Current Psychiatry Reports

, Volume 10, Issue 3, pp 249–257 | Cite as

Medically serious adverse effects of newer antidepressants

Article

Abstract

Although safer than tricyclic antidepressants and monoamine oxidase inhibitors, the newer antidepressants may be associated with certain medically serious adverse effects, of which cardiovascular adverse effects, seizures, abnormal bleeding, hyponatremia, and agranulocytosis are discussed in this review. Data regarding the incidence and risk factors are summarized, and strategies for reducing the risk of these adverse effects and managing them are suggested. Identification of risk factors, appropriate antidepressant choice, and, when possible, careful monitoring may substantially reduce the incidence of these adverse effects and the morbidity associated with them.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References and Recommended Reading

  1. 1.
    Anderson IM: Selective serotonin reuptake inhibitors versus tricyclic antidepressants: a meta-analysis of efficacy and tolerability. J Affect Disord 2000, 58:19–36.PubMedCrossRefGoogle Scholar
  2. 2.
    Roos JC: Cardiac effects of antidepressant drugs. A comparison of the tricyclic antidepressants and fluvoxamine. Br J Clin Pharmacol 1983, 15(Suppl 3):439S–445S.PubMedGoogle Scholar
  3. 3.
    Roose SP, Laghrissi-Thode F, Kennedy JS: Comparison of paroxetine and nortriptyline in depressed patients with ischemic heart disease. JAMA 1998, 279:287–291.PubMedCrossRefGoogle Scholar
  4. 4.
    Rasmussen SL, Overø KF, Tanghøj P: Cardiac safety of citalopram: prospective trials and retrospective analyses. J Clin Psychopharmacol 1999, 19:407–415.PubMedCrossRefGoogle Scholar
  5. 5.
    Goodnick PJ, Jerry J, Parra F: Psychotropic drugs and the ECG: focus on the QTc interval. Expert Opin Pharmaco ther 2002, 3:479–498.CrossRefGoogle Scholar
  6. 6.
    Glassman AH, O’Connor CM, Califf RM, et al.: Sertraline treatment of major depression in patients with acute MI or unstable angina. JAMA 2002, 288:701–709.PubMedCrossRefGoogle Scholar
  7. 7.
    Richelson E: Pharmacokinetic drug interactions of new antidepressants: a review of the effects on the metabolism of other drugs. Mayo Clin Proc 1997, 72:835–847.PubMedGoogle Scholar
  8. 8.
    Serebruany VL, Glassman AH, Malinin AI, et al.; Sertraline AntiDepressant Heart Attack Randomized Trial Study Group: Platelet/endothelial biomarkers in depressed patients treated with the selective serotonin reuptake inhibitor sertraline after acute coronary events: the Sertraline AntiDepressant Heart Attack Randomized Trial (SAD-HART) Platelet Substudy. Circulation 2003, 108:939–944.PubMedCrossRefGoogle Scholar
  9. 9.
    Siepmann T, Ziemssen T, Mueck-Weymann M, et al.: The effects of venlafaxine on autonomic functions in healthy volunteers. J Clin Psychopharmacol 2007, 27:687–691.PubMedGoogle Scholar
  10. 10.
    Mackay FR, Dunn NR, Martin RM, et al.: Newer antidepressants: a comparison of tolerability in general practice. Br J Gen Pract 1999, 49:892–896.PubMedGoogle Scholar
  11. 11.
    Thase ME: Effects of venlafaxine on blood pressure: a meta-analysis of original data from 3744 depressed patients. J Clin Psychiatry 1998, 59:502–508.PubMedGoogle Scholar
  12. 12.
    Feighner JP: Cardiovascular safety in depressed patients: focus on venlafaxine. J Clin Psychiatry 1995, 56:574–579.PubMedGoogle Scholar
  13. 13.
    Baca E, Roca M, Garcia-Calvo C, Prieto R: Venlafaxine extended-release in patients older than 80 years with depressive syndrome. Int J Geriatr Psychiatry 2006, 21:337–343.PubMedCrossRefGoogle Scholar
  14. 14.
    Johnson EM, Whyte E, Mulsant BH, et al.: Cardiovascular changes associated with venlafaxine in the treatment of latelife depression. Am J Geriatr Psychiatry 2006, 14:796–802.PubMedCrossRefGoogle Scholar
