81 - References

References

Depression and anxiety disorders CHAPTER 3 Summary ■ ■Tricyclics (but not lofepramine) have an established link to ion channel blockade and cardiac arrhythmia, especially in overdose. ■ ■Non-­tricyclics generally have a very low risk of inducing arrhythmia. ■ ■Sertraline is recommended post MI, but other SSRIs and mirtazapine are also likely to be safe. ■ ■Bupropion, citalopram, escitalopram, moclobemide and venlafaxine should be used with caution or avoided in those at risk of serious arrhythmia (those with heart failure, left ventricular hypertrophy, previous arrhythmia or MI). An ECG should be performed at baseline and 1 week after every increase in dose if any of these drugs are used in at-risk patients. ■ ■TCAs (with the exception of lofepramine) are best avoided completely in patients at risk of serious arrhythmia. If use of a TCA cannot be avoided, an ECG should be performed at baseline, 1 week after each increase in dose and periodically throughout treatment. Frequency will be determined by the stability of the cardiac disorder. Advice from a cardiology specialist should be sought. ■ ■The arrhythmogenic potential of TCAs and other antidepressants is dose related. Consideration should be given to ECG monitoring of all patients prescribed doses towards the top of the licensed range and those who are prescribed other drugs that, through pharmacokinetic (e.g. fluoxetine) or pharmacodynamic (e.g. diuretics) mechanisms, may add to the risk posed by the drug. References

1. Taylor D. Antidepressant drugs and cardiovascular pathology: a clinical overview of effectiveness and safety. Acta Psychiatr Scand 2008; 118:434–442.
2. Whang W, et al. Depression and risk of sudden cardiac death and coronary heart disease in women: results from the Nurses’ Health Study. J Am Coll Cardiol 2009; 53:950–958.
3. Nemeroff CB, et al. Heartache and heartbreak: the link between depression and cardiovascular disease. Nat Rev Cardiol 2012; 9:526–539.
4. Thanacoody HK, et al. Tricyclic antidepressant poisoning: cardiovascular toxicity. Toxicol Rev 2005; 24:205–214.
5. Sicouri S, et al. Sudden cardiac death secondary to antidepressant and antipsychotic drugs. Expert Opin Drug Saf 2008; 7:181–194.
6. Weeke P, et al. Antidepressant use and risk of out-­of-­hospital cardiac arrest: a nationwide case–time–control study. Clin Pharmacol Ther 2012; 92:72–79.
7. Leonard CE, et al. Antidepressants and the risk of sudden cardiac death and ventricular arrhythmia. Pharmacoepidemiol Drug Saf 2011; 20:903–913.
8. Hong HK, et al. Block of the human ether-­a-­go-­go-­related gene (hERG) K+ channel by the antidepressant desipramine. Biochem Biophys Res Commun 2010; 394:536–541.
9. Coupland C, et al. Antidepressant use and risk of cardiovascular outcomes in people aged 20 to 64: cohort study using primary care database. BMJ 2016; 352:i1350.
10. Prasitlumkum N, et al. Antidepressants and risk of sudden cardiac death: a network meta-­analysis and systematic review. Med Sci (Basel) 2021; 9:26.
11. Khalifa M, et al. Mechanism of sodium channel block by venlafaxine in guinea pig ventricular myocytes. J Pharmacol Exp Ther 1999; 291:280–284.
12. Colbridge MG, et al. Venlafaxine in overdose: experience of the National Poisons Information Service (London centre). J Toxicol Clin Toxicol 1999; 37:383.
13. Blythe D, et al. Cardiovascular and neurological toxicity of venlafaxine. Hum Exp Toxicol 1999; 18:309–313.
14. Combes A, et al. Conduction disturbances associated with venlafaxine. Ann Intern Med 2001; 134:166–167.
15. Isbister GK. Electrocardiogram changes and arrhythmias in venlafaxine overdose. Br J Clin Pharmacol 2009; 67:572–576.
16. Whyte IM, et al. Relative toxicity of venlafaxine and selective serotonin reuptake inhibitors in overdose compared to tricyclic antidepressants. QJM 2003; 96:369–374.
17. Feighner JP. Cardiovascular safety in depressed patients: focus on venlafaxine. J Clin Psychiatry 1995; 56:574–579.
18. Abbas R, et al. Lack of an effect of supratherapeutic dose of venlafaxine on cardiac repolarization in healthy subjects. Clin Pharmacol Drug Dev 2022; 11:100–111.

