Torsade de Pointes Episodes under Treatment with Selective Serotonin Reuptake Inhibitors

Selective serotonin-reuptake inhibitors (SSRIs) are the most commonly prescribed antidepressants and are generally well tolerated. Specifically, less cardiovascular toxicity has been reported in comparison with tricyclic antidepressants. However, an increasing number of case reports and reviews of pharmacovigilance and toxicology databases describes an association of life-threatening cardiac arrhythmias known as torsade de pointes (TdP) with the use of citalopram and fluoxetine in therapeutic and toxic doses. In therapeutic doses, SSRI-associated Tdp concerned patients with additional risk factors such as concomitant cardiovascular disease, age over 65 years, female sex, hypokalemia and hypomagnesemia. Prolongation of the QTc interval predisposing to the occurrence of TdP has been observed with all SSRIs in supratherapeutic concentrations.

References

• 1 Altmann D, Eggmann U, Ammann P. Medikamentös induzierte Verlängerung des QT-Intervalls.  Wien Klin Wochenschr. 2008;  120 128-135
• 2 Appleby M, Mbewu A, Clarke B. Fluoxetine and ventricular rorsade – is there a link?.  Int J Cardiol. 1995;  49 178-180
• 3 Astrom-Lilja C, Odeberg JM, Ekman E. et al . Drug-induced torsades de pointes: a review of the Swedish pharmacovigilance database.  Pharmacoepidemiol Drug Safety. 2008;  17 587-592
• 4 Blaschke D, Parwani AS, Huemer M. et al . Torsade de pointes during combined treatment with risperidone and citalopram.  Pharmacopsychiatry. 2007;  40 294-295
• 5 Brugisser M, Bravo A, Bodner M. Medikamenten-assoziiertes Long-QT-Syndrom [Medication associated long QT syndrome].  Praxis. 2009;  98 1409-1415
• 6 de Gregorio C, Morabito G, Cerrito M. et al . Citalopram-induced long QT syndrome and torsade de pointes: Role for committant therapies and illnesses.  Int J Cardiol. 2009;  DOI: doi:10.1016/j.ijcard.2009.05.060, available online
• 7 Gupta A, Lawrence AT, Krishnan K. et al . Current concepts in the mechanisms and management of drug-induced QT prolongation and torsade de pointes.  Am Heart J. 2007;  153 891-899
• 8 Hayes B, Klein-Schwarz W, Clark R. et al . Comparison of toxicity of acute overdoses with citalopram and escitalopram.  J Emerg Med. 2008;  39 44-48
• 9 Isbister GK, Bowe SL, Dawson A. et al . Relative toxicity of selective serotonin reuptake inhibitors (SSRIs) in overdose.  J Toxicol Clin Toxicol. 2004;  42 277-285
• 10 Jimmink A, Caminada K, Ng H. et al . Clinical toxicity of citalopram after acute intoxication with the sole drug or in combination with other drugs: overview of 26 cases.  Ther Drug Monit. 2008;  30 365-371
• 11 Kanjanauthai S, Kanluen T, Charreonthaitawee P. Citalopram induced torsade de pointes, a rare life threatening side effect.  Int J Cardiol. 2009;  131 333-334
• 12 Lherm T, Lottin F, Larbi D. et al . [Torsades de pointes after poisoning with fluoxetine alone].  Presse Med. 2000;  29 306-307 (in French)
• 13 Meuleman C, Jourdain P, Bellorini M. et al . Citalopram et torsades de pointes: A propos d'un cas [citalopram and torsades de pointes: A case report].  Archives des maladies du coeur et des vaisseaux. 2001;  94 1021-1024 (in French)
• 14 Sala M, Coppa F, Cappuciati C. et al . Antidepressants: Their effects on cardiac channels, QT prolongation and torsade de pointes.  Curr Opin Investigational Drugs. 2006;  7 256-263
• 15 Tarabar A, Hoffman R, Nelson L. Citalopram overdose: late presentation of torsades de pointes (TdP) with cardiac arrest.  J Med Toxicol. 2008;  4 101-105
• 16 van Gorp F, Whyte I, GK I. Clinical and ECG effects of escitalopram overdose.  Ann Emerg Med. 2009;  54 404-408
• 17 van Noord C, Straus SMJM, Sturkenboom MCJM. et al . Psychotropic drugs associated with corrected QT interval prolongation.  J Clin Psychopharmacology. 2009;  29 9-15
• 18 Wilting I, Samals OM, Holwerda NJ. et al . QTc prolongation and torsades de pointes in an elderly woman taking fluoxetine.  Am J Psychiatry. 2006;  163 325
• 19 Witchel H, Pabbathi V, Hofmann G. et al . Inhibitory actions of the selective serotonin re-uptake inhibitor citalopram on HERG and ventricular calcium currents.  FEBS Lett. 2002;  512 59-66
• 20 Woosley RL. Arizona CERT – QT Drug Lists by Risk Groups (accessed 10.6.2010), at.  http://www.azcert.org/med-prosl.cfm

Correspondence