Tricyclic and heterocyclic antidepressants

Meet the patient

A 19-year-old woman is brought to the emergency department drowsy and tachycardic, two hours after swallowing a handful of her mother's amitriptyline tablets. Her ECG shows a wide QRS and a tall terminal R wave in lead aVR. The medical registrar asks the psychiatry registrar on call: "How worried are we, and what do we reach for?"^[3][5]

This is the TCA topic in one patient. Tricyclics still work — sometimes better than what replaced them — but every prescription carries a lethality tax, and the overdose in front of you is a sodium-channel and sodium-bicarbonate problem before it is a psychiatric one. Everything below is the consultant-level answer to that resus bay question, and to the safer one: "When is a TCA the right drug, and how do you keep the bottle from killing them?"^[3][8][16]

References20ShowHide

1. [1]Cipriani A, Furukawa TA, Salanti G, et al. Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis Lancet, 2018.PMID 29477251
2. [2]Anderson IM Selective serotonin reuptake inhibitors versus tricyclic antidepressants: a meta-analysis of efficacy and tolerability J Affect Disord, 2000.PMID 10760555
3. [3]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.PMID 4022081
4. [4]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.PMID 7618783
5. [5]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.PMID 21436332
6. [6]Bradberry SM, Thanacoody HK, Watt BE, Thomas SH, Vale JA Management of the cardiovascular complications of tricyclic antidepressant poisoning: role of sodium bicarbonate Toxicol Rev, 2005.PMID 16390221
7. [7]Kerr GW, McGuffie AC, Wilkie S Tricyclic antidepressant overdose: a review Emerg Med J, 2001.PMID 11435353
8. [8]Buckley NA, McManus PR Fatal toxicity of serotoninergic and other antidepressant drugs: analysis of United Kingdom mortality data BMJ, 2002.PMID 12468481
9. [9]Henry JA, Alexander CA, Sener EK Relative mortality from overdose of antidepressants BMJ, 1995.PMID 7866123
10. [10]Hawton K, Bergen H, Simkin S, et al. Toxicity of antidepressants: rates of suicide relative to prescribing and non-fatal overdose Br J Psychiatry, 2010.PMID 20435959
11. [11]Perry PJ, Zeilmann C, Arndt S Tricyclic antidepressant concentrations in plasma: an estimate of their sensitivity and specificity as a predictor of response J Clin Psychopharmacol, 1994.PMID 7962678
12. [12]Glassman AH, Perel JM, Shostak M, et al. Clinical implications of imipramine plasma levels for depressive illness Arch Gen Psychiatry, 1977.PMID 843179
13. [13]Hiemke C, Bergemann N, Clement HW, et al. Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology: Update 2017 Pharmacopsychiatry, 2018.PMID 28910830
14. [14]Whyte IM, Dawson AH, Buckley NA Relative toxicity of venlafaxine and selective serotonin reuptake inhibitors in overdose compared to tricyclic antidepressants QJM, 2003.PMID 12702786
15. [15]Greist JH, Jefferson JW, Kobak KA, et al. Efficacy and tolerability of serotonin transport inhibitors in obsessive-compulsive disorder. A meta-analysis Arch Gen Psychiatry, 1995.PMID 7811162
16. [16]Malhi GS, Bell E, Bassett D, et al. The 2020 Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for mood disorders Aust N Z J Psychiatry, 2021.PMID 33353391
17. [17]Kennedy SH, Lam RW, McIntyre RS, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder: Section 3. Pharmacological Treatments Can J Psychiatry, 2016.PMID 27486148
18. [18]Lam RW, Kennedy SH, Adams C, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) 2023 Update on Clinical Guidelines for Management of Major Depressive Disorder Can J Psychiatry, 2024.PMID 38711351
19. [19]Lavonas EJ, Akpunonu PD, Arens AM, et al. 2023 American Heart Association Focused Update on the Management of Patients With Cardiac Arrest or Life-Threatening Toxicity Due to Poisoning Circulation, 2023.PMID 37721023
20. [20]Geddes JR, Carney SM, Davies C, et al. Relapse prevention with antidepressant drug treatment in depressive disorders: a systematic review Lancet, 2003.PMID 12606176