A new study published in the Annals of Child Neurology has strongly recommended lamotrigine (LTG) as a complementary therapy for children with Lennox-Gastaut syndrome (LGS).

The study found that 92.1% of the LGS patients received valproate (VPA) simultaneously, and 54.5% of them were reported to have a significant (>50%) reduction in seizure frequency, indicating the effectiveness of LTG as an adjunctive therapy for LGS patients.

The study was a single-center retrospective study of 38 children diagnosed with LGS and received LTG as an adjunctive therapy between October 2020 and March 2022 at the Severance Children’s Hospital, Seoul, South Korea. The primary treatment outcome was the change in seizure frequency at 3, 6, and 12 months after LTG initiation. Favorable treatment response was defined as a 50% or above reduction in seizure frequency.

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Study results showed that the principal seizure semiology at LTG initiation was tonic-clonic, found in 15 (39.5%) patients, followed by spasm in 14 (36.8%), myoclonic in 3 (7.9%), atonic in 5 (13.2%), and absence in 1 (2.6%) patient. Moreover, the median quantity of antiseizure medications (ASMs) was reported to be 3.95, while the most prevalent concomitant ASMs were VPA (92.1%), followed by levetiracetam (60.5%), and topiramate (52.6%).

Furthermore, it was found that after 3 months of LGS initiation, the seizure frequency reduced by more than 50% in 47.4% of the patients, while after 6 months, 55.6% of patients showed a favorable response. In addition, 5 patients (5/11) responded to the treatment after 12 months of therapy initiation. The results also showed that 3 patients exhibited myoclonic seizures at the start of therapy, and more than 50% amelioration in seizure frequency occurred at 3 and 6-month follow-up visits. 

“Our study adds to the current knowledge regarding ASM treatment in patients with LGS, whose seizures are mostly intractable,” the authors highlighted.

LGS is a rare severe type of epilepsy that typically manifests in children between 2 and 5 years old. This disease is characterized by multiple drug-resistant seizures, including tonic seizures and cognitive and behavioral impairments that may not be present at the onset of seizures. In addition, it is also characterized by the diffuse slow spike-and-wave and generalized paroxysmal fast activity on the electroencephalography.

Treating LGS is challenging and typically requires a combination of therapies, including polytherapy with ASMs, cannabidiol, surgery, and a ketogenic diet. Since 1993, the US FDA has approved 5 drugs for treating LGS: clobazam, felbamate, LTG, rufinamide, and topiramate.

A recent has found that using LTG and rufinamide in combination with other therapies significantly reduced seizure frequency in LGS patients. LTG is effective in reducing tonic, tonic-clonic, and atonic seizures, but conflicting reports exist on its effectiveness in treating myoclonic and atypical absence seizures.


Shin HJ, Ko A, Kim SH et al. Efficacy and safety of lamotrigine adjunctive therapy in Lennox-Gastaut Syndrome. Ann Child Neurol. Published online March 9, 2023. doi:10.26815/acn.2022.00437