International Journal of Clinical Pharmacy

, Volume 40, Issue 3, pp 589–598 | Cite as

Comparative efficacy of antiepileptic drugs for patients with generalized epileptic seizures: systematic review and network meta-analyses

  • Marília Silveira de Almeida CamposEmail author
  • Lorena Rocha Ayres
  • Manuela Roque Siane Morelo
  • Fabiana Angelo Marques Carizio
  • Leonardo Régis Leira Pereira
Review Article


Background Valproate is a widely prescribed antiepileptic drug for generalized epilepsies, due to the extensive knowledge on its efficacy since it is on the market for many decades. However, a large number of new antiepileptic medicines was introduced into clinical practice and may be better options for treatment, considering that these medicines differ in terms of efficacy spectrum. Despite extensive research, questions regarding which medicine would constitute the first option for the monotherapy treatment of generalized epilepsy remain. Aim of the Review To compare the relative efficacy of all available antiepileptic drugs in the monotherapy treatment of generalized epileptic seizures; and also to compare all antiepoileptig drugs with valproate, which is the current first-line treatment for generalized epilepsy. Methods A systematic review for randomized controlled clinical trials was performed. Network meta-analyses used Bayesian random effects model. Sensitivity analyses determined the results´ robustness. The relative probability of two efficacy outcomes (“Seizure free” and “Therapeutic inefficacy”) to happen for each medcicine was calculated using the Surface Under the Cumulative Ranking Curve. Results Seven papers (1809 patients) studied the efficacy of valproate, lamotrigine, phenytoin, carbamazepine, topiramate, levetiracetam, and phenobarbital in the treatment of generalized tonicclonic, tonic, and clonic seizures. Phenytoin demonstrated to be inferior to valproate in leaving the patient free of these seizures types [OR: 0.50 (95% CrI 0.27, 0.87)]. Lamotrigine (61%) showed the highest probability of presenting the outcome “Seizure free”, followed by levetiracetam (47%), topiramate (44%), and valproate (38%) in the treatment of generalized tonic–clonic, tonic, and clonic seizures. Meanwhile, valproate exhibited greater chance of presenting the outcome “Therapeutic inefficacy” (62%). Regarding absence seizures itself, there was no difference in the efficacy of lamotrigine and ethosuximide when compared to valproate. However, the ranking indicates that ethosuximide (52%) and valproate (47%) are both more likely than lamotrigine to keep the patient free of seizures. Conclusions Lamotrigine, levetiracetam, and topiramate are as effective as valproate for treating generalized tonic–clonic, tonic, and clonic seizures. Meanwhile, valproate and ethosuximide are the best options for the treatment of absence seizures promoting better control of seizures, which is the primary goal of pharmacotherapy.


Anticonvulsants Bayes theorem Generalized epilepsy Literature review Meta-analysis 



No funding was received in support of this work.

Conflicts of interest

The authors have no conflicts of interest.

Supplementary material

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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Marília Silveira de Almeida Campos
    • 1
    • 2
    Email author
  • Lorena Rocha Ayres
    • 3
  • Manuela Roque Siane Morelo
    • 2
  • Fabiana Angelo Marques Carizio
    • 2
  • Leonardo Régis Leira Pereira
    • 1
    • 2
  1. 1.School of PharmacyFederal University of Rio Grande do SulPorto AlegreBrazil
  2. 2.School of Pharmaceutical Sciences of Ribeirão Preto – University of São PauloRibeirão PretoBrazil
  3. 3.Department of Pharmaceutical SciencesFederal University of Espírito SantoVitóriaBrazil

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