The Legacy Impact of the CATIE Study on Healthcare Policy and Psychiatric Resident Education: A Cross-Sectional Mixed-methods Survey of U.S. Psychiatry Residency and State Medical Directors

The Legacy Impact of the CATIE Study on Healthcare Policy and Psychiatric Resident Education: A Cross-Sectional Mixed-methods Survey of U.S. Psychiatry Residency and State Medical Directors | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article The Legacy Impact of the CATIE Study on Healthcare Policy and Psychiatric Resident Education: A Cross-Sectional Mixed-methods Survey of U.S. Psychiatry Residency and State Medical Directors Leon Ravin, Cole Edwards, Alexander Lin This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8770465/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Objective: The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study has had a lasting impact on the treatment of schizophrenia, yet its current role in psychiatric education and treatment policy remains unclear. This study aimed to assess how the CATIE trial is taught in U.S. psychiatry residency programs and whether its findings influence state-level treatment protocols. Methods: A cross-sectional mixed-methods survey was distributed to U.S. psychiatry residency program directors and members of the National Association of State Mental Health Program Directors (NASMHPD) Medical Directors Council. The survey included closed-ended and open-ended questions assessing the educational and policy relevance of the CATIE study. Quantitative data were summarized descriptively, and qualitative responses were analyzed thematically and categorized by sentiment. Participation was voluntary and anonymous, and institutional review board exemption was obtained. Results: A total of 75 responses were analyzed, including 60 psychiatry residency program directors and 15 NASMHPD medical directors. Among residency directors, 57% reported teaching the CATIE study for its clinical significance, 32% for its historical relevance, and 12% did not routinely include it in training. In contrast, 80% of state medical directors reported that CATIE findings no longer inform treatment protocols or formulary decisions. Qualitative responses highlighted CATIE’s continued educational value for teaching study design, clinical decision-making, and the evolution of antipsychotic therapy, while also noting concerns regarding generalizability. These findings underscore a widening gap between academic instruction and policy application of psychiatric evidence. Conclusions: The CATIE study continues to serve as a valuable educational tool in psychiatric training, yet its influence on state-level clinical policy appears limited. These findings highlight a divergence between academic and institutional priorities and suggest a need for updated research that reflects contemporary clinical realities and pharmacologic advancements. CATIE antipsychotic attitudes survey Figures Figure 1 Figure 2 Figure 3 1. Introduction The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) was a landmark 2005 study that significantly advanced understanding of antipsychotic treatment for schizophrenia. This nationwide, public health–focused randomized clinical trial (RCT) compared the effectiveness of older first-generation antipsychotics (FGAs) with newer second-generation antipsychotics (SGAs) across multiple treatment sites, aiming to reflect real-world clinical practice in the United States. At the time, there were growing concerns that SGAs, though widely prescribed, cost nearly ten times more than FGAs despite offering only marginally improved outcomes. Evaluating the comparative effectiveness of these agents was therefore critical to promoting evidence-based, cost-efficient prescribing. The study enrolled more than 1,400 participants with schizophrenia, excluding those with schizoaffective or developmental disorders, neurocognitive impairment, treatment resistance, or unstable medical conditions. Participants were followed for 18 months to assess long-term outcomes in typical care settings. CATIE was a double-blind RCT in which patients were randomly assigned to one of five FDA-approved antipsychotics: four SGAs (olanzapine, quetiapine, risperidone, ziprasidone) or the FGA perphenazine, with no placebo group. The primary outcome was time to treatment discontinuation, reflecting a composite measure of efficacy and tolerability. Investigators also assessed secondary outcomes such as symptom control, adverse effects, and overall functioning (National Institute of Mental Health, 2005). In Phase 1, most participants discontinued treatment before 18 months, prompting Phase 2, which included two optional pathways. The efficacy pathway compared clozapine to SGAs among patients with inadequate prior response, while the tolerability pathway compared ziprasidone to alternative SGAs among patient’s intolerant of previous treatment (McEvoy, 2006). These phases provided valuable insights into treatment sequencing and clinical