letter to the editor

Duloxetine-induced life-threatening long QT syndrome 1651 3

Duloxetine hydrochloride (DH) is a potent inhibitor of norepinephrine and serotonin reuptake, with low impact on dopamine uptake. In patients unresponsive to selec-tive serotonin reuptake inhibitors, the administration of DH and bupropion (BUP) is an effective switching strategy [1].

DH is generally well tolerated, with nausea, dry mouth, and fatigue being the most common treatment-emergent adverse effects. There are few reports of cardiovascular adverse effects of DH. Cardiovascular adverse effects do not appear to result in sustained blood pressure elevations, QTc-interval prolongation, or other electrocardiographic changes [2]. DH does not affect on ventricular repolar-ization and QT prolongation [3]. Among patients with congenital long QT interval, each 10  ms increase in the rate-corrected QT (QTc) interval is associated with a 5–7 % exponential increase in risk for torsades de pointes [4].

The present article describes a case of prolonged QTc and life-threatening arrhythmias in a patient treated with DH.

A 52-year-old Slovenian female was admitted in Sep-tember 2012 to a psychiatric department, because of resistant major depressive disorder (MDD). Her medica-tions before hospitalization included BUP 300  mg daily and zolpidem 5 mg daily. She had no known childhood health problems and reported no previous syncope, palpitations, dyspnea, or seizures. She could not recall having undergone electrocardiogram (ECG) in the past. There was no family history of sudden cardiac death. Baseline laboratory results collected on admission included a normal platelet count, normal liver enzymes, and liver function tests. Treatment with DH titrated from 30 to 90  mg daily was introduced by her psychiatrist in the hospital, which was followed by gradual symptoms of improvement. A 12-lead ECG showed a normal QT inter-val (QTc) of 388 ms; heart rate and blood pressure were

also normal. After two months of this treatment, palpi-tations and loss of consciousness were reported with increased heart rate (76  bpm), sinus arrhythmia, and prolonged QT (QTc= 460  ms) interval. These findings were attributed to adverse effect associated with DH use. Clinical pharmacist advised dose reduction to 30 mg of DH daily. After 1 week of dose reduction, cardiovascular status returned to normal (QTc = 412 ms, 65 bpm, Fig. 1). Symptoms of MDD were treated successfully with com-bination treatment. She left the hospital 2 weeks later, on 30 daily of DH and 300 mg daily of BUP and she tolerated this therapy very well.

There was no evidence of prolonged QTc interval or any other cause of cardiovascular failure before DH was introduced. The majority of the interactions with DH are reported to be mediated by cytochrome P450 (CYP) enzymes. CYP2D6 has a major role in the metab-olism of BUP, so we believe that pharmacokinetic drug interaction with DH and BUP occurred, which led to toxic concentration of DH. DH and BUP are moderate inhibitors of CYP2D6, and interaction is possible, but only at high doses [1]. A moderately prolonged QTc (> 440  ms) in BUP was reported [5]. Our patient was also treated with BUP in therapeutic doses, so we do not believe that BUP-induced cardiovascular failure had occurred.

To control symptoms of resistant MDD a dose reduc-tion could be used in treating patients with DH to avoid high impact on symptoms of MDD. No other medication was changed regarding dosage regime in this time. We recommend that clinicians thoroughly investigate family history for sudden deaths and perform a baseline ECG before prescribing DH. We also recommend routine ECG testing during DH therapy, as well as the avoidance of DH by patients with the diagnosis of concealed long QT syndrome.

In conclusion, even though DH is generally known to be a well-tolerated and safe drug, physicians and clinical pharmacists should be aware of the risk of cardiovascular adverse effects associated with DH use.

Wiener klinische WochenschriftThe Central European Journal of Medicine

Wien Klin Wochenschr (2013) 125:165–166DOI 10.1007/s00508-013-0330-6

Duloxetine-induced life-threatening long QT syndromeMatej Štuhec

M. Štuhec, PharmD ()Psychiatric Hospital Ormoz, Ptujska Cesta 33, Ormoz, Sloveniae-mail: matejstuhec@gmail.com

Received: 4 December 2012 / Accepted: 28 January 2013 / Published online: 26 February 2013© Springer-Verlag Wien 2013

166 Duloxetine-induced life-threatening long QT syndrome

letter to the editor

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Conflict of interestThe authors have no personal affiliations, financial re-lationship, or any commercial interest to disclose rela-tive to this article. The submitted report or any essential part of it is not published or simultaneously submitted to other publications prior to its appearance in this journal.

References

1. Rosso G, Rigardetto S, Bogetto F, Maina G. A randomized, single-blind, comparison of duloxetine with bupropion in the treatment of SSRI-resistant major depression. J Affect Disorders. 2012;136:172–6.

2. Hunziker ME, Suehs BT, Bettinger TL, Crismon ML. Dulox-etine hydrochloride: a new dual-acting medication for the treatment of major depressive disorder. Clin Ther. 2005;27:1126–43.

3. Zhang L, Chappell J, Gonzales CR, Small D, Knadler MP, Callaghan JT, et al. QT effects of duloxetine at suprathera-peutic doses: a placebo and positive controlled study. J Cardiovasc Pharm. 2007;49:146–53.

4. Drew BJ, Ackerman MJ, Funk M, et al. Prevention of tors-ade de pointes in hospital settings: a scientific statement from the American Heart Association and the Ameri-can College of Cardiology Foundation. J Am Coll Cardiol. 2010;55:934–47.

5. Isbister GK, Balit CR. Bupropion overdose: QTc prolon-gation and its clinical significance. Ann Pharmacother. 2003;37:999–1002.

Fig. 1 Electrocardiogram showing prolonged QTc (a: 460 ms) when receiving duloxetine 90 mg daily and normal QTc (b: 412 ms) after dose reduction of duloxetine