The efficacy of lamotrigine after failure of the first administration of valproate in treating epilepsy: a systematic review and meta-analysis

Ann Palliat Med. 2022 Jan;11(1):113-122. doi: 10.21037/apm-21-3555.


Background: Epilepsy is a long-term recurrent chronic brain disease that can cause significant emotional burden to the patient and their family, as well as huge economic costs to society. Timely and accurate diagnosis of epilepsy, together with early and standardized treatments can effectively control seizures and restore the patient's quality of life and reduce the economic burden. This meta-analysis examined the efficacy of lamotrigine administration in patients with epilepsy.

Methods: A literature search was performed in the PubMed, Embase, and OVID-Medline databases to identify articles related to epilepsy and lamotrigine that were published from the establishment of the database to April 2021. The keywords used for the literature search included "epilepsy", "sodium valproate", "lamotrigine", "effectiveness", and "therapeutic effect". It uses Cochrane review manual 5.3 to evaluate the quality of the included literature and review manager 5.3 software for meta-analysis.

Results: A total of 9 studies involving 1,864 patients with epilepsy were included in this meta-analysis. The results revealed that, after treatment failure with the first drug of valproic acid, the total effective rate of lamotrigine treatment had an odds ratio (OR) of 2.21 with a 95% confidence interval (CI) of 1.15 to 4.27 (Z=2.37; P=0.02). The total adverse reaction rate (OR =0.70; 95% CI: 0.55 to 0.88; Z=2.98; P=0.003) and the improvement rate of epilepsy associated with lamotrigine treatment (OR =4.22; 95% CI: 1.00 to 17.84; Z=1.96; P=0.05) were all significantly higher than that of other drug treatments.

Discussion: A total of 9 articles were included in this meta-analysis to examine the efficacy of lamotrigine in the treatment of epilepsy. The clinical efficacy of lamotrigine addition therapy was found to be superior to lamotrigine replacement therapy, and the incidence of adverse reactions was lower than that of lamotrigine replacement therapy. However, due to the low methodological quality of the included literatures, this conclusion should be further verified using large sample and high-quality randomized double-blinded experiments.

Keywords: Epilepsy; effectiveness; lamotrigine; meta-analysis; sodium valproate.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Epilepsy* / drug therapy
  • Humans
  • Lamotrigine / therapeutic use
  • Quality of Life
  • Triazines / therapeutic use
  • Valproic Acid* / therapeutic use


  • Triazines
  • Valproic Acid
  • Lamotrigine