Unmasking of brugada syndrome by lithium

Circulation. 2005 Sep 13;112(11):1527-31. doi: 10.1161/CIRCULATIONAHA.105.548487. Epub 2005 Sep 6.


Background: The characteristic ECG pattern of ST-segment elevation in V1 and V2 in the Brugada syndrome is dynamic; it is often intermittently present in affected individuals and can be unmasked by sodium channel blockers, including antiarrhythmic drugs and tricyclic antidepressants. We report here 2 patients who developed the Brugada ECG pattern after administration of lithium, a commonly used drug not previously reported to block cardiac sodium channels.

Methods and results: Lithium induced transient ST-segment elevation (type 1 Brugada pattern) in right precordial leads at therapeutic concentrations in 2 patients with bipolar disorder. Lithium withdrawal in the patients resulted in reversion to type 2 or 3 Brugada patterns or resolution of ST-T abnormalities. In Chinese hamster ovary cells transfected with SCN5A, which encodes the cardiac sodium channel, lithium chloride caused concentration-dependent block of peak INa at levels well below the therapeutic range (IC50 of 6.8+/-0.4 micromol/L).

Conclusions: The widely used drug lithium is a potent blocker of cardiac sodium channels and may unmask patients with the Brugada syndrome.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Animals
  • Antimanic Agents / administration & dosage
  • Antimanic Agents / adverse effects*
  • Antimanic Agents / therapeutic use
  • Bipolar Disorder / drug therapy
  • Bundle-Branch Block / chemically induced*
  • Cricetinae
  • Cricetulus
  • Dose-Response Relationship, Drug
  • Electrophysiology
  • Female
  • Humans
  • Ion Channel Gating / drug effects
  • Lithium Chloride / administration & dosage
  • Lithium Chloride / adverse effects*
  • Lithium Chloride / therapeutic use
  • Male
  • Muscle Proteins / genetics
  • Muscle Proteins / metabolism
  • Muscle Proteins / physiology
  • NAV1.5 Voltage-Gated Sodium Channel
  • Ovary / cytology
  • Ovary / metabolism
  • Patch-Clamp Techniques
  • Sodium Channels / genetics
  • Sodium Channels / metabolism
  • Sodium Channels / physiology
  • Transfection


  • Antimanic Agents
  • Muscle Proteins
  • NAV1.5 Voltage-Gated Sodium Channel
  • SCN5A protein, human
  • Sodium Channels
  • Lithium Chloride