Cardiovascular adverse effects of newer antidepressants

Expert Review of Neurotherapeutics

Volumn 14, Issue 5, 2014, Pages 539-551

  Mago, Rajnish ^a   Tripathi, Neeta ^b   Andrade, Chittaranjan ^c  

^a THOMAS JEFFERSON UNIVERSITY   (United States)

^b Department of Psychopharmacology National Institute of Mental Health and Neurosciences ^*

^c NATIONAL INSTITUTE OF MENTAL HEALTH AND NEUROSCIENCES   (India)

Author keywords

adverse effects; antidepressants; blood pressure; cardiovascular; electrocardiogram; orthostatic hypotension; QT interval; selective serotonin reuptake inhibitors; serotonin norepinephrine reuptake inhibitors; side effects

Indexed keywords

AGOMELATINE; AMFEBUTAMONE; ANTIDEPRESSANT AGENT; DESVENLAFAXINE; DULOXETINE; MILNACIPRAN; MIRTAZAPINE; NORADRENALIN; REBOXETINE; SEROTONIN; SEROTONIN UPTAKE INHIBITOR; VENLAFAXINE; VORTIOXETINE;

BLOOD PRESSURE; CARDIAC PATIENT; CARDIOVASCULAR DISEASE; CARDIOVASCULAR FUNCTION; CARDIOVASCULAR RISK; CLINICAL TRIAL (TOPIC); CONTROLLED CLINICAL TRIAL (TOPIC); DRUG INDUCED DISEASE; DRUG MEGADOSE; ENANTIOMER; FOOD AND DRUG ADMINISTRATION; HEART RATE VARIABILITY; HIGH RISK POPULATION; HUMAN; META ANALYSIS (TOPIC); QT INTERVAL; REVIEW; SYSTEMATIC REVIEW; CHEMICALLY INDUCED; DEPRESSION; MEDLINE; STATISTICS AND NUMERICAL DATA;

ANTIDEPRESSIVE AGENTS; CARDIOVASCULAR DISEASES; DEPRESSION; HUMANS; MEDLINE;

EID: 84899049736     PISSN: 14737175     EISSN: 17448360     Source Type: Journal    
DOI: 10.1586/14737175.2014.908709     Document Type: Review

References (107)

