  • QRS complex widening,
  • rightward shift in axis of terminal 40 milliseconds of QRS complex (best observed as a terminal R wave in lead aVR),
  • prolongation of QT and PR intervals,
  • ST segment depression and T wave changes.
• QRS complex > 0.1 seconds, R/S ratio in aVR > 0.7 associated with increased incidence of seizures and dysrhythmias.
• QRS interval > 0.16 seconds associated with 50% incidence of ventricular dysrhythmias.
• Serum antidepressant levels do not correlate well with toxicity or outcome.

• Avoid: procainamide, disopyramide, quinidine, sotalol, and bretylium; may aggravate cardiotoxicity.
• Avoid phenytoin.
• Physostigmine is contraindicated.
• Hemodynamic and neurologic effects are unpredictable and may result in seizures, bradycardia, asystole, and death.
• Flumazenil is contraindicated in any patient with an altered level of consciousness who may have taken a cyclic antidepressant, as it may precipitate intractable seizures and death.
• Respiratory acidosis will worsen toxicity.

A. Cardiac monitoring

• Asymptomatic patients should have continuous ECG monitoring, and monitoring of vital signs for at least 6 hours after admission.
• Symptomatic patients should be monitored for 24 hours after resolution of symptoms.

B. Activated charcoal may be useful for recent ingestions. Avoid repeated doses as may increase risk of ileus and aspiration.

C. Glasgow Coma Scale (GCS) < 8 and hemodynamic instability require intubation.

D. Monitor vital signs, electrolytes, and 12-lead electrocardiogram (ECG).

• Blood gases in symptomatic patients.
• Serum antidepressant levels do not correlate well with toxicity or outcome.

E. Treat QRS > 0.1 second and other conduction abnormalities (e.g. R_aVR ³ 3 mm)

• IV sodium bicarbonate boluses (2-3 ampoules or 1-2 mEq/kg).
• Repeat boluses every 3-5 minutes until QRS interval narrows or until serum pH reaches 7.55.
• IV sodium bicarbonate boluses are preferred over sodium bicarbonate infusions; boluses may be more effective at overcoming sodium channel blockade (theoretical).
• Monitor for hypokalemia and fluid overload.
• Hypertonic saline may be useful if pH has reached 7.55 and QRS widening still present.

F. Ventricular dysrhythmias refractory to IV sodium bicarbonate may respond to lidocaine.

• Lidocaine lowers seizure threshold and should be used with caution.
• Hypertonic saline may also be considered.
• IV magnesium sulfate may be useful for refractory dysrhythmias (efficacy not established).
• Avoid: procainamide, disopyramide, quinidine, sotalol, and bretylium; may aggravate cardiotoxicity.
• Unclear whether amiodarone is detrimental. Prolonged resuscitation has been successful.

G. Sinus tachycardia or supraventricular tachycardia rarely requires treatment as increased heart rate may be needed to maintain cardiac output. Caution: Use of beta-blockers to treat supraventricular tachycardia may exacerbate toxicity (additive hypotensive and negative inotropic effects).

H. Bradydysrhythmias may be treated with isoproterenol or transvenous pacing.

• Dopamine and epinephrine also effective.
• Atropine is rarely effective.
• Prolonged resuscitation has been effective in several cases.

I. Hypotension unresponsive to IV fluids and patient positioning should be treated with IV sodium bicarbonate boluses (2-3 ampoules or 1-2 mEq/kg).

• If hypotension persists, use vasopressors.
• Norepinephrine may be more effective than dopamine.

J. Seizures and agitation should be controlled with IV benzodiazepines.

• Seizures refractory to high-dose benzodiazepine should be treated with barbiturates, propofol, general anesthesia or neuromuscular paralysis (with continuous EEG monitoring).
• Avoid phenytoin.

K. IV lipid emulsion therapy should be considered in patients refractory to standard resuscitation measures or who are rapidly deteriorating despite therapy.

• Symptomatic patients should be monitored for 24 hours after resolution of symptoms.
• Patients with dysrhythmias, hypotension and seizures will need to be admitted to an ICU setting.

• If requires ICU care that is not available locally.

• BC Drug and Poison Information Centre 604-682-5050, or 1-800-567-8911.

• Patients may be discharged after observation periods have been met and the patient’s psychiatric condition has been treated if the overdose was intentional.

1. Poison Management Manual (PMM), BC Drug and Poison Information Centre, 2015.

   
   

2. Body R, Bartram T, Azam F, Mackway-Jones K. Guidelines in Emergency Medicine Network (GEMNet): guideline for the management of tricyclic antidepressant overdose. Emerg Med J. 2011 Apr;28(4):347-68. doi: 10.1136/emj.2010.091553.

   
   

3. Bailey B, Buckley NA, Amre DK. A meta-analysis of prognostic indicators to predict seizures, arrhythmias, or death after tricyclic antidepressant overdose. Clin Toxicol 2004;42(6):877-888.

   
   

4. Boenert MT, Lovejoy FH.  Value of the QRS duration versus the serum drug level in predicting seizures and ventricular arrhythmias after an acute overdose of tricyclic antidepressants.  New Eng J Med.  1985; 313: 474- 9.

   
   

5. Liebelt EL, Francis PD, Woolf AD. ECG lead aVR versus QRS interval in predicting seizures and arrhythmias in acute tricyclic antidepressant toxicity. Ann Emerg Med 1995;26:195-201.