Glutamate receptors as targets for new pharmacological treatments in schizophrenia

Despite the introduction of a number of new generation antipsychotics deficits have remained in the pharmacological treatment of schizophrenia patients. The effect of these drugs on negative symptoms or cognitive deficits for instance is still small and rather unsatisfactory. In addition, there are patients who, despite optimal pharmacologic treatment, still have psychotic symptoms. These problems have led to the investigation of alternative treatment strategies which include the attempt to potentiate the effect of traditional dopamine receptor antagonists with glutamatergic medications. A number of well controlled but rather small preliminary studies have been carried out. This combination seems to be useful especially regarding an improvement of negative symptoms and cognitive deficits. Effect sizes are modest and depend on the antipsychotics that were used as base treatments. Improvements correlate with plasma (and CSF levels) of the adjunctive experimental treatments (glycine, D-serine). The field awaits larger confirmatory studies as well as the exploration of drugs which influence the glutamatergic system through other sites such as AMPA or metabotropic glutamate receptors.