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Letters to the Editor

QTc Prolongation in a Young Healthy Patient Receiving Citalopram 40 mg

QTc Prolongation in a Young Healthy Patient Receiving Citalopram 40 mg

To the Editor: Citalopram is a selective serotonin reuptake inhibitor (SSRI) recommended for treatment of major depressive disorder (MDD) and other psychiatric conditions such as anxiety disorders.1,2 Like other SSRI agents, in premarketing research citalopram has been shown to have a safe cardiac profile within normal serum range compared to tricyclic antidepressants.2,3 However, studies4-10 have reported that citalopram may cause torsades de points arrhythmia and QTc prolongation in some patients.

Accordingly, in 2011, the US Food and Drug Administration (FDA)11 published a warning concerning QTc prolongation with citalopram doses greater than 40 mg/d. In 2012, the FDA limited the maximum daily dose to 20 mg for high-risk individuals.12

 

Case report. In 2015, a 29-year-old man with MDD was admitted to a psychiatric ward in Tehran, Iran. He had attempted suicide twice in the past few weeks by hanging himself. He was immediately rescued and transported to a general hospital and discharged after a thorough evaluation. He had no personal or family history of medical conditions including cardiac problems.

During this hospitalization, he received 10 sessions of electroconvulsive therapy (ECT), and citalopram was prescribed in an initial dose of 10 mg/d, gradually reaching 40 mg/d. The ECT sessions were completed before the daily 40-mg dose was reached. In addition to citalopram, quetiapine 25 mg was also started and then gradually titrated to 100 mg twice daily. The pretreatment electrocardiogram (ECG) showed a QTc interval of 400 ms. After 33 days of taking citalopram (4 days of 40 mg/d), another ECG was ordered. Mean QTc was calculated in the leads 2, V5, and V6 using the Bazett formula (QTc = QT/RR0.5).13 Measurement on these leads are known to exhibit the greatest positive and negative predictive values in detection of abnormal QTc.14 The longest QTc measured was 477 ms in lead 2. His vital signs were stable (blood pressure: 90/60 mm Hg, heart rate: 75 bpm, and respiratory rate: 15 breaths/min). The heart examination was unremarkable. Biochemical tests (blood urea nitrogen, creatinine, sodium, potassium, calcium, phosphorous, magnesium) were completed, and the findings were within normal limits.

The patient was offered further cardiac and genetic tests, which he refused. A daily ECG was also requested. After the citalopram dose was decreased to 20 mg/d, his QTc interval returned to borderline level (442 ms). Citalopram was tapered and discontinued within 8 days. The patient was discharged with a QTc of 418 ms, which is within normal limits.

 

Citalopram is mainly metabolized in the liver via multiple isoforms of cytochrome P450 (CYP). CYP2C19, one of those isoenzymes with high genetic polymorphism, is mainly involved in citalopram N-demethylation.15-17 Although this drug may prevent torsades de points within the clinical serum range,18 desmethylcitalopram may cause QTc prolongation in large doses.19 In previous studies,8,9 in contrast to our case, QTc prolongation was mainly seen in patients with overdoses, cardiac problems, and electrolyte disturbances or in combination with CYP2C19 inhibitors. Therefore, one possible explanation for our findings might be that the patient is a poor metabolizer of CYP2C19.

Quetiapine could have contributed to QTc prolongation in our patient; however, this is not probable for a couple of reasons. First, QTc measurements returned to a normal range despite continuation of quetiapine. Furthermore, there is paucity of research supporting QTc prolongation caused by quetiapine, and these studies are limited by small sample sizes,20 patients with history of heart disease, and use of higher doses of both quetiapine and citalopram.21

Therefore, despite the need to replicate our findings, the probability of QTc prolongation with citalopram use should be kept in mind even in a young healthy patient with no known history of heart disease or electrolyte imbalance.

References

1. Pollock BG. Citalopram: a comprehensive review. Expert Opin Pharmacother. 2001;2(4):681-698. PubMed CrossRef

2. Keller MB. Citalopram therapy for depression: a review of 10 years of European experience and data from US clinical trials. J Clin Psychiatry. 2000;61(12):896-908. PubMed CrossRef

3. Parker NG, Brown CS. Citalopram in the treatment of depression. Ann Pharmacother. 2000;34(6):761-771. PubMed CrossRef

4. Deshmukh A, Ulveling K, Alla V, et al. Prolonged QTc interval and torsades de pointes induced by citalopram. Tex Heart Inst J. 2012;39(1):68-70. PubMed

