Citalopram and QT prolongation
Authors:
Štefan Alušík 1; Zoltán Paluch 2
Authors‘ workplace:
Katedra vnitřního lékařství IPVZ, Praha
1; Ústav farmakologie 2. LF UK, Praha
2
Published in:
Vnitř Lék 2017; 63(12): 952-956
Category:
Reviews
Overview
In 2011/2012, the US Food and Drug Administration issued a warning about the effect of citalopram on the QT interval and decreased its dosing. Further studies addressing this issue have been published since then. The authors were interested to know whether or not the studies have furnished new information that could modify or further specify the FDA-issued recommendations. After analyzing the most relevant studies, the authors concluded that even papers published within the last 5 years confirmed that, of the SSRI class of drugs, citalopram prolongs the QT interval most significantly. While the QT interval prolongation in young and otherwise healthy individuals is small and treatment with citalopram relatively safe, in elderly comorbid patients with polypharmacy, use of even currently recommended doses may result in significant QT interval prolongation. Hence, the decision about future therapy will depend on the degree of risk of each individual patient. Judging by the most recent data, citalopram is not more effective compared with the other SSRIs. As a result, therapy with citalopram will presumably show a declining trend, particularly in elderly patients.
Key words:
citalopram – escitalopram – QT interval – SSRI
Sources
1. Rentsch D, Dumont P, Borgacci S et al. Prevalence and treatment of depression in a hospital department of internal medicine. Gen Hosp Psychiatry 2007; 29(1): 25–31.
2. FDA Drug Safety Communication: Abnormal heart rhythms associated with high doses of Celexa (citalopram hydrobromide). Dostupné z WWW: <http://www.fda.gov/Drugs/DrugSafety/ucm269086.htm>.
3. FDA Drug Safety Communication: Revised recommendations for Celexa (citalopram hydrobromide) related to a potential risk of abnormal heart rhythms with high doses. Dostupné z WWW: <https://www.fda.gov/Drugs/DrugSafety/ucm297391.htm>.
4. Gerlach LB, Kales HC, Maust DT et al. Unintended consequences of adjusting citalopram prescriptions following the 2011 FDA warning. Am J Geriatr Psychiatry 2016; 25(4):407–414. Dostupné z WWW: <http://dx.doi.org/10.1016/j.jagp.2016.11.010>.
5. Friesen K, Budgen SC. The effectiveness and limitations of regulatory warnigs for the safe prescribing of citalopram. Drug Health Patient Saf 2015; 7: 139–145. Dostupné z DOI: <http://dx.doi.org/10.2147/DHPS.S91046>.
6. Austin J, Yi K, Agius M et al. The impact of guidance on citalopram´s effects on the period on the practice of clinicians. Psychiatr Danub 2014; 26(Suppl 1): S226-S230.
7. Hyttel J, Bogeso KP, Perregaard J et al. The pharmacological effect of citalopram residues in the (S)-(+)-enantiomer. J Neural Transm Gen Sect 1992; 88(2): 157–160.
8. Baumann P. Pharmacology and pharmacokinetics of citalopram and other SSRIs. Int Clin Psychopharmacol 1996; 11(Suppl 1): 5–11.
9. Informace dostupné z WWW: <https://www.drugs.com/pro/citalopram-tablets.html-experiment>.
10. Celexa (citalopram hydrobromide). Dostupné z WWW: <https://www.drugs.com/pro/celexa.html>.
11. Osteen JD, Sampson KJ, Kass RS. The cardiac IKs channel, complex indeed. Proc Natl Acad Sci USA 2010; 107(44): 18751–18752. Dostupné z DOI: <http://dx.doi.org/10.1073/pnas.1014150107>.
12. Hancox JC, McPate MJ, El Harchi A et al. The hERG potassium channel and hERG screening for drug-induced torsades de pointes. Pharmacol Ther 2008; 119(2): 118–132. Dostupné z DOI: <http://dx.doi.org/10.1016/j.pharmthera.2008.05.009>.
13. Guo J, Wang T, Yang T et al. Interaction between the cardiac rapidly (IKr) and slowly (IKs) activating delayed rectifier potassium channels revealed by low K+ – induced hERG endocytic degradation. J Biol Chem 2011; 286(40): 34664–34674. Dostupné z DOI: <http://dx.doi.org/10.1074/jbc.M111.253351>.