1. Kessler RC, Chiu WT, Demler O, et al. Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry 2005;62:617-27
2. Niranjan A, Corujo A, Ziegelstein RC, Nwulia E. Depression and heart disease in US adults. Gen Hosp Psychiatry 2012;34: 254-61
3. Glassman AH, Shapiro PA. Depression and the course of coronary artery disease. Am J Psychiatry 1998;155:4-11
4. Jiang W, Davidson JR. Antidepressant therapy in patients with ischemic heart disease. Am Heart J 2005;150: 871-81
5. Taylor D. Antidepressant drugs and cardiovascular pathology: a clinical overview of effectiveness and safety. Acta Psychiatr Scand 2008;118(6):434-42
6. Andrade C, Chethan KB, Sandarsh S. Cardiovascular mechanisms of SSRI drugs and their benefits and risks in ischemic heart disease and heart failure. Int Clin Psychopharmacol 2013;28(3):145-55
7. Mago R, Mahajan R, Thase M. Medically serious AEs of newer antidepressants. Curr Psychiatry Rep 2008;10:249-57
8. Waring WS. Clinical use of antidepressant therapy and associated cardiovascular risk. Drug Healthc Patient Saf 2012;4:93-101
9. Rapport MM, Green AA, Page IH. Serum vasoconstrictor, serotonin; isolation and characterization. J Biol Chem 1948;176: 1243-51
10. Watts SW, Morrison SF, Davis RP, Barman SM. Serotonin and blood pressure regulation. Pharmacol Rev 2012;64(2): 359-88
11. Nebigil CG, Maroteaux L. A novel role for serotonin in heart. Trends Cardiovasc Med 2001;11:329-35
12. Kaumann AJ, Levy FO. 5-Hydroxytryptamine receptors in the human cardiovascular system. Pharmacol Ther 2006;111:674-706
13. Danchin N, Beurrier D, Buffet P, et al. Vasomotor disorders in the atherosclerotic coronary artery. Are there practical repercussions today? Rev Prat 1992;42: 2133-5
14. Hong E, Castillo C, Flores E, Mercedes F. Serotoninergic receptors and cardiovascular diseases. Gac Med Mex 1994;130:131-3
15. Ishida T, Hirata K, Sakoda T, et al. 5-HT1Dbeta receptor mediates the supersensitivity of isolated coronary artery to serotonin in variant angina. Chest 1998;113:243-4
16. Ishida T, Kawashima S, Hirata KI, et al. Serotonin-induced hypercontraction through 5-hydroxytryptamine 1B receptors in atherosclerotic rabbit coronary arteries. Circulation 2001;103:1289-95
17. Fricchione GL, Woznicki RM, Klesmer J, Vlay SC. Vasoconstrictive effects and SSRIs. J Clin Psychiatry 1993;54:71-2
18. Sanguinetti MC, Jiang C, Curran ME, Keating MT. A mechanistic link between an inherited and an acquired cardiac arrhythmia: HERG encodes the IKr potassium channel. Cell 1995;81(2): 299-307
19. Thomas D, Gut B, Wendt-Nordahl G, Kiehn J. The antidepressant drug fluoxetine is an inhibitor of human ether-a-go-go related gene (HERG) potassium channels. J Pharmacol Exp Ther 2002;300(2):543-8
20. Witchel HJ, Pabbathi VK, Hofmann G, et al. Inhibitory actions of the selective serotonin re-uptake inhibitor citalopram on HERG and ventricular L-type calcium currents. FEBS Lett 2002;512(1-3):59-66
21. Rajamani S, Eckhardt LL, Valdivia CR, et al. Drug-induced long QT syndrome: hERG K+ channel block and disruption of protein trafficking by fluoxetine and norfluoxetine. Br J Pharmacol 2006;149: 481-9
22. Ramage AG. Central cardiovascular regulation and 5-hydroxytryptamine receptors. Brain Res Bull 2001;256: 425-39
23. Ramage AG, Daly MB. The central action of the 5-HT2 receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2- aminopropane (DOI) on cardiac inotropy and vascular resistance in the anaesthetized cat. Br J Pharmacol 1998;125: 1172-9
24. Vieweg WV, Hasnain M, Howland RH, et al. Citalopram, QTc interval prolongation, and torsade de pointes. How should we apply the recent FDA ruling? Am J Med 2012;125:859-68