decision-making. CATIE ultimately demonstrated that the studied medications were broadly comparable in effectiveness, though olanzapine yielded slightly better symptom control at the expense of significant metabolic side effects. Perphenazine, a low-cost FGA, performed similarly to the newer agents, challenging assumptions of SGA superiority. Clozapine again emerged as most effective for treatment-resistant schizophrenia (Lieberman, 2005). Despite these contributions, CATIE’s generalizability to contemporary practice has been questioned due to several design and methodological factors. Several pertinent criticisms are listed below. The CATIE study was a randomized clinical trial that excluded patients with various co-morbid diagnoses or treatment resistance. Individuals recruited for RCTs often represent an atypical minority as they are typically the most adherent and are more likely to meet inclusion criteria. Up to 90% of patients screened for participation in RCTs such as CATIE are ineligible due to refusal, substance abuse, suicidal or antisocial behavior, or mental or physical comorbidity, limiting applicability to general clinical practice (Hofer, 2000; Tiihonen 2017). The CATIE study did not evaluate the efficacy of long-acting injectable antipsychotics (LAIs). Adherence rates to LAIs have been noted to range from 85% to 96% and are often an option for patients (Peuskens, 2010; Heyscue 1998). Multiple studies have suggested that the use of LAIs increases time to treatment failure, first psychiatric hospitalization, re-hospitalization, and arrest (Alphs, 2015; Maestri, 2018). One study noted decreased healthcare costs if LAIs were initiated shortly after diagnosis (Munday, 2019). The CATIE study did not investigate the use of antipsychotics with partial D2-agonist action (e.g. aripiprazole) or more novel mechanisms such as M1/M4-agonism (e.g. xanomeline and trospium chloride), each of which are increasingly used today. The CATIE study did not study the use of two or more antipsychotics. Some studies have suggested that antipsychotic polypharmacy is associated with a longer time to discontinuation (Weiser, 2021). Several studies published since 2005 have shown other antipsychotics to be safer and more effective than olanzapine in treating schizophrenia. The antipsychotics studied in CATIE had mostly similar effectiveness with a modest increase in time to discontinuation with the use of olanzapine. This finding, modest as it may be, appears to have influenced the research community to use olanzapine as a ‘standard’ with which antipsychotic efficacy can be measured. It is likewise often chosen as a first-line treatment. The CATIE study did not focus on outcomes such as treatment interruptions, the need for multiple medications, arrest, incarceration, the frequency, number, or duration of psychiatric hospitalizations, increased psychiatric services to prevent hospitalization, or mortality. While these limitations highlight challenges in applying CATIE findings directly to modern clinical settings, the study’s impact on antipsychotic research, mental health policy, and psychiatric education remains substantial. Subsequent analyses have called for integrating CATIE-derived evidence into state mental health programs and residency training curricula. Medicaid and other public health systems continue to reference CATIE in formulary development, although this reliance has been questioned for potentially limiting access to lower-cost, equally effective FGAs. To better understand how CATIE findings continue to shape practice and training, this study examined their role in U.S. psychiatry residency education and state-level policy implementation. 2. Methods 2.1 Ethical Considerations The study protocol was reviewed and approved by the University of Nevada, Las Vegas Institutional Review Board (IRB#: UNLV-2023-464) and granted an exemption under Category 2 on April 23, 2025. All procedures complied with institutional and federal guidelines for research involving human participants. Participation was voluntary, and completion of the online survey indicated informed consent. No financial or other incentives were provided. 2.2 Data Security and Confidentiality All study procedures adhered to applicable data privacy laws and institutional policies. The web-based survey was administered via Qualtrics (Provo, UT), which maintains industry-standard data encryption and secure access protocols. The platform did not store or share identifiable information beyond the initial data collection. Email addresses used to prevent duplicate responses were deleted immediately after data verification and were not exported outside the Qualtrics environment. Survey results were accessible only to authorized members of the research team through secure login via Okta identity authentication. 2.3 Participants This cross-sectional mixed-methods study surveyed two key stakeholder groups: (1) members of the Medical Directors Council of the National Association of State Mental Health Program Directors (NASMHPD) and (2) directors of U.S.