Tricyclic Antidepressant Toxicity Medication
- Author: Vivian Tsai, MD, MPH, FACEP; Chief Editor: Asim Tarabar, MD more...
Treatment of cyclic antidepressant (CA) toxicity focuses on airway management, dysrhythmias, seizures, and hypotension. Sodium bicarbonate, benzodiazepines, and norepinephrine are the drugs of choice for these complications.
This agent prevents further absorption of drug and other co-ingestants from the GI tract.
Emergency treatment in poisoning caused by drugs and chemicals. Network of pores present in activated charcoal adsorbs 100-1000 mg of drug per gram of charcoal. May be administered with or without cathartic (eg, Sorbitol 70%), except in young pediatric patients, where electrolyte imbalance may be of concern. Does not dissolve in water.
For maximum effect, administer within 30 min of ingesting poison.
Sodium bicarbonate is indicated for QRS intervals greater than 100 milliseconds, seizures, acidosis (pH level < 7), hypotension, cardiac arrest, or dysrhythmia. Antidysrhythmic agents may be helpful. However, avoid certain drugs that exacerbate the cardiac effects of CAs, such as quinidine and procainamide (class IA), flecainide (class IC), and bretylium and amiodarone (class III). Vasopressors are used for the treatment of hypotension not corrected by intravenous fluids.
First-line therapy for QRS interval >100 milliseconds or if dysrhythmias are present. Correction of acidosis promotes protein binding of CA and improves myocardial contractility. Doses or IV drip may be administered with a pH goal of 7.5-7.55. Monitor and replace potassium as needed to prevent hypokalemia.
Class IB antiarrhythmic that increases electrical stimulation threshold of ventricle, suppressing automaticity of conduction through tissue. Second DOC for CA dysrhythmias.
Stimulates beta1- and alpha-adrenergic receptors, which, in turn, increases cardiac muscle contractility, heart rate, and vasoconstriction. As a result, systemic blood pressure and coronary blood-flow increases. DOC to treat hypotension refractory to fluid resuscitation in CA toxicity. Dopamine is second-line and less effective.
Benzodiazepines are preferred for treatment of seizures. Do not use barbiturates in patients with hypotension. Do not use phenytoin in patients with dysrhythmias.
Sedative hypnotic with short onset of effects and relatively long half-life (longer than diazepam).
By increasing the action of GABA, which is a major inhibitory neurotransmitter in the brain, may depress all levels of CNS, including limbic and reticular formation.
Monitoring patient's blood pressure after administering dose is important. Adjust prn.
Depresses all levels of CNS (eg, limbic and reticular formation), possibly by increasing activity of GABA. Shorter acting than lorazepam.
Used as alternative in termination of refractory status epilepticus. Because water soluble, takes approximately 3 times longer than diazepam to peak EEG effects. Thus, clinician must wait 2-3 min to fully evaluate sedative effects before initiating procedure or repeating dose.
Used for seizures not responding to benzodiazepines. Significant respiratory depression; patient may require endotracheal intubation.
Magnesium sulfate has been successfully used in an overdose with refractory ventricular fibrillation. Animal studies have shown that magnesium sulphate converted ventricular tachycardia to sinus rhythm in 9 of 10 rats.
Given parenterally, magnesium decreases acetylcholine in motor nerve terminals and acts on myocardium by slowing rate of S-A node impulse formation and prolonging conduction time. May be helpful in treating ventricular fibrillation in TCA toxicity, but further study is needed.
Liebelt EL. Cyclic antidepressants. In: Hoffman RS, Howland MA, Lewin NA, Nelson LS, Goldfrank LR, eds. Goldfrank's Toxicologic Emergencies. 10th ed. 2015.
Shenouda R, Desan PH. Abuse of tricyclic antidepressant drugs: a case series. J Clin Psychopharmacol. 2013 Jun. 33(3):440-2. [Medline].
Heard K, Cain BS, Dart RC, Cairns CB. Tricyclic antidepressants directly depress human myocardial mechanical function independent of effects on the conduction system. Acad Emerg Med. 2001 Dec. 8(12):1122-7. [Medline].
Mowry JB, Spyker DA, Brooks DE, McMillan N, Schauben JL. 2014 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 25th Annual Report. Clin Toxicol (Phila). 2015. 53(10):962-1147. [Medline]. [Full Text].
Rosenbaum TG, Kou M. Are one or two dangerous? Tricyclic antidepressant exposure in toddlers. J Emerg Med. 2005 Feb. 28(2):169-74. [Medline].