414 The Maudsley® Prescribing Guidelines in Psychiatry CHAPTER 3 19. Martinez C, et al. Use of venlafaxine compared with other antidepressants and the risk of sudden cardiac death or near death: a nested case–control study. BMJ 2010; 340:c249. 20. Cooper JM, et al. Desvenlafaxine overdose and the occurrence of serotonin toxicity, seizures and cardiovascular effects. Clin Toxicol (Phila) 2017; 55:18–24. 21. Downes MA, et al. QTc abnormalities in deliberate self-­poisoning with moclobemide. Intern Med J 2005; 35:388–391. 22. Kelly CA, et al. Comparative toxicity of citalopram and the newer antidepressants after overdose. J Toxicol Clin Toxicol 2004; 42:67–71. 23. Grundemar L, et al. Symptoms and signs of severe citalopram overdose. Lancet 1997; 349:1602. 24. Mohammed R, et al. Prolonged QTc interval due to escitalopram overdose. J Miss State Med Assoc 2010; 51:350–353. 25. Isbister GK, et al. Bupropion overdose: QTc prolongation and its clinical significance. Ann Pharmacother 2003; 37:999–1002. 26. Service JA, et al. QT prolongation and delayed atrioventricular conduction caused by acute ingestion of trazodone. Clin Toxicol (Phila) 2008; 46:71–73. 27. Dattilo PB, et al. Prolonged QT associated with an overdose of trazodone. J Clin Psychiatry 2007; 68:1309–1310. 28. de Boer RA, et al. QT interval prolongation after sertraline overdose: a case report. BMC Emerg Med 2005; 5:5. 29. Abbas R, et al. A thorough QT study to evaluate the effects of a supratherapeutic dose of sertraline on cardiac repolarization in healthy subjects. Clin Pharmacol Drug Dev 2020; 9:307–320. 30. Maljuric NM, et  al. Use of selective serotonin re-­uptake inhibitors and the heart rate corrected QT interval in a real-­life setting: the population-­based Rotterdam Study. Br J Clin Pharmacol 2015; 80:698–705. 31. van Haelst IM, et al. QT interval prolongation in users of selective serotonin reuptake inhibitors in an elderly surgical population: a cross-­ sectional study. J Clin Psychiatry 2014; 75:15–21. 32. Beach SR, et al. Meta-­analysis of selective serotonin reuptake inhibitor-­associated QTc prolongation. J Clin Psychiatry 2014; 75:e441–449. 33. Castro VM, et al. QT interval and antidepressant use: a cross sectional study of electronic health records. BMJ 2013; 346:f288. 34. Zivin K, et  al. Evaluation of the FDA warning against prescribing citalopram at doses exceeding 40  mg. Am J Psychiatry 2013; 170:642–650. 35. Ray WA, et al. High-­dose citalopram and escitalopram and the risk of out-­of-­hospital death. J Clin Psychiatry 2017; 78:190–195. 36. Lin YT, et al. Selective serotonin reuptake inhibitor use and risk of arrhythmia: a nationwide, population-­based cohort study. Clin Ther 2019; 41:1128–1138.e8. 37. Farhat H, et al. Citalopram and escitalopram: mechanisms of cardiotoxicity, toxicology predisposition and risks of use in geriatric and hemodialysis populations. Glob Cardiol Sci Pract 2024; 2024:e202434. 38. Faraj P, et al. Pro-­arrhythmic effect of escitalopram and citalopram at serum concentrations commonly observed in older patients: a study based on a cohort of 19,742 patients. EBioMedicine 2023; 95:104779. 39. Dubovsky SL. Pharmacokinetic evaluation of vortioxetine for the treatment of major depressive disorder. Expert Opin Drug Metab Toxicol 2014; 10:759–766. 40. Alam MY, et al. Safety, tolerability, and efficacy of vortioxetine (Lu AA21004) in major depressive disorder: results of an open-­label, flexible-­ dose, 52-­week extension study. Int Clin Psychopharmacol 2014; 29:36–44. 41. Wang Y, et al. Effect of vortioxetine on cardiac repolarization in healthy adult male subjects: results of a thorough QT/QTc study. Clin Pharmacol Drug Dev 2013; 2:298–309. 42. Donazzolo Y, et al. Evaluation of the effects of therapeutic and supra-­therapeutic doses of agomelatine on the QT/QTc interval: a phase I, randomised, double-­blind, placebo-­controlled and positive-­controlled, cross-­over thorough QT/QTc study conducted in healthy volunteers. J Cardiovasc Pharmacol 2014; 64:440–451. 43. Edwards J, et al. Vilazodone lacks proarrhythmogenic potential in healthy participants: a thorough ECG study. Int J Clin Pharmacol Ther 2013; 51:456–465. 44. Mago R, et al. Safety and tolerability of levomilnacipran ER in major depressive disorder: results from an open-­label, 48-­week extension study. Clin Drug Investig 2013; 33:761–771. 45. Periclou A, et al. Effects of milnacipran on cardiac repolarization in healthy participants. J Clin Pharmacol 2010; 50:422–433. 46. Glassman AH, et al. Sertraline treatment of major depression in patients with acute MI or unstable angina. JAMA 2002; 288:701–709. 47. van Melle JP, et al. Effects of antidepressant treatment following myocardial infarction. Br J Psychiatry 2007; 190:460–466. 48. Strik JJ, et al. Efficacy and safety of fluoxetine in the treatment of patients with major depression after first myocardial infarction: findings from a double-­blind, placebo-­controlled trial. Psychosom Med 2000; 62:783–789. 49. Rigotti NA, et al. Bupropion for smokers hospitalized with acute cardiovascular disease. Am J Med 2006; 119:1080–1087. 50. Alqdwah-­Fattouh R, et al. Differential effects of antidepressant subgroups on risk of acute myocardial infarction: a nested case–control study. Br J Clin Pharmacol 2020; 86:2040–2050. 51. Wu CS, et al. Use of antidepressants and risk of hospitalization for acute myocardial infarction: a nationwide case-­crossover study. J Psychiatr Res 2017; 94:7–14. 52. Lesperance F, et  al. Effects of citalopram and interpersonal psychotherapy on depression in patients with coronary artery disease: the Canadian Cardiac Randomized Evaluation of Antidepressant and Psychotherapy Efficacy (CREATE) trial. JAMA 2007; 297:367–379. 53. Astrom-­Lilja C, et al. Drug-­induced torsades de pointes: a review of the Swedish pharmacovigilance database. Pharmacoepidemiol Drug Saf 2008; 17:587–592. 54. Angermann CE, et al. Effect of escitalopram on all-­cause mortality and hospitalization in patients with heart failure and depression: the MOOD-­HF randomized clinical trial. JAMA 2016; 315:2683–2693. 55. Hedrick R, et al. The impact of antidepressants on depressive symptom severity, quality of life, morbidity, and mortality in heart failure: a systematic review. Drugs Context 2020; 9:2020-­5-­4.

