Cited by 69Schizophrenia research and treatmentTreatment of Major DepressionNeuroscience and Neuropharmacology Research

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The potential role of lamotrigine in schizophrenia

Large, Charles H., Webster, Elizabeth L., Goff, Donald C.·2005·Psychopharmacology

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Abstract

Rationale Atypical antipsychotic drugs are the drugs of choice for the treatment of schizophrenia. However, despite advances, no treatments have been established for patients who fail to improve with the most effective of these, clozapine. The inhibition of dopamine transmission through blockade of dopamine D2 receptors is considered to be essential for antipsychotic efficacy, but it is postulated that modulation of glutamate transmission may be equally important. In support of this, symptoms similar to schizophrenia can be induced in healthy volunteers using N-methyl-D-aspartate (NMDA) antagonist drugs that are also known to enhance glutamate transmission. Furthermore, lamotrigine, which can modulate glutamate release, may add to or synergise with atypical antipsychotic drugs, some of which may themselves modulate glutamate transmission.Objectives We examine the evidence for the efficacy of lamotrigine. We consider how this fits with a glutamate neuron dysregulation hypothesis of the disorder. We discuss mechanisms by which lamotrigine might influence neuronal activity and glutamate transmission, and possible ways in which the drug might interact with antipsychotic medications.Results Data from four clinical studies support the efficacy of adjunctive lamotrigine in the treatment of schizophrenia. In addition, and consistent with a glutamate neuron dysregulation hypothesis of schizophrenia, lamotrigine can prevent the psychotic symptoms or behavioural disruption induced by NMDA receptor antagonists in healthy volunteers or rodents.Conclusions The efficacy of lamotrigine is most likely explained within the framework of a glutamate neuron dysregulation hypothesis, and may arise primarily through the drugs ability to influence glutamate transmission and neural activity in the cortex. The drug is likely to act through inhibition of voltage-gated sodium channels, though other molecular interactions cannot be ruled out. Lamotrigine may add to or synergise with some atypical antipsychotic drugs acting on glutamate transmission; alternatively, they may act independently on glutamate and dopamine systems to bring about a combined therapeutic effect. We propose new strategies for the treatment of schizophrenia using a combination of anti-dopaminergic and anti-glutamatergic drugs.

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“As discussed earlier, drugs that negatively modulate glutamate transmission, such as 5-HT2a antagonists (Mirjana et al. 2004; Ceglia et al. 2004) and mGluR2/3 agonists (Schoepp and Marek 2002; Carter et al.”
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Authors: Large, C. H., Webster, E. L., & Goff, D. C.
Affiliations: GlaxoSmithKline (Italy) (IT)
GlaxoSmithKline (United States) (US)
Massachusetts General Hospital (US)
Corresponding author: Large, Charles H.
ORCID: Large, Charles H.
Webster, Elizabeth L.
Goff, Donald C.
Venue: Psychopharmacology
Publisher: Springer Science and Business Media LLC
Published: 2005-07-06
Volume: 181
Issue: 3
Pages: 415-436
ISSN: 0033-3158 (ISSN-L)
1432-2072
DOI: 10.1007/s00213-005-0020-9
OpenAlex: W2039572620
Cited by: 69
References: 282
Citations by year: 2025: 1 · 2024: 1 · 2023: 4 · 2022: 1 · 2020: 1 · 2019: 1 · 2018: 1 · 2017: 3 · 2016: 1 · 2015: 5 · 2014: 1 · 2013: 2 · 2012: 4
FWCI: 1.09
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Psychopharmacology (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords: lamotrigine, schizophrenia, glutamatergic neurotransmission, NMDA receptor antagonists, atypical antipsychotics, adjunctive therapy, dopamine D2 receptor, voltage-gated sodium channels, drug synergy
MeSH terms: Lamotrigine, Animals, Anticonvulsants, Brain, Disease Models, Animal, Drug Synergism, Drug Therapy, Combination, Humans, Schizophrenia, Schizophrenic Psychology, Antipsychotic Agents, Triazines, Glutamic Acid, Rats

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The potential role of lamotrigine in schizophrenia

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