A Placebo-controlled Efficacy Study of IV Ceftriaxone for Refractory Psychosis

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.

Conditions

• Psychosis
• Schizophrenia
• Schizoaffective Disorder

Interventions

DRUG

ceftriaxone

2 grams of ceftriaxone given daily, Monday to Friday, excluding major holidays, for a total of 40 doses

DRUG

Normal Saline

50 cc of normal saline, daily, Monday through Friday, except for major holidays, for a total of 40 normal saline infusions.

Sponsors & Collaborators

• National Alliance for Research on Schizophrenia and Depression

  collaborator OTHER

• New York State Psychiatric Institute

  collaborator OTHER

• Research Foundation for Mental Hygiene, Inc.

  lead OTHER

Principal Investigators

• Brian A Fallon, MD · New York State Psychiatric Institute

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

55 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2007-10-10

Primary Completion

2011-03-02

Completion

2011-03-17

Countries

• United States

Study Locations