Depression and anxiety disorders CHAPTER 3 56. Sherwood A, et al. Effects of exercise and sertraline on measures of coronary heart disease risk in patients with major depression: results from the SMILE-­II randomized clinical trial. Psychosom Med 2016; 78:602–609. 57. Wang Z, et al. Exploring the correlation between cardiovascular adverse events and antidepressant use: a retrospective pharmacovigilance analysis based on the FDA Adverse Event Reporting System database. J Affect Disord 2024; 367:96–108. 58. Yokohara S, et al. Psychotherapeutic drug-­induced life-­threatening arrhythmias: a retrospective analysis using the Japanese adverse drug event report database. J Arrhythm 2023; 39:928–936. 59. Cao Y, et al. Associations of antidepressants with atrial fibrillation and ventricular arrhythmias: a systematic review and meta-­analysis. Front Cardiovasc Med 2022; 9:840452. 60. Biffi A, et al. Antidepressants and the risk of arrhythmia in elderly affected by a previous cardiovascular disease: a real-­life investigation from Italy. Eur J Clin Pharmacol 2018; 74:119–129. 61. Aakjaer M, et al. Serious arrhythmia in initiators of citalopram, escitalopram, and other selective serotonin reuptake inhibitors: a population-­ based cohort study in older adults. Clin Transl Sci 2022; 15:2105–2115. 62. Crome P. The toxicity of drugs used for suicide. Acta Psychiatr Scand Suppl 1993; 371:33–37. 63. Cheeta S, et al. Antidepressant-­related deaths and antidepressant prescriptions in England and Wales, 1998–2000. Br J Psychiatry 2004; 184:41–47. 64. Buckley NA, et al. Fatal toxicity of serotoninergic and other antidepressant drugs: analysis of United Kingdom mortality data. BMJ 2002; 325:1332–1333. 65. Buckley NA, et al. Greater toxicity in overdose of dothiepin than of other tricyclic antidepressants. Lancet 1994; 343:159–162. 66. Morgan O, et al. Fatal toxicity of antidepressants in England and Wales, 1993–2002. Health Stat Q 2004; (23):18–24. 67. Taylor D, et al. The cardiovascular safety of tricyclic antidepressants in overdose and in clinical use. Ther Adv Psychopharmacol 2024; 14:20451253241243297. 68. Egberts ACG, et al. Channeling of three newly introduced antidepressants to patients not responding satisfactorily to previous treatment. J Clin Psychopharmacol 1997; 17:149–155. 69. Mines D, et al. Prevalence of risk factors for suicide in patients prescribed venlafaxine, fluoxetine, and citalopram. Pharmacoepidemiol Drug Saf 2005; 14:367–372. 70. Chan AN, et al. A comparison of venlafaxine and SSRIs in deliberate self-­poisoning. J Med Toxicol 2010; 6:116–121. 71. Hasnain M, et al. Escitalopram and QTc prolongation. J Psychiatry Neurosci 2013; 38:E11.