Journal
PHARMACOPSYCHIATRY
Volume 47, Issue 4-5, Pages 121-130Publisher
GEORG THIEME VERLAG KG
DOI: 10.1055/s-0034-1383657
Keywords
schizophrenia; glutamate; NMDA receptor; clozapine; glycine
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We discuss the relevance of the glutamate hypothesis in explaining cognitive disturbances and negative symptoms in schizophrenia. 4 lines of evidence support the hypothesis that glutamate deregulation, mainly through dysfunction of the N-methyl-D-aspartate (NMDA) receptor, is an important underlying mechanism of schizophrenia. Glutamate pathways are promising sites for intervention. Glutamate agonists combined with non-clozapine antipsychotics and glutamate antagonists augmented to clozapine show interesting clinical benefits in refractory schizophrenia. We illustrate how unique properties of the NMDA receptor antagonist memantine in addition to clozapine, may cause improvement of positive, negative and cognitive symptoms of schizophrenia.
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