25. Nutt DJ, Feetam CL. What one hand giveth the other taketh away: some unpredicted effects of enantiomers in psychopharmacology. J Psychopharmacol 2010;24:1137-41
26. Van Ravenswaaij-Arts CM, Kollee LA, Hopman JC, et al. Heart rate variability. Ann Intern Med 1993;118:436-47
27. van Zyl LT, Hasegawa T, Nagata K. Effects of antidepressant treatment on heart rate variability in major depression: a quantitative review. Biopsychosoc Med 2008;2:12
28. Kemp AH, Quintana DS, Gray MA, et al. Impact of depression and antidepressant treatment on heart rate variability: a review and meta-analysis. Biol Psychiatry 2010;67: 1067-74
29. Dawood T, Lambert EA, Barton DA, et al. Specific serotonin reuptake inhibition in major depressive disorder adversely affects novel markers of cardiac risk. Hypertens Res 2007;30:285-93
30. MacLean MR, Dempsie Y. Serotonin and pulmonary hypertension-from bench to bedside? Curr Opin Pharmacol 2009;9(3): 281-6
31. Andrade C. Selective serotonin reuptake inhibitors and persistent pulmonary hypertension of the newborn. J Clin Psychiatry 2012;73(5):e601-5
32. Schroeder C, Jordan J. Norepinephrine transporter function and human cardiovascular disease. Am J Physiol Heart Circ Physiol 2012;303: H1273-82
33. Colucci VJ, Berry BD. Heart failure worsening and exacerbation after venlafaxine and duloxetine therapy. Ann Pharmacother 2008;42:882-7
34. Abdelmawla AH, Langley RW, Szabadi E, Bradshaw CM. Comparison of the effects of venlafaxine, desipramine, and paroxetine on noradrenaline- and methoxamine-evoked constriction of the dorsal hand vein. Br J Clin Pharmacol 1999;48:345-54
35. Khalifa M, Daleau P, Turgeon J. Mechanism of sodium channel block by venlafaxine in guinea pig ventricular myocytes. J Pharmacol Exp Ther 1999;291:280-4
36. Chalon SA, Granier LA, Vandenhende FR, et al. Duloxetine increases serotonin and norepinephrine availability in healthy subjects: a double-blind, controlled study. Neuropsychopharmacology 2003;28: 1685-93
37. Detke M, Iyengar S, Henck JW, et al. Cardiovascular effects of duloxetine: preclinical and clinical findings. Presented at: American College of Neuropsychopharmacology 44th Annual Meeting; 11-15 December 2005; Waikoloa (HI), USA
38. Rasmussen SL, Overø KF, Tanghøj P. Cardiac safety of citalopram: prospective trials and retrospective analyses. J Clin Psychopharmacol 1999;19:407-15
39. Nyth AL, Gottfries CG, Lyby K, et al. A controlled multicentre clinical study of citalopram and placebo in elderly depressed patients with and without concomitant dementia. Acta Psychiatr Scand 1992;86: 138-45
40. Amsterdam JD, Garcia-Espana F, Fawcett J, et al. Blood pressure changes during short-term fluoxetine treatment. J Clin Psychopharmacol 1999;19(1):9-14
41. Goodnick PJ, Jerry J, Parra F. Psychotropic drugs and the ECG: focus on the QTc interval. Expert Opin Pharmacother 2002;3: 479-98
42. FDA Drug Safety Communication: Abnormal heart rhythms associated with high doses of Celexa (citalopram hydrobromide). 2011. Available from: http://www.fda.gov/Drugs/DrugSafety/ucm269086.htm
43. FDA Drug Safety Communication: Revised recommendations for Celexa (citalopram hydrobromide) related to a potential risk of abnormal heart rhythms with high doses. 2012. Available from: http://www.fda.gov/Drugs/DrugSafety/ ucm297391.htm
44. Darpo B. The thorough QT/QTc study 4 years after the implementation of the ICH E14 guidance. Br J Pharmacol 2010;159: 49-57
45. Porsteinsson AP, Drye LT, Pollock BG, et al. CitAD Research Group. Effect of citalopram on agitation in Alzheimer disease: the CitAD randomized clinical trial. JAMA 2014;311(7):682-91
46. Isbister GK, Bowe SJ, Dawson A, Whyte IM. Relative toxicity of selective serotonin reuptake inhibitors (SSRIs) in overdose. J Toxicol Clin Toxicol 2004;42: 277-85
