Can Lamotrigine Cause Tachycardia?
Lamotrigine is not typically associated with tachycardia; instead, it more commonly causes bradycardia and cardiac conduction abnormalities, including ventricular arrhythmias, particularly at supratherapeutic doses or in vulnerable populations. 1, 2, 3
Cardiac Effects of Lamotrigine
Primary Cardiac Concerns
Lamotrigine acts as a Class Ib sodium channel blocker on cardiac tissue (NaV 1.5 channels), similar to mexiletine, though with weaker potency and rapid binding kinetics that typically do not cause clinically significant conduction slowing at therapeutic doses. 4
The FDA issued a warning in March 2021 regarding lamotrigine's potential to cause cardiac rhythm and conduction abnormalities, based on in vitro data showing effects at clinically achievable concentrations. 2, 3
Bradycardia, not tachycardia, is the more commonly reported rhythm disturbance, with documented cases of sinus bradycardia in patients taking lamotrigine that resolved upon discontinuation. 3
Ventricular Arrhythmias (More Serious Concern)
Ventricular tachycardia (VT) has been associated with lamotrigine use, particularly in adult patients with bipolar disorder, where a statistically significant increased risk was demonstrated (adjusted HR 1.326,95% CI 1.122-1.568, p<0.01) compared to alternative medications. 5
Wide complex tachycardia and cardiac arrest have been reported in overdose situations, occurring in approximately 6% of documented cases, with cardiovascular toxicities primarily affecting adults at serum concentrations >25 mg/L. 6
Structural heart disease notably increases the risk of ventricular arrhythmias in patients taking lamotrigine. 5
Conduction Abnormalities
Prolonged PR intervals and QRS widening can occur, though a retrospective study in Veterans found only 7.3% of patients had EKG abnormalities potentially related to lamotrigine, even in this vulnerable population with high rates of cardiac comorbidities. 2
Conduction delays may occur with overdose, though sodium bicarbonate showed limited efficacy (no response in 4 of 9 cases), while lipid emulsion therapy demonstrated some benefit in refractory cases. 6
Clinical Monitoring Recommendations
Baseline Assessment
Obtain baseline complete blood count, liver function tests, and renal function tests before initiating lamotrigine therapy. 7
Perform baseline ECG in patients with cardiac risk factors, including those with structural heart disease, conduction abnormalities, or taking concomitant sodium channel blocking medications. 2
High-Risk Populations Requiring Enhanced Monitoring
Patients with structural heart disease have substantially elevated risk for ventricular arrhythmias. 5
Patients taking concomitant sodium channel blockers (nearly 48% in one study) require careful monitoring, as additive effects may increase arrhythmia risk. 2
Pediatric patients ≤3.5 years old appear more susceptible to CNS toxicity and seizures at lower serum concentrations (threshold ≥3.8 mg/L) compared to adults (≥25.6 mg/L). 6
Patients with bipolar disorder demonstrated the strongest association with ventricular tachycardia in real-world data. 5
Important Clinical Caveats
Lamotrigine should never be stopped abruptly; gradual tapering over 2-4 weeks is required to minimize withdrawal symptoms and prevent seizure recurrence. 8
Exceeding recommended initial dosing increases the risk of serious rash, which remains a more common and well-established adverse effect than cardiac complications. 7, 2
The clinical significance of in vitro cardiac effects remains uncertain, as large retrospective studies have not demonstrated high rates of clinically meaningful cardiac complications at therapeutic doses, with no deaths attributed to cardiac rhythm or conduction causes in one Veterans Affairs study of 233 patients. 2, 4
Mood stabilizers as a class, including lamotrigine, carbamazepine, and valproate, have generally not been associated with severe arrhythmias, distinguishing them from other psychotropic medications like certain antipsychotics and antidepressants that carry higher cardiac risk. 1