Glutamatergic agents for schizophrenia: current evidence and perspectives

  title={Glutamatergic agents for schizophrenia: current evidence and perspectives},
  author={Mathias Zink and Christoph U. Correll},
  journal={Expert Review of Clinical Pharmacology},
  pages={335 - 352}
  • M. Zink, C. Correll
  • Published 28 April 2015
  • Psychology, Medicine
  • Expert Review of Clinical Pharmacology
Suboptimal outcomes in schizophrenia are a consequence of lacking insight into the etiology, biomarkers and treatment-relevant subgroups, the therapeutic restriction to dopaminergic-modulating antipsychotics that fail to significantly improve negative and cognitive symptoms, non-adherence, and, in the case of treatment-resistance, the underutilization of clozapine. Evidence suggests additional, extra-dopaminergic abnormalities in amino acid neurotransmission, particularly the glutamatergic… 
Treating Negative Symptoms in Schizophrenia: an Update
From this perspective, identification of biomarkers and/or endophenotypes permitting earlier diagnosis and intervention may serve to improve treatment efficacy as well as outcomes.
Efficacy of N-methyl-D-aspartate receptor modulator augmentation in schizophrenia: A meta-analysis of randomised, placebo-controlled trials
The results indicate that N-methyl-D-aspartate receptor modulators, particularly with glycine, D-serine and sarcosine, are more beneficial than the placebo in treating schizophrenia, and the effects extended to both positive and negative symptoms, when augmented with antipsychotics other than clozapine.
Mirtazapine in schizophrenia - an undeservedly overlooked option?
It is concluded that further well-designed RCTs and real-world effectiveness studies are needed to determine whether add-on mirtazapine should be recommended for difficult-to-treat schizophrenia.
Glutamate modulators for treatment of schizophrenia
Cystine/Glutamate Antiporter in Schizophrenia: From Molecular Mechanism to Novel Biomarker and Treatment
Investigation of the expression of system xc− genes in the peripheral white blood cells of patients with schizophrenia can facilitate better understanding of the mental disorder and future development of novel biomarkers and treatments for schizophrenia.
N100 Repetition Suppression Indexes Neuroplastic Defects in Clinical High Risk and Psychotic Youth
N100 adaptation was reduced in CHR and psychosis, particularly among participants <13 years old, and decreased change in the N100 amplitude with tone repetition may be a useful marker of defects in neuroplastic mechanisms measurable early in life.
Effects of acute memantine administration on MATRICS Consensus Cognitive Battery performance in psychosis: Testing an experimental medicine strategy
Any potential clinical utility of these predictive markers for pro-cognitive effects of MEM in subgroups of CPD patients cannot be inferred without a validating clinical trial.
Ascorbic Acid to Manage Psychiatric Disorders
This review aims to explore basic and human studies that implicate ascorbic acid as a potential therapeutic strategy and possible mechanisms involved in the beneficial effects of this vitamin for the management of psychiatric disorders.
Improving our understanding of the in vivo modelling of psychotic disorders: A protocol for a systematic review and meta‐analysis
A shallow, but broad unbiased overview of experiments looking at the in vivo modelling of psychotic disorders using a systematic review and meta‐analysis to quantitatively review both studies characterizing a model and experiments that investigate the effects of novel therapeutic options.
Ketamine Alters Functional Gamma and Theta Resting-State Connectivity in Healthy Humans: Implications for Schizophrenia Treatment Targeting the Glutamate System
Results are in line with resting-state patterns seen in people who have schizophrenia and argue for a crucial role of the glutamate system in mediating dysfunctional gamma- and theta-band-connectivity in schizophrenia.


Glutamate signaling in the pathophysiology and therapy of schizophrenia
Metabotropic glutamate receptors: potential drug targets for the treatment of schizophrenia.
Recent progress in elucidating the pharmacology and function of group II mGlu and mGLU5 receptors is discussed in the context of current hypotheses on the pathophysiology of schizophrenia and the need for new and better antipsychotics.
Neural Basis for the Ability of Atypical Antipsychotic Drugs to Improve Cognition in Schizophrenia
Data indicate chronic treatment with tandospirone, a partial 5-HT1A agonist, recover stress-induced lactate production in the prefrontal cortex of a rat model of schizophrenia, which is expected to promote the development of novel therapeutics for the improvement of functional outcome in people with schizophrenia.
d-serine and schizophrenia: an update
Evidence suggests that research on the next generation of antipsychotic agents should include studies on increasing brain levels of d-serine or mimicking its action on the NMDA receptor.
Antipsychotic treatment modulates glutamate transport and NMDA receptor expression
This review summarizes the current knowledge on effects of FGAs and SGAs on glutamate transport and receptor expression derived from pharmacological studies and indicates that serotonergic effects of SGAs represent important targets for further clinical research.
Emerging drugs for schizophrenia: an update
Although modifications and variations of antidopaminergic mechanisms are expected to be successful, the added benefits will likely remain small, at least regarding enhanced efficacy for negative symptoms, cognition and functional outcomes.
Glutamate modulators as potential therapeutic drugs in schizophrenia and affective disorders
Substances regulating activation/inhibition of the NMDA receptor have been investigated in schizophrenia and major depression and are promising in therapeutic approaches of negative symptoms, cognition, and mood and should be investigated to elucidate neural mechanisms underlying efficacy.
Activation of mGlu2/3 receptors as a new approach to treat schizophrenia: a randomized Phase 2 clinical trial
The data suggest that mGlu2/3 receptor agonists have antipsychotic properties and may provide a new alternative for the treatment of schizophrenia.
Augmentation with pregabalin in schizophrenia.
Treating anxious syndromes in schizophrenia with pregabalin can be effective and tolerable and further investigations should differentiate schizophrenic subsyndromes of anxiety and evaluate benefits and risks of preGabalin in comparison to placebo and active competitors.