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

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Abstract

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.

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Authors and Affiliations

  1. School of Pharmacy, Federal University of Rio Grande do Sul, Porto Alegre, Brazil

    Marília Silveira de Almeida Campos & Leonardo Régis Leira Pereira

  2. School of Pharmaceutical Sciences of Ribeirão Preto – University of São Paulo, Ribeirão Preto, SP, Brazil

    Marília Silveira de Almeida Campos, Manuela Roque Siane Morelo, Fabiana Angelo Marques Carizio & Leonardo Régis Leira Pereira

  3. Department of Pharmaceutical Sciences, Federal University of Espírito Santo, Vitória, ES, Brazil

    Lorena Rocha Ayres

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Campos, M.S.d.A., Ayres, L.R., Morelo, M.R.S. et al. Comparative efficacy of antiepileptic drugs for patients with generalized epileptic seizures: systematic review and network meta-analyses. Int J Clin Pharm 40, 589–598 (2018). https://doi.org/10.1007/s11096-018-0641-9

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