[Review of cases of prolonged QTC and wave burst arrhythmia in patients treated with methadone]

Abstract

Introduction: For the past 40 years, methadone has been known to be an efficient treatment of substitution. Its use allowed a significant reduction in the mortality related to opioid addiction. Since 2001, many articles have reported some cases of syncope, wave burst arrhythmia, ventricular tachycardia due to prolonged QT interval and sudden death secondary to cardiac arrest, with a risk of prolongation of the QT interval above 440 ms (men) and 460 ms (women). Many explorations have helped in understanding the physiopathology by showing that opioids, including methadone, cause a blockage of the potassium channels of the gene HERG K+P. This event could slow the repolarisation and the atrioventricular cardiac synchronization and could induce ventricular arrhythmia.

Literature findings: Nearly 20 studies showed a prolonged QT interval secondary to methadone in patients exhibiting the following features: (1) patients with cardiac pathologies, notably bradycardia, congenital long QT interval, myocardial pathologies related to AIDS and electrolyte disturbances; (2) patients receiving concomitant treatment with substances known to prolong QT interval, such as psychoactive stimulants, narcoleptics, tricyclic antidepressants, antiarrhythmic agents, macrolids, quinolones, non diuretic hypokalemiants and certain corticoids; (3) patients receiving treatments that inhibit methadone's metabolism, particularly those that act on the cytochrome P450 3A4 such as SSRI, antifungal agents, some macrolids and some retroviral agents. Many recent studies, while evaluating the dose-dependent effect of methadone on the QT prolongation, showed a tendency to a prolonged QT when using higher doses of methadone.

Conclusion: Screening for these risk factors should be carried out before prescribing methadone. EKG should not be systematically performed unless the conditions described above are present or if a higher dose of methadone is needed.