The effect of topiramate plasma concentration on linguistic behavior, verbal recall and working memory.

This is the first study of the effect of topiramate on linguistic behavior and verbal recall using a computational linguistics system for automated language and speech analysis to detect and quantify drug-induced changes in speech recorded during discourse-level tasks. Healthy volunteers were administered a single, 100-mg oral dose of topiramate in two double-blind, randomized, placebo-controlled, crossover studies. Subjects' topiramate plasma levels ranged from 0.23 to 2.81 μg/mL. We found a significant association between topiramate levels and impairment on measures of verbal fluency elicited during a picture description task, correct number of words recalled on a paragraph recall test, and reaction time recorded during a working memory task. Using the tools of clinical pharmacology and computational linguistics, we elucidated the relationship between the determinants of a drug's disposition as reflected in plasma concentrations and their impact on cognitive functioning as reflected in spoken language discourse.