CATIE- Schizophrenia Trial

Summary

The CATIE Schizophrenia Trial is part of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Project. The schizophrenia trial is being conducted to determine the long-term effects and usefulness of antipsychotic medications in persons with schizophrenia. It is designed for people with schizophrenia who may benefit from a medication change. The study involves the newer atypical antipsychotics (olanzapine, quetiapine, risperidone, clozapine, and ziprasidone)and the typical antipsychotics (perphenazine and fluphenazine decanoate). All participants will receive an initial comprehensive medical and psychiatric evaluation and will be closely followed throughout the study. For most participants the study will last up to 18 months. Everyone in the study will be offered an educational program about schizophrenia and family members will be encouraged to participate.

Timeline

Start

2000-12

Primary completion

—

Completion

2004-12

Outcome

Mixed primary results

release “CATIE found that for Zyprexa the average time to discontinuation was 9.2 months as compared with 4.6 months for quetiapine” lilly.com ↗

release “The differences were statistically significant for olanzapine compared with risperidone and quetiapine, but not for perphenazine or ziprasidone.” lilly.com ↗

Publications

• Background Davis SM, Koch GG, Davis CE, LaVange LM. Statistical approaches to effectiveness measurement and outcome-driven re-randomizations in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) studies. Schizophr Bull. 2003;29(1):73-80. doi: 10.1093/oxfordjournals.schbul.a006993.
• Background Keefe RS, Mohs RC, Bilder RM, Harvey PD, Green MF, Meltzer HY, Gold JM, Sano M. Neurocognitive assessment in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) project schizophrenia trial: development, methodology, and rationale. Schizophr Bull. 2003;29(1):45-55. doi: 10.1093/oxfordjournals.schbul.a006990.
• Background Lieberman JA, Stroup TS. Guest editors' introduction: what can large pragmatic clinical trials do for public mental health care? Schizophr Bull. 2003;29(1):1-6. doi: 10.1093/oxfordjournals.schbul.a006979. No abstract available.
• Background Rosenheck R, Doyle J, Leslie D, Fontana A. Changing environments and alternative perspectives in evaluating the cost-effectiveness of new antipsychotic drugs. Schizophr Bull. 2003;29(1):81-93. doi: 10.1093/oxfordjournals.schbul.a006994.
• Background Sernyak MJ, Leslie D, Rosenheck R. Use of system-wide outcomes monitoring data to compare the effectiveness of atypical neuroleptic medications. Am J Psychiatry. 2003 Feb;160(2):310-5. doi: 10.1176/appi.ajp.160.2.310.
• Background Stroup TS, McEvoy JP, Swartz MS, Byerly MJ, Glick ID, Canive JM, McGee MF, Simpson GM, Stevens MC, Lieberman JA. The National Institute of Mental Health Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) project: schizophrenia trial design and protocol development. Schizophr Bull. 2003;29(1):15-31. doi: 10.1093/oxfordjournals.schbul.a006986.
• Background Swartz MS, Perkins DO, Stroup TS, McEvoy JP, Nieri JM, Haak DC. Assessing clinical and functional outcomes in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia trial. Schizophr Bull. 2003;29(1):33-43. doi: 10.1093/oxfordjournals.schbul.a006989.
• Background Stroup TS, Appelbaum PS. Evaluation of "subject advocate" procedures in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia study. Schizophr Bull. 2006 Jan;32(1):147-52. doi: 10.1093/schbul/sbj026. Epub 2005 Nov 10.
• Results Lieberman JA, Stroup TS, McEvoy JP, Swartz MS, Rosenheck RA, Perkins DO, Keefe RS, Davis SM, Davis CE, Lebowitz BD, Severe J, Hsiao JK; Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Investigators. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med. 2005 Sep 22;353(12):1209-23. doi: 10.1056/NEJMoa051688. Epub 2005 Sep 19.
