Table S1. Review of case studies on psychotropic-induced Brugada-pattern ECGs / Brugada syndrome

(1)

S.No Author (year) Country Age

(yrs) Gender Diagnosis Cardiac

symptoms HR

(beats/min) QTc (ms)

Leads showing

ST segment changes

Bruagda

type Genetic

testing Medical

illness Psychotropics OD / IAT

Time to onset (as mentioned in the report)

Outcome

Tricyclic antidepressants (TCAs) 1 Tada et al

(2001)¹ USA 33 M NA

Ventricular tachycardia /fibrillation /cardiac

arrest

NA 526 V1-V2 NA NA NA Nortriptyline OD NA NA

2 Babaliaros and

Hurst (2002)² USA 77 F Bipolar

Disorder NA 60 NA V1–V3 NA NA NA Desipramine IAT 26 days

Resolved after agent withdrawal /stoppage

3 Bigwood et al

(2005)³ New

Zealand 48 M Suicide

attempt** Dyspnea,

Syncope 72 460 V1-V2 NA NA Pneumonia Nortriptyline OD 40 hours

4 Chow et al

(2005)⁴ Canada 42 M Major

Depression

arrest

NA NA NA Type 1 SCN5A

+ve

Asthma, Obstructive

sleep apnea Desipramine NA NA NA

5

Roberts- Thomson, Teo,

& Young (2007)⁵

Australia 39 M Bipolar

Disorder None NA 540 V1-V3 Type 1 NA None Amitriptyline IAT NA Sudden

death

6 Bebarta and Waksman

(2007)⁶

USA 50 M NA NA NA NA V1-V3 NA NA None Amitriptyline OD 2 hours

Resolved with sodium bicarbonate

injection

7 Akhtar and Goldschlager

(2006)⁷ USA 44 M Major

Depression NA 52 NA V1-V2 NA NA NA Desipramine OD 7 hours

injection

8 Mooren et al

(2008)⁸ Netherlands 52 F Major

Depression

Ventricular tachycardia

/fibrillation NA NA V1-V2 NA NA NA Amitriptyline OD NA

(2)

/cardiac arrest

symptoms HR

Leads showing

ST segment changes

Bruagda

type Genetic

testing Medical

Outcome

9 Chan et al

(2008)⁹ Hong Kong 42 M Somatoform

disorder NA 120 465 V1-V3 Type 1 NA NA Amitriptyline OD NA Sudden

death 10 Ahmed and

Omar (2009)¹⁰ USA 56 F Major

Depression NA NA NA V1-V3 Type 1 NA NA Amitriptyline OD NA NA

11 Meert et al

(2009)¹¹ Belgium 57 F Major

Depression Syncope 70 NA V1-V2 Type 1 NA None TCA (Generic

name NA) OD NA

injection

12 Tashiro et al

(2009)¹² Japan 40 M Major

Depression Syncope NA NA V1-V2 NA NA NA Nortriptyline IAT NA

13 Kiran (2010)¹³ India 28 F Suicide

attempt** None 100 500 V1-V3 Type 1 NA None Dotheipin OD NA

Resolved after overdose correction

measures

14 Palaniswamy et

al (2010)¹⁴ USA 58 M Major

Depression None 106 500 V1-V3 Type 1 SCN5A -

ve None Amitriptyline OD NA

injection

15 Kofune et al

(2013)¹⁵ Japan 60 M Major

Depression NA NA NA V1-V2 NA NA NA Nortriptyline IAT 4.5 months

16 Jung et al

(2013)¹⁶ USA 42 M Bipolar

Disorder Syncope 117 NA V1-V3 Type 1,2 NA Hepatitis C

and HIV Amitriptyline OD 8 hours

injection

17 Chen and Sangha (2014)¹⁷

USA 46 M Mixed anxiety

and depressive disorder

Syncope NA NA NA Type 1 NA None Nortriptyline IAT Few

months

Resolved after placement

of automatic

(3)

