Because standard antipsychotics don’t do much for the negative symptoms of schizophrenia (such as affective flattening and paucity of speech), there has been a fair amount of interest in the so-called “hypoglutaminergic hypothesis” of schizo- phrenia. This was first prompted by the observation that the recreational drugs PCP (angel dust) and ketamine (the date rape drug) can cause shizophrenia-like symptoms in abusers. Both drugs block NMDA glutamine receptors; this prompted some small positive studies of glycine and cycloserine in schizophrenics, both of which stimulate glutaminergic neuro- transmission.
These results led to the large CONSIST trial, in which 165 patients with schizophre- nia or schizoaffective disorder were ran- domly assigned to glycine, D-cycloserine, or placebo. But after 16 weeks of treat- ment, there were no differences in either negative symptoms or cognitive symptoms among the three treatments (Buchanan RW et al., Am J Psychiatry 2007;164:1593- 1602).
TCPR’s Take: These results are very disappointing and essentially put the kai- bosh on development of these particular agents for schizophrenia. Trying to redeem the results, the researchers point out that the glycine dose used was rather low (0.7 mg/kg. as opposed to two positive studies that used 0.8 mg/kg). Nonetheless, don’t expect to see either of these compounds being marketed any time soon.
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