SUMMARYAlthough no randomized studies have demonstrated a positive impact of therapeutic drug monitoring (TDM) on clinical outcome in epilepsy, evidence from nonrandomized studies and everyday clinical experience does indicate that measuring serum concentrations of old and new generation antiepileptic drugs (AEDs) can have a valuable role in guiding patient management provided that concentrations are measured with a clear indication and are interpreted critically, taking into account the whole clinical context. Situations in which AED measurements are most likely to be of benefit include (1) when a person has attained the desired clinical outcome, to establish an individual therapeutic concentration which can be used at subsequent times to assess potential causes for a change in drug response; (2) as an aid in the diagnosis of clinical toxicity; (3) to assess compliance, particularly in patients with uncontrolled seizures or breakthrough seizures; (4) to guide dosage adjustment in situations associated with increased pharmacokinetic variability (e.g., children, the elderly, patients with associated diseases, drug formulation changes); (5) when a potentially important pharmacokinetic change is anticipated (e.g., in pregnancy, or when an interacting drug is added or removed); (6) to guide dose adjustments for AEDs with dose-dependent pharmacokinetics, particularly phenytoin.

These results support the idea that tonic-clonic seizures are an important proximate cause of SUDEP. This information creates a risk profile for SUDEP that may help direct preventative efforts.

Adjunctive therapy with levetiracetam was effective and well tolerated in controlling partial seizures.

Pregnancy increases LTG clearance by >50%. This effect occurs early in pregnancy and reverts quickly after delivery. LTG levels should be monitored before, during, and after pregnancy.

Zonisamide is a synthetic 1,2-benzisoxazole-3-methanesulfonamide with anticonvulsant properties. The sulfamoyl group on zonisamide was expected to suppress seizures in a manner similar to another sulfonamide analogue, acetazolamide, through inhibition of carbonic anhydrase. However, this does not appear to be the primary mechanism of action since zonisamide requires much higher doses than acetazolamide to achieve equivalent titration in vivo. Studies with cultured neurons indicate that zonisamide blocks repetitive firing of voltage-sensitive sodium channels and reduces voltage-sensitive T-type calcium currents without affecting L-type calcium currents. Its dual mechanism of action may explain its efficacy in patients resistant to other antiepileptic drugs (AEDs). Zonisamide has a pharmacokinetic profile favorable for clinical use. It is rapidly and completely absorbed and has a long half-life (63-69h in healthy volunteers) which allows twice-daily, or even once-daily, dosing. Zonisamide is not highly bound to plasma proteins. Consequently, it does not affect protein binding of other highly protein-bound AEDs. Furthermore, zonisamide does not induce its own metabolism and does not induce liver enzymes. However, since zonisamide is metabolized by cytochrome P450, liver enzyme-inducing AEDs will increase zonisamide clearance, and dosage adjustments may be necessary when it is used in combination with certain AEDs.