14. Šatková J, Bebarová M. Funkční význam hERG: od fyziologické role po cíl protinádorové terapie. Vnitř Lék 2017; 63(2): 114–123.
15. Nachimuthu S, Assar MD, Schussler JM. Drug-induced QT interval prolongation: mechanisms and clinical management. Ther Adv Drug Saf 2012; 3(5): 241–253. Dostupné z DOI: <http://dx.doi.org/10.1177/2042098612454283>.
16. Bazett HC. An analysis of the time-relations of electrocardiograms. Heart 1920; 7: 353–367.
17. Fridericia L. Die systolendauer in Elektrokardiogramm bei normalen Menschen und bei Herzkranken. Acta Med Scand 1920; 53: 469–486.
18. Hodges M, Salerno D, Erlien D. Bazett´s QT correction reviewed: evidence that linear QT correction for heart rate is better. J Am Coll Cardiol 1983; 1: 694.
19. Dmitrenko AA, Sides GD, Winters KJ et al. Electrocardiogram reference ranges derived from a standard clinical trial population. Drug Inf J 2005; 39(4): 395–405. Dostupné z DOI: <https://doi.org/10.1177/009286150503900408>.
20. Rautaharju PM, Mason JW, Akiyama T. New age-and sex-specific criteria for QT prolongation based on rate correction formulas that minimize bias at the upper normal limits. Int J Cardiol 2014; 174(3): 535–540. Dostupné z DOI: <http://dx.doi.org/10.1016/j.ijcard.2014.04.133>.
21. Sagie A, Larson MG, Goldberg RJ et al. An improved method for adjusting the QT interval for heart rate (the Framingham Heart Study). Am J Cardiol 1992; 70(7): 797–801.
22. Dessertenne F. Ventricular tachycardia with 2 variable opposing foci. Arch Mal Coeur Vaiss 1966; 59(2): 263–272.
23. Viskin S. The QT interval: Too long, too short or just right. Heart Rhythm 2009; 6(5): 711–715. Dostupné z DOI: <http://dx.doi.org/10.1016/j.hrthm.2009.02.044>.
24. Postema PG, Wilde AA. The measurement of the QT interval. Curr Cardiol Rev 2014; 10(3): 287–294.
25. Aström-Lilja C, Odberg JM, Ekman E et al. Drug-induced torsades de pointes: a review of the Swedish pharmacovigilance database. Pharmacoepidemiol Drug Saf 2008; 17(6): 587–592. Dostupné z DOI: <http://dx.doi.org/10.1002/pds.1607>.
26. Maljuric NM, Noordam R, Aarts N et al. Use of selective serotonin re-uptake inhibitors and the QT interval in a real-life setting: the population – based Rotterdam Study. Br J Clin Pharmacol 2015; 80(4): 698–705. Dostupné z DOI: <http://dx.doi.org/10.1111/bcp.12681>.
27. Castro VM, Clements CC, Murphy SN et al. QT interval and antidepressant use: a cross sectional study of electronic health records. BMJ 2013; 346: f288. Dostupné z DOI: <http://dx.doi.org/10.1136/bmj.f288>.
28. Weeke P, Jensen A, Folke F et al. Antidepressant use and risk of-out-hospital cardiac arrest: A nationwide case-time-control study. Clin Pharm Ther 2012; 92(1): 72–79. Dostupné z DOI: <http://dx.doi.org/10.1038/clpt.2011.368>.
29. Czaja A, Valuck RJ, Anderson MD. Comparative safety of selective serotonin reuptake inhibitors among pediatric users with respect to adverse cardiac events. Pharmacoepidemiol Drug Saf 2013; 22(6): 607–614.
30. Uchida M, Spencer AE, Biederman J et al. A systematic evaluation of the QTc interval and antidepressant in youth: An electronic health record study. J Dev Behav Pediatr 2015; 36(6): 434–439. Dostupné z DOI: <http://dx.doi.org/10.1097/DBP.0000000000000188>.
31. Drye LT, Spragg D, Devanand DP et al. Ad Research Group. Changes in QTc interval in the citalopram for agitation in Alzheimer‘s disease (CitAD) randomized trial. PLoS One 2014; 9(6): e98426. Dostupné z DOI: <http://dx.doi.org/10.1371/journal.pone.0098426>.