defibrillato r

symptoms HR

Leads showing

ST segment changes

Bruagda

type Genetic

testing Medical

Outcome

18 Adams et al

(2017)¹⁸ USA 26 F Major

Depression None 107 494 V2 Type 1,2 NA Type I DM Amitriptyline OD 24 hours

injection

19 Anguita et al

(2020)¹⁹ Spain 56 F Major

Depression Syncope NA NA V1–V3 Type 1 NA DM, HTN,

Epilepsy Amitriptyline IAT NA

20 Otero et al

(2020)²⁰ USA 34 F Bipolar

Disorder

arrest

140 NA V1-V2 Type 1 NA HTN Nortriptyline OD NA

injection Mood stabilizers

1 Darbar et al

(2005)²¹ Netherlands 26 M Bipolar

Disorder Syncope NA NA V1-V3 Type 1 &

2 SCN5A -

ve NA Lithium IAT 2 months

Type 1 progressed to type 2 &

then type 3 with eventual normalizati

on 2 Darbar et al

(2005)²¹ Netherlands 65 M Bipolar

Disorder Syncope NA NA NA Type 1 SCN5A -

ve NA Lithium IAT 20 years Resolved

after dose reduction

3

Bernhard Strohmer, Christiana Schernthaner

(2007)²²

Austria 64 F Bipolar

2 NA NA Lithium IAT 1 month

of automatic defibrillato

r 4 Sandras et al

(2007)²³ France 36 M Bipolar

3 NA NA Lithium IAT 15 years NA

(4)

symptoms HR

Leads showing

ST segment changes

Bruagda

type Genetic

testing Medical

Outcome

5 Laske et al

(2007)²⁴ Germany 42 M Schizoaffectiv

e disorder Syncope NA NA V1-V3 NA NA NA Lithium IAT 8 years

6 Pirotte et al

(2008)²⁵ USA 42 M Mental

retardation NA 65 NA V1-V3 Type 1 &

2 NA NA Lithium IAT 14 days

7 Chandra &

Chandra

(2009)²⁶ USA 38 M Bipolar

Disorder

arrest

NA NA V1-V2 Type 1 NA NA Lithium IAT 1 year

of automatic defibrillato

r 8 Wright &

Salehian

(2010)²⁷ USA 49 M Bipolar

Disorder None 64 479 V1-V2 Type 1 NA NA Lithium IAT 3 months Resolved

after dose reduction

9 Lorente and

Duran (2015)²⁸ Spain 50 M Schizoaffectiv

e disorder Syncope NA NA V1-V3 Type 1 NA Septic

shock Lithium IAT NA

10 Asil et al

(2017)²⁹ Turkey 48 F Bipolar

Disorder Palpitations NA NA V1-V2 Type 1 NA NA Lithium IAT NA

11 Ota et al

(2017)³⁰ Japan 61 M Schizophrenia NA 90 NA V1-V3 NA NA

Acute pneumonia, Hyperthyro

idism

Carbamazepin

e IAT 11 months

12 Schneir &

Masom

(2020)³¹ USA 48 F Bipolar

Disorder Syncope 86 NA V1-V2 Type 1 NA

Hiatal hernia, hyperchole sterolemia,

HTN, obesity, and type II

DM

Lithium toxicity induced by

lisinopril

IAT 14 days

Type 1 progressed

to type 2 with eventual normalizati

on

(5)

symptoms HR

Leads showing

ST segment changes

Bruagda

type Genetic

testing Medical

Outcome

13 Strimel et al

(2010)³² USA 22 F NA NA NA 475 NA Type 2 NA

Temporal lobe

epilepsy Lamotrigine IAT 1 year

14 Rodrigues et al

(2013)³³ Portugal 52 F Major

depression Chest pain NA NA V1-V2 Type 1 NA HTN,

Dyslipidem ia

Lamotrigine IAT 5 months

15 Crawford et al

(2015)³⁴ USA 58 M Bipolar

disorder NA NA NA V1-V3 Type 1 SCN5A

-ve NA Lithium IAT NA

16 Ravi et al

(2020)³⁵ USA 74 F Bipolar

disorder NA NA 420 V1-V2 Type 1 NA

Benign frontal meningiom

a

Lithium IAT 8 days

Resolved after agent withdrawal /stoppage TCA and mood stabilizer

1 Mufti et al

(2018)³⁶ USA 44 F

Mixed anxiety and depressive

disorder NA 97 494 V1-V2 NA NA NA Amitriptyline

and lithium OD NA

and magnesium

injection Antipsychotics

1 Copetti et al

(2004)³⁷ Italy 58 F Suicide

attempt** NA NA NA NA NA NA NA Thioridazine OD NA

2 Chong and Eversheim

(2015)³⁸ Australia 49 M Schizophrenia NA NA NA V1-V3 NA NA NA Clozapine IAT NA

3 Laboudi et al

(2018)³⁹ Morocco 25 M Schizophrenia Syncope 78 400 V1-V3 Type 1 NA NA Risperidone IAT 48 hours

