Key result
Lamotrigine exposure was associated with a significantly increased risk of ventricular tachycardia compared to alternative agents in adults with bipolar disorder (HR 1.326).
Why the study?
Whether lamotrigine is associated with ventricular tachycardia in patients with bipolar disorder, partial seizures, and generalized tonic-clonic seizures with and without structural heart disease remains controversial.
Does lamotrigine increase the risk of ventricular tachycardia in adult patients with bipolar disorder, partial seizures, or generalized tonic-clonic seizures compared to alternative agents?
Cohort (n=426,057)
Does lamotrigine increase the risk of ventricular tachycardia in adult patients with bipolar disorder, partial seizures, or generalized tonic-clonic seizures compared to alternative agents?
Hazard Ratio: 1.326 (95% CI 1.122–1.568)
Absolute Event Rate: 0.79% vs 0.68%
p-value: p=<0.01
Lamotrigine use is associated with a statistically significant increased risk of ventricular tachycardia in adults with bipolar disorder, highlighting the need for cardiac vigilance in this population.
May warrant ECG monitoring in bipolar patients on lamotrigine; leaves open causality and relevance to epilepsy.
Whether lamotrigine (LTG) is associated with ventricular tachycardia (VT) in bipolar disorder (BPD), partial seizures (PSZ) and generalized tonic-clonic seizures (GTSZ) with and without structural heart disease (SHD) remains controversial leading to a real-world comparative cohort observational study. A retrospective observational comparative safety study was performed using a large healthcare claims database of adult participants, analyzing the risk of VT incidence. Patients diagnosed with BPD, PSZ or GTSZ where free from supraventricular (SVT) or VT during the 6-month baseline period. Exposure to LTG versus commonly prescribed alternative agents was the CTR. One-year cumulative VT incidence was calculated for GTSZ, PSZ and BPD using Kaplan-Meier estimator adjusted for baseline characteristics. The analytic cohort included 153,852 LTG and 213,593 CTR for BPD, 10,275 LTG and 24,971 CTR for PSZ, and 5,860 LTG and 17,506 CTR for GTSZ. The 1-year VT cumulative incidence from LTG or CTR free from was 0.79% vs. 0.68% in BPD, 0.76% vs. 0.58% in PSZ, and 0.93% vs. 0.40% in GTSZ cohorts, The adjusted HR [95% CI] estimates were 1.326 [1.122-1.568, p < 0.01], 1.403 [0.920-2.138, p = 0.11], and 1.180 [0.607-2.295, p = 0.63]. In adult participants with BPD, LTG has a statistically significant association to increase VT risk compared to commonly prescribed alternatives.
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Kim et al. (2025) conducted a cohort in Bipolar disorder, partial seizures, and generalized tonic-clonic seizures (n=426,057). Lamotrigine vs. Alternative medications (e.g., lithium, quetiapine, valproate, carbamazepine, levetiracetam) was evaluated on 1-year cumulative incidence of ventricular tachycardia in the bipolar disorder cohort (HR 1.326, 95% CI 1.122-1.568, p=<0.01). Lamotrigine exposure was associated with a significantly increased risk of ventricular tachycardia compared to alternative agents in adults with bipolar disorder (HR 1.326).
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