title: Comparative effects of glycine and D-cycloserine on persistent negative symptoms in schizophrenia: a retrospective analysis.
abstract: Phencyclidine (PCP), ketamine and other N-methyl-D-aspartate (NMDA) antagonists induce schizophrenia-like symptoms in normal volunteers, suggesting that endogenous dysfunction or dysregulation of NMDA receptors may contribute to the pathophysiology of schizophrenia. Glycine and D-cycloserine are potential treatments for persistent negative symptoms of schizophrenia. Seventeen patients were identified who participated in double-blind trials of both agents. Significant clinical improvement was observed during both trials. However, the degree of improvement was significantly larger during glycine, than D-cycloserine, treatment on both an individual subject and group level. Previous analyses have documented effectiveness of glycine, and to a lesser extent D-cycloserine, within separate patient populations. This analysis provides the first direct comparison of glycine and D-cycloserine effects within the same population, and suggests first, that NMDA agonists are effective in treatment of persistent negative symptoms of schizophrenia, and, second, that full agonists, such as glycine and D-serine, may be more effective than partial agonists such as D-cycloserine. Similar findings are apparent when data are considered from all trials with NMDA agonists performed to date. Overall, the findings indicate that agents which potentiate NMDA transmission may be therapeutically beneficial in treatment of persistent symptoms of schizophrenia.
authors.affiliation: Ezrath Nashim-Sarah Herzog Memorial Hospital, P.O. Box 35300, Givat Shaul, Jerusalem, Israel. heresco@md.huji.ac.il
authors.forename: Uriel
authors.initials: U
authors.lastname: Heresco-Levy
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Javitt
mesh_terms: D000328:Adult; D000963:Antimetabolites / Q000494:pharmacology / Q000627:therapeutic use*; D014150:Antipsychotic Agents / Q000627:therapeutic use; D002746:Chlorpromazine / Q000627:therapeutic use; D003523:Cycloserine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D005998:Glycine / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D012189:Retrospective Studies; D012559:Schizophrenia / Q000175:diagnosis / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D012720:Severity of Illness Index; D009435:Synaptic Transmission / Q000187:drug effects
chemical_list: D000963:Antimetabolites; D014150:Antipsychotic Agents; D016194:Receptors, N-Methyl-D-Aspartate; D003523:Cycloserine; D005998:Glycine; D002746:Chlorpromazine