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Editor's Correspondence
August 9/23, 2010

Does Methadone Prolong QTc Intervals by Depleting Testosterone Levels?—Reply

Author Affiliations

Author Affiliations: Unit of Biochemistry and Clinical Psychopharmacology, Center for Psychiatric Neurosciences, Department of Psychiatry, Hospital of Cery (Drs Ansermot, Crettol Wavre, and Eap), Service of Cardiology (Dr Schläpfer), Center of Clinical Epidemiology, Institute of Social and Preventive Medicine (Dr Faouzi), and Clinical Chemistry Laboratory, Department of Pathology and Laboratory Medicine (Dr Rey), Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne, Lausanne, Switzerland; Addiction Research Group at the Department of Psychiatry and Psychotherapy, LVR-Hospital Essen, Hospital of the University of Duisburg-Essen, Essen, Germany (Drs Albayrak and Scherbaum); Phénix Foundation, Chêne-Bougeries, Geneva, Switzerland (Drs Croquette-Krokar, Bourquin, and Déglon); and School of Pharmaceutical Sciences, University of Geneva and University of Lausanne, Geneva (Dr Eap).

Arch Intern Med. 2010;170(15):1407-1408. doi:10.1001/archinternmed.2010.283

In reply

We read with great interest the comments of Daniell on our article showing a QTc interval reduction after substitution of (R,S)-methadone by (R)-methadone in opioid-dependent patients.1 Based on the hypothesis of a prolongation of the QTc interval through a depletion of testosterone levels induced by methadone (1.7- to 2.6-fold lower testosterone plasma levels were measured in patients receiving opiates compared with controls2), Daniell suggests that the reduction of QTc interval observed in our study could be due to an increase of testosterone levels. We believe that this is an unlikely mechanism for several reasons. First, methadone, mainly (S)-methadone, is a potent inhibitor of the cardiac human ether-à-go-go–related gene (hERG) voltage-gated potassium channel, which is implicated in the repolarization of the cardiac action potential, directly related to the QTc interval.3 In addition, morphine strongly decreases testosterone levels in men4 and should therefore increase the QTc interval, which is not the case,5 and which is in agreement with the fact that morphine is not an hERG channel inhibitor.3

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