Efficacy and Adverse Effects of Established and New Antiepileptic Drugs*

Abstract

Antiepileptic drug (AED) selection is based primarily on efficacy for specific seizure types and epileptic syndromes. However, efficacy is often similar for the different AEDs, and other properties such as adverse effects, pharmacokinetic properties, and cost may also be of importance. For idiopathic generalized epilepsies with absence, tonic-clonic, and myoclonic seizures, the AED of choice is valproate (VPA). Secondarily generalized epilepsies with tonic, atonic, and other seizure types are difficult to treat with any single AED or combination of AEDs. The AEDs of choice for absence seizures are ethosuximide (ESM) and VPA. For control of primary generalized tonic-clonic seizures, any of the other major AEDs can be effective. If VPA cannot be prescribed, carbamazepine (CBZ), phenobarbital (PB), phenytoin (PHT), or primidone (PRM) may be effective, but ESM or a benzodiazepine (BZD) must be added to control associated absence or myoclonic seizures. The AEDs of first choice for partial epilepsies with partial and secondarily generalized tonic-clonic seizures are CBZ and PHT. Increasing evidence suggests that VPA is a good alternative when CBZ and PHT fail. PB and PRM are second-choice selections because of adverse effects. A combination of two of the five standard AEDs may be necessary to treat intractable seizures, but no studies have been done to indicate an optimal combination. Other epilepsy syndromes such as neonatal and infantile epilepsies, febrile epilepsy, alcoholic epilepsy, and status epilepticus require specific AED treatment. Ultimately, AED selection must be individualized. No "drug of choice" can be named for all patients. The expected efficacy for the seizure type, the importance of the expected adverse effects, the pharmacokinetics, and the cost of the AEDs all must be weighed and discussed with the patient before a choice is made. A number of new AEDs with unique mechanisms of action, pharmacokinetic properties, and fewer adverse effects hold important promise of improved epilepsy treatment.

Anticonvulsant Activity of Carissa carandas Linn. Root Extract in Experimental Mice

“…The current therapy of epilepsy with modern antiepileptic drugs is associated with side effects, dose-related and chronic toxicity, as well as teratogenic effects, and approximately 30% of the patients continue to have seizures with current antiepileptic drugs therapy [2][3][4] . Traditional systems of medicine are popular in developing countries and up to 80% of the population relies on traditional medicines or folk remedies for their primary health care need 5 .…”

Correlation between Anticonvulsant Activity and Inhibitory Action on Glial γ-Aminobutyric Acid Uptake of the Highly Selective Mouse γ-Aminobutyric Acid Transporter 1 Inhibitor 3-Hydroxy-4-amino-4,5,6,7-tetrahydro-1,2-benzisoxazole and ItsN-Alkylated Analogs

“…Today, the primary use of the benzodiazepines as anticonvulsants is in the acute treatment of status epilepticus. Although effective as broad-spectrum antiseizure drugs, the clinical utility of the barbiturates is limited by the development of cognitive impairment and behavioral modifications [for reviews, see Devinsky (1995) and Mattson (1995)]. …”

NMDA‐ But Not Kainate‐Mediated Events Reduce Efficacy of Some Antiepileptic Drugs Against Generalized Tonic‐Clonic Seizures in Mice

“…The results of this study seem to shed some light on the nature of drug resistance, which is observed among a prominent proportion of patients with epilepsy (26). The administration of subconvulsive doses of NMDA or kainate may be considered the factor reflecting the increased level of endogenous EAA agonists such as glutamate and its analogues.…”