to 59.40)low mental state no clinically significant improvement(add-on glycine)there is no evidence of clear advantage of using add-on glutamatergic to standard antipsychotic medication. these findings are based on data of low quality.rr 0.92 (0.79 to 1.08)low adverse effects constipation(add-on glycine or d-serine)there is no clarity from very limited data. additional glutamatergic could cause constipation or help avoid it. data are very limited. rr 0.61 (0.06 to 6.02)very low insomnia(add-on glycine or d-serine)additional glutamatergic may help or cause insomnia - it is not clear from the very limited data.rr 0.61 (0.13 to 2.84)very low missing outcomes quality of lifethis outcome was not reported in any studies psychotomimetic glutamate antagonists ketamine and pcp were observed to produce significant similarities to schizophrenia. ketamine produces more similar symptoms (hallucinations, withdrawal) without observed permanent effects (other than ketamine tolerance). both arylcyclohexamines have some(um) affinity to d2 and as triple reuptake inhibitors. pcp is representative symptomatically, but does appear to cause brain structure changes seen in schizophrenia. although unconfirmed, dizocilpine discovered by a team at merck seems to model both the positive and negative effects in a manner very similar to schizophreniform disorders. possible glutamate based treatment an early clinical trial by eli lilly of the drug ly2140023 has shown potential for treating schizophrenia without the weight gain and other side-effects associated with conventional anti-psychotics. a trial in 2009 failed to prove superiority over placebo or olanzapine, but lilly explained this as being due to an exceptionally high placebo response. however, eli lilly terminated further development of the compound in 2012 after it failed in phase iii clinical trials. this drug acts as a selective agonist at metabotropic mglur2 and mglur3 glutamate receptors (the mglur3 gene has previously been associated with schizophrenia). studies of glycine (and related co-agonists at the nmda receptor) added to conventional anti-psychotics have also found some evidence that these may improve symptoms in schizophrenia. animal models research done on mice in early 2009 has shown that when the neuregulin-1\erbb post-synaptic receptor genes are deleted, the dendritic spines of glutamate neurons initially grow, but break down during later development. this led to symptoms (such as disturbed social function, inability to adapt to predictable future stressors) that overlap with schizophrenia. this parallels the time delay for symptoms setting in with schizophrenic humans who usually appear to show normal development until early adulthood. disrupted in schizophrenia 1 is a gene that is disrupted in schizophrenia. notes and references lisman je, coyle jt, green rw, et al. 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