-based psychiatry residency training programs. These participants were purposefully selected for their leadership roles in clinical psychiatry and psychiatric education, as well as their capacity to provide insight into how major research findings influence both policy and training. Email distribution lists were obtained directly from organizational leaders and verified for accuracy. A standardized recruitment email described the study objectives, provided a secure Qualtrics survey link, and informed recipients that participation was voluntary. Reminder emails were sent approximately one month after the initial invitation. The survey remained open for two months, during which 80 total responses were received; after response rates plateaued, data collection was closed for analysis. 2.4 Survey Instrument Participants accessed the survey link after reviewing the consent statement. The survey consisted of a brief instrument containing two multiple-choice items and one optional open-ended question. The closed-ended questions captured whether the CATIE study was taught in psychiatry residency programs and whether its findings influenced state treatment protocols or formulary decisions. The open-ended item allowed participants to provide additional comments or perspectives regarding the educational or clinical relevance of the CATIE trial (Table 1 ). The survey items were adapted by the research team and reviewed by two content experts in psychiatric education and policy for clarity and face validity. A brief pilot test with three faculty members ensured accessibility and comprehension. The finalized survey was distributed electronically via Qualtrics, a platform familiar to most academic and clinical professionals. Table 1 lists the questions that were asked of the residency program directors and NASMHPD medical directors, respectively. Bold text was used to highlight key phrases and appeared to participants as it does below. Table 1 Survey Questions Administered to Psychiatry Residency Program Directors and State Medical Directors For US-based psychiatric residency program directors Which of the following best describes your program’s current practice of utilizing the CATIE study in psychiatric resident education? 1. Our program educates the residents about the CATIE study because of its historical significance in understanding the effectiveness of treatment interventions available for treatment of schizophrenia in early 2000s. 2. Our program educates residents about the CATIE study because of its clinical significance in understanding the effectiveness of treatment interventions for schizophrenia. 3. Our program does not routinely review CATIE study as part of resident training. For medical directors, members of National Association of State Mental Health Program Directors (NASMHPD) Medical Directors Council Please select the response that best describes your state mental health program’s current practice of utilizing the CATIE study in formulating treatment recommendations: 1. Our state mental health treatment programs rely on the findings of the CATIE study to determine treatment protocols and/or formulary options for treatment of patients with schizophrenia. 2. Our state mental health treatment programs do not rely on the findings of the CATIE study to determine treatment protocols and/or formulary options for treatment of patients with schizophrenia. 2.3 Data Analysis Quantitative data were analyzed descriptively to summarize response frequencies and proportions for each survey item. Responses from psychiatry residency program directors and state medical directors were examined separately to allow comparison between educational and policy perspectives. Categorical variables were summarized as counts and percentages. Qualitative data from open-ended responses were analyzed using a conventional content analysis approach. Two members of the research team independently reviewed and coded all free-text comments to identify recurring ideas and sentiments regarding the CATIE study. Codes were grouped into themes that reflected participants’ perceptions of CATIE’s clinical, educational, and policy relevance. Each response was further classified by sentiment (positive, negative, or neutral). Coding discrepancies were discussed and resolved through consensus to enhance reliability. This mixed-methods analytic strategy allowed integration of quantitative findings with qualitative insights to determine whether the CATIE study was being taught in psychiatric residency programs, why it is being taught in residency programs, and whether it is being used to influence policy decision-making at state mental health treatment programs. We were also interested to survey for any other general trends that might have emerged from participants’ responses. 