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

Inclusion Criteria: 1. Adult age 18-55 (Self Report) 2. Persistent positive symptoms of psychosis despite at least three adequate trials of anti-psychotics as defined by the Texas medical Algorithm Project - one of which is clozapine unless there is a contra-indication. (Review of medical records and conversation with prior treating psychiatrist). 3. Significant positive symptoms, including delusions and/or hallucinations. (Clinical evaluation/interview) 4. Diagnosis of schizophrenia or schizoaffective disorder (DSM-IV Diagnostic Checklist) 5. Patients will be on a stable dose of antipsychotic medication for at least 8 weeks prior to randomization or 4 months if Clozaril (Clinical evaluation) 6. Negative Urine Toxicology (Urine collection at the time of initial evaluation) 7. Patients on other antidepressants/mood stabilizers (except PRN benzodiazepines) will be at the same dose for at least 2 months prior to starting this trial. (Clinical evaluation \& record review.) 8. Patient's current treatment has been optimized (Review of medical records and conversation with treating psychiatrist) 9. Patient is likely to tolerate the departure from clinical management required of study participants (Review of medical records and conversation with treating psychiatrist) 10. There is no significant risk of self-injury or violence based on recent history and current mental state (Review of medical records and conversation with treating psychiatrist) - Exclusion Criteria: 1. Penicillin or cephalosporin allergy (Self-report) 2. Agitation such that patient is likely to be unable to tolerate having an IV line in place.(Behavioral Observation) 3. Current Lyme disease that has not been treated previously. Current or history of liver, kidney, or gall bladder disease or elevated liver function test, elevated BUN over/Cr at screening. Unstable medical illness. History of gall stones (without subsequent cholecystectomy), hypereosinophilic syndrome, sickle cell disease, immunodeficiency or blood clotting disorder. History of inflammatory bowel disease, colon cancer, or C.difficile colitis. (Review of medical history, screening blood test). 4. Inability to be an inpatient for at least 8 weeks. (Discussion with patient (\& family if indicated)) 5. A history of IV drug abuse. (Review of medical history) 6. Inability to provide informed consent. (Capacity will be assessed by a clinical MD.) 7. Patients who had received IV antibiotic therapy within the last year (Review of medical history) 8. Pregnancy or lactation. For females of child bearing age, the pregnancy test is performed pre-randomization. Since this test cannot detect the very early stage of pregnancy (10 day period between fertilization and implantation), an effective birth control method or sexual abstinence is required during the 15 days before the MR scan and randomization. (Interview \& urine pregnancy test pre-randomization) 9. For subjects participating in the MRSpectroscopy component: Current or past history of claustrophobia (Interview and history) 10. For subjects participating in the MRSpectroscopy component Metal implants or paramagnetic objects contained within the body which may pose a risk to the subject or interfere with the MR scan, as determined in consultation with a neuroradiologist and according to the guidelines set forth in the following reference book commonly used by neuroradiologists: "Guide to MR procedures and metallic objects", F.G. Shellock, Lippincott Williams and Wilkins, NY 2001. (Interview and history) 11. History of self-injurious behaviour or other behaviour that might complicate the insertion and maintenance of an angiocath, in the past 2 years (Interview and History) 12. Patient is currently taking Cyclosporine (Interview and Medical records review) \-