47. van Gorp F, Whyte IM, Isbister GK. Clinical and ECG effects of escitalopram overdose. Ann Emerg Med 2009;54(3): 404-8
48. Citalopram and risk of QT prolongation. Available from: www.hma.eu/fileadmin/dateien/Human-Medicines/CMD-h-/Product-Information/ PhVWP-Recommendations/Citalopram/CMDh-PhVWP-033-2011-Rev0.pdf
49. Escitalopram and risk of QT prolongation. Available from: www.hma.eu/fileadmin/dateien/Human-Medicines/CMD-h-/Product-Information/ PhVWP-Recommendations/CMDhPhVW0442012-January12.pdf
50. Celexa (citalopram hydrobromide): Drug Safety Communication - Abnormal Heart Rhythms Associated With High Doses. 2013. Available from: http://www.fda.gov/Safety/MedWatch/SafetyInformation/ SafetyAlertsforhumanmedicalproducts/ucm269481.htm
51. Dubnov-Raz G, Juurlink DN, Fogelman R, et al. Antenatal use of selective serotonin-reuptake inhibitors and QT interval prolongation in newborns. Pediatrics 2008;122:e710-15
52. Roose SP, Laghrissi-Thode F, Kennedy JS. Comparison of paroxetine and nortriptyline in depressed patients with ischemic heart disease. JAMA 1998;279:287-91
53. Roose SP, Glassman AH, Attia E, et al. Cardiovascular effects of fluoxetine in depressed patients with heart disease. Am J Psychiatry 1998;155:660-5
54. Strik JJ, Honig A, Lousberg R, 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;62:783-9
55. Glassman AH, O'Connor CM, Califf RM, et al. Sertraline treatment of major depression in patients with acute MI or unstable angina. JAMA 2002;288: 701-9
56. O'Connor CM, Jiang W, Kuchibhatla M, et al. SADHART-CHF Investigators. Safety and efficacy of sertraline for depression in patients with heart failure: results of the SADHART-CHF (Sertraline Against Depression and Heart Disease in Chronic Heart Failure) trial. J Am Coll Cardiol 2010;56:692-9
57. Jimmink A, Caminada K, Hunfeld NG, Touw DJ. Clinical toxicology of citalopram after acute intoxication with the sole drug or in combination with other drugs: overview of 26 cases. Ther Drug Monit 2008;30:365-71
58. Friberg LE, Isbister GK, Duffull SB. Pharmacokinetic-pharmacodynamic modeling of QT interval prolongation following citalopram overdoses. Br J Clin Pharmacol 2006;61:177-90
59. Andrade C. Drug interactions in the treatment of depression in patients with ischemic heart disease. J Clin Psychiatry 2012;73:e1475-7
60. Andrade C. Drug interactions in the treatment of depression in patients receiving beta blocker drugs. J Clin Psychiatry 2013;74:e75-8
61. Andrade C. Selective serotonin reuptake inhibitor drug interactions in patients receiving statins. J Clin Psychiatry 2014;75; In press
62. Andrade C, Sandarsh S, Chethan KB, Nagesh KS. Serotonin reuptake inhibitor antidepressants and abnormal bleeding: a review for clinicians and a reconsideration of mechanisms. J Clin Psychiatry 2010;71: 1565-75
63. Scheen AJ. Sibutramine on cardiovascular outcome. Diabetes Care 2011;34(Suppl 2): S114-19
64. Siepmann T, Ziemssen T, Mueck-Weymann M, et al. The effects of venlafaxine on autonomic functions in healthy volunteers. J Clin Psychopharmacol 2007;27:687-91
65. Thase ME. Effects of venlafaxine on blood pressure: a meta-analysis of original data from 3744 depressed patients. J Clin Psychiatry 1998;59:502-8
66. Mbaya P, Alam F, Ashim S, Bennett D. Cardiovascular effects of high dose venlafaxine XL in patients with major depressive disorder. Hum Psychopharmacol 2007;22:129-33
67. Isbister GK. Electrocardiogram changes and arrhythmias in venlafaxine overdose. Br J Clin Pharmacol 2009;67:572-6
68. Howell C, Wilson AD, Waring WS. Cardiovascular toxicity due to venlafaxine poisoning in adults: a review of 235 consecutive cases. Br J Clin Pharmacol 2007;64:192-7
