Abstracts

Antiepileptic drugs (AEDs) can produce untoward cognitive effects. Healthy volunteer studies are frequently used to demonstrate differential cognitive effects across AEDs. It is unknown, however, how well the results of healthy volunteer studies compare to those from patients with epilepsy. Here we compare overlapping cognitive measures in two previously reported studies examining the cognitive effects of lamotrigine and topiramate; one study was in healthy volunteers and the other was in patients with epilepsy., The healthy volunteer study employed a multicenter, double-blind, randomized crossover design with two 12-week treatment periods (7 week titration, 4 week maintenance) in 75 adults (47 completers, 63%). Target doses were 300 mg/day for both LTG and TPM. Subjects were tested at the end of each antiepileptic drug (AED) treatment period and during two drug-free conditions.
The patient study used a multicenter, double-blind, randomized, parallel group design in 192 adults with partial seizures (124 completers, 65%). Target doses of LTG (500 mg/day) or TPM (300 mg/day) were given in adjunctive therapy to carbamazepine or phenytoin (8 week titration, 8 week maintenance). Patients were tested at baseline and end of titration and maintenance.
Comparison of LTG-TPM differences were made for each of the overlapping cognitive measures: Controlled Word Association Test (COWA), Grooved Pegboard (GPB), Stroop test (color and color-word), and Symbol Digit Modalities Test (SDMT)., Patients performed worse than healthy volunteers on all measures at baseline. Performances on LTG were better than TPM for both patients and healthy volunteers on COWA and SDMT, for patients only on Stroop color-word, and for controls only on GBP and Stroop color. The magnitude of differences was smaller for patients., Despite multiple differences in study design, the relative cognitive differences were similar in patients and healthy volunteers. The lower magnitude of differences in patients could be related to various factors including the lower baseline performance of patients, epilepsy, or study design differences.[table1], (Supported by GlaxoSmithKline.)