): Our long-term studies of first episode schizophrenia patients have clearly indicated excellent initial responsiveness of positive psychotic symptoms to treatment with conventional antipsychotic medications. However, in the years immediately following this initial good response, morbidity increases: cognitive functioning improves with treatment but remains impaired in multiple domains, social/occupational adjustment is poor or worse for 25% of the patients, 15% develop a deficit state and the incidence of tardive dyskinesia is 6% per year of conventional antipsychotic exposure. Relapses, often multipl ones, are the rule and are usually precipitated by medication noncompliance. Prevention of this morbidity is the major clinical challenge in treating first episode patients and is the focus of this application. There is some evidence that the second generation antipsychotic drugs may have superior efficacy in terms of these outcome domains. However, these newer agents have been studied primarily in chronic and/or treatment resistant patient samples and there are virtually no long term studies or studies comparing the new drugs with one another. We propose to study them in the population that has the potential for maximum responsiveness and long-term benefit-patients with schizophrenia who are being treated for the first time. Specifically, we will randomly assign first episode patients to treatment with olanzapine, risperidone or ziprasidone. Treatment will be for 3 years. Outcome measures for the initial episode will include psychopathology (positive, negative and affective symptoms), side effects, neurocognition (executive function, memory and attention), social and occupational function and service utilization. The effects on long term course will be measured in terms of frequency and timing of relapses, level of recovery from subsequent episodes and prospectively assessed course of psychopathology, neurocognitive function, social/vocational function and service utilization. The results will provide a basis for informed treatment choices for clinicians as well as address the crucial question of the potential of the new treatments to improve the longitudinal course of this devastating illness.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH060004-02
Application #
2891177
Study Section
Special Emphasis Panel (ZMH1-CRB-X (02))
Program Officer
Hsiao, John
Project Start
1998-09-30
Project End
2003-05-31
Budget Start
1999-06-01
Budget End
2000-05-31
Support Year
2
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Long Island Jewish Medical Center
Department
Type
DUNS #
City
New Hyde Park
State
NY
Country
United States
Zip Code
11040
Lyall, A E; Pasternak, O; Robinson, D G et al. (2018) Greater extracellular free-water in first-episode psychosis predicts better neurocognitive functioning. Mol Psychiatry 23:701-707
Schwehm, Andrew; Robinson, Delbert G; Gallego, Juan A et al. (2016) Age and Sex Effects on White Matter Tracts in Psychosis from Adolescence through Middle Adulthood. Neuropsychopharmacology 41:2473-80
Sarpal, Deepak K; Argyelan, Miklos; Robinson, Delbert G et al. (2016) Baseline Striatal Functional Connectivity as a Predictor of Response to Antipsychotic Drug Treatment. Am J Psychiatry 173:69-77
Sarpal, Deepak K; Lencz, Todd; Malhotra, Anil K (2016) In Support of Neuroimaging Biomarkers of Treatment Response in First-Episode Schizophrenia. Am J Psychiatry 173:732-3
Sarpal, Deepak K; Robinson, Delbert G; Lencz, Todd et al. (2015) Antipsychotic treatment and functional connectivity of the striatum in first-episode schizophrenia. JAMA Psychiatry 72:5-13
Trampush, Joey W; Lencz, Todd; DeRosse, Pamela et al. (2015) Relationship of Cognition to Clinical Response in First-Episode Schizophrenia Spectrum Disorders. Schizophr Bull 41:1237-47
Zhang, Jian-Ping; Robinson, Delbert G; Gallego, Juan A et al. (2015) Association of a Schizophrenia Risk Variant at the DRD2 Locus With Antipsychotic Treatment Response in First-Episode Psychosis. Schizophr Bull 41:1248-55
Argyelan, Miklos; Gallego, Juan A; Robinson, Delbert G et al. (2015) Abnormal resting state FMRI activity predicts processing speed deficits in first-episode psychosis. Neuropsychopharmacology 40:1631-9
Robinson, Delbert G; Gallego, Juan A; John, Majnu et al. (2015) A Randomized Comparison of Aripiprazole and Risperidone for the Acute Treatment of First-Episode Schizophrenia and Related Disorders: 3-Month Outcomes. Schizophr Bull 41:1227-36
Ikuta, Toshikazu; Robinson, Delbert G; Gallego, Juan A et al. (2014) Subcortical modulation of attentional control by second-generation antipsychotics in first-episode psychosis. Psychiatry Res 221:127-34

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