Reply to "Psychotic Symptoms Associated With Topiramate: Cognitive Side Effects or Worsening of Psychosis"?

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Sir: We appreciate the comments of Dr. Duggal regarding our data concerning worsening of psychosis after replacement of adjunctive valproate with topiramate in a patient with schizophrenia. We agree completely with Dr. Duggal concerning hypotheses suggesting that N-methyl-D-aspartate (NMDA) receptor hypofunction, dampened γ-aminobutyric acid (GABA)ergic inhibition, and excessive stimulation of the kainic acid/α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) class of glutamate receptors occur in at least some patients with schizophrenia. Such a condition of "hypoglutamatergia" has been hypothesized to result in "paradoxical" excessive stimulation of the kainic acid/AMPA receptors and excitotoxicity, which in turn might explain the progressive psychosocial and cognitive deterioration seen in a subgroup of schizophrenia patients.¹