In approximately 70 percent of all patients with epilepsy, the seizures are controlled completely or almost completely by medications; in an additional 20 to 25 percent, the attacks are significantly reduced in number and severity. In a series reported by Kwan and Brodie approximately 20 years ago but probably still reflecting current  circumstances almost half of patients with a new seizure disorder were controlled with first agent tried, another approximately 15 percent respond to a second as monotherapy, and the third choice controls very few instances—the remaining cases are considered treatment-resistant. In more modern series, such as the one reported by Bonnett and colleagues, the response to a first agent of a newer class was similar but subsequent agent cumulatively was somewhat more successful, achieving 75 percent control. More importantly, the simultaneous use of medications presents special problems and the rates of suppression of seizures with each additional drug are low and generally not additive. This approach, however, may not apply to combinations of some of the newer drugs.
An additional question regards whether to start treatment immediately in an adult with a first unprovoked seizure. The MESS trial, which randomized large groups of patients after a first unprovoked seizure to either immediate treatment or none (Marson and colleagues) concluded that the treated group had fewer subsequent seizures at 6 months (18 vs 26 percent), 2 years (32 vs 39 percent), and 5 years (42 vs 51 percent) and the differences were larger for those who had multiple seizures before randomization and the time to the next seizure was delayed. However, the differences became less significant over time and the side effects of the medications, as judged by practical factors such as keeping a job, were no different between groups. The death rates were comparable. Therefore, factors such as tolerance of the medications, patient preferences, and nature of work must be taken into account when making decisions regarding antiepileptic medicines. Guidelines from the American Academy of Neurology generally accord with these views (Krumholz et al).
Table 15-5 lists the most commonly used drugs along with their dosages, effective blood levels, and serum half-lives. Because of the long half-lives of phenytoin, phenobarbital, and ethosuximide, these drugs need be taken only once daily, preferably at bedtime. Valproate and carbamazepine have shorter half-lives, and their administration should be spaced during the day. It is useful to be familiar with the serum protein-binding characteristics of antiepileptic drugs and the interactions among these drugs, and between antiepileptic and other drugs.
Certain drugs are somewhat more effective in one type of seizure than in another, and it is necessary to use the proper drugs in optimum dosages for different circumstances. Initially, only one drug should be used and the dosage increased until sustained therapeutic levels have been attained. If the first drug does not control seizures, a different one should be tried, but frequent shifting of drugs is not advisable; each should be given an adequate trial before another is substituted. A general approach to the choice of drug in certain common forms of epilepsy is given in Table 15-6 for adults and Table 15-7 for children, but it must be noted that there are a number of drugs that may be appropriate in each circumstance. Furthermore, the antiepileptic drugs have approved purposes as assigned by the FDA (Federal Drug Administration) and the EMA (European Medicines Agency). These are more restrictive than are found in general use but it is worthwhile being familiar with the standing of various medications. A tabular summary of these approvals, main uses, and their dates of inception that divide the agents into three generations can be found in a review by Schmidt that is current as of 2016.