Methadone and Prolonged QT Syndrome

While only a small fraction of opioids prescribed, methadone accounts for one-third of opioid overdose deaths.

Although people often associate methadone with addiction treatment, this is a common opioid analgesic used for chronic moderate to severe pain. The half-life of methadone is longer compared to other opioid analgesics and can be unpredictable. Methadone prescribing is complex and is associated with one-third of the opioid overdose deaths, while it only accounts for a low percentage of opioid prescriptions. Methadone has its advantages, including the long duration of action and low cost, so it remains a popular first choice drug on insurance formularies. Due to the complexity of methadone dosing and the potential cardiac complications, many physicians shy away from prescribing it.

Methadone is on the list of several other medications that can cause drug-induced prolongation of the QT interval, leading to torsade de pointes, a rare but potentially fatal arrhythmia. Before starting a patient on daily doses of methadone, it is essential to take a thorough cardiac and family history, which may often include a baseline EKG or one within 30 days based on the risks. Chronic pain patients are commonly on other medications in addition to their methadone regimen, and it is essential to identify the drugs that can potentially lead to the prolongation of the QT. Medications such as trazodone, tricyclic antidepressants, and SSRIs are often prescribed in addition to methadone, increasing the chances of cardiac side effects, including prolonged QT syndrome.

Even though the consensus has typically been that higher doses of methadone place the patient at higher risk for developing prolonged QT syndrome, a study demonstrated that a subset of  patients receiving low daily doses developed QT prolongation. The overall assumption amongst specialists prescribing methadone for chronic pain is that the longer the patient is on the medication and the higher the dose, the higher the chances of developing cardiac side effects. Although many studies conclude that there is a positive association between prolonged QT and methadone, several other additional factors contribute. For all these reasons above, patients on methadone treatment should have frequent follow-up appointments with individualized risk assessments that consider multiple factors.

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