Melanson SE, Lewandrowski EL, Griggs DA, Flood JG. Interpreting tricyclic antidepressant measurements in urine in an emergency department setting: comparison of two qualitative point-of-care urine tricyclic antidepressant drug immunoassays with quantitative serum chromatographic analysis. J Anal Toxicol. 2007 Jun. 31(5):270-5. [Medline].
Christophersen AB, Levin D, Hoegberg LC, Angelo HR, Kampmann JP. Activated charcoal alone or after gastric lavage: a simulated large paracetamol intoxication. Br J Clin Pharmacol. 2002 Mar. 53(3):312-7. [Medline].
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 Aug. 26(2):195-201. [Medline].
Thanacoody HK, Thomas SH. Tricyclic antidepressant poisoning: cardiovascular toxicity. Toxicol Rev. 2005. 24(3):205-14. [Medline].
Monteban-Kooistra WE, van den Berg MP, Tulleken JE. Brugada electrocardiographic pattern elicited by cyclic antidepressants overdose. Intensive Care Med. 2006 Feb. 32(2):281-5. [Medline]. [Full Text].
Goldgran-Toledano D, Sideris G, Kevorkian JP. Overdose of cyclic antidepressants and the Brugada syndrome. N Engl J Med. 2002 May 16. 346(20):1591-2. [Medline].
[Guideline] Woolf AD, Erdman AR, Nelson LS, Caravati EM, Cobaugh DJ, Booze LL, et al. Tricyclic antidepressant poisoning: an evidence-based consensus guideline for out-of-hospital management. Clin Toxicol (Phila). 2007. 45(3):203-33. [Medline]. [Full Text].
McCabe JL, Cobaugh DJ, Menegazzi JJ, Fata J. Experimental tricyclic antidepressant toxicity: a randomized, controlled comparison of hypertonic saline solution, sodium bicarbonate, and hyperventilation. Ann Emerg Med. 1998 Sep. 32(3 Pt 1):329-33. [Medline].
Weinberg G, Ripper R, Feinstein DL, Hoffman W. Lipid emulsion infusion rescures dogs from bupivacaine-induced cardiac toxicity. Reg Anesth Pain Med. May 2003. 28(3):198-202. [Medline].
Rothschild L, Bern S, Oswald S, Weinberg G. Intravenous lipid emulsion in cliniccal toxicology. Scandinavian Journal of Trauma, resuscitation, and Emergency Medicine. Oct 2010. 18:51:[Medline]. [Full Text].
Martyn Harvey, Grant Cave. Case report: successful lipid resuscitation in multi-drug overdose with predominant tricyclic antidepressant toxidrome. International Journal of Emergency Medicine. Feb 2012. 5:8. [Medline]. [Full Text].
Michael Stephen Blaber, Jamal Nasir Khan, Judith Anne Brebner, Rachel McColm. "Lipid Rescue" for tricyclic antidepressant cardiotoxicity. The Journal of Emergency Medicine. Jan 2012. [Medline].
Knudsen K, Abrahamsson J. Magnesium sulphate in the treatment of ventricular fibrillation in amitriptyline poisoning. Eur Heart J. 1997 May. 18(5):881-2. [Medline].
Knudsen K, Abrahamsson J. Effects of magnesium sulfate and lidocaine in the treatment of ventricular arrhythmias in experimental amitriptyline poisoning in the rat. Crit Care Med. 1994 Mar. 22(3):494-8. [Medline].
O'Connor N, Greene S, Dargan P, Wyncoll D, Jones A. Prolonged clinical effects in modified-release amitriptyline poisoning. Clin Toxicol (Phila). 2006. 44(1):77-80. [Medline].
Boehnert MT, Lovejoy FH Jr. Value of the QRS duration versus the serum drug level in predicting seizures and ventricular arrhythmias after an acute overdose of tricyclic antidepressants. N Engl J Med. 1985 Aug 22. 313(8):474-9. [Medline].
Frommer DA, Kulig KW, Marx JA, Rumack B. Tricyclic antidepressant overdose. A review. JAMA. 1987 Jan 23-30. 257(4):521-6. [Medline].
Kerr GW, McGuffie AC, Wilkie S. Tricyclic antidepressant overdose: a review. Emerg Med J. 2001 Jul. 18(4):236-41. [Medline]. [Full Text].
Roberge RJ, Krenzelok EP. Prolonged coma and loss of brainstem reflexes following amitriptyline overdose. Vet Hum Toxicol. 2001 Feb. 43(1):42-4. [Medline].
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. [Medline].