  15. 15.
    Mbaya P, Alam F, Ashim S, Bennett D: Cardiovascular effects of high dose venlafaxine XL in patients with major depressive disorder. Hum Psychopharmacol 2007, 22:129–133.PubMedCrossRefGoogle Scholar
  16. 16.
    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, 64:192–197.PubMedCrossRefGoogle Scholar
  17. 17.
    Buckley NA, McManus PR: Fatal toxicity of serotoninergic and other antidepressant drugs: analysis of United Kingdom mortality data. BMJ 2002, 325:1332–1333.PubMedCrossRefGoogle Scholar
  18. 18.
    Stahl SM, Grady MM, Moret C, Briley M: SNRIs: their pharmacology, clinical efficacy, and tolerability in comparison with other classes of antidepressants. CNS Spectr 2005, 10:732–747.PubMedGoogle Scholar
  19. 19.
    Perahia DG, Pritchett YL, Kajdasz DK, et al.: A randomized, double-blind comparison of duloxetine and venlafaxine in the treatment of patients with major depressive disorder. J Psychiatr Res 2008, 42:22–34.PubMedCrossRefGoogle Scholar
  20. 20.
    Lessard E, Yessine MA, Hamelin BA, et al.: Influence of CYP2D6 activity on the disposition and cardiovascular toxicity of the antidepressant agent venlafaxine in humans. Pharmacogenetics 1999, 9:435–443.PubMedCrossRefGoogle Scholar
  21. 21.
    Thase ME, Tran PV, Wiltse C, et al.: Cardiovascular profile of duloxetine, a dual reuptake inhibitor of serotonin and norepinephrine. J Clin Psychopharmacol 2005, 25:132–140.PubMedCrossRefGoogle Scholar
  22. 22.
    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, 30:437–455.PubMedCrossRefGoogle Scholar
  23. 23.
    Gahimer J, Wernicke J, Yalcin I, et al.: A retrospective pooled analysis of duloxetine safety in 23,983 subjects. Curr Med Res Opin 2007, 23:175–184.PubMedCrossRefGoogle Scholar
  24. 24.
    Derby MA: The effects of supratherapeutic doses of duloxetine on blood pressure and pulse rate. J Cardiovasc Pharmacol 2007, 49:384–393.PubMedCrossRefGoogle Scholar
  25. 25.
    Raskin J, Wiltse CG, Dinkel JJ, et al.: Safety and tolerability of duloxetine at 60 mg once daily in elderly patients with major depressive disorder. J Clin Psychopharmacol 2008, 28:32–38.PubMedCrossRefGoogle Scholar
  26. 26.
    Zhang L, Chappell J, Gonzales CR, et al.: QT effects of duloxetine at supratherapeutic doses: a placebo and postive controlled study. J Cardiovasc Pharmacol 2007, 49:146–153.PubMedCrossRefGoogle Scholar
  27. 27.
    Roose SP, Dalack GW, Glassman AH, et al.: Cardiovascular effects of bupropion in depressed patients with heart disease. Am J Psychiatry 1991, 148:512–516.PubMedGoogle Scholar
  28. 28.
    Belson MG, Kelley TR: Bupropion exposures: clinical manifestations and medical outcome. J Emerg Med 2002, 23:223–230.PubMedCrossRefGoogle Scholar
  29. 29.
    Druteika D, Zed PJ: Cardiotoxicity following bupropion overdose. Ann Pharmacother 2002, 36:1791–1795.PubMedCrossRefGoogle Scholar
  30. 30.
    Shepherd G: Adverse effects associated with extra doses of bupropion. Pharmacotherapy 2005, 25:1378–1382.PubMedCrossRefGoogle Scholar
  31. 31.
    Shrier M, Díaz JE, Tsarouhas N: Cardiotoxicity associated with bupropion overdose. Ann Emerg Med 2000, 35:100.PubMedGoogle Scholar
  32. 32.
    Curry SC, Kashani JS, LoVecchio F, Holubek W: Intraventricular conduction delay after bupropion overdose. J Emerg Med 2005, 29:299–305.PubMedCrossRefGoogle Scholar
  33. 33.
    Morazin F, Lumbroso A, Harry P, et al.: Cardiogenic shock and status epilepticus after massive bupropion overdose. Clin Toxicol (Phila) 2007, 45:794–797.Google Scholar
  34. 34.
    Isbister GK, Balit CR: Bupropion overdose: QTc prolongation and its clinical significance. Ann Pharmacother 2003, 37:999–1002.PubMedCrossRefGoogle Scholar
  35. 35.
    Montgomery SA: Safety of mirtazapine: a review. Int Clin Psychopharmacol 1995, 10(Suppl 4):37–45.PubMedCrossRefGoogle Scholar