• Results McEvoy JP, Lieberman JA, Stroup TS, Davis SM, Meltzer HY, Rosenheck RA, Swartz MS, Perkins DO, Keefe RS, Davis CE, Severe J, Hsiao JK; CATIE Investigators. Effectiveness of clozapine versus olanzapine, quetiapine, and risperidone in patients with chronic schizophrenia who did not respond to prior atypical antipsychotic treatment. Am J Psychiatry. 2006 Apr;163(4):600-10. doi: 10.1176/ajp.2006.163.4.600.
• Results Stroup TS, Lieberman JA, McEvoy JP, Swartz MS, Davis SM, Rosenheck RA, Perkins DO, Keefe RS, Davis CE, Severe J, Hsiao JK; CATIE Investigators. Effectiveness of olanzapine, quetiapine, risperidone, and ziprasidone in patients with chronic schizophrenia following discontinuation of a previous atypical antipsychotic. Am J Psychiatry. 2006 Apr;163(4):611-22. doi: 10.1176/ajp.2006.163.4.611.
• Results Rosenheck RA, Leslie DL, Sindelar J, Miller EA, Lin H, Stroup TS, McEvoy J, Davis SM, Keefe RS, Swartz M, Perkins DO, Hsiao JK, Lieberman J; CATIE Study Investigators. Cost-effectiveness of second-generation antipsychotics and perphenazine in a randomized trial of treatment for chronic schizophrenia. Am J Psychiatry. 2006 Dec;163(12):2080-9. doi: 10.1176/ajp.2006.163.12.2080.
• Results Essock SM, Covell NH, Davis SM, Stroup TS, Rosenheck RA, Lieberman JA. Effectiveness of switching antipsychotic medications. Am J Psychiatry. 2006 Dec;163(12):2090-5. doi: 10.1176/ajp.2006.163.12.2090.
• Strobl EV, Kim S. Learning Outcomes That Maximally Differentiate Psychiatric Treatments. Int J Methods Psychiatr Res. 2026 Jun;35(2):e70074. doi: 10.1002/mpr.70074.
• Fabbri C, Leggio GM, Drago F, Serretti A. Imputed expression of schizophrenia-associated genes and cognitive measures in patients with schizophrenia. Mol Genet Genomic Med. 2022 Jun;10(6):e1942. doi: 10.1002/mgg3.1942. Epub 2022 Apr 30.
• Beaudoin M, Hudon A, Giguere CE, Potvin S, Dumais A. Prediction of quality of life in schizophrenia using machine learning models on data from Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia trial. Schizophrenia (Heidelb). 2022 Mar 21;8(1):29. doi: 10.1038/s41537-022-00236-w.
• Miller BJ, McEvoy JP, McCall WV. Insomnia, Suicidal Ideation, and Suicide Attempts in the Clinical Antipsychotic Trials of Intervention Effectiveness. J Clin Psychiatry. 2021 Mar 23;82(3):20m13338. doi: 10.4088/JCP.20m13338.
• Pathak S, Jiang Y, DiPetrillo L, Todtenkopf MS, Liu Y, Correll CU. Course of Psychosis in Schizophrenia With Alcohol Use Disorder: A Post Hoc Analysis of the Clinical Antipsychotic Trials of Intervention Effectiveness in Schizophrenia Phase 1 Study. J Clin Psychiatry. 2020 Mar 17;81(2):19m12731. doi: 10.4088/JCP.19m12731.
• Ozzoude M, Nakajima S, Plitman E, Chung JK, Kim J, Iwata Y, Caravaggio F, Takeuchi H, Uchida H, Graff-Guerrero A, Gerretsen P. The effects of illness severity, cognition, and estimated antipsychotic dopamine receptor occupancy on insight into the illness in schizophrenia: An analysis of clinical antipsychotic trials of intervention effectiveness (CATIE) data. Prog Neuropsychopharmacol Biol Psychiatry. 2019 Mar 8;89:207-213. doi: 10.1016/j.pnpbp.2018.08.033. Epub 2018 Aug 30.
• Van Dyke P, Thomas KL. Concomitant calcium channel blocker and antipsychotic therapy in patients with schizophrenia: Efficacy analysis of the CATIE-Sz phase 1 data. Ann Clin Psychiatry. 2018 Feb;30(1):6-16.
• Xavier RM, Pan W, Dungan JR, Keefe RSE, Vorderstrasse A. Unraveling interrelationships among psychopathology symptoms, cognitive domains and insight dimensions in chronic schizophrenia. Schizophr Res. 2018 Mar;193:83-90. doi: 10.1016/j.schres.2017.07.002. Epub 2017 Jul 8.
• Bahorik AL, Greeno CG, Cochran G, Cornelius JR, Eack SM. Motivation deficits and use of alcohol and illicit drugs among individuals with schizophrenia. Psychiatry Res. 2017 Jul;253:391-397. doi: 10.1016/j.psychres.2017.04.012. Epub 2017 Apr 5.
