Project Summary

Brian A. Fallon, M.D., M.P.H., (Independent Investigator 2006) of Columbia University and the New York State Psychiatric Institute, aims to study if the antibiotic ceftriaxone may reduce psychosis in hospitalized schizophrenia patients. Research has shown ceftriaxone may have a unique neuroprotective effect by decreasing extracellular glutamate in the nervous system and by increasing glutamate transporter proteins. Glutamate is a major excitatory neurotransmitter which when dysregulated can cause problems with memory, attention, movement, sensation and perception. Although overactivity of the dopamine neurotransmitter system is believed to play a role in psychosis, other neurotransmitters, such as glutamate, may also be involved because not all patients respond to antipsychotic drugs that lower dopamine activity. Also, drugs that block the glutamate receptor NMDA cause symptoms of psychosis in healthy people, presumably by increased synaptic glutamate producing excitatory neurotoxicity. Agents that reduce excess glutamate activity are neuroprotective. Dr. Fallon has shown that ceftriaxone can improve cognition in patients with persistent cognitive deficits after Lyme disease. Whether the effect was due to its antimicrobial or glutamate effect is uncertain. The proposed study will investigate if the antibiotic can decrease psychotic symptoms in patients with refractory psychotic disorders. In this study, 28 patients undergoing standardized antipsychotic therapy will be randomly assigned to a 40 day treatment of either IV placebo or IV ceftriaxone. The first 20 patients will also have brain imaging using magnetic resonance spectroscopy before and after treatment to evaluate prefrontal cortical glutamatergic activity. Reduction in hallucinations and/or delusions and improved mood and cognition will be monitored. Findings may provide a new treatment for patients with refractory psychosis and a new way to study human glutamate activity.

Program Area: SCHIZOPHRENIA/PSYCHOTIC DISORDERS\Schizophrenia

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