The influence of established and new antiepileptic drugs on visual perception. 1. A placebo-controlled, double-blind, single-dose study in healthy volunteers

Abstract

The influence of single oral dosages of carbamazepine (CBZ), valproic acid, vigabatrin (VGB), lamotrigine (LTG), gabapentin (GBP), and losigamone (LSG) on visual perception was investigated in ten healthy volunteers according to a double-blind, placebo-controlled, cross-over study design. The test battery comprised visual acuity, the Lanthony-D-15-désaturé colour perception test, increment, postadaptation and transient tritanopia threshold measurements, perception threshold assessment for monochromatic and chromatic gaussian dots, monochromatic gratings and gratings of differing spatial frequency, and critical flicker fusion tests with various stimuli. The only consistent and partly significant effects were seen after VGB and GBP. After VGB, increment, postadaptation and transient tritanopia thresholds and the critical flicker fusion increased, whereas GBP led to a somewhat converse profile. The other tests were not influenced consistently by any antiepileptic drug (AED). We conclude that: (i) gamma-amino-butyric acid-(GABA)-related properties as under the prototype drug VGB result in specific alterations of the transient tritanopia phenomenon which is consistent with the physiological hypothesis for this retinal paradigm based on extracellular recordings in primates. The possible mechanisms why VGB improved critical flicker fusion as the only AED in this trial are discussed. The profile of GBP indicates a unique mechanism of action. We have not observed specific influences on visual perception under AEDs which act mainly via alterations of ion membrane conductance. The transient tritanopia and flicker fusion paradigms we used appear to be promising to investigate antiepileptic drugs with hitherto unknown modes of actions in human noninvasively.