New Studies Challenge FDA Warning on Cardiac Risks of Lamotrigine

Recent studies have brought new evidence to light regarding the cardiac safety of lamotrigine, an antiseizure medication widely used in the treatment of epilepsy. Conducted by researchers at the University of Calgary and Rutgers University, these studies suggest that lamotrigine does not significantly increase the risk of cardiac issues compared to levetiracetam, another commonly prescribed antiseizure drug. The findings, published on June 11, 2025, in the journal Neurology, challenge an FDA warning issued in 2020 that suggested potential cardiac risks associated with lamotrigine use in certain patients.

The FDA's warning stemmed from in vitro studies and case reports highlighting arrhythmias in patients with underlying heart conditions. However, this new research utilizes real-world data from over 150,000 patients, providing a more comprehensive analysis of the drug's safety profile. According to Dr. Gloria Y.F. Ho, a visiting scholar at Rutgers University and lead author of one of the studies, "Our study was done in people, had a comparator, and also looked at several subgroups. And we did not find an increased risk" for cardiac outcomes.

In the first cohort study, the researchers analyzed data from over 53,000 patients in the United States and the United Kingdom. They found no significant difference in the incidence of ventricular tachycardia or ventricular fibrillation (VT/VF) between those initiating treatment with lamotrigine and those using levetiracetam. Specifically, the adjusted hazard ratio for VT/VF was 0.73 for lamotrigine users in the Medicare dataset, compared to 0.75 in the UK Clinical Practice Research Datalink.

The second cohort study, which included nearly 12,000 new lamotrigine users and 150,000 levetiracetam users, also reported no significant differences in the rates of ventricular arrhythmia and sudden cardiac arrest (VA/SCA). The results indicated similar incidence rates, with 7 cases per 1000 person-years for lamotrigine and 8.2 for levetiracetam. Notably, lamotrigine users with a history of arrhythmias demonstrated a significantly reduced risk for VA/SCA, further undermining the FDA's warning.

Dr. Samuel W. Terman, from the University of Calgary and co-author of the first study, emphasized that these findings provide substantial evidence against the concerns raised in the FDA warning. He stated, "This study provides Class III evidence that lamotrigine did not significantly increase the 2-year cumulative incidence of VT/VF in adult patients with epilepsy."

Despite the promising results, experts urge caution. Dr. Leah J. Blank, an assistant professor of neurology at the Icahn School of Medicine at Mount Sinai, acknowledged the studies' limitations due to their observational nature. She stated, "While these data suggest that lamotrigine likely is safe in clinical practice, we must consider patient-specific factors when prescribing."

The implications of these findings are significant, particularly for older adults with epilepsy who may also have underlying heart conditions. Dr. Ho noted that the current FDA warning could deter clinicians from prescribing lamotrigine to patients who could benefit from it due to concerns over cardiac risks.

As the FDA continues to evaluate such studies as part of its ongoing efforts to ensure public health safety, no immediate changes to the warning label have been announced. A representative stated that the agency does not comment on specific studies but incorporates them into the broader evaluation of drug safety.

In conclusion, the recent findings challenge the long-held perception of lamotrigine's cardiac risks and may influence future prescribing practices. Further research is necessary to fully understand the drug's safety profile, particularly in diverse patient populations, and to address the ongoing concerns regarding its use in patients with pre-existing cardiovascular conditions.