3. Results 3.1 Participants Seventy-five completed responses were analyzed. Sixty-four responses were from residency program directors (80%) while 16 responses were from NASMHPD medical directors (20%). Four residency program directors and one NASMHPD medical director did not complete the survey and their responses were not included in the analysis. The survey was sent to 104 NASMHPD medical directors yielding a response rate of roughly 15%, nearly double the average response rate reported in seven NASMHPD surveys distributed from October to December of 2025 (average 8%, range 2.9–23%). We were unable to determine the response rate of residency program directors due to limitations on access to the recruitment email list. Response rates to each question are listed in Fig. 1 , Fig. 2 , and Fig. 3 below. The optional free-response question collected 23 responses. Free responses were then read and roughly categorized into expressing either positive sentiment toward the CATIE trial, negative sentiment, or not expressing an opinion. Eleven respondents expressed positive sentiment. Some notable comments are listed below: The lack of compliance 18 months later is always surprising to residents and is important for them to understand. It also is one of the largest studies with multiple sites and demonstrated no meaningful difference between typical and atypical as far as efficacy goes, but also shows clozapine seems to work best. It’s still referenced often today. The CATIE finding regarding olanzapine's superiority in managing symptoms has been upheld in both the 2019 (oral) and 2022 (oral and LAI) systematic reviews and network metaanalyses of antipsychotic medications, both published in The Lancet. It's a great example of an effectiveness study, in comparison to clinical trials (efficacy studies). It's also a great example of how, mostly, most antipsychotics don't separate out well from each other in terms of effectiveness. Two respondents expressed negative sentiment: CATIE is flawed because the drugs were not tried at equipotent D2 dosages. Side effects are different among the different agents and clozapine is a different animal. It does not work through D2 and has different efficacy. It's a dated study and does not include newer therapeutic options. Ten left comments that were neither positive nor negative, often commenting simply whether or not the CATIE trial is used at a given program. One other notable response is listed below: After the CATIE findings were published, our state agency developed and published practice guidelines for the state psychiatric hospitals and community mental health programs. However, support for these was not continued and no current treatment protocols for antipsychotics are supported by the state other than the evidence-based guidelines available, such as by the APA. Providers from at least 20 states participated in the survey and response rates roughly estimate nationwide population trends. States such as New York, California, and Florida had 2–3 respondents each, whereas North Dakota, Kentucky, Ohio, New Mexico, and others with similar population density had roughly one respondent each. Apart from a relative under-representation of states in the US south (i.e. Texas, Mississippi, Alabama), responses came from a fairly representative cross-section of US-based providers. These results suggest that the survey respondents’ range of views about the CATIE trial may be roughly generalizable to nationwide trends. 4. Discussion The survey results highlighted several notable trends. Participants voiced diverse opinions about the utility of the CATIE study, its reasons for being taught, and the ways in which it is used. This appears to capture the fact that the CATIE study remains a topic of discussion among professionals and suggests that our survey reached a variety of leaders in US academic and clinical programs. Although 57% of residency program directors stated that they teach the CATIE trial due to its clinical significance, 80% of NASMHPD medical directors indicated that they do not use the findings of the CATIE study to determine treatment protocols or formulary treatment options. This may suggest that some residency program directors overestimate the use of CATIE results in clinical practice. Alternatively, and perhaps more likely, this result may highlight differences between psychiatric practice in academic settings and state psychiatric institutions. These institutions vary widely in their patient populations, resource availability, and institutional goals among other factors, which may at least partly explain how some of these differences arise. 