Modulation of brain and serum glutamatergic concentrations following a switch from conventional neuroleptics to olanzapine

Donald C. Goff, John Hennen, In Kyoon Lyoo, Guochuan Tsai, Lawrence L. Wald, A. Eden Evins, Deborah A. Yurgelun-Todd, Perry F. Renshaw

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101 Scopus citations


Background: Recent evidence suggests that effects upon glutamatergic transmission may contribute to the therapeutic action of certain atypical antipsychotic agents. Methods: Glutamate concentrations were measured in serum and were estimated (Glx/Cr) in cingulate cortex by proton magnetic resonance spectroscopy (MRS) in schizophrenia patients while they were being treated with conventional neuroleptics and then 8 weeks after switching to olanzapine. Serum glutamate concentrations were obtained from 11 subjects, and MRS estimates of Glx/Cr were available from 10 subjects at both time points. Results: Serum glutamate concentrations significantly increased after the switch from conventional agents to olanzapine; brain glutamate (Glx/Cr) did not change significantly; however, brain glutamate (Glx/Cr) concentrations increased significantly in patients who exhibited an improvement in negative symptoms with olanzapine compared with patients with no change or worsening of negative symptoms. Conclusions: Comparisons performed following the switch from conventional agents to olanzapine are consistent with previous studies of clozapine and provide additional preliminary evidence supporting the hypothesis that effects on excitatory amino acid activity may contribute to olanzapine's efficacy for treating negative symptoms.

Original languageEnglish
Pages (from-to)493-497
Number of pages5
JournalBiological Psychiatry
Issue number6
StatePublished - 15 Mar 2002

Bibliographical note

Funding Information:
This study was supported by a grant from Eli Lilly and Company.


  • Clozapine
  • Glutamate
  • Negative symptoms
  • Olanzapine
  • Schizophrenia
  • Spectroscopy


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