What is the effect of amphetamine on the corrected QT (QTc) interval in a patient?

From the Guidelines

The corrected QT interval in patients with amphetamine use should be closely monitored due to the potential risk of QT prolongation, as evidenced by the American Heart Association's update to practice standards for electrocardiographic monitoring in hospital settings 1. When assessing the risk of QT prolongation in patients taking amphetamines, it is essential to calculate the corrected QT interval (QTc) using Bazett's formula (QTc = QT/√RR) or automated ECG measurements.

• A QTc greater than 450ms in males or 460ms in females is considered prolonged, with values exceeding 500ms indicating significant risk.
• Baseline ECG before starting treatment and follow-up ECGs during dose adjustments are recommended for patients on amphetamines.
• If QTc prolongation occurs, consider dose reduction or medication discontinuation, and address other factors that can further prolong QT interval, including electrolyte abnormalities (particularly hypokalemia, hypomagnesemia), concomitant QT-prolonging medications, and structural heart disease. Key considerations in managing patients with amphetamine use and potential QT prolongation include:
• Monitoring for symptoms of arrhythmias such as palpitations, dizziness, or syncope, which warrant immediate medical attention.
• Avoiding other QT-prolonging medications, as noted in the context of cocaine use, which can prolong the QT interval for several days after ingestion 1.
• Recognizing that amphetamine use can lead to cardiac risks, including ventricular arrhythmias and ischemia, similar to those associated with cocaine use 1.

From the Research

Corrected QT Interval in Patients with Amphetamine

• The use of amphetamines has been associated with an increased risk of cardiovascular problems, including QT interval prolongation 2, 3, 4.
• Studies have shown that amphetamines can cause minor increases in heart rate and blood pressure, but the evidence for statistically or clinically significant increases in QTc is limited 2, 4.
• One study found that dexamphetamine elicited increased heart rate and corrected QT time (QTc) prolongation in both habitual recreational users and healthy controls, but the QTc prolongation was attenuated in users compared to non-users 3.
• Another study found a positive correlation between comorbid amphetamine use frequency and QTc interval change in methadone maintenance patients 5.
• The risk factors for QTc-prolongation include hypokalemia, use of diuretics, antiarrhythmic drugs, and QTc-prolonging drugs, but the evidence for amphetamines as a risk factor is not strong 6.
• Overall, the evidence suggests that amphetamines may be associated with an increased risk of QTc prolongation, but the risk is generally considered to be low 2, 4.

Key Findings

• Amphetamines can cause minor increases in heart rate and blood pressure 2, 4.
• The evidence for statistically or clinically significant increases in QTc is limited 2, 4.
• QTc prolongation was attenuated in habitual recreational amphetamine users compared to non-users 3.
• Comorbid amphetamine use frequency is positively correlated with QTc interval change in methadone maintenance patients 5.

Study Implications

• Electrocardiogram monitoring should be performed among patients who are at risk of frequently using amphetamines during methadone maintenance treatment 5.
• The benefits of treating individual patients with ADHD with amphetamines outweigh the risks, but great caution is advised when considering stimulant and non-stimulant medications for patients with a personal or family history of cardiovascular disease 2.