Abstract:It is currently estimated that about 20%–30% of adults and 10%–40% of children diagnosed with epilepsy suffer from
uncontrolled or poorly controlled seizures, despite optimal medical management. In addition to its huge economic costs, treatment-refractory epilepsy has a widespread impact on patients’ health-related quality of life. The present paper focuses on the concepts of
refractory and difficult-to-treat seizures and their pharmacological management. Evidence on efficacy and tolerability of rational phar-macotherapy with antiepileptic drug combinations and of non-pharmacological treatment options such as epilepsy surgery, neurostimu-lation, metabolic treatment and herbal remedies is reviewed. The importance of early identification of the underlying etiology of the
specific epilepsy syndrome is emphasized, to inform early prognosis and therapeutic strategies.