Antidepressant Toxicity Medication
- Author: Jeena Jacob, MD, PharmD; Chief Editor: Asim Tarabar, MD more...
The mainstay of specific treatment of significant TCA-related toxicity is NaHCO3 administered in conjunction with supportive care, including aggressive airway support, antiseizure, vasopressor, and dysrhythmic medications. Indications for NaHCO3 administration include QRS widening, hypotension, dysrhythmias, and seizures that are associated with QRS widening. NaHCO3 replaces lidocaine as the drug of choice for ventricular tachycardia following TCA overdose in a variation of the usual ACLS guidelines. Hypotension with evidence of shock not responsive to judicious fluid therapy and sodium bicarbonate are indications for pressors.
Contraindicated medications include beta-blockers, calcium channel blockers, and class IA (procainamide, quinidine, disopyramide, moricizine), class IC (flecainide, propafenone), and possibly class III (bretylium, amiodarone, sotalol) antidysrhythmics.
Activated charcoal is not routinely indicated. In cases of altered mental status, the benefits of charcoal need to be weighed against the risk of aspiration. Therefore, prior to charcoal administration, the airway needs to be secured in patients with an altered mental status. Since the anticholinergic effects of TCAs delay gastric emptying and slow GI motility, this may allow efficacy for charcoal when administered relatively late postingestion.
Binds TCAs, limiting absorption. Clinical benefit has not been demonstrated clearly.
Serum alkalinization with NaHCO3 is the first-line and most effective therapy for arrhythmias. Vasopressors can be useful in correcting hypotension. Lidocaine is the second-line agent behind alkalinization for arrhythmias. Class IA and IC antiarrhythmic agents (eg, procainamide, disopyramide, quinidine, flecainide, encainide) are contraindicated, as are beta-blockers and calcium channel blockers.
First-line drug for cardiovascular morbidity in TCA poisoning. Provides exogenous sodium to overcome the competitive fast sodium channel blockade produced by TCA, and produces an alkalemia (or reverses acidemia) that mitigates the fast sodium channel blockade by TCA.
Indicated for QRS widening, dysrhythmias, hypotension, and seizures that are associated with QRS widening. Patient can be monitored and given boluses of bicarbonate prn if QRS widening and block resolves with initial treatment. Maintain serum potassium levels (see Precautions below). Resolution of QRS widening is a reasonable endpoint for NaHCO3 administration. However, because it may recur, patients who have had QRS widening need to be on a cardiac monitor that is being continuously monitored.
Other vasopressors may also be used. Norepinephrine's vasopressive effect is from its alpha alpha-adrenergic agonist properties. Vasopressors are indicated for persistent hypotension not responsive to judicious fluid loading and sodium bicarbonate.
Has alpha-agonist effects that include increased peripheral vascular resistance, reversed peripheral vasodilatation, systemic hypertension, and vascular permeability. Beta-agonist effects of epinephrine include bronchodilatation, chronotropic cardiac activity, and positive inotropic effects.
Strong postsynaptic alpha-receptor stimulant with little beta-adrenergic activity that produces vasoconstriction of arterioles in the body. Increases peripheral venous return. Generally not used as a first-line agent. Correct volume deficits before administration.
Secondary to NaHCO3 for dysrhythmias due to TCA toxicity. Class IB antiarrhythmic that increases electrical stimulation threshold of the ventricle, suppressing automaticity of conduction through the tissue. Second-line agent for treatment of ventricular dysrhythmias.
Most seizures are short, self-limited, and may resolve before treatment can be administered; however, if prolonged greater than several minutes or repetitive, treatment is indicated. Controversy exists about the indications for sodium bicarbonate with seizures. A trial of NaHCO3 is recommended for seizures that are associated with QRS widening, after benzodiazepine treatment. If seizures are refractory to all treatment, paralysis is indicated to stop motor activity and resultant metabolic acidosis. Benzodiazepines may calm a patient presenting with agitation secondary to the anticholinergic effects. However, their use may exacerbate CNS depression from TCA overdose, so their use for this indication must be accompanied by aggressive monitoring and management of the airway.
Increasing the action of GABA, a major inhibitory neurotransmitter, may depress all levels of CNS, including limbic and reticular formation.
Depresses all levels of CNS (eg, limbic and reticular formation) by increasing activity of GABA.
Not used often because of the preferable safety profile of benzodiazepines but an effective antiseizure medication.
Busch SH, Frank RG, Leslie DL, Martin A, Rosenheck RA, Martin EG, et al. Antidepressants and suicide risk: how did specific information in FDA safety warnings affect treatment patterns?. Psychiatr Serv. 2010 Jan. 61(1):11-6. [Medline]. [Full Text].
