Meta-analysis of the efficacy of adjunctive NMDA receptor modulators in chronic schizophrenia.
- Surendra P Singh, Vidhi Singh
- CNS drugs
UNLABELLED Glutamatergic system--the main excitatory brain system is involved in the pathophysiology of schizophrenia. The ionotropic glutamatergic NMDAreceptor participates in mechanisms of controlling neurotransmitter systems such as the dopaminergic, noradrenergic, serotoninergic ones and plays an important role in cognitive functioning. Glycine is a natural coagonist of the NMDA receptor and according to the hypoNMDA hypothesis treatment with its high doses (max. 60g orally per day) can improve symptomatology of schizophrenia, e.g., negative symptoms and cognitive functions. AIM If there is a correlation between plasma levels (before and after using glycine) and severity of symptoms (at the first and last assessment), then low baseline plasma concentrations could be an indication for choosing glycine in treatment, moreover a useful prognosing tool and finally a support of glutamatergic hypothesis of schizophrenia. METHODS 28 patients with a diagnosis of schizophrenia according to ICD-10 diagnostic criteria (Table 1) in stable clinical condition and antipsychotic medication (typical and atypical agents) for min. 3 months, had completed a 6 week, prospective and open label study (32 patients enrolled). Between 2 visits patients received glycine in high oral doses (0.8 g/kg/day). Before and afterwards the glycine treatment, psychiatric and cognitive function examination was performed based on PANSS, Trail making test (TMT), Stroop test and Wisconsin card sorting test (WCST). In parallel glycine plasma levels were assessed. RESULTS There was a significant reduction in positive, negative, general psychopathology and total PANSS score during the study (Table 2). Also cognitive parameters significantly improved during 6 weeks of glycine use. Serum levels of glycine were markedly higher at the end of our project, but only improvement in part 2 of TMT correlates with changes in aminoacid serum concentrations (p = 0.02). CONCLUSIONS Our results suggest that augmentation of antipsychotic treatment (typical and atypical neuroleptics) with glycine can have a positive influence on schizophrenic symptoms there in cognitive dysfunction, but glycine plasma levels were not a useful predictor of recovery in our patients. Correlation between improvement in performance of TMT and serum level increase suggests that glycine and NMDA receptor can be involved in psychopathology of schizophrenia and cognitive functioning, e.g., working memory