Lamotrigine and Bradycardia: Clinical Evidence and Considerations
Lamotrigine can cause bradycardia, particularly in susceptible individuals, though it is not among the most common adverse effects of the medication. This risk should be considered when prescribing lamotrigine, especially in patients with pre-existing cardiac conditions.
Evidence on Lamotrigine and Cardiac Effects
Lamotrigine is classified as a mood stabilizer that has generally not been associated with severe arrhythmias, unlike some other psychotropic medications that have well-established cardiac risks 1.
However, in 2020, the US Food and Drug Administration (FDA) added a warning to lamotrigine's label regarding its potential to cause cardiac rhythm and conduction abnormalities, based on in vitro data suggesting Class IB antiarrhythmic effects at clinically achievable concentrations 2.
There have been documented cases of bradycardia associated with lamotrigine use, including a case report of an adolescent who developed bradycardia after starting lamotrigine for antidepressant augmentation, with heart rate normalizing after the medication was tapered and discontinued 3.
Mechanism of Cardiac Effects
Lamotrigine exerts its antiepileptic action by blocking voltage-gated sodium channels in neurons, but research indicates it may also block cardiac sodium channels (INa) 4.
A study using patch clamp technique on cardiomyocytes from epileptic rats found that lamotrigine inhibited 60% of INa peak amplitude and reduced cardiac excitability, particularly in epileptic animals 4.
This sodium channel blocking effect provides a mechanistic explanation for potential cardiac conduction abnormalities, including bradycardia.
Risk Factors and Monitoring
Patients with pre-existing cardiac conditions may be at higher risk for lamotrigine-induced bradycardia 2.
Concomitant use of other medications that affect cardiac conduction, particularly other sodium channel blockers, may increase the risk of cardiac complications 2.
A retrospective study of Veterans prescribed lamotrigine found that nearly half (47.9%) were also prescribed concomitant sodium channel blocking medication, which could potentially compound cardiac risks 2.
Severe Adverse Events
While most lamotrigine overdoses follow a benign course, there have been severe cases reported, including a case of a 19-year-old who ingested 4g of lamotrigine and developed complete heart block, multiorgan failure, and death 5.
A recent observational cohort study found that lamotrigine was associated with an increased risk of ventricular tachycardia compared to commonly prescribed alternatives, particularly in patients with bipolar disorder 6.
Clinical Recommendations
Consider baseline ECG evaluation before starting lamotrigine, particularly in patients with known cardiac disease or those taking other medications that affect cardiac conduction 3.
Monitor heart rate and cardiac symptoms during lamotrigine initiation and dose adjustments, especially in high-risk patients 2.
Be particularly cautious when combining lamotrigine with other medications known to affect cardiac conduction, such as other sodium channel blockers 2.
Consider dose reduction or discontinuation if clinically significant bradycardia develops during lamotrigine treatment 3.
For symptomatic bradycardia that is unresponsive to medication discontinuation, temporary pacing may be considered in cases of persistent hemodynamically unstable bradycardia 1.
In conclusion, while lamotrigine is generally considered to have a favorable cardiac safety profile compared to many other psychotropic medications, clinicians should be aware of its potential to cause bradycardia and other cardiac conduction abnormalities, particularly in susceptible individuals or those taking concomitant medications that affect cardiac conduction.