Cassels C. FDA Suicide Warnings Change Antidepressant Prescribing Patterns, but Physicians Ignore Monitoring Recommendations. Medscape Today. Available at http://www.medscape.com/viewarticle/715952. Accessed: February 8, 2010.
Cassels C. FDA Suicide Warnings About Antidepressants Cut Rates of Depression Diagnosis and TreatmentExperts Call for FDA to Reconsider Black-Box Warning on Antidepressants. Medscape Today. Available at http://www.medscape.com/viewarticle/704235. Accessed: February 8, 2010.
Bailey B, Buckley NA, Amre DK. A meta-analysis of prognostic indicators to predict seizures, arrhythmias or death after tricyclic antidepressant overdose. J Toxicol Clin Toxicol. 2004. 42(6):877-88. [Medline].
Barry JD, Durkovich DW, Williams SR. Vasopressin treatment for cyclic antidepressant overdose. J Emerg Med. 2006 Jul. 31(1):65-8. [Medline].
Bebarta VS, Phillips S, Eberhardt A, et al. Incidence of Brugada electrocardiographic pattern and outcomes of these patients after intentional tricyclic antidepressant ingestion. Am J Cardiol. 2007 Aug 15. 100(4):656-60. [Medline].
Bronstein AC, Spyker DA, Cantilena LR Jr, et al. 2012 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS). Clin Toxicol (Phila). 2013 Dec. 51(10):949-1229. [Medline]. [Full Text].
Brooks M. Antidepressant-Induced Liver Injury Underestimated. Available at http://www.medscape.com/viewarticle/818512. Accessed: January 6, 2014.
Fletcher SE, Case CL, Sallee FR, et al. Prospective study of the electrocardiographic effects of imipramine in children. J Pediatr. 1993 Apr. 122(4):652-4. [Medline].
Graudins A, Dowsett RP, Liddle C. The toxicity of antidepressant poisoning: is it changing? A comparative study of cyclic and newer serotonin-specific antidepressants. Emerg Med (Fremantle). 2002 Dec. 14(4):440-6. [Medline].
Høegholm A, Clementsen P. Hypertonic sodium chloride in severe antidepressant overdosage. J Toxicol Clin Toxicol. 1991. 29(2):297-8. [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].
Liebelt EL, Ulrich A, Francis PD, et al. Serial electrocardiogram changes in acute tricyclic antidepressant overdoses. Crit Care Med. 1997 Oct. 25(10):1721-6. [Medline].
McCabe JL, Cobaugh DJ, Menegazzi JJ, et al. 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].
McKenzie MS, McFarland BH. Trends in antidepressant overdoses. Pharmacoepidemiol Drug Saf. 2007 May. 16(5):513-23. [Medline].
McKinney PE, Rasmussen R. Reversal of severe tricyclic antidepressant-induced cardiotoxicity with intravenous hypertonic saline solution. Ann Emerg Med. 2003 Jul. 42(1):20-4. [Medline].
Monteban-Kooistra WE, van den Berg MP, Tulleken JE, et al. Brugada electrocardiographic pattern elicited by cyclic antidepressants overdose. Intensive Care Med. 2006 Feb. 32(2):281-5. [Medline].
Obrador D, Ballester M, Carrio I, et al. Presence, evolving changes, and prognostic implications of myocardial damage detected in idiopathic and alcoholic dilated cardiomyopathy by 111In monoclonal antimyosin antibodies. Circulation. 1994 May. 89(5):2054-61. [Medline].
Svens K, Ryrfeldt A. A study of mechanisms underlying amitriptyline-induced acute lung function impairment. Toxicol Appl Pharmacol. 2001 Dec 15. 177(3):179-87. [Medline].
Thanacoody HK, Thomas SH. Tricyclic antidepressant poisoning : cardiovascular toxicity. Toxicol Rev. 2005. 24(3):205-14. [Medline].
Tran TP, Panacek EA, Rhee KJ, et al. Response to dopamine vs norepinephrine in tricyclic antidepressant-induced hypotension. Acad Emerg Med. 1997 Sep. 4(9):864-8. [Medline].
Voican CS, Corruble E, Naveau S, Perlemuter G. Antidepressant-Induced Liver Injury: A Review for Clinicians. Am J Psychiatry. 2013 Dec 20. [Medline].
Woolf AD, Erdman AR, Nelson LS, et al. Tricyclic antidepressant poisoning: an evidence-based consensus guideline for out-of-hospital management. Clin Toxicol (Phila). 2007. 45(3):203-33. [Medline].
Zuidema X, Dünser MW, Wenzel V, et al. Terlipressin as an adjunct vasopressor in refractory hypotension after tricyclic antidepressant intoxication. Resuscitation. 2007 Feb. 72(2):319-23. [Medline].