32% of residency program directors reported teaching the CATIE trial due to historical significance, and 12% responded that they do not routinely teach the CATIE trial to residents. This suggests that nearly half of participating residency directors do not see the CATIE trial as particularly meaningful in clinical practice. Several respondents endorsed strengths of the CATIE trial beyond what was immediately reported in the study. Residency program directors tend to agree that it remains a landmark study, and it is frequently utilized as an example to teach study design, to train critical reading skills, and to discuss the possible utility of other antipsychotics such as clozapine and long-acting injectable formulations. Respondents also note the importance of phase 2 of the trial, in which patients who failed to achieve symptomatic relief in phase 1 often had marked reduction in symptoms of schizophrenia when switched to clozapine. A particular strength of this study is that the questionnaire was brief, accessible, and gathered a sizable number of responses. The optional free-response question was particularly popular among respondents highlighting apparent interest in discussing the CATIE trial still today. The results of this study are limited in that responses were gathered from roughly half of the states and may have appealed to respondents naturally involved in academic discussions. It is difficult to assess whether the opinions expressed apply to providers in private practice, for example. Future studies may consider surveying opinions more broadly. Our results suggest that psychiatric providers nationwide continue to hold a variety of opinions regarding the CATIE study. Respondents remain particularly concerned that the study did not investigate the use of LAIs, that it did not compare the effectiveness of FGAs or SGAs to clozapine, and that the trial is not entirely generalizable despite the investigators’ best efforts. It should also be noted that academic metrics used to investigate the clinical efficacy of antipsychotic medications (i.e. measuring reductions in PANSS scores) may provide a narrow view of these medications’ overall efficacy. State providers and hospital administrators remain interested in outcomes such as patient readmission rates, lengths of stay, frequency of arrests, and the total costs of health care rather than the price of a given antipsychotic. Institutional differences-of-interest are again highlighted by these survey results and remain relevant when discussing CATIE today. 5. Conclusion We conducted a brief survey assessing opinions of the CATIE study among psychiatry residency program directors and state psychiatric program directors. The results generally reaffirmed that CATIE remains a topic of interest among psychiatric providers and that opinions of the study remain varied. Particular differences of opinion were seen between residency program directors and NASMHPD medical directors, highlighting likely differences in institutional aims. We hope that the results of this survey encourage further discussion about the CATIE trial and additional research into its use in clinical practice. The survey results reveal an evolving relationship between the CATIE study and its role in psychiatric education and clinical practice. While many residency program directors continue to teach CATIE for its clinical and historical significance, its practical influence on treatment decisions appears limited particularly in state psychiatric systems. This divergence underscores the differing priorities and constraints between academic and institutional settings, where factors such as patient acuity, resource availability, and administrative goals shape how evidence is applied. The findings also highlight the enduring educational value of the CATIE trial. Despite its limitations it remains a useful tool for teaching study design, critical appraisal, and the nuanced application of antipsychotic treatment strategies, including the use of clozapine and long-acting injectable antipsychotics. These insights suggest that while CATIE retains relevance, future research and training should increasingly reflect the broader clinical realities and evolving pharmacologic landscape of psychiatric care. Declarations No funding was received for the publication of this article. The authors have no competing interests to disclose. The study protocol was reviewed and approved by the University of Nevada, Las Vegas Institutional Review Board (IRB#: UNLV-2023-464) and granted an exemption under Category 2 on April 23, 2025. All procedures complied with institutional and federal guidelines for research involving human participants. Participation was voluntary, and completion of the online survey indicated informed consent. No financial or other incentives were provided. Informed consent was obtained from all individual participants included in the study. All participants consented to the submission of collected responses for publication. All data remains available to members of the research team via Qualtrics survey tool and may be shared at readers’ request if appropriate. Leon Ravin developed study design and contributed to writing manuscript. Cole Edwards and Alexander Lin assisted in developing study design, facilitating data collection, and writing manuscript. Funding No funding was received for the publication of this article. Competing Interests The authors have no competing interests to disclose. Ethics