Drug-induced Brugada Syndrome

Yee Guan Yap; Elijah R. Behr; A. John Camm


Europace. 2009;11(8):989-994. 

In This Article


Lithium is a commonly used drug in the treatment of depressive and bipolar affective disorders. Cardiac side effects have been described at both therapeutic and toxic serum levels in adult patients. Lithium has been associated with non-specific T wave abnormalities (inverted, flattened, or bifid T waves) without QT prolongation.[46] Other conduction defects and rhythm disturbances have also been reported, including sinus node dysfunction, atrial flutter, atrioventricular block, right bundle-branch block, left anterior hemiblock, ventricular tachycardia, and ventricular fibrillation.[47,48]

Recently, two cases of lithium therapy unmasking the type 1 Brugada ECG pattern have been reported, both with other features suggestive of the Brugada syndrome.[49] In one of the patients, the type 1 pattern occurred when lithium levels were therapeutic. Lithium withdrawal in both patients resulted in resolution of ECG abnormalities. In Chinese hamster ovary cells transfected with SCN5A, which encodes the cardiac sodium channel, lithium chloride caused potent cardiac sodium channel blockade in a concentration-dependent manner at levels well below the therapeutic range (IC50 of 6.8 ± 0.4 µmol/L). This is the probable mechanism of action in unmasking patients with underlying Brugada syndrome.[49] Whether the induction of the type 1 ECG pattern in patients without other features of Brugada syndrome indicates an increased risk for sudden cardiac death is unclear.


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