A Placebo-controlled Efficacy Study of IV Ceftriaxone for Refractory Psychosis
Status:
Unknown status
Trial end date:
1969-12-31
Target enrollment:
Participant gender:
Summary
Many patients with schizophrenia and schizoaffective disorder have symptoms that persist,
including hallucinations or delusions, despite adequate pharmacotherapy with antipsychotic
drug. Glutamate is a major excitatory neurotransmitter in the brain that has been implicated
in several brain diseases. NMDA antagonist drugs cause symptoms of psychosis in otherwise
normal persons. It is postulated that reduced NMDA receptor mediated neurotransmission leads
to an increase in synaptic glutamate. Excessive synaptic concentrations of glutamate can
produce excitatory neurotoxicity. Agents which reduce excess glutamate activity are
neuroprotective. This therapeutic strategy has been applied to schizophrenia through the use
of compounds that reduce presynaptic release of glutamate or otherwise decrease excessive
postsynaptic stimulation, including lamotrigine, memantine and a m-GLU-R2 agonist (LY354740)
with the hypothesized result of a reduction in psychotic symptoms.
Recently it was shown that a commonly available antibiotic (ceftriaxone) has the unique
neuroprotective function of decreasing the amount of extracellular glutamate in nervous
system tissue by increasing the number of glutamate transporter proteins. Our clinical
experience with patients who have refractory psychosis and past Lyme disease indicates that
in some patients psychosis may improve with IV ceftriaxone therapy. Whether this improvement
was due to its antimicrobial or glutamate effect or a placebo effect is uncertain. In a
placebo-controlled design, this study investigates the ability of ceftriaxone to decrease
psychotic symptoms in patients with refractory psychotic disorders. In addition, the study
will examine glutamatergic functional activity before and after treatment using brain imaging
with magnetic resonance spectroscopy.
Phase:
Phase 1/Phase 2
Details
Lead Sponsor:
Research Foundation for Mental Hygiene, Inc.
Collaborator:
National Alliance for Research on Schizophrenia and Depression