General principles of epilepsy treatment
AEDs treat the symptom of epilepsy, not the underlying condition.
Treatment with AEDs does not prevent the development of epilepsy.
Treatment with AEDs reduces the possibility of recurrent seizures after a first seizure.
The goal of treatment is to minimize seizure frequency while keeping adverse drug effects at minimum.
Treatment facts
About 50% of patients will become seizure free on the first AED and >90% of them will do so at moderate doses.
Tolerability is as important as efficacy in overall effectiveness.
The most common reason for treatment failure is non-compliance.
3 or more AEDs are not more effective than 2 AEDs.
The probability of seizure remission decreases with each tried treatment regimen. ~50% of patients will reach remission on first treatment regime, ~37% on the second, ~24% on the third, ~16% on the fourth and ~13% on the fifth and sixth.
When combination treatment is chosen one should avoid AEDs with similar side-effect profiles.
The combination of AEDs with different mechanisms of action might theoretically be more efficient than of AEDs with similar mechanisms of action. Available data suggest this to be true for valproate / lamotrigine. Other combinations have not been proven to be superior.
The newer AEDs are generally not more efficient than traditional AEDs.
Pharmacokinetics of AEDs
All AEDs are “dirty drugs” - they bind to multiple molecular targets and have a wide range of effects and adverse reactions.
The therapeutic index (TI = ED50 / TD50) of most AEDs is small.
There is limited data on the “therapeutic range” of AED serum concentrations, especially for the newer AEDs. Broad generalisations are made but variation between individuals is significant.
Steady state serum concentration is reached after ~5 drug half-lives.
Serum concentration should be measured at steady state, just before the next dose in order to approximate the “trough” concentration.
The newer AEDs have generally less plasma protein binding, cause less enzyme inductions/inhibitions and have lower interaction rates than the traditional AEDs (with some exceptions).