More than 30 % of adults with epilepsy do not fully control on the currently available antiepileptic drugs (AEDs). For these and many other patients, combinations of agents, often possessing different mechanisms of actions, are employed with the aim of achieving seizure freedom or the best available prognosis in terms of reduced seizure numbers and severity. This review discusses my own approach to optimising outcomes in as many of these patients as possible by adjusting the drug burden using a combination of two, three or sometimes four or more AEDs. Modes of drug action are reviewed and practical strategies for treating different patients with drug-resistant epilepsy have been explored. Only for sodium valproate with lamotrigine is there good evidence of synergism. The final part of this practical paper consists of six individual illustrative cases with appropriate comments.
Keywords: Antiepileptic drugs; Mechanisms of action; Psychiatric comorbidities; Quality of life; Rational polytherapy; Seizure freedom.