Tricyclic antidepressant toxicity


  • Abbreviation: TCA
  • Used in depression and neuropathic pain
  • Serious toxicity is almost always seen within 6hr of ingestion
  • Coingestants that impair metabolism through cytochrome P450 often increase severity of toxicity
    • Cocaine can produce the same sodium blockade effect and exacerbate as TCA overdose

Ingestion amount

  • <1mg/kg: Nontoxic
  • >10mg/kg: Life-threatening
  • >1gm: Commonly fatal

Clinical Features

Differential Diagnosis

Anticholinergic toxicity Causes

Sodium Channel Blockade Toxidrome


ECG in TCA toxicity
  • An urine positive test result suggests only use of a TCA or another drug that cross-reacts with the screen (antimuscarinic, antipsychotic, carbamazepine, etc.)
  • Quantitative serum level does not correlate with severity of illness


GI Decontamination

Cardiac Toxicity[5]

Sodium Bicarbonate

  • Indications:
    • QRS >100ms, terminal RAD >120 deg, Brugada pattern, ventricular dysrhythmias
  • Initial Dosing:
    • Give 1-2 mEq/kg as rapid IVP; may repeat as necessary (stop if pH > 7.50-7.55)
    • May give as 3 ampules of 8.4% NaHCO3 (150 mEq) or 7.5% NaHCO3 (134 mEq)
  • Infusion Dosing[6]
    • Mix 125-150 mEq of NaHCO3 in 1L of D5W; infuse at 250 mL/hr
  • Treatment Goal:
    • QRS <100ms
    • pH 7.50-7.55
    • May continue for 12-24hrs due to the drugs redistribution from tissue
  • Treatment Monitoring
    • Monitor for volume overload, hypocalcemia, hypokalemia, hypernatremia, metabolic alkalosis
    • Aggressively replace serum electrolytes


  • Consider in patients unable to tolerate NaHCO3 (renal failure, pulm/cerebral edema)
  • Hyperventilate to pH of 7.50 - 7.55 (same as bicarb administration)


  • At 1.5 mg/kg, consider lidocaine for ventricular dysrhythmias if NaHCO3 alone is ineffective
  • Competitively inhibits sodium channel blockade effects of TCAs
Avoid IA, IC antiarrhythmics, Beta-Blockers, Calcium Channel Blockers, and amiodarone


  • Consider for ventricular dysrhythmias resistant to NaHCO3 and lidocaine

Synchronized cardioversion

  • Appropriate in patients with persistent unstable tachydysrhythmias

NEVER Use Physostigmine

  • NEVER use physostigmine in TCA overdose as the combination leads to lethal bradyarrhythmias[7]
    • Due to dose dependent AV blockade by physostigmine
    • TCA toxicity and physostigmine interact synergistically to cause AV conduction delays



  • After repeat fluid boluses and with sodium load from NaHCO3 norepinepherine should be the first line vasopressor
  • ECMO is a successful adjunct for refractory hypotension after maximal therapy has failed
  • May also consider 200 ml of hypertonic 3% saline for refractory hypotension and ventricular dysrhythmias despite maximal alkalinization (pH > 7.55)


  • Not useful for enhancing elimination due to the large volume of distribution and high lipid solubility


  • 1.5 mL/kg bolus over 2-3 minutes if life-threatening toxicity refractory to bicarbonate administration
  • May be repeated once in 5 minutes if no improvement, followed by an infusion of 0.25 ml/kg/min for 15-30 minutes


  • Consider discharging patients who remain asymptomatic after 6hr of observation
  • Patients with decreased level of consciousness or seizures should be admitted to ICU

See Also


  1. Dawson AH, Buckley NA. Pharmacological management of anticholinergic delirium – theory, evidence and practice. Br J Clin Pharmacol. 2015;81(3):516-24.
  2. 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. Aug 1995;26(2):195-201
  3. Goldgran-Toledano D, Sideris G, Kevorkian JP. Overdose of cyclic antidepressants and the Brugada syndrome. N Engl J Med. May 16 2002;346(20):1591-2
  4. Monteban-Kooistra WE, van den Berg MP, Tulleken JE. Brugada electrocardiographic pattern elicited by cyclic antidepressants overdose. Intensive Care Med. Feb 2006;32(2):281-5
  5. Thanacoody HK, Thomas SH. Tricyclic antidepressant poisoning: cardiovascular toxicity. Toxicol Rev. 2005;24(3):205-14
  6. Seger DL, Hantsch C, Zavoral T, Wrenn K. Variability of recommendations for serum alkalinization in tricyclic antidepressant overdose: a survey of U.S. Poison Center medical directors. J Toxicol Clin Toxicol. 2003;41(4):331-8
  7. Schneider G. Never Use Physostigmine in a TCA Overdose. Emergency Medicine News: May 2003 - Volume 25 - Issue 5 - p 44.