Blood (serum/plasma) antiepileptic drug (AED) therapeutic drug monitoring (TDM) 
has proven to be an invaluable surrogate marker for individualizing and 
optimizing the drug management of patients with epilepsy. Since 1989, there has 
been an exponential increase in AEDs with 23 currently licensed for clinical 
use, and recently, there has been renewed and extensive interest in the use of 
saliva as an alternative matrix for AED TDM. The advantages of saliva include 
the fact that for many AEDs it reflects the free (pharmacologically active) 
concentration in serum; it is readily sampled, can be sampled repetitively, and 
sampling is noninvasive; does not require the expertise of a phlebotomist; and 
is preferred by many patients, particularly children and the elderly. For each 
AED, this review summarizes the key pharmacokinetic characteristics relevant to 
the practice of TDM, discusses the use of other biological matrices with 
particular emphasis on saliva and the evidence that saliva concentration 
reflects those in serum. Also discussed are the indications for salivary AED 
TDM, the key factors to consider when saliva sampling is to be undertaken, and 
finally, a practical protocol is described so as to enable AED TDM to be applied 
optimally and effectively in the clinical setting. Overall, there is compelling 
evidence that salivary TDM can be usefully applied so as to optimize the 
treatment of epilepsy with carbamazepine, clobazam, ethosuximide, gabapentin, 
lacosamide, lamotrigine, levetiracetam, oxcarbazepine, phenobarbital, phenytoin, 
primidone, topiramate, and zonisamide. Salivary TDM of valproic acid is probably 
not helpful, whereas for clonazepam, eslicarbazepine acetate, felbamate, 
pregabalin, retigabine, rufinamide, stiripentol, tiagabine, and vigabatrin, the 
data are sparse or nonexistent.