32. Coupland C, Hill T, Morris R 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. Dostupné z DOI: <http://dx.doi.org/10.1136/bmj.i1350>.
33. Beach SR, Kostic WJ, Celano CM et al. Meta-analysis of selective serotonin reuptake inhibitor-associated QTc prolongation. J Clin Psychiatry 2014; 75(5): e441-e449. Dostupné z DOI: <http://dx.doi.org/10.4088/JCP.13r08672>.
34. Qirjazi E, McArthur E, Nash DM et al. Risk of ventricular arrhythmia with citalopram and escitalopram: A population-based study. PLoS One 2016; 11(8): e0160768. Dostupné z DOI: <http://dx.doi.org/10.1371/journal.pone.0160768>.
35. Nosé M, Bighelli I, Castellazzi M et al. STAR NETWORK GROUP. Prevalence and correlates of QTc prolongation in Italian psychiatric care: cross-sectional multicentre study. Epidemiol Psychiatr Sci 2016; 25(6): 532–540.
36. Prokeš M, Suchopár J. Prodloužení intervalu QT způsobené léky. Med praxi 2014; 11(1): 34–39. Dostupné z WWW: <https://www.medicinapropraxi.cz/magno/med/2014/mn1.php>.
37. Wiśniovska B, Tylutky Z, Wyszogrodska G et al. Drug-drug interactions and QT prolongation as a commonly assessed cardiac effect-comprehensive overview of clinical trials. BMC Pharmacol Toxicol 2016; 17: 12. Dostupné z DOI: <http://dx.doi.org/10.1186/s40360–016–0053–1>.
38. Gjestad C, Westin AA, Skogwoll E et al. Effect of proton pump inhibitors on the serum concentrations of the selective serotonin reuptake inhibitors citalopram, escitalopram and sertraline. Ther Drug Monit 2015; 37(1): 90–97. Dostupné z DOI: <http://dx.doi.org/10.1097/FTD.0000000000000101>.
39. Richter T, Alusik S, Paluch Z et al. Suppressive effect of citalopram on plasma concentration of thromboxane B2. Scand J Clin Lab Invest 2015; 75(7): 615–620. Dostupné z DOI: <http://dx.doi.org/10.3109/00365513.2015.1066848>.
40. Schächtele S, Tümena T, Gasmann KG et al. Co-prescription of QT-interval prolonging drugs: An analysis in a large cohort of geriatric patients. PLoS One 2016; 11(5): 0155649. Dostupné z DOI: <http://dx.doi.org/10.1371/journal.pone.0155649>.
41. Malek NM, Grosset KA, Stewart D et al. Prescription of drugs with potential adverse effects on cardiac conduction in Parkinson‘s disease. Parkinsonism Relat Disord 2013; 19(6): 586–589. Dostupné z DOI: <http://dx.doi.org/10.1016/j.parkreldis.2013.02.004>.
42. Richter T, Paluch Z, Alusik S. The non-antidepressant effect of citalopram: a clinician´s perspective. Neuroendocrinol Lett 2014; 35(1): 7–12.
43. Alusik S, Kalatova D, Paluch Z. Serotonin syndrome. Neuro Endocrinol Lett 2014; 35(4): 265–273.
44. Citalopram, escitalopram: no more effective than other SSRIs, but more toxic. Prescrire Int 2016; 25(170): 98.
45. Citalopram, escitalopram and QT prolongation. Prescrire Int 2016; 25(174): 209–211.
46. Funk KA, Bostwick JR. A comparison of the risk of QT prolongation among SSRIs. Ann Pharmacother 2013; 47(10): 1330–1341. Dostupné z DOI: <http://dx.doi.org/10.1177/1060028013501994>.
47. Keller DL. Prescribe escitalopram instead of citalopram. Am J Med 2013; 126(6): e21. Dostupné z DOI: <http://dx.doi.org/10.1016/j.amjmed.2012.10.024>.
48. Zhang Y, Baranchuk A, Hancox JC. Towards limiting QT interval prolongation and arrhythmia risk in citalopram use. Cardiol J 2014; 21(5):
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Internal Medicine
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