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Attenuation of the neuropsychiatric effects of ketamine with lamotrigine: support for hyperglutamate

Attenuation of the neuropsychiatric effects of ketamine with lamotrigine: support for hyperglutamate

  1. Jatelka
    Archives of General Psychiatry 2000 Mar;57(3):270-6

    Anand A (http://www.ncbi.nlm.nih.gov/sites/e...l.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus), Charney DS (http://www.ncbi.nlm.nih.gov/sites/e...l.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus), Oren DA (http://www.ncbi.nlm.nih.gov/sites/e...l.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus), Berman RM (http://www.ncbi.nlm.nih.gov/sites/e...l.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus), Hu XS (http://www.ncbi.nlm.nih.gov/sites/e...l.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus), Cappiello A (http://www.ncbi.nlm.nih.gov/sites/e...l.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus), Krystal JH (http://www.ncbi.nlm.nih.gov/sites/e...l.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus).

    Background: The cognitive, behavioral, and mood effects of N-methyl-D-aspartate (NMDA) receptor antagonists, such as phencyclidine and ketamine, have been used to study the effects of NMDA receptor dysfunction. Pharmacological modulation of the effects of NMDA receptor antagonists, such as ketamine, may lead to development of novel therapeutic agents for psychiatric illnesses such as schizophrenia. Preclinical studies indicate that some ketamine effects may be mediated through increased glutamate release. In this study, we tested the hypothesis that lamotrigine, a drug reported to inhibit glutamate release, will reduce the neuropsychiatric effects of ketamine in humans. METHOD: Healthy subjects (n = 16) completed 4 test days involving the administration of lamotrigine, 300 mg by mouth, or placebo 2 hours prior to administration of ketamine (0.26 mg/kg by intravenous bolus and 0.65 mg/kg per hour by intravenous infusion) or placebo in a randomized order under double-blind conditions. Behavioral and cognitive assessments were performed at baseline and after administration of the medications. RESULTS: Lamotrigine significantly decreased ketamine-induced perceptual abnormalities as assessed by the Clinician-Administered Dissociative States Scale (P