Background: Antiepileptic drugs (AEDs) can be associated with neurotoxic side effects including cognitive dysfunction, a problem of considerable importance given the usual long-term course of treatment. Pregabalin is a relatively new AED widely used for the treatment of seizures and some types of chronic pain including fibromyalgia. We measured the cognitive effects of 12 weeks of pregabalin in healthy volunteers.
Methods: Thirty-two healthy volunteers were randomized in a double-blind parallel study to receive pregabalin or placebo (1:1). Pregabalin was titrated over 8 weeks to 600 mg/d. At baseline, and after 12 weeks of treatment, all subjects underwent cognitive testing. Test-retest changes in all cognitive and subjective measures were Z scored against test-retest regressions previously developed from 90 healthy volunteers. Z scores from the placebo and pregabalin groups were compared using Wilcoxon tests.
Results: Thirty subjects completed the study (94%). Three of 6 target cognitive measures (Digit Symbol Substitution Test, Stroop Color-Word Interference Test, Controlled Oral Word Association Test) revealed significant test-retest differences between the pregabalin and placebo groups, all showing negative effects with pregabalin (p < 0.05).
These cognitive effects were paralleled by complaints on the Portland Neurotoxicity Scale, a subjective measure of neurotoxicity (p < 0.01). [This scale is “a brief patient-based survey of neurotoxicity complaints commonly encountered with the use of antiepileptic drugs.”]
Conclusion: At conventional doses and titration, pregabalin induced mild negative cognitive effects and neurotoxicity complaints in healthy volunteers. These effects are one factor to be considered in the selection and monitoring of chronic AED therapy.
Class of Evidence: This study provides Class I evidence that pregabalin 300 mg BID negatively impacts cognition on some tasks in healthy volunteers.
Source: Neurology, Mar 2010. 2;74(9):755-61. PMID: 20194915, by Salinsky M, Storzbach D, Munoz S. Oregon Health & Science University, Portland, Oregon, USA. [Email: Salinsky@ohsu.edu]