Pharmacopsychiatry 1998; 31: 104-109
DOI: 10.1055/s-2007-979354
Original Papers

© Georg Thieme Verlag Stuttgart · New York

The NMDA Antagonist Model for Schizophrenia: Promise and Pitfalls

W. M. Abi-Saab1 , 2 , 3 , D. C. D'Souza1 , 2 , B. Moghaddam1 , J. H. Krystal1 , 2 , 3
  • 1Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06519, USA
  • 2Psychiatry Service, VA Connecticut Healthcare System, West Haven, CT 06516, USA
  • 3Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, New Haven, CT 06519, USA
Further Information

Publication History

Publication Date:
20 April 2007 (online)


Drug models have been extensively used to study the pathophysiology of schizophrenia. While they provide good insight into the neurobiology of this disorder, they have several shortcomings, which if known, help in the interpretation of results. In this paper we will discuss these shortcomings in general, and in relation to the N-methyl D-aspartate antagonist model for schizophrenia. This model has recently received a great deal of attention since both phencyclidine and the structurally related drug ketamine, produce symptoms that extend beyond psychosis per se to include other symptoms associated with schizophrenia. In fact, subanesthetic doses of ketamine in healthy individuals produce not only paranoia and perceptual alterations but also thought disorder, negative symptoms, cognitive deficits, as well as impairment on a number of electro-physiologic tests known to be abnormal in schizophrenia. These effects of ketamine will be discussed with a particular emphasis on implications for the pathophysiology and therapeutics of this disorder.