Options after the first antiepileptic drug has failed

Long-term antiepileptic drug (AED) treatment is the standard therapy for epilepsies. In about 60% of patients, the first AED tried usually leads to seizure control. After failure of the first AED, it is important to achieve seizure control rapidly and without side effects. Combining the first drug with an add-on drug appears to be more effective than a second monotherapy. However, no scientifically based data are available that favor any particular drug combination. Along with pharmacokinetic considerations, clinical experience is an important determinant in choosing a second AED for use as an add-on. The time needed to introduce a particular AED is a further consideration. The simultaneous introduction of two add-on drugs, one requiring slow titration and one permitting rapid introduction, may be a useful strategy. If the quickly introduced drug is effective as an add-on, introduction of a slowly titrated second add-on can be obviated. If the quickly introduced drug reduces seizure frequency, the patient's quality of life is improved during titration of the second add-on. If the second, slowly titrated drug is more effective than the quickly introduced one, the less-effective drug can be withdrawn. This strategy also allows a direct comparison between two add-on drugs at the same time.