(6)

symptoms HR

Leads showing

ST segment changes

Bruagda

type Genetic

testing Medical

Outcome

4 Sawyer et al

(2017)⁴⁰ Australia 44 M Schizophrenia Chest pain NA NA V1-V3 Type 1 NA NA Clozapine IAT 14 days

Resolved after agent withdrawal /stoppage Selective Serotonin Reuptake Inhibitors (SSRIs)

1 Stirnimann et

al (2009)⁴¹ Switzerland 60 M Major Depression

arrest

NA NA V1-V3 Type 1 SCN5A

+ve NA Fluvoxamine IAT 4 months

2 Sawhney et al

(2010)⁴² UK 48 F Obsessive

Compulsive Disorder

Syncope NA NA V1-V2 Type 1 NA NA Paroxetine IAT NA

3 Ottaviani

(2019)⁴³ Italy 44 F Major

Depression Syncope NA NA NA Type 1 NA

Cerebral aneurysms,

Allergy to drugs (NSAIDs,

MRI Contrast)

Fluoxetine,

Topiramate IAT NA

Others

1 Aouate et al

(2005)⁴⁴ France 24 M Suicide

attempt** Chest pain NA NA NA Type 2 NA NA Propranolol OD NA

of automatic defibrillator

2

Levine &

LoVecchio

(2009)⁴⁵ USA 29 M Major

Depression NA 153 NA V1-V3 NA NA Hypercoles

trolemia Diphenhydram

ine OD 30 minutes

injection

3 Rennyson &

Littmann

(2010)⁴⁶ USA 34 F Major

Depression NA Bradycardia NA V1-V2 Type 1 NA NA Propranolol OD NA

(7)

*F-Female, M-Male, HR-Heart rate, OD-Overdose, IAT-Iatrogenic, NA-Not available/not mentioned, DM-Diabetes Mellitus, HTN-Hypertension

**Suicide attempt by drug overdose References:

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2. Babaliaros VC, Hurst JW. Tricyclic antidepressants and the Brugada syndrome: an example of Brugada waves appearing after the administration of desipramine. Clin Cardiol.

2002;25(8):395–398.

3. Bigwood B, Galler D, Amir N, et al. Brugada syndrome following tricyclic antidepressant overdose. Anaesth Intensive Care. 2005; 33(2):266–270.

4. Chow BJW, Gollob M, Birnie D. Brugada syndrome precipitated by a tricyclic antidepressant. Heart. 2005; 91(5):651.

5. Roberts-Thomson KC, Teo KSL, Young GD. Drug-induced Brugada syndrome with ST-T wave alternans and long QT. Intern Med J. 2007; 37(3):199–200.

6. Bebarta VS, Waksman JC. Amitriptyline-induced Brugada pattern fails to respond to sodium bicarbonate. Clinical Toxicology. 2007; 45(2):186–188.

7. Akhtar M, Goldschlager NF. Brugada electrocardiographic pattern due to tricyclic antidepressant overdose. J Electrocardiol. 2006; 39(3):336–339.

8. Mooren K, Voogel AJ, Tan HL. Brugada syndrome induced by amitriptyline toxicity. Neth J Med. 2008 ;66(8):358–359.

9. Chan HY, Chan YC, Lau FL. Reversal of Brugada electrocardiographic pattern with sodium bicarbonate solution after amitriptyline overdose. Clinical Toxicology. 2008; 46(9):892–896.

10. Ahmed SH, Omar B. Brugada pattern unmasked by tricyclic antidepressant. Clin Cardiol. 2009 ;32(7): E3.

11. Meert A, Vermeersch N, Beckers R, et al. Brugada-like ECG pattern induced by tricyclic antidepressants. European Journal of Emergency Medicine. 2010;17(6):325–327.