• Moodie EE, Karran JC, Shortreed SM. A case study of SMART attributes: a qualitative assessment of generalizability, retention rate, and trial quality. Trials. 2016 May 14;17(1):242. doi: 10.1186/s13063-016-1368-3.
• Jakubovski E, Carlson JP, Bloch MH. Prognostic subgroups for remission, response, and treatment continuation in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) trial. J Clin Psychiatry. 2015 Nov;76(11):1535-45. doi: 10.4088/JCP.14m09320.
• Takeuchi H, Fervaha G, Remington G. Effect of Antipsychotic Dosing Regimen on Neurocognition in Schizophrenia. J Clin Psychopharmacol. 2015 Dec;35(6):728-30. doi: 10.1097/JCP.0000000000000424. No abstract available.
• Fervaha G, Agid O, Takeuchi H, Lee J, Foussias G, Remington G. Relationship between symptomatic improvement and overall illness severity in patients with schizophrenia. J Clin Psychopharmacol. 2015 Apr;35(2):128-33. doi: 10.1097/JCP.0000000000000286.
• Fervaha G, Agid O, Takeuchi H, Foussias G, Lee J, Remington G. Clinical and functional outcomes in people with schizophrenia with a high sense of well-being. J Nerv Ment Dis. 2015 Mar;203(3):187-93. doi: 10.1097/NMD.0000000000000266.
• Fervaha G, Takeuchi H, Lee J, Foussias G, Fletcher PJ, Agid O, Remington G. Antipsychotics and amotivation. Neuropsychopharmacology. 2015 May;40(6):1539-48. doi: 10.1038/npp.2015.3. Epub 2015 Jan 8.
• Fervaha G, Takeuchi H, Agid O, Lee J, Foussias G, Remington G. Determinants of patient-rated and clinician-rated illness severity in schizophrenia. J Clin Psychiatry. 2015 Jul;76(7):924-30. doi: 10.4088/JCP.14m09128.
• Fervaha G, Zakzanis KK, Foussias G, Graff-Guerrero A, Agid O, Remington G. Motivational deficits and cognitive test performance in schizophrenia. JAMA Psychiatry. 2014 Sep;71(9):1058-65. doi: 10.1001/jamapsychiatry.2014.1105.
• Marques TR, Levine SZ, Reichenberg A, Kahn R, Derks EM, Fleischhacker WW, Rabinowitz J, Kapur S. How antipsychotics impact the different dimensions of Schizophrenia: a test of competing hypotheses. Eur Neuropsychopharmacol. 2014 Aug;24(8):1279-88. doi: 10.1016/j.euroneuro.2014.04.001. Epub 2014 Apr 24.
• Fervaha G, Foussias G, Agid O, Remington G. Motivational and neurocognitive deficits are central to the prediction of longitudinal functional outcome in schizophrenia. Acta Psychiatr Scand. 2014 Oct;130(4):290-9. doi: 10.1111/acps.12289. Epub 2014 May 22.
• Fervaha G, Agid O, Takeuchi H, Foussias G, Remington G. Effect of antipsychotic medication on overall life satisfaction among individuals with chronic schizophrenia: findings from the NIMH CATIE study. Eur Neuropsychopharmacol. 2014 Jul;24(7):1078-85. doi: 10.1016/j.euroneuro.2014.03.001. Epub 2014 Mar 15.
• Fervaha G, Foussias G, Siddiqui I, Agid O, Remington G. Abbreviated quality of life scales for schizophrenia: comparison and utility of two brief community functioning measures. Schizophr Res. 2014 Apr;154(1-3):89-92. doi: 10.1016/j.schres.2014.02.013. Epub 2014 Mar 11.
• Witt K, Hawton K, Fazel S. The relationship between suicide and violence in schizophrenia: analysis of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) dataset. Schizophr Res. 2014 Apr;154(1-3):61-7. doi: 10.1016/j.schres.2014.02.001. Epub 2014 Feb 26.
• Takeuchi H, Fervaha G, Uchida H, Suzuki T, Bies RR, Gronte D, Remington G. Impact of once- versus twice-daily perphenazine dosing on clinical outcomes: an analysis of the CATIE data. J Clin Psychiatry. 2014 May;75(5):506-11. doi: 10.4088/JCP.13m08695.
• Bahorik AL, Newhill CE, Queen CC, Eack SM. Letter to the editor: Critique of Bahorik et al. (2013)--'Underreporting of drug use among individuals with schizophrenia: prevalence and predictors'--a reply. Psychol Med. 2014 Feb;44(3):670-1. doi: 10.1017/s0033291713002560. No abstract available.
