Definitions
Treatment failure	Treatments have no effect on seizures. This can be due to drug resistance, toxicity, pharmacokinetics / pharmacodynamics, noncompliance. Treatment failure is not necessarily drug resistance.
Resistance to a treatment	Lack or reduction in efficacy of a treatment to control seizures, at treatment schedules that would be expected to have the desired biologic effect. Limitations: Effective treatment schedules are usually deduced by population responses and corresponding peripheral blood levels, as target exposure and modification cannot easily be documented in vivo, particularly in humans. Peripheral blood levels do not however reflect accurately the presence or effects of a treatment in the targeted brain regions of an individual.
Drug resistant epilepsy (DRE)	“Failure of adequate trials of two tolerated and appropriately chosen and used antiseizure medication (ASM) schedules (whether as monotherapies or in combination) to achieve sustained seizure freedom”. 4 It is assumed that DRE mechanisms may be independent of a specific treatment’s mechanism of action and extend across various medical treatments. Limitations: An individual may still respond to a different treatment, albeit the probability is significantly lower. Partial seizure response may still be a welcome effect for certain individuals or guide the design of more effective treatments.
Tolerance	A subject’s diminished response to a treatment after repeated exposure to the treatment, which occurs when the body adapts to the treatment.
Therapeutic levels	Levels of a treatment that can affect the desired biologic effect at the target organ. Limitations: Brain levels cannot be usually measured in live subjects. Therapeutic blood levels may not always reflect the levels of a treatment at the target brain region that generates seizures; lack of effect may be also due to inability to reach and modify the function of the target organ or brain region.