Anticonvulsant Toxicity: Clinical and EEG Effects

.Epilepsy has been known since antiquity, however, there was no satisfactory treatment until the discovery of bromides in 1857 which was the beginning of the modern era of anticonvulsant treatment for seizure disorder. Despite the most serious side effects of psychosis and skin rashes, bromides remained the mainstay of treatment until phenobarbital was introduced in 1912. The bromides were then replaced by phenobarbital. The most significant development is the introduction of diphenylhydantoin (phenytoin) in 1938. The other milestones in the development of anticonvulsant treatment for epilepsy consist of introduction of trimethadione in 1946, primidone (mysoline) in 1954, ethosuximide (zarontin) in 1960, carbamazepine (tegretol) in 1974, clonazepam (clonopin) in 1975 and valproic acid (depakote) in 1978.The first and foremost task before treatment of epilepsy is to make the diagnosis. Does the patient have true seizures and if so, what type of seizure? The answers to these questions are important because the treatment depends on the type of seizure. The purpose of treatment of epilepsy is to decrease or stop the seizures. This should be tried by instituting maximal doses with minimal or no side effects. Monotherapy is better than polytherapy. Monotherapy used in maximal tolerable doses will control the seizures in most of the patients. Poly therapy exposes the patient to various side effects. The most common types of seizures are generalized tonic-clonic, complex and simple partial seizures with or without secondary generalization. The most useful anticonvulsants currently employed are the following; phenobarbital, phenytoin, carbamazepine, primidone, ethosuximide, valproic acid or valproate, clonazepam, and diazepam. Diazepam is used mainly for status epilepticus. Clonazepam and diazepam both belong to the benzodiazepine group of drugs. Phenytoin or carbamazepine appears to be the drug of choice in most of the cases of generalized or partial seizures. Valproate is most effective in primay generalized tonic-clonic seizure associated with spike-wave discharges in the EEG with or without photosensitivity. Ethosuximide is recommended for typical absence seizure. If this fails then valproate or if necessary then clonazepam should be tried. Clonazepam is most effective in myoclonic or atonic seizures, atypical absences, infantile spasms and Lennox-Gastaut syndrome. The clinical toxicity of the previously mentioned commonly used drugs and their effects on EEG will be discussed in the following paragraphs.