Clozapine blunts N-methyl-D-aspartate antagonist-induced psychosis: A study with ketamine

Anil K. Malhotra, Caleb M. Adler, Sasha D. Kennison, Igor Elman, David Pickar, Alan Breier

Research output: Contribution to journalArticlepeer-review

173 Scopus citations


Several lines of evidence suggest that the glutamatergic N-methyl-D- aspartate (NMDA) receptor is involved in the antipsychotic efficacy of the atypical antipsychotic agent clozapine. Clinical data on the interaction between clozapine's mechanism of action and NMDA receptor function have been lacking secondary to a paucity of pharmacologic probes of the NMDA system. We have utilized a double-blind, placebo-controlled infusion paradigm with subanesthetic doses of the NMDA antagonist ketamine to test the hypothesis that clozapine would blunt ketamine-induced psychotic symptoms in schizophrenic patients. Ten schizophrenic patients underwent ketamine infusions while antipsychotic drug free and also during treatment with clozapine. Antipsychotic drug-free patients experienced increases in ratings of positive and negative symptoms. Clozapine treatment significantly blunted the ketamine-induced increase in positive symptoms. These data suggest that NMDA receptor function may be involved in the unique antipsychotic efficacy of clozapine.

Original languageEnglish (US)
Pages (from-to)664-668
Number of pages5
JournalBiological Psychiatry
Issue number8
StatePublished - Oct 15 1997
Externally publishedYes


  • Atypical antipsychotic
  • Clozapine
  • Ketamine
  • N-methyl-D- aspartate
  • Psychosis
  • Schizophrenia

ASJC Scopus subject areas

  • Biological Psychiatry


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