Information obtained from ClinicalTrials.gov on May 22, 2013 Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00202306 SMRI 01-038 E/01/028 NCT00202306 Indicated Prevention of Psychotic Disorders With Low-Dose Lithium An Open-Labeled, Parallel-Group, Single-Blinded (Rater) Pilot Study to Investigate the Neuroprotective Effects of of Low-Dose Lithium in Young Subjects at Ultra High Risk (UHR) of Developing a First-Episode Psychotic Disorder Melbourne Health Other National Institute of Mental Health (NIMH) NIH Melbourne Health Australia: National Health and Medical Research Council This study investigates the neuroprotective properties of low-dose lithium in young individuals at ultra-high risk of developping a first psychotic episode. Fourty individuals having some symptoms of an emerging psychotic disorders (without meeting the threshold for a full-blown mental illness) will be treated with a low dose of lithium (about a third of the dose that is usually used to treat acute mania). We will assess the progression of the conditions of these individuals on a montly bases for a year. We will do behavioural, cognitive and imaging assessments prior start of the treatment, after three months and one year. We hope to demonstrate that low dose lithium will stop or even reverse the progression of disease. We expect that behavioral, cognitive and in vivo brain imaging parameters in those individuals treated with low dose lithium improve, compared to the monitoring group. To investigate whether low-dose lithium is an effective agent in indicated prevention amongst subjects at ultra-high risk of developing a psychotic disorder. This aim will be achieved by treating a high-risk patient population with low-dose lithium (450mg/day) and investigating its effects using clinical, neuropsychological, neuroimaging and cell biological approaches. We will recruit 30 patients considered to be at ultra-high risk of developing a first psychotic episode, currently receiving treatment at the Personal Assessment and Crisis Evaluation (PACE) clinic in Melbourne, Australia. PACE criteria for identifying patients at high risk include subjects with a family history of psychosis and a decrease in functioning (30% GAF) AND/OR attenuated psychotic symptoms AND/OR brief psychotic symptoms (BLIPS) resolving without treatment. Patients who give informed consent will receive treatment with a slow release form of low dose lithium for a period of a year, plus supportive therapy. Patients who do not consent will receive supportive therapy only. Assessments will be conducted at baseline, twelve weeks and one year post-recruitment. Assessments will include cognitive functioning, structural MRI, 1H-MRS at 3Tesla and cell biological parameters (bcl-2, AP-1; NIMH, Washington DC). In addition, all patients will be seen on a monthly basis for a clinical interview, covering psychopathology, global functioning, and quality of life. Recruiting November 2001 Phase 4 Interventional Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment Symptomatic improvement Cognitive improvement Brain structural change (grey matter, ventricle to brain ratio) Brain metabolic changes (Proton Magnetic Resonance Spectroscopy) Transition rate to Psychosis Quality of life serum apoptosis parameters (eg. bcl2) 30 Schizophrenia Bipolar Disorder Psychotic Disorders Drug lithium carbonate Inclusion Criteria: - Attenuated psychotic symptoms - Self-limited brief psychotic episode - Family History of psychosis and decrease in functioning over last year Exclusion Criteria: - Organic causes of subthreshold psychotic symptoms (eg. epilepsy) - More than one week of neuroleptic treatment Both 15 Years 30 Years No Gregor E Berger, MD Principal Investigator University of Melbourne, Department of Psychiatry, ORYGEN Research Centre Gregor E Berger, MD +61 3 9342 2800 2863 gregor@unimelb.edu.au Patrick D McGorry, MD PhD +61 3 9342 2800 2850 mcgorry@ariel.unimelb.edu.au ORYGEN Youth Health, PACE Clinic

Parkville Victoria 3052 Australia

Recruiting Gregor E Berger, MD +61 3 9342 2800 2863 gregor@unimelb.edu.au Patrick D McGorry, MD +61 3 9342 2800 2850 mcgorry@ariel.unimelb.edu.au Gregor E Berger, MD Principal Investigator Australia http://www.ORYGEN.org.au Description of Unit of Neuroprotection in Young People (UNYP) Berger GE, Wood S, McGorry PD. Incipient neurovulnerability and neuroprotection in early psychosis. Psychopharmacol Bull. 2003 Spring;37(2):79-101. Review. 14566217 September 2005 March 8, 2007 September 14, 2005 at risk mental state prodrome ultra high risk first episode psychosis schizophrenia bipolar disorder No Bipolar Disorder Psychotic Disorders Mental Disorders Schizophrenia Lithium Lithium Carbonate