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1 Fellow Department of Cardiology Charite-Universitätsmedizin Berlin
Campus Virchow-Klinikum Berlin, Germany
2 Professor, Head Department of Cardiology Charite-Universitätsmedizin
Berlin Campus Virchow-Klinikum
3 Assistant Professor Department of Cardiology
Charite-Universitätsmedizin Berlin Campus Virchow-Klinikum Augustenburger
Platz 1 13353 Berlin, Germany fax 40-30-450565936
wilhelm.haverkamp{at}charite.de
Published Online, September 6, 2005. www.theannals.com, DOI 10.1345/aph.1G277
Case Report. A 39-year-old man was admitted after experiencing recurrent episodes of syncope. Due to abuse of multiple drugs, the patient was enrolled in a methadone maintenance treatment program (120 mg/day). Because of an anxiety disorder, he regularly received doxepin 100 mg/day; there was no further medical history, and he was taking no other medication. He presented to a hospital because of episodes of tachycardia. Metoprolol 50 mg/day was started for prophylaxis; methadone and doxepin were continued at the same dose. Retrospective analysis of an electrocardiogram (ECG) revealed sinus tachycardia (115 beats/min) and a normal QT interval (407 msec). During the next few weeks he developed recurrent episodes of syncope.
On admission to our hospital, the ECG revealed sinus bradycardia (47 beats/min) with a prolonged QT interval (542 msec). Urine screening for methadone and doxepin was positive; no other drugs tested positive. Serum potassium (4.7 mEq/L), magnesium (0.78 mEq/L), and creatinine (0.79 mg/dL) levels were normal; there was no family history of arrhythmias. An ECG recorded several years before methadone treatment showed a normal QT interval (400 msec) and heart rate (87 beats/min), excluding congenital prolongation of QT interval.
Methadone, doxepin, and metoprolol were discontinued; QT interval and heart rate then normalized. However, withdrawal symptoms developed, and levomethadone 40 mg/day was prescribed. The QT interval remained within normal limits. The patient was advised to avoid ß-blockers in the future.
Discussion. Both methadone and doxepin are able to prolong myocardial repolarization and, in predisposed individuals, may cause TdP.1,2 In our patient, it is likely that syncope developing in the setting of drug-induced QT prolongation may have resulted from TdP-like tachyarrhythmias. However, such arrhythmias were not documented.
Usually, TdP occurs shortly after initiation of therapy. Nevertheless, as our case demonstrates, it may develop during long-term treatment. The late occurrence of the arrhythmia can be attributed to bradycardia resulting from newly prescribed metoprolol.3 Other factors that may lead to TdP during long-term therapy are changes in dose, reinitiating therapy after discontinuation, or electrolyte disorders.4
Maintenance therapy was continued with levomethadone. The influence of methadone on myocardial potassium channels has been investigated only for the racemate; data on the effect of levomethadone are not available.
The combination of substances with proarrhythmic potential raises the risk of developing QT prolongation and TdP. However, in our patient, metoprolol-induced bradycardia can be considered to have played a major role in the likely manifestation of TdP as a cause of recurrent syncope. Our case underlines the necessity to be aware of proarrhythmic effects, as well as factors and other clinical circumstances like hypokalemia or bradycardia, under which QT prolongation and TdP may become manifest.
References
This article has been cited by other articles:
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  M. J. Krantz, J. Martin, B. Stimmel, D. Mehta, M. C.P. Haigney, and for the Center for Substance Abuse Treatment Cardi QTc Interval Screening in Methadone Treatment: the CSAT Consensus Guideline Ann Intern Med, December 1, 2008; (2008) 0000605-200901060-00302. [Abstract] [Full Text] [PDF]
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