Effect of lamotrigine on plasma GABA levels in healthy humans

Lamotrigine, a new anticonvulsant, has been reported to be useful in treating bipolar depression, rapid cycling, and other phases of bipolar disorder. However, the mechanism of action underlying its efficacy in mood disorders is still not known. Since there is evidence for gamma-aminobutyric acid (GABA) involvement in the pathophysiology and treatment response of patients with bipolar disorder, this study was designed to examine the effect of lamotrigine on plasma GABA levels in healthy humans. Eleven healthy volunteers with no lifetime history of psychiatric illness or family history in first-degree relatives were recruited. Each subject received lamotrigine 100 mg/day for 1 week. Blood samples for assay of plasma levels of GABA were taken from each subject before and after administration of lamotrigine. Plasma GABA levels were analyzed using high-pressure liquid chromatography (HPLC) with fluorescence detection after derivatization with o-phthaldialdehyde (OPA). We found no significant difference in the plasma GABA levels of the study subjects before and after treatment with lamotrigine. The finding of this study suggests that lamotrigine in the dose used in this study does not appear to enhance GABA levels in humans. (C) 2003 Elsevier Science Inc. All rights reserved.