Prior to the introduction of second-generation antiepileptic drugs in the early 1990s, the pharmacological management of epilepsy was relatively simple. Only a handful of drugs was available, so making a choice among them was relatively easy. Today, with about 25 different antiseizure medications on the market, drug selection is a much more complex process. In fact, the existence of a broad pharmacological armamentarium is a mixed blessing. On one hand, as each drug differs from the others, a wide choice of medications means that physicians have unprecedented opportunities to tailor treatment choices to the characteristics of the patient. On the other hand, familiarization with the indications, contraindications, specific properties and dosing schedules of 25 different drugs is no easy task, and suboptimal knowledge could result in incorrect prescribing and related harmful consequences.

Optimal drug selection in epilepsy can be summarized as the process that leads to identification of the medication whose properties represent the best match for the characteristics of the patient, keeping in mind that the ultimate goal is to achieve seizure control in the absence of adverse effects impacting negatively on quality of life. Critical pharmacological properties to be considered in this process include (i) spectrum of activity against the patient's seizure types; (ii) comparative efficacy in controlling the seizures; (iii) adverse effect profile, including teratogenicity; (iv) positive or negative influence on the patient's comorbidities; and (v) drug interaction potential. Additional properties to be considered include the presence (or absence) of regulatory approval for the patient's seizure type or syndrome, any need for prolonged dose titration, optimal frequency of administration, availability of convenient formulations (particularly for children), any requirements for laboratory monitoring and, not least, cost and affordability. Individual factors affecting drug selection include age, gender, child-bearing potential, seizure type, seizure frequency, epilepsy syndrome, specific genotypes predisposing to adverse drug reactions, comorbidities and co-medications.

This chapter reviews the evidence base for rational drug selection in specific epilepsy syndromes and conditions, emphasizing advantages and disadvantages of possible treatment options in a variety of clinical situations.