  36. 36.
    Organon: Remeron full prescribing information with medication guide. http://www.remeronsoltab.com/Authfiles/Images/292_73427.pdf. Accessed January 11, 2008.
  37. 37.
    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, 69:606–613.PubMedCrossRefGoogle Scholar
  38. 38.
    LoVecchio F, Riley B, Pizon A, Brown M: Outcomes after isolated mirtazapine (Remeron) supratherapeutic ingestions. J Emerg Med 2008, 34:77–78.PubMedCrossRefGoogle Scholar
  39. 39.
    McIntyre RS, Soczynska JK, Konarski JZ, Kennedy SH: The effect of antidepressants on lipid homeostasis: a cardiac safety concern? Expert Opin Drug Saf 2006, 5:523–537.PubMedCrossRefGoogle Scholar
  40. 40.
    Preskorn SH, Fast GA: Tricyclic antidepressant-induced seizures and plasma drug concentration. J Clin Psychiatry 1992, 53:160–162.PubMedGoogle Scholar
  41. 41.
    Settle EC Jr: Bupropion sustained release: side effect profile. J Clin Psychiatry 1998, 59(Suppl 4):32–36.PubMedGoogle Scholar
  42. 42.
    Dunner DL, Zisook S, Billow AA, et al.: A prospective safety surveillance study for bupropion sustained-release in the treatment of depression. J Clin Psychiatry 1998, 59:366–373.PubMedGoogle Scholar
  43. 43.
    Ruffmann C, Bogliun G, Beghi E: Epileptogenic drugs: a systematic review. Expert Rev Neurother 2006, 6:575–589.PubMedCrossRefGoogle Scholar
  44. 44.
    Thundiyil JG: Evolving epidemiology of drug-induced seizures reported to a poison control center system. J Med Toxicol 2007, 3:15–19.PubMedGoogle Scholar
  45. 45.
    Shepherd G, Velez LI, Keyes DC: Intentional bupropion overdoses. Emerg Med 2004, 27:147–151.CrossRefGoogle Scholar
  46. 46.
    Montgomery SA: Antidepressants and seizures: emphasis on newer agents and clinical implications. Int J Clin Pract 2005, 59:1435–1440.PubMedCrossRefGoogle Scholar
  47. 47.
    Kanner AM, Kozak AM, Frey M: The use of sertraline in patients with epilepsy: is it safe? Epilepsy Behav 2000, 1:100–105.PubMedCrossRefGoogle Scholar
  48. 48.
    Hovorka J, Herman E, Nemcová I: Treatment of interictal depression with citalopram in patients with epilepsy. Epilepsy Behav 2000, 1:444–447.PubMedCrossRefGoogle Scholar
  49. 49.
    Thomé-Souza MS, Kuczynski E, Valente KD: Sertraline and fluoxetine: safe treatments for children and adolescents with epilepsy and depression. Epilepsy Behav 2007, 10:417–425.PubMedCrossRefGoogle Scholar
  50. 50.
    Whyte IM, Dawson AH, Buckley NA: Relative toxicity of venlafaxine and selective serotonin reuptake inhibitors in overdose compared to tricyclic antidepressants. QJM 2003, 96:369–374.PubMedCrossRefGoogle Scholar
  51. 51.
    Halperin D, Reber G: Influence of antidepressants on hemostasis. Dialogues Clin Neurosci 2007, 9:47–59.PubMedGoogle Scholar
  52. 52.
    Yuan Y, Tsoi K, Hunt RH: Selective serotonin reuptake inhibitors and risk of upper GI bleeding: confusion or confounding? Am J Med 2006, 119:719–727.PubMedCrossRefGoogle Scholar
  53. 53.
    Bak S, Tsiropoulos I, Kjaersgaard JO, et al.: Selective serotonin reuptake inhibitors and the risk of stroke: a population-based case-control study. Stroke 2002, 33:1465–1473.PubMedCrossRefGoogle Scholar
  54. 54.
    Jakovljevic D, Tuomilehto J: Use of selective serotonin reuptake inhibitors and the risk of stroke: is there reason for concern? Stroke 2002, 33:1448–1449.PubMedCrossRefGoogle Scholar
  55. 55.
    Kharofa J, Sekar P, Haverbusch M, et al.: Selective serotonin reuptake inhibitors and risk of hemorrhagic stroke. Stroke 2007, 38:3049–3051.PubMedCrossRefGoogle Scholar
  56. 56.
    de Abajo FJ, Jick H, Derby L, et al.: Intracranial haemorrhage and use of selective serotonin reuptake inhibitors. Br J Clin Pharmacol 2000, 50:43–47.PubMedCrossRefGoogle Scholar