5. de Gregorio C, Morabito G, Cerrito M, et al. Citalopram-induced long QT syndrome and torsade de pointes: role for concomitant therapy and disease. Int J Cardiol. 2011;148(2):226-228. PubMed CrossRef

6. Vieweg WVR, 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(9):859-868. PubMed CrossRef

7. Wenzel-Seifert K, Wittmann M, Haen E. QTc prolongation by psychotropic drugs and the risk of torsade de pointes. Dtsch Arztebl Int. 2011;108(41):687-693. PubMed

8. Musshoff F, Schmidt P, Madea B. Fatality caused by a combined trimipramine-citalopram intoxication. Forensic Sci Int. 1999;106(2):125-131. PubMed CrossRef

9. Fayssoil A, Issi J, Guerbaa M, et al. Torsade de pointes induced by citalopram and amiodarone. Ann Cardiol Angeiol (Paris). 2011;60(3):165-168. PubMed CrossRef

10. Castro VM, Clements CC, Murphy SN, et al. QT interval and antidepressant use: a cross sectional study of electronic health records. BMJ. 2013;346(3):f288. PubMed CrossRef

11. US Food and Drug Administration. FDA Drug Safety Communication. Abnormal heart rhythms associated with high doses of Celexa (citalopram hydrobromide). August 24, 2011. https://wayback.archive-it.org/7993/20170722185911/https://www.fda.gov/Drugs/DrugSafety/ucm269086.htm. Accessed August 21, 2018.

12. US Food and Drug Administration. FDA Drug Safety Communication. Revised recommendations for Celexa (citalopram hydrobromide) related to a potential risk of abnormal heart rhythms with high doses. March 24, 2011. https://www.fda.gov/Drugs/DrugSafety/ucm297391.htm. Accessed August 21, 2018.

13. Bazett HCAN. Analysis of the time-relations of electrocardiograms. Ann Noninvasive Electrocardiol. 1997;2(2):177-194. CrossRef

14. Mönnig G, Eckardt L, Wedekind H, et al. Electrocardiographic risk stratification in families with congenital long QT syndrome. Eur Heart J. 2006;27(17):2074-2080. PubMed CrossRef

15. Olesen OV, Linnet K. Studies on the stereoselective metabolism of citalopram by human liver microsomes and cDNA-expressed cytochrome P450 enzymes. Pharmacology. 1999;59(6):298-309. PubMed CrossRef

16. Rochat B, Amey M, Gillet M, et al. Identification of three cytochrome P450 isozymes involved in N-demethylation of citalopram enantiomers in human liver microsomes. Pharmacogenetics. 1997;7(1):1-10. PubMed CrossRef

17. Yu B-N, Chen G-L, He N, et al. Pharmacokinetics of citalopram in relation to genetic polymorphism of CYP2C19. Drug Metab Dispos. 2003;31(10):1255-1259. PubMed CrossRef

18. Gonzalez FJ. Molecular genetics of the P-450 superfamily. Pharmacol Ther. 1990;45(1):1-38. PubMed CrossRef

19. Engebretsen KM, Harris CR, Wood JE. Cardiotoxicity and late onset seizures with citalopram overdose. J Emerg Med. 2003;25(2):163-166. PubMed CrossRef

20. Sala M, Lazzaretti M, De Vidovich G, et al. Electrophysiological changes of cardiac function during antidepressant treatment. Ther Adv Cardiovasc Dis. 2009;3(1):29-43. PubMed CrossRef

21. Digby G, Machaalany J, Malik P, et al. Multifactorial QT interval prolongation. Cardiol J. 2010;17(2):184-188. PubMed

Fatemeh Sadat Mirfazeli, MDa

F_m_tums@yahoo.com

Amir Shabani, MDb

aDepartment of Psychiatry, Iran University of Medical Science, School of Medicine, Tehran, Iran

bMental Health Research Center, Mood Disorders Research Group, Iran University of Medical Sciences, Tehran, Iran

Potential conflicts of interest: None.

Funding/support: None.

Patient consent: Permission was received from the patient to publish this case report, and information was de-identified to protect anonymity.

Published online: August 30, 2018.

Prim Care Companion CNS Disord 2018;20(4):17l02248

To cite: Mirfazeli FS, Shabani A. QTc prolongation in a young healthy patient receiving citalopram 40 mg. Prim Care Companion CNS Disord. 2018;20(4):17l02248.

To share: https://doi.org/10.4088/PCC.17l02248

© Copyright 2018 Physicians Postgraduate Press, Inc.

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