Case Presentation: A 65-year-old man with a history of opioid use disorder and non-ischemic cardiomyopathy with an implantable cardioverter-defibrillator (ICD) presented after witnessed syncope. The son witnessed shocks from the ICD. Interrogation of the ICD revealed multiple episode of polymorphic ventricular tachycardia. Upon presentation, he was somnolent with no focal neurologic deficits. Laboratory evaluation showed a normal complete blood count, normal kidney and liver function, and a negative troponin. Electrolytes demonstrated mild hypokalemia and mild hypomagnesaemia. An electrocardiogram (ECG) revealed a prolonged corrected QT interval (QTc) of 691. Treatment included initiation of an amiodarone infusion and correction of minor electrolyte abnormalities. After initiation of amiodarone, the patient did not have any further episodes of polymorphic ventricular tachycardia.
Upon further discussion with the patient, he revealed that his methadone dose had been increased to 70 milligrams daily one-week prior at an opioid treatment program. The patient was recommended to permanently discontinue use of methadone due to QTc prolongation.
Discussion: The use of methadone is becoming increasingly more commonplace as a treatment for chronic pain and opioid use disorder. While beneficial in many cases, methadone can cause serious side effects such as hypotension and QTc prolongation. The prolongation of the QTc interval can lead to torsades de pointes, a ventricular arrhythmia leading to sudden cardiac death.
The QTc prolonging effect of methadone has been well established. Over 20% of patients receiving the drug demonstrate a prolonged QTc interval on EKG. The effect of methadone on QTc prolongation is dose-dependent with higher doses resulting in increased risk of arrhythmia. Longer duration of methadone use and interaction with other QTc prolonging medications also increases risk of arrhythmia. The FDA issued a “black box warning” for methadone regarding the risks of QTc prolongation. Guidelines from the American Pain Society recommend a baseline EKG for patients with risk factors for QTc prolongation, including heart failure. If the QTc>500 ms, the guidelines recommend switching to an alternative opioid therapy.
Due to the concerns for opioid abuse, methadone for the treatment of opioid use disorder is restricted to treatment programs. Often, as in this case, these substance abuse treatment programs are in separate healthcare systems than primary or subspecialty care. This fragmented care led to a disconnect in health information and likely contributed to this adverse effect. Communication between providers and education of patients on risks are essential to ensuring safe delivery of care.
Conclusions: Methadone is a long-acting opioid used for treatment of opioid use disorders and chronic pain. Providers should use caution when prescribing or adjusting methadone in patients at risk for arrhythmias as QTc prolongation is a known complication of methadone use.