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Letters to the Editor
July 2002

Effects of NMDA Receptor Antagonists: Implications for the Pathophysiology of Schizophrenia

Arch Gen Psychiatry. 2002;59(7):663-664. doi:

We appreciate the interest of Drs Shim and Adityanjee in the mechanistic implications of our study, which described the interactive effects of lamotrigine and ketamine in healthy human subjects.1 They question whether reductions in N-methyl-D-aspartate receptor (NMDAR) function produced by ketamine in fact enhance regional glutamatergic neurotransmission via non-NMDARs. Because of this concern, they question whether lamotrigine reduces the hyperglutamatergic effects of ketamine or whether it attenuates ketamine's effects through other mechanisms. In response to these queries, it is important to point out that the study in question is quite limited in its capacity to determine how lamotrigine attenuates ketamine's effects. The fact that lamotrigine reduced the psychotogenic and cognitive effects of ketamine, but potentiated the euphoric effects of ketamine, may have mechanistic significance. For example, it suggests that lamotrigine is not simply antagonizing the effects of ketamine at the NMDAR. Preclinical research may provide insight into the interactive effects of lamotrigine and ketamine.