• Laber EB, Lizotte DJ, Ferguson B. Set-valued dynamic treatment regimes for competing outcomes. Biometrics. 2014 Mar;70(1):53-61. doi: 10.1111/biom.12132. Epub 2014 Jan 8.
• Fervaha G, Agid O, Takeuchi H, Foussias G, Remington G. Clinical determinants of life satisfaction in chronic schizophrenia: data from the CATIE study. Schizophr Res. 2013 Dec;151(1-3):203-8. doi: 10.1016/j.schres.2013.10.021. Epub 2013 Nov 1.
• Fervaha G, Agid O, Takeuchi H, Foussias G, Remington G. Life satisfaction among individuals with schizophrenia in the Clinical Antipsychotic Trial of Intervention Effectiveness (CATIE) study. Am J Psychiatry. 2013 Sep;170(9):1061-2. doi: 10.1176/appi.ajp.2013.13010060. No abstract available.
• Takeuchi H, Suzuki T, Bies RR, Remington G, Mamo DC, Pollock BG, Mimura M, Uchida H. Estimated dopamine D2 receptor occupancy from plasma concentrations of atypical antipsychotics and subjective experience/drug attitude in schizophrenia: an analysis of the CATIE data. Schizophr Res. 2013 Nov;150(2-3):373-9. doi: 10.1016/j.schres.2013.08.033. Epub 2013 Sep 9.
• Tsuboi T, Bies RR, Suzuki T, Mamo DC, Pollock BG, Graff-Guerrero A, Mimura M, Uchida H. Hyperprolactinemia and estimated dopamine D2 receptor occupancy in patients with schizophrenia: analysis of the CATIE data. Prog Neuropsychopharmacol Biol Psychiatry. 2013 Aug 1;45:178-82. doi: 10.1016/j.pnpbp.2013.05.010. Epub 2013 May 29.
• Fervaha G, Remington G. Validation of an abbreviated quality of life scale for schizophrenia. Eur Neuropsychopharmacol. 2013 Sep;23(9):1072-7. doi: 10.1016/j.euroneuro.2012.11.009. Epub 2012 Dec 9.
• Levine SZ, Rabinowitz J, Faries D, Lawson AH, Ascher-Svanum H. Treatment response trajectories and antipsychotic medications: examination of up to 18 months of treatment in the CATIE chronic schizophrenia trial. Schizophr Res. 2012 May;137(1-3):141-6. doi: 10.1016/j.schres.2012.01.014. Epub 2012 Feb 7.
• Sakurai H, Bies RR, Stroup ST, Keefe RS, Rajji TK, Suzuki T, Mamo DC, Pollock BG, Watanabe K, Mimura M, Uchida H. Dopamine D2 receptor occupancy and cognition in schizophrenia: analysis of the CATIE data. Schizophr Bull. 2013 May;39(3):564-74. doi: 10.1093/schbul/sbr189. Epub 2012 Jan 30.
• Levine SZ, Rabinowitz J, Ascher-Svanum H, Faries DE, Lawson AH. Extent of attaining and maintaining symptom remission by antipsychotic medication in the treatment of chronic schizophrenia: evidence from the CATIE study. Schizophr Res. 2011 Dec;133(1-3):42-6. doi: 10.1016/j.schres.2011.09.018. Epub 2011 Oct 14.
• Addington DE, Mohamed S, Rosenheck RA, Davis SM, Stroup TS, McEvoy JP, Swartz MS, Lieberman JA. Impact of second-generation antipsychotics and perphenazine on depressive symptoms in a randomized trial of treatment for chronic schizophrenia. J Clin Psychiatry. 2011 Jan;72(1):75-80. doi: 10.4088/JCP.09m05258gre. Epub 2010 Sep 21.
• Caroff SN, Davis VG, Miller DD, Davis SM, Rosenheck RA, McEvoy JP, Campbell EC, Saltz BL, Riggio S, Chakos MH, Swartz MS, Keefe RS, Stroup TS, Lieberman JA; CATIE Investigators. Treatment outcomes of patients with tardive dyskinesia and chronic schizophrenia. J Clin Psychiatry. 2011 Mar;72(3):295-303. doi: 10.4088/JCP.09m05793yel. Epub 2010 Aug 10.
• Meyer JM, McEvoy JP, Davis VG, Goff DC, Nasrallah HA, Davis SM, Hsiao JK, Swartz MS, Stroup TS, Lieberman JA. Inflammatory markers in schizophrenia: comparing antipsychotic effects in phase 1 of the clinical antipsychotic trials of intervention effectiveness study. Biol Psychiatry. 2009 Dec 1;66(11):1013-22. doi: 10.1016/j.biopsych.2009.06.005. Epub 2009 Jul 29.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Clozapine	Other / unclassified	—	—
Subject	Olanzapine	Small molecule	—	—
Subject	Perphenazine	Small molecule	—	—
Subject	Quetiapine	Small molecule	—	—
Subject	Risperidone	Other / unclassified	—	—
Subject	Ziprasidone	Small molecule	—	—
Background	Fluphenazine Decanoate	Small molecule	—	—

Indications