Clozapine Augmented with Glutamate Modulators in Refractory Schizophrenia: A Review and Metaanalysis

Clozapine is an efficacious antipsychotic drug for patients with treatment-resistant schizophrenia, but does not sufficiently improve these symptoms in a substantial proportion of this population. There is no convincing evidence for the efficacy of any clozapine augmentation strategy. New evidence suggests that glutamate receptors are a candidate target for therapeutic effects in schizophrenia. We present an overview of studies assessing the potential clinical utility of adding glutamatergic agents to clozapine. We conducted 3 metaanalyses of data on positive, negative and overall symptoms of schizophrenia, analysing results from 3 studies on clozapine augmentation with glycine, 6 studies on lamotrigine add-on therapy to clozapine and 4 studies on topiramate addition to clozapine.