RESUMO
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.
Assuntos
Anticonvulsivantes/uso terapêutico , Epilepsia Generalizada/tratamento farmacológico , Ácido Valproico/uso terapêutico , Teorema de Bayes , Epilepsia Generalizada/fisiopatologia , Humanos , Metanálise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
Several newer antiepileptic drugs (AEDs) have been introduced into clinical practice, offering choices for individualizing the treatment of epilepsy since AEDs have different efficacy and tolerability profiles. In particular, questions exist regarding which AEDs are the best options for the monotherapy of focal epilepsy. Is carbamazepine (CBZ), which is considered the standard treatment for focal epilepsy, still the best option for monotherapy of focal epilepsy, despite the emergence of new AEDs? In this systematic review, we compared the relative tolerability of all available AEDs for monotherapy of all types of epilepsy as well as their efficacy in the monotherapy of focal epilepsy. In addition, we compared CBZ with other AEDs for the monotherapy of focal epilepsy. We performed a search of the MEDLINE/PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL) databases for randomized controlled clinical trials. To compare the relative efficacy and tolerability of the AEDs, we performed network meta-analyses using a Bayesian random-effects model. Sensitivity analyses were conducted to determine the robustness of the results. A total of 65 studies were included in this review, composing 16,025 patients. Clobazam, levetiracetam, lamotrigine, oxcarbazepine, sulthiame, topiramate, and valproate had the best efficacy profiles and demonstrated no evidence of superiority or inferiority compared with CBZ. However, CBZ showed the greatest risk of patient discontinuation due to intolerable adverse reactions, whereas lamotrigine had the best safety profile and an 81% probability of being the best for the tolerability outcome of patient withdrawals from the study due to intolerable adverse reactions, followed by sulthiame (60%) and clobazam (51%). The newer AEDs-levetiracetam, lamotrigine, oxcarbazepine, sulthiame, and topiramate-should be considered for monotherapy of focal epilepsy because they were demonstrated to be as effective as the older ones (CBZ, clobazam, and valproate) for the treatment of focal epilepsy and were more tolerable. Lamotrigine was the AED with the best tolerability profile, suggesting that it may be the best option for the treatment of focal epilepsy in children and adults.