approval The study protocol was reviewed and approved by the University of Nevada, Las Vegas Institutional Review Board (IRB#: UNLV-2023-464) and granted an exemption under Category 2 on April 23, 2025. All procedures complied with institutional and federal guidelines for research involving human participants. Participation was voluntary, and completion of the online survey indicated informed consent. No financial or other incentives were provided. Consent to participate Informed consent was obtained from all individual participants included in the study. Consent to publish All participants consented to the submission of collected responses for publication. Data availability All data remains available to members of the research team via Qualtrics survey tool and may be shared at readers’ request if appropriate. Author Contribution LR developed study design and contributed to writing manuscript. CE and AL assisted in developing study design, facilitating data collection, and writing manuscript. Data Availability All data remains available to members of the research team via Qualtrics survey tool and may be shared at readers’ request if appropriate. References Online article (Sept. 2005). Questions and Answers about the NIMH Clinical Antipsychotic Trials of Intervention Effectiveness Study (Catie) - Phase 1 Results. National Institute of Mental Health , U.S. Department of Health and Human Services. Journal article Heyscue, B. E., Levin, G. M., & Merrick, J. P. (1998). Compliance with depot antipsychotic medication by patients attending outpatient clinics. Psychiatr Serv. ;49(9):1232-4. 10.1176/ps.49.9.1232 . PMID: 9735970. Journal article Hofer, A., Hummer, M., Huber, R., Kurz, M., Walch, T., & Fleischhacker, W. W. (2000). Selection bias in clinical trials with antipsychotics. J Clin Psychopharmacol . ;20(6):699–702. 10.1097/00004714-200012000-00019 . PMID: 11106145. Journal, L., Alphs, M. D., Carmela Benson, P. D., Kimberly Cheshire-Kinney, M. S. M. S. H. P., Jean-Pierre, B. A., Lindenmayer, M. D., Lian Mao, P. D., Stephen, C., & Rodriguez, M. S. (2015). Lynn Starr, MD Real-World Outcomes of Paliperidone Palmitate Compared to Daily Oral Antipsychotic Therapy in Schizophrenia. A Randomized, Open-Label, Review Board-Blinded 15-Month Study. Journal Of Clinical Psychiatry , 76 (5), 554–561. Journal article Lieberman, J. A., Stroup, T. S., McEvoy, J. P., Swartz, M. S., Rosenheck, R. A., Perkins, D. O., Keefe, R. S., Davis, S. M., Davis, C. E., Lebowitz, B. D., Severe, J., & Hsiao, J. K. (2005). Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Investigators. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med. ;353(12):1209-23. 10.1056/NEJMoa051688 . Epub 2005 Sep 19. Erratum in: N Engl J Med. 2010;363(11):1092-3. PMID: 16172203. Journal article Maestri, T. J., Mican, L. M., Rozea, H., & Barner, J. C. (2018). Do Long-Acting Injectable Antipsychotics Prevent or Delay Hospital Readmission? Psychopharmacology Bulletin , 48 (3), 8–15. Journal article McEvoy, J. P., Lieberman, J. A., Stroup, T. S., Davis, S. M., Meltzer, H. Y., Rosenheck, R. A., Swartz, M. S., Perkins, D. O., Keefe, R. S., Davis, C. E., Severe, J., & Hsiao, J. K. (2006). 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. ;163(4):600 – 10. 10.1176/ajp.2006.163.4.600 . PMID: 16585434. Journal article Munday, J., Greene, M., Chang, E., Hartry, A., Yan, T., & Broder, M. S. (2019). Early initiation of long-acting injectable antipsychotic treatment is associated with lower hospitalization rates and healthcare costs in patients with schizophrenia: real-world evidence from US claims data. Current Medical Research And Opinion , 35 (7), 1231–1239. Epub 2019 Jan 31. PMID: 30649965. Journal article Peuskens, J., Olivares, J. M., Pecenak, J., Tuma, I., Bij de Weg, H., Eriksson, L., Resseler, S., Akhras, K., & Jacobs, A. (2010). Treatment retention with risperidone long-acting injection: 24-month results from the Electronic Schizophrenia Treatment Adherence Registry (e-STAR) in six countries. Curr Med Res Opin. ;26(3):501-9. 10.1185/03007990903488670 . PMID: 20014981. Journal article Tiihonen, J., Haukka, J., Taylor, M., Haddad, P. M., Patel, M. X., & Korhonen, P. (2011). A nationwide cohort study of oral and depot antipsychotics after first hospitalization for schizophrenia. Am J Psychiatry. ;168(6):603-9. doi: 10.1176/appi.ajp.2011.10081224. Epub 2011 Mar 1. Erratum in: Am J Psychiatry. 2012;169(2):223. PMID: 21362741. Journal article Tiihonen, J., Mittendorfer-Rutz, E., Majak, M., et al. (2017). Real-World Effectiveness of Antipsychotic Treatments in a Nationwide Cohort of 29 823 Patients With Schizophrenia. JAMA Psychiatry , 74 (7), 686–693. 10.1001/jamapsychiatry.2017.1322 Journal article Weiser, M., Davis, J. M., Brown, C. H., Slade, E. P., Fang, L. J., Medoff, D. R., Buchanan, R. W., Levi, L., Davidson, M., & Kreyenbuhl, J. (2021). Differences in Antipsychotic Treatment Discontinuation Among Veterans With Schizophrenia in the U.S. Department of Veterans Affairs. Am J Psychiatry. ;178(10):932–940. 