  57. 57.
    Ramasubbu R: Cerebrovascular effects of selective serotonin reuptake inhibitors: a systematic review. Clin Psychiatry 2004, 65:1642–1653.CrossRefGoogle Scholar
  58. 58.
    Singhal AB, Topcuoglu MA, Dorer DJ: SSRI and statin use increases the risk for vasospasm after subarachnoid hemorrhage. Neurology 2005, 64:1008–1013.PubMedGoogle Scholar
  59. 59.
    Weinrieb RM, Auriacombe M, Lynch KG, et al.: A critical review of selective serotonin reuptake inhibitor-associated bleeding: balancing the risk of treating hepatitis C-infected patients. J Clin Psychiatry 2003, 64:1502–1510.PubMedCrossRefGoogle Scholar
  60. 60.
    Dalton SO: Use of selective serotonin reuptake inhibitors and risk of upper gastrointestinal tract bleeding: a population-based cohort study. Arch Intern Med 2003, 163:59–64.PubMedCrossRefGoogle Scholar
  61. 61.
    Liskin B, Walsh BT, Roose SP, Jackson W: Imipramine-induced inappropriate ADH secretion. J Clin Psychopharmacol 1984, 4:146–147.PubMedCrossRefGoogle Scholar
  62. 62.
    Bagley SC, Yaeger D: Hyponatremia associated with bupropion, a case verified by rechallenge. J Clin Psychopharmacol 2005, 25:98–99.PubMedCrossRefGoogle Scholar
  63. 63.
    Hoyle GE, Chua M, Soiza RL: Prevalence of hyponatremia in elderly patients. J Am Geriatr Soc 2006, 54:1473; author reply 1473–1474.PubMedCrossRefGoogle Scholar
  64. 64.
    Bouman WP, Pinner G, Johnson H: Incidence of selective serotonin reuptake inhibitor (SSRI) induced hyponatraemia due to the syndrome of inappropriate antidiuretic hormone (SIADH) secretion in the elderly. Int J Geriatr Psychiatry 1998, 13:12–15.PubMedCrossRefGoogle Scholar
  65. 65.
    Fabian TJ, Amico JA, Kroboth PD, et al.: Paroxetine-induced hyponatremia in older adults: a 12-week prospective study. Arch Intern Med 2004, 164:327–332.PubMedCrossRefGoogle Scholar
  66. 66.
    Roxanas M, Hibbert E, Field M: Venlafaxine hyponatraemia: incidence, mechanism and management. Aust N Z J Psychiatry 2007, 41:411–418.PubMedCrossRefGoogle Scholar
  67. 67.
    Wilkinson TJ, Begg EJ, Winter AC, Sainsbury R: Incidence and risk factors for hyponatraemia following treatment with fluoxetine or paroxetine in elderly people. Br J Clin Pharmacol 1999, 47:211–217.PubMedCrossRefGoogle Scholar
  68. 68.
    Kirby D, Ames D: Hyponatraemia and selective serotonin re-uptake inhibitors in elderly patients. Int J Geriatr Psychiatry 2001, 16:484–493.PubMedCrossRefGoogle Scholar
  69. 69.
    Wijnen HH, van Schendel FM, Olde Rikkert MG, et al.: Hyponatraemia during the use of selective serotonin re-uptake inhibitors (SSRIs): reports from 1992–2002 [in Dutch]. Ned Tijdschr Geneeskd 2004, 148:1921–1924.PubMedGoogle Scholar
  70. 70.
    Looper KJ: Potential medical and surgical complications of serotonergic antidepressant medications. Psychosomatics 2007, 48:1–9.PubMedCrossRefGoogle Scholar
  71. 71.
    Howland RH: Unusual & serious adverse effects of SSRIs: recognition & management. J Psychosoc Nurs Ment Health Serv 2007, 45:15–18.Google Scholar
  72. 72.
    Jacob S, Spinler SA: Hyponatremia associated with selective serotonin-reuptake inhibitors in older adults. Ann Pharmacother 2006, 40:1618–1622.PubMedCrossRefGoogle Scholar
  73. 73.
    Davis J, Barkin RL: Clinical pharmacology of mirtazapine: revisited. Am Fam Physician 1999, 60:1101.PubMedGoogle Scholar
  74. 74.
    Remeron [package insert]. http://hcp.remeron.com. Accessed March 11, 2008.
  75. 75.
    Elliott AJ, Roy-Byrne PP: Mirtazapine for depression in patients with human immunodeficiency virus. J Clin Psychopharmacol 2000, 20:265–267.PubMedCrossRefGoogle Scholar

Copyright information

© Current Medicine Group LLC 2008

Authors and Affiliations

  1. 1.Mood Disorders ProgramThomas Jefferson UniversityPhiladelphiaUSA

Personalised recommendations