Can carbamazepine (CBZ) cause bradycardia?

Carbamazepine and Bradycardia: Risk Assessment

Yes, carbamazepine can cause bradycardia, particularly in patients with pre-existing cardiac conduction abnormalities, though this effect is uncommon in most patients with normal cardiac function. 1, 2

Cardiac Effects of Carbamazepine

Mechanism and Risk Factors

• Carbamazepine has class 1A and 1B antiarrhythmic properties that can depress sinus node function and delay atrioventricular conduction 2
• The FDA label specifically warns that carbamazepine should be used with caution in patients with a history of cardiac conduction disturbance, including second- and third-degree AV heart block 1
• AV heart blocks have been reported following carbamazepine treatment, generally but not exclusively in patients with underlying ECG abnormalities or risk factors for conduction disturbances 1

Evidence on Bradycardia Risk

• In patients with pre-existing cardiac conduction system abnormalities, carbamazepine can cause significant prolongation of the PQ interval by approximately 16 msec (9%) and prolongation of the HV interval 2
• For most patients without pre-existing cardiac disease, carbamazepine appears to be relatively safe from a cardiovascular perspective 3, 4
• A 24-hour ECG monitoring study of 48 patients aged 40 years or older on continuous carbamazepine treatment found no increased risk of bradyarrhythmias compared to an age-stratified reference group 4
• A study in pediatric epilepsy patients showed no significant electrocardiographic abnormalities or changes in left ventricular function during 1-year follow-up 3

Clinical Implications

Monitoring Recommendations

• Before initiating carbamazepine therapy, a detailed history and physical examination should be performed with particular attention to cardiac history 1
• Patients with pre-existing cardiac conduction disorders should be monitored more closely for potential bradycardia or heart block 1, 2
• The European Heart Journal guidelines classify mood stabilizers like carbamazepine as generally not associated with severe arrhythmia, though they note that lithium (another mood stabilizer) has been associated with bradycardia 5

Risk in Overdose

• Even in carbamazepine toxicity (levels >12 μg/mL), clinically significant cardiovascular toxicity is rare 6
• No correlation was found between carbamazepine concentration and heart rate or PR, QRS, or corrected QT intervals in overdose cases 6

Special Considerations

Drug Interactions

• Caution should be taken when carbamazepine is used concomitantly with other medications that affect cardiac conduction 1
• Carbamazepine is listed as a drug to avoid with ivabradine due to its strong CYP3A4 inducer properties, which could affect the metabolism of cardiac medications 5
• The American Heart Association guidelines note carbamazepine as a sodium channel blocker that can cause cardiovascular effects similar to class Ia or Ic antidysrhythmics 5

Potential Benefits

• Interestingly, one study found that carbamazepine may have an antiarrhythmic effect, reducing ectopic supraventricular beats in young epileptic patients without heart disease 7

Conclusion

While carbamazepine can cause bradycardia, this effect is primarily concerning in patients with pre-existing cardiac conduction abnormalities. For most patients without cardiac disease, the risk appears minimal. However, appropriate cardiac monitoring is warranted, especially in high-risk populations.