Glutamatergic drugs for schizophrenia: a systematic review and meta-analysis.
OBJECTIVE
To evaluate the efficacy of glutamatergic drugs, acting agonistically on the N-methyl-D-aspartate (NMDA) or the non-NMDA receptors, in schizophrenia.


METHODS
All relevant randomized controlled trials of glutamatergic drugs for schizophrenia were obtained from the Cochrane Schizophrenia Group's Register of Trials without any language or year limitations. Trials were classified according to their methodological quality. For binary and continuous data, relative risks and weighted (WMD) or standardized mean differences (SMD) were calculated, respectively.


RESULTS
Eighteen short-term trials with 343 randomized patients were included in the meta-analysis. In all of these trials, glycine, D-serine, D-cycloserine or ampakine CX516 was used to augment antipsychotics. NMDA receptor co-agonists glycine and D-serine are effective in reducing negative symptoms (N = 132, fixed effect model SMD = -0.66, 95% CI -1.02 to -0.29, p = 0.0004) of schizophrenia, the magnitude of the effect is moderate. D-Cycloserine, a partial agonist of NMDA receptors, is less effective towards negative symptoms (N = 119, fixed effect model SMD = -0.11, 95% CI -0.48 to 0.25, p = 0.6). Positive symptoms fail to respond to glutamatergic medication. Available derived data on cognitive functioning do not indicate a significant effect of glycine or D-serine (N = 80, random effect model WMD = -2.79, 95% CI -6.17 to 0.60, p = 0.11).


CONCLUSIONS
In the current limited data set, a moderate amelioration of negative symptoms of schizophrenia was found, but no other statistically significant beneficial effects on symptoms of schizophrenia.
Tuominen
Harri J
HJ
Department of Psychiatry, University of Helsinki, P.O. Box 320, FIN-00029 Helsinki University Central Hospital, Finland.
Tiihonen
Jari
J
Wahlbeck
Kristian
K
D003024:Clozapine / Q000378:metabolism / Q000627:therapeutic use*; D003523:Cycloserine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use*; D004149:Dioxoles / Q000378:metabolism / Q000627:therapeutic use*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D018683:Excitatory Amino Acid Agents / Q000494:pharmacology / Q000627:therapeutic use*; D005998:Glycine / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D006836:Hydro-Lyases / Q000494:pharmacology / Q000627:therapeutic use*; D008972:Molindone / Q000378:metabolism / Q000627:therapeutic use*; D010880:Piperidines / Q000378:metabolism / Q000627:therapeutic use*; D012559:Schizophrenia / Q000188:drug therapy*
C097396:1-(quinoxalin-6-ylcarbonyl)piperidine; D004149:Dioxoles; D018683:Excitatory Amino Acid Agents; D010880:Piperidines; D003523:Cycloserine; D006836:Hydro-Lyases; C101950:D-serine dehydratase; D003024:Clozapine; D008972:Molindone; D005998:Glycine