Human brain GABA levels rise after initiation of vigabatrin therapy but fail to rise further with increasing dose

Abstract

Using ¹H spectroscopy, we measured occipital lobe GABA levels serially in 18 patients enrolled in an ongoing open label trial of vigabatrin. Brain GABA levels were elevated twofold in patients taking vigabatrin (3 to 4 gld) compared with nonepileptic subjects. Serial measurements suggested that brain GABA rose in proportion to vigabatrin dose up to 3 gld. Doubling the dose from 3 to 6 gld failed to increase brain GABA further. Serial measurements on three patients taking 6 gld showed a gradual decrease in brain GABA in two patients over 1 to 2 years of treatment. These observations suggest that GABA synthesis may decrease at high GABA levels.