12. Tashiro N, Sato N, Talib AK, et al. Brugada syndrome case: difficult differentiation between a concealed form and tricyclic antidepressant-induced Brugada sign. Intern Med. 2009;

48(17):1535–1539.

13. Kiran H. Dosulepin overdose Brugada-like ECG pattern: case report. Reactions. 2010;1317:4.

14. Palaniswamy C, Selvaraj DR, Chugh T, et al. Brugada electrocardiographic pattern induced by amitriptyline overdose. Am J Ther. 2010 ;17(5):529–532.

15. Kofune M, Kofune T, Ohkubo K, et al. Electrocardiographic changes upon tricyclic antidepressant administration mimicking Brugada syndrome. Intern Med. 2013;52(12):1427.

16. Jung SH, Ugwu C, Hussain N. Amitriptyline Toxicity Mimicking ST Segment Elevation Myocardial Infarction: A Case Report And Review Of The Literature. The Internet Journal of

Cardiology. 2013;11(1)/IJC/11/1/1593

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17. Chen JJ, Sangha RS. Treatment of anxiety and depression in a patient with brugada syndrome. Case Rep Psychiatry. 2014:478397.

18. Adams C, Abdulhak A, Gebska M, et al. Acute Brugada ECG Pattern Induced by Mild Amitriptyline Overdose. Ann Case Rep. 2017;10:2574–7754.

19. Fernández-Anguita MJ, Martínez-Mateo V, Cejudo Díaz Del Campo L, Galindo et al. The Brugada pattern in a patient treated with amitriptyline. Neurologia. 2020; 35(2):138–140.

20. Otero D, Petrovic M, Liao SL. Brugada Phenocopy: A Case of Incessant Ventricular Tachycardia in a Patient with Tricyclic Antidepressant Overdose. Methodist Debakey Cardiovasc J.

2020;16(3):245–248.

21. Darbar D, Yang T, Churchwell K, et al. Unmasking of Brugada syndrome by lithium. Circulation. 2005;112(11):1527–1531.

22. Strohmer B, Schernthaner C. Brugada syndrome unmasked by lithium therapy. Wiener klinische Wochenschrift. 2007;119(9):282–282.

23. Sandras R, Lesaffre F, Lacotte J, Nazeyrollas P. Un syndrome de Brugada majoré par un traitement au lithium [Brugada syndrome unmasked by lithium treatment]. Presse Med. 2007;36(4 Pt 1):612–614.

24. Laske C, Soekadar SR, Laszlo R, et al. Brugada syndrome in a patient treated with lithium. Am J Psychiatry. 2007;164(9):1440–1441.

25. Pirotte MJ, Mueller JG, Poprawski T. A case report of Brugada-type electrocardiographic changes in a patient taking lithium. Am J Emerg Med. 2008 ;26(1): 113.e1-3.

26. Chandra PA, Chandra AB. Brugada syndrome unmasked by lithium. Southern medical journal. 2009;102(12):1263–1265.

27. Wright D, Salehian O. Brugada-type electrocardiographic changes induced by long-term lithium use. Circulation. 2010 ;122(6):e 418-419.

28. Gentille-Lorente DI, Lechuga-Durán I. Brugada type 1 pattern and lithium therapy. Actas Esp Psiquiatr. 2015 ;43(6):235–236.

29. Asil S, Canpolat U, Kaya EB, et al. Case series of three different scenarios with drug-induced Brugada patterns: fact or fiction? Turk Kardiyol Dern Ars. 2017;45(7):650–654.

30. Ota H, Kawamura Y, Sato N, et al. A carbamazepine-induced Brugada-type electrocardiographic pattern in a patient with schizophrenia. Internal Medicine. 2017;56(22):3047–3050.

31. Schneir A, Masom CP. Lithium Toxicity from the Addition of an ACE Inhibitor with an Unexpected Type I Brugada Pattern ECG: Case Files of the Medical Toxicology Fellowship at the University of California, San Diego. J Med Toxicol. 2020;16(3):321–328.

32. Strimel WJ, Woodruff A, Cheung P, et al. Brugada-like electrocardiographic pattern induced by lamotrigine toxicity. Clin Neuropharmacol. 2010;33(5):265–267.

33. Rodrigues R, Amador P, Rassi L, et al. Brugada pattern in a patient medicated with lamotrigine. Rev Port Cardiol. 2013;32(10):807–810.

