Lamotrigine and Atrial Flutter: Safety and Management
Lamotrigine can be safely continued in patients with atrial flutter, as recent high-quality evidence demonstrates no increased risk of cardiac arrhythmias, including atrial arrhythmias, compared to other antiseizure medications. 1
Evidence Supporting Safety
A 2025 target trial emulation study using two large datasets (Medicare and UK CPRD) directly examined lamotrigine's cardiac safety profile in over 50,000 patients. The study found lamotrigine was associated with a slightly lower (though not statistically significant) 2-year cumulative incidence of ventricular arrhythmias compared to levetiracetam (Medicare: -0.6%, 95% CI -1.2% to 0.0%; CPRD: -0.1%, 95% CI -0.3% to 0.1%). 1 Importantly, sensitivity analyses specifically examining atrial arrhythmias showed similar reassuring results, with no increased risk. 1
A 2023 retrospective study in Veterans—a particularly vulnerable population with high rates of cardiac comorbidities—found that among 96 patients on lamotrigine who had EKGs performed, only 7.3% showed any potential EKG abnormalities, with no deaths attributable to cardiac rhythm or conduction causes. 2 Notably, 87.5% of these patients had pre-existing cardiac diagnoses, and 47.9% were on concomitant sodium channel blocking medications. 2
Management Approach
Continue Lamotrigine Without Dose Adjustment
- No dose adjustment of lamotrigine is required solely based on the presence of atrial flutter. 1, 2
- The evidence does not support discontinuation or dose reduction of lamotrigine in patients who develop atrial flutter. 1
Address the Atrial Flutter Appropriately
For acute symptomatic atrial flutter with hemodynamic instability or respiratory distress:
- Immediate synchronized electrical cardioversion is first-line treatment, starting at 50-100J. 3
- If cardioversion must be delayed, use IV beta-blockers (esmolol preferred) or calcium channel blockers (diltiazem) for temporary rate control. 3
For stable atrial flutter:
- Catheter ablation of the cavotricuspid isthmus (CTI) is the most effective long-term rhythm control strategy, with success rates exceeding 90%. 4, 5
- For acute pharmacological cardioversion, ibutilide or dofetilide are first-line agents. 4, 5
- Flecainide and propafenone can be used in patients without structural heart disease, though caution is needed regarding potential 1:1 AV conduction. 4
Anticoagulation Considerations
- Atrial flutter carries similar stroke risk to atrial fibrillation and requires the same anticoagulation approach. 5
- For atrial flutter ≥48 hours or unknown duration, anticoagulate for at least 3 weeks before and 4 weeks after cardioversion. 5, 4
Drug Interaction Considerations
No clinically significant interactions exist between lamotrigine and standard atrial flutter treatments:
- Lamotrigine does not interact with rate-control agents (beta-blockers, calcium channel blockers, digoxin). 5
- Lamotrigine does not interact with antiarrhythmic drugs used for atrial flutter (ibutilide, dofetilide, flecainide, propafenone, amiodarone). 5
- No dose adjustments are needed when combining lamotrigine with these cardiac medications. 1, 2
Important Clinical Caveats
The 2020 FDA warning about lamotrigine and cardiac effects was based on in vitro data suggesting Class IB antiarrhythmic properties at clinically achievable concentrations. 2 However, this has not translated to clinically significant adverse outcomes in real-world populations, including those with pre-existing cardiac disease. 1, 2
If monitoring is desired for reassurance:
- Baseline and periodic EKGs can be obtained, though routine monitoring is not required based on current evidence. 2
- Focus monitoring efforts on patients with multiple cardiac risk factors or those on multiple sodium channel blocking agents. 2
Rate control in atrial flutter may be more challenging than in atrial fibrillation due to less concealed AV nodal conduction, but this is unrelated to lamotrigine use. 3