69. Paul J, Behrle JA, Richards LS, et al. Effect of desvenlafaxine succinate on QT interval in healthy adult female subjects: a double-blind, placebo and moxifloxacin-controlled crossover study. Presented at: Annual Meeting of the American Psychiatry Association; 20-25 May 2006; Toronto, Canada
70. Clayton AH, Kornstein SG, Rosas G, et al. An integrated analysis of the safety and tolerability of desvenlafaxine compared with placebo in the treatment of major depressive disorder. CNS Spectr 2009;14: 183-95
71. PRISTIQ® (desvenlafaxine) Extended-Release Tablets, for oral use. 2011. Available from: http://labeling.pfizer.com/showlabeling.aspx?id=497
72. Wernicke J, Lledó A, Raskin J, et al. An evaluation of the cardiovascular safety profile of duloxetine: findings from 42 placebo-controlled studies. Drug Saf 2007;30(5):437-55
73. Fischer F, Vonderlin N, Seyler C, et al. Acute and subacute effects of the selective serotonin-noradrenaline reuptake inhibitor duloxetine on cardiac hERG channels. Naunyn Schmiedebergs Arch Pharmacol 2013;386:795-804
74. Derby MA, Zhang L, Chappell JC, et al. The effects of supratherapeutic doses of duloxetine on blood pressure and pulse rate. J Cardiovasc Pharmacol 2007;49:384-93
75. Zhang L, Chappell J, Gonzales CR, et al. QT effects of duloxetine at supratherapeutic doses: a placebo and positive controlled study. J Cardiovasc Pharmacol 2007;49(3): 146-53
76. Mago R, Mahajan R, Thase M. Levomilnacipran: a newly approved drug for treatment of major depressive disorder. Expert Rev Clin Pharmacol 2014;7(2): 137-45
77. Forest Pharmaceuticals, Inc. FETZIMA™ (levomilnacipran) extended-release capsules, for oral use. Available from: http://www.fetzimahcp. com/
78. Mago R, Forero G, Greenberg WM, 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;33:761-71
79. Sambunaris A, Bose A, Gommoll CP, et al. A phase III, double-blind, placebo-controlled, flexible-dose study of levomilnacipran extended-release in patients with major depressive disorder. J Clin Psychopharmacol 2014;34(1):1-10
80. Gommoll C, Bose A, Li H, Edwards J. A randomized double-blind, placebo-controlled, flexible-dose study of levomilnacipran in patients with major depressive disorder. Presented at: 24th Annual US Psychiatric and Mental Health Congress; 7-10 November 2011; Las Vegas, NV, USA
81. Bakish D, Bose A, Gommoll C, et al. Levomilnacipran ER 40 mg and 80 mg in patients with major depressive disorder: a phase III, randomized, double-blind, fixed-dose, placebo-controlled study. J Psychiatry Neurosci 2014;39:40-9
82. Shiovitz T, Bose A, Greenberg WM, et al. The efficacy and safety of levomilnacipran SR in the prevention of relapse in major depressive disorder: results from a Phase III clinical trial. Poster presented at: 25th Annual US Psychiatric and Mental Health Congress; 8-11 November 2012; San Diego, CA, USA
83. Rigotti NA, Thorndike AN, Regan S, et al. Bupropion for smokers hospitalized with acute cardiovascular disease. Am J Med 2006;119:1080-7
84. Planer D, Lev I, Elitzur Y, et al. Bupropion for smoking cessation in patients with acute coronary syndrome. Arch Intern Med 2011; 27(171):1055-60
85. Thase ME, Haight BR, Johnson MC, et al. A randomized, double-blind, placebo-controlled study of the effect of sustained-release bupropion on blood pressure in individuals with mild untreated hypertension. J Clin Psychopharmacol 2008; 28(3):302-7
86. BTA Pharmaceuticals. Wellbutrin XL Prescribing Information. Revised February 2010. Available from: http://wellbutrinxl.com/Portals/24/Documents/ WellbutrinXL-Full-Prescribing-Information.pdf
87. Belson MG, Kelley TR. Bupropion exposures: clinical manifestations and medical outcome. J Emerg Med 2002;23: 223-30
