Methadone is a long-acting synthetic opioid medication used primarily in two medical contexts: treating opioid use disorder (OUD) as part of medication-assisted treatment and managing chronic, severe pain. Despite its widespread use, methadone’s safety profile includes potential effects on the cardiovascular system. While the most common concern is its impact on the heart’s electrical rhythm, its influence on blood pressure is also medically relevant.
The Clinical Relationship Between Methadone and Blood Pressure
Methadone, like other opioids, can sometimes cause a drop in blood pressure, known as hypotension, especially when treatment is initiated or in cases of overdose. This acute effect is often accompanied by a slowed heart rate (bradycardia). Ambulatory patients may also experience orthostatic hypotension, a sudden drop in pressure upon standing that can lead to dizziness or fainting.
In the long-term setting of methadone maintenance treatment (MMT), high blood pressure is frequently observed, but it is not always a direct pharmacological effect of the drug. Research suggests that hypertension in MMT patients often correlates with factors like increased Body Mass Index (BMI) and weight gain, which occur due to improved stability and lifestyle changes. While some studies report only small direct increases in systolic blood pressure (approximately 5–10 mmHg), methadone’s long-term use coincides with the development of hypertension due to these secondary health changes. Regular blood pressure monitoring is therefore important.
How Methadone Affects Cardiac Function
Methadone’s influence on the circulatory system stems from its pharmacological actions on cardiac cells and the nervous system. The most recognized cardiac effect is its potential to prolong the corrected QT interval (QTc) on an electrocardiogram (ECG). This occurs because methadone blocks the human ether-a-go-go-related gene (hERG) potassium channel in the heart. Inhibiting this channel slows the repolarization phase of the heart’s electrical cycle, increasing the risk of a life-threatening arrhythmia called Torsades de Pointes.
The risk of QTc prolongation is dose-dependent, meaning higher methadone doses are associated with a greater effect. Methadone also affects other cardiovascular regulatory systems, including the autonomic nervous system. Structurally, methadone acts as a calcium channel antagonist, similar to certain calcium channel blockers. This action contributes to a decrease in heart rate and is a mechanism behind the observation of hypotension and bradycardia.
Monitoring and Addressing Cardiovascular Concerns
A proactive approach to cardiovascular health is an integral part of methadone treatment due to the potential for blood pressure changes and serious rhythm disturbances. Medical providers require a baseline ECG before a patient starts methadone therapy. Follow-up ECGs are performed approximately 30 days after starting the medication and then annually, provided the methadone dosage remains stable.
More frequent ECG monitoring is necessary when the methadone dose exceeds 100 milligrams per day or following any significant dose increase, as the risk of QTc prolongation rises with higher concentrations. If the QTc interval exceeds 500 milliseconds, immediate medical intervention is required, often involving dose reduction or discontinuation of methadone. Clinicians also focus on correcting risk factors, such as low levels of potassium or magnesium, which can exacerbate cardiotoxic effects. Patients are advised on lifestyle modifications, including nutrition and physical activity, to mitigate the risk of weight gain and subsequent hypertension.