34. Crawford RR, Higdon AN, Casey DB, et al. Multiple lithium-dependent Brugada syndrome unmasking events in a bipolar patient. Clin Case Rep. 2015 ;3(1):14–18.

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35. Ravi V, Serafini NJ, Pulipati P, et al. Lithium-Induced Brugada pattern: a case report and review of literature. Cureus. 2020;12(7).

36. Mufti M, Joea R, Patel V, et al. Drug Overdose Leading to Unmasking of Brugada Syndrome. J Med Cases. 2018 24;9(6):179–182.

37. Copetti R, Proclemer A, Pillinini P. Brugada-like ECG abnormalities during thioridazine overdose. Br J Clin Pharmacol. 2005;59(5):608.

38. Chong JH, Eversheim F. Clozapine-induced reversible Brugada Syndrome. GSTF J Adv Med Res. (JAMR). 2015;1(3).

39. Laboudi F, Slimani G, Gourani ME et al. Neuroleptic-Induced Brugada Syndrome-A Case Report. Int J Med Sci. 2018;5.

40. Sawyer M, Goodison G, Smith L, et al. Brugada pattern associated with clozapine initiation in a man with schizophrenia. Intern Med J. 2017 ;47(7):831–833.

41. Stirnimann G, Petitprez S, Abriel H, et al. Brugada syndrome ECG provoked by the selective serotonin reuptake inhibitor fluvoxamine. Europace. 2010;12(2):282–283.

42. Sawhney V, Thomas G, Webster P, et al. Resolution of Brugada-pattern ECG after withdrawal of the selective serotonin reuptake inhibitor paroxetine. Heart. 2010 ;96(14):1165–1166.

43. Ottaviani C, Luciani M, Bentivegna E, et al. Drug-Induced Brugada Syndrome in a Psychiatric Patient: a Case Report. SN Compr Clin Med. 2019;1(8):637–641.

44. Aouate P, Clerc J, Viard P, et al. Propranolol intoxication revealing a Brugada syndrome. J Cardiovasc Electrophysiol. 2005;16(3):348–351.

45. Levine M, Lovecchio F. Diphenhydramine-induced Brugada pattern. Resuscitation. 2010;81(4):503–504.

Table S1. Review of case studies on psychotropic-induced Brugada-pattern ECGs / Brugada syndrome

*F-Female, M-Male, HR-Heart rate, OD-Overdose, IAT-Iatrogenic, NA-Not available/not mentioned, DM-Diabetes Mellitus, HTN-Hypertension

3. Bigwood B, Galler D, Amir N, et al. Brugada syndrome following tricyclic antidepressant overdose. Anaesth Intensive Care. 2005; 33(2):266–270.

8. Mooren K, Voogel AJ, Tan HL. Brugada syndrome induced by amitriptyline toxicity. Neth J Med. 2008 ;66(8):358–359.

13. Kiran H. Dosulepin overdose Brugada-like ECG pattern: case report. Reactions. 2010;1317:4.

17. Chen JJ, Sangha RS. Treatment of anxiety and depression in a patient with brugada syndrome. Case Rep Psychiatry. 2014:478397.

21. Darbar D, Yang T, Churchwell K, et al. Unmasking of Brugada syndrome by lithium. Circulation. 2005;112(11):1527–1531.

26. Chandra PA, Chandra AB. Brugada syndrome unmasked by lithium. Southern medical journal. 2009;102(12):1263–1265.

31. Schneir A, Masom CP. Lithium Toxicity from the Addition of an ACE Inhibitor with an Unexpected Type I Brugada Pattern ECG: Case Files of the Medical Toxicology Fellowship at the University of California, San Diego. J Med Toxicol. 2020;16(3):321–328.

36. Mufti M, Joea R, Patel V, et al. Drug Overdose Leading to Unmasking of Brugada Syndrome. J Med Cases. 2018 24;9(6):179–182.

41. Stirnimann G, Petitprez S, Abriel H, et al. Brugada syndrome ECG provoked by the selective serotonin reuptake inhibitor fluvoxamine. Europace. 2010;12(2):282–283.

46. Rennyson SL, Littmann L. Brugada-pattern electrocardiogram in propranolol intoxication. Am J Emerg Med. 2010 ;28(2):256.e7-8.