88. Tulen JH, Bruijn JA, de Man KJ, et al. Cardiovascular variability in major depressive disorder and effects of imipramine or mirtazapine (Org 3770). J Clin Psychopharmacol 1996;16(2): 135-45
89. Merck and Co., Inc. REMERON® mirtazapine tablets. Available from: www.merck.com/product/usa/pi-circulars/r/remeron/remerontablets-pi.pdf
90. Honig A, Kuyper AM, Schene AH, et al. MIND-IT investigators. Treatment of post-myocardial infarction depressive disorder: a randomized, placebo-controlled trial with mirtazapine. Psychosom Med 2007;69:606-13
91. Waring WS, Good AM, Bateman DN. Lack of significant toxicity after mirtazapine overdose: a five-year review of cases admitted to a regional toxicology unit. Clin Toxicol 2007;45:45-50
92. LoVecchio F, Riley B, Pizon A, Brown M. Outcomes after isolated mirtazapine (Remeron) supratherapeutic ingestions. J Emerg Med 2008;34:77-8
93. Eyding D, Lelgemann M, Grouven U, et al. Reboxetine for acute treatment of major depression: systematic review and meta-analysis of published and unpublished placebo and selective serotonin reuptake inhibitor controlled trials. BMJ 2010;341: c4737
94. Fleishaker JC, Francom SF, Herman BD, et al. Lack of effect of reboxetine on cardiac repolarization. Clin Pharmacol Ther 2001;70:261-9
95. Tanum L. Reboxetine: tolerability and safety profile in patients with major depression. Acta Psychiatr Scand Suppl 2000;101(Suppl 402):37-40
96. Versiani M, Amin M, Chouinard G. Double-blind, placebo-controlled study with reboxetine in inpatients with severe major depressive disorder. J Clin Psychopharmacol 2000;20(1):28-34
97. Agelink MW, Ullrich H, Baumann B, et al. Effects of reboxetine, a selective norepinephrine reuptake inhibitor, on sympathetic and parasympathetic outflow to the heart: preliminary data. Psychopharmacology (Berl) 2002;163(2): 151-6
98. Reboxetine Prescribing Information. Available from: http://www.medicines. org. uk/emc/medicine/8386
99. Forest Pharmaceuticals, Inc. VIIBRYD® (vilazodone HCl) Tablets for oral administration. Available from: http://www.viibrydhcp.com/
100. Edwards J, Sperry V, Adams MH, et al. Vilazodone lacks proarrhythmogenic potential in healthy participants: a thorough ECG study. Int J Clin Pharmacol Ther 2013;51:456-65
101. Millan MJ, Gobert A, Lejeune F, et al. The novel melatonin agonist agomelatine (S20098) is an antagonist at 5-hydroxytryptamine2C receptors, blockade of which enhances the activity of frontocortical dopaminergic and adrenergic pathways. J Pharmacol Exp Ther 2003;306(3):954-64
102. Valdoxan: EPAR - Product Information. 2013. Available from: http://www.ema. europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/ 000915/human-med-001123. jsp&mid=WC0b01ac058001d124
103. Howland RH. A benefit-risk assessment of agomelatine in the treatment of major depression. Drug Saf 2011;34:709-31
104. Citrome L. Vortioxetine for major depressive disorder: a systematic review of the efficacy and safety profile for this newly approved antidepressant - what is the number needed to treat, number needed to harm and likelihood to be helped or harmed? Int J Clin Pract 2014;68(1):60-82
105. Takeda Pharmaceuticals America, Inc. 2013. BRINTELLIX® (vortioxetine) tablets, for oral use. Prescribing information. Available from: https://www.brintellixhcp.com/ [Accessed 3 January 2014]
106. Katona C, Hansen T, Olsen CK. A randomized, double-blind, placebo-controlled, duloxetine-referenced, fixed-dose study comparing the efficacy and safety of Lu AA21004 in elderly patients with major depressive disorder. Int Clin Psychopharmacol 2012;27:215-23
107. Roose SP, Miyazaki M. Pharmacologic treatment of depression in patients with heart disease. Psychosom Med 2005; 67(Suppl 1):S54-7