Strategies for Optimizing Antiepileptic Drug Therapy in Elderly People

Thomas E. Lackner, Pharm.D., FASCP


Pharmacotherapy. 2002;22(3) 

In This Article

Serum AED Concentration Monitoring

Measuring AED SDCs is especially useful in elderly people since AED adverse reactions may be difficult to distinguish from common disease symptoms or adverse reactions of other drugs. In particular, debilitated elderly individuals may not realize the importance or be able to communicate symptoms of an adverse reaction, in which case the SDC serves as a surrogate marker of toxicity. Even in the absence of an established therapeutic SDC range, the SDC at which an individual patient achieves optimum disease control without bothersome adverse effects is a benchmark for future reference. Finally, SDCs can facilitate assessment of suspected patient nonadherence. The value of routine measurement in all patients receiving AEDs with an established therapeutic SDC range is controversial but may, by revealing a progressive change in concentration, avert a loss of efficacy or toxicity. Routine measurement is primarily effective in individuals who are cognitively impaired, have comorbidity, take other drugs whose symptoms can mimic or conceal AED adverse effects, have a history of adverse AED reactions, have unexplained fluctuations in SDC, or require a high-normal or supranormal SDC for disease management. Since unexplained intrapatient variability in serum phenytoin concentrations is not uncommon, periodic routine measurement of this agent is beneficial.[236] Indications for more vigilant than usual SDC measurement include unexpected clinical response such as loss of disease control, tube feedings (phenytoin) with a fluctuating SDC, and after the addition and discontinuation (if an interaction is observed) of drugs known to interact with the AED.

Because advanced age and/or disease can decrease drug elimination and prolong the time to reach steady-state SDC of several AEDs, steady-state SDC measurement after beginning therapy and dosage adjustment may have to be delayed.

Evaluation of the total SDC is appropriate when binding-protein concentrations are normal or less than 80% of the AED is ordinarily bound to plasma protein. Factors that warrant measurement of unbound SDC of a highly protein-bound AED are a reduction in plasma albumin or increased a1-acid glycoprotein (AAG) concentration, the presence of conditions known to alter the binding-protein concentration, an unanticipated low or declining total SDC, disparate clinical response and total SDC, and possibly the need to maintain a high-normal total SDC for disease management. Once an abnormal ratio of unbound and total SDC is established, it is not necessary to measure both total and unbound SDCs since this is not known to improve SDC interpretation and it increases cost. The direct cost of determining the unbound concentration can be lower than that of determining the total concentration. For example, the cost for a total phenytoin SDC measurement approximates $76.00, compared with $56.00 for an unbound concentration.