Clozapine augmented with glutamate modulators in refractory schizophrenia: a review and metaanalysis

Pharmacopsychiatry. 2014 Sep;47(6):185-94. doi: 10.1055/s-0034-1383656. Epub 2014 Jul 7.

Abstract

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.

Publication types

  • Meta-Analysis
  • Review

MeSH terms

  • Animals
  • Antipsychotic Agents / therapeutic use*
  • Clozapine / therapeutic use*
  • Drug Synergism
  • Excitatory Amino Acid Agents / therapeutic use*
  • Glutamic Acid / metabolism*
  • Humans
  • Schizophrenia / drug therapy*

Substances

  • Antipsychotic Agents
  • Excitatory Amino Acid Agents
  • Glutamic Acid
  • Clozapine