10.1176/appi.ajp.2020.20111657 . Epub 2021 Jul 14. PMID: 34256606. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8770465","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":585422658,"identity":"5cd2ff5a-bab4-43dd-8996-ec7310f9c2d9","order_by":0,"name":"Leon Ravin","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA3ElEQVRIie3PsQqCQBzH8X8EuhzeehH0DIrQFD2LfwTHKFoaFcGWwDVo7AUc27o4aJJagxqSwBdoauvCpoZLt6D7Dv/tw48/gE73g1mv48HAA2iH7VrEqEggSSuK6xMA0YR0RcmKzXFEzd38NoYLhnS9Z0piBX2G+XnaWWAUL6HEkJWBmhBwbUzOmHFJCAgXWO7aamLeJTng9ljUJsS5YsIxY9VKD+jCuX4hE0l8XJ6KaEVs0TOYgUpCiZntHskQ09TndzIThFLBuYp8JJ8wmNcAvIebbOh0Ot0/9ASQ80euPiA2rQAAAABJRU5ErkJggg==","orcid":"","institution":"Nevada Department of Health and Human Services","correspondingAuthor":true,"prefix":"","firstName":"Leon","middleName":"","lastName":"Ravin","suffix":""},{"id":585422659,"identity":"605253c3-b3f7-435c-b5d9-8458bacba69b","order_by":1,"name":"Cole Edwards","email":"","orcid":"","institution":"University of Nevada, Las Vegas","correspondingAuthor":false,"prefix":"","firstName":"Cole","middleName":"","lastName":"Edwards","suffix":""},{"id":585422660,"identity":"21afaada-627a-4965-bf78-f350bbccfce7","order_by":2,"name":"Alexander Lin","email":"","orcid":"","institution":"University of Nevada, Las Vegas","correspondingAuthor":false,"prefix":"","firstName":"Alexander","middleName":"","lastName":"Lin","suffix":""}],"badges":[],"createdAt":"2026-02-03 03:38:19","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8770465/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8770465/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":101989282,"identity":"867b07ec-a71a-48ff-af4a-ac231fd8ab3c","added_by":"auto","created_at":"2026-02-05 19:12:20","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":36137,"visible":true,"origin":"","legend":"\u003cp\u003eQ1: Please select the title that most accurately describes your role.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8770465/v1/1e268d17918e1352275c519e.png"},{"id":101989280,"identity":"f1eddaa3-6cf0-4c89-a644-a0bbf753e25d","added_by":"auto","created_at":"2026-02-05 19:12:20","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":49285,"visible":true,"origin":"","legend":"\u003cp\u003eQ2, Residency program directors: Our program educates residents about the CATIE study because of its historical vs clinical significance vs insignificance.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-8770465/v1/f55eecbf58ec615bf96cedd5.png"},{"id":102295651,"identity":"46d0d96e-ee08-4621-a77e-44bbc822b378","added_by":"auto","created_at":"2026-02-10 10:13:33","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":50087,"visible":true,"origin":"","legend":"\u003cp\u003eQ2, NASMHPD Medical Directors Council: Our state treatment protocols rely vs does not rely on findings of CATIE study.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-8770465/v1/7d224f1750b281b66fe64946.png"},{"id":102298887,"identity":"0109cae6-310b-4afb-a88f-5abd62ec3482","added_by":"auto","created_at":"2026-02-10 11:01:03","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":841627,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8770465/v1/adb480e0-194c-4f35-b690-d30afa078fd4.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"The Legacy Impact of the CATIE Study on Healthcare Policy and Psychiatric Resident Education: A Cross-Sectional Mixed-methods Survey of U.S. Psychiatry Residency and State Medical Directors","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eThe \u003cem\u003eClinical Antipsychotic Trials of Intervention Effectiveness\u003c/em\u003e (CATIE) was a landmark 2005 study that significantly advanced understanding of antipsychotic treatment for schizophrenia. This nationwide, public health\u0026ndash;focused randomized clinical trial (RCT) compared the effectiveness of older first-generation antipsychotics (FGAs) with newer second-generation antipsychotics (SGAs) across multiple treatment sites, aiming to reflect real-world clinical practice in the United States.\u003c/p\u003e \u003cp\u003eAt the time, there were growing concerns that SGAs, though widely prescribed, cost nearly ten times more than FGAs despite offering only marginally improved outcomes. Evaluating the comparative effectiveness of these agents was therefore critical to promoting evidence-based, cost-efficient prescribing.\u003c/p\u003e \u003cp\u003eThe study enrolled more than 1,400 participants with schizophrenia, excluding those with schizoaffective or developmental disorders, neurocognitive impairment, treatment resistance, or unstable medical conditions. Participants were followed for 18 months to assess long-term outcomes in typical care settings. CATIE was a double-blind RCT in which patients were randomly assigned to one of five FDA-approved antipsychotics: four SGAs (olanzapine, quetiapine, risperidone, ziprasidone) or the FGA perphenazine, with no placebo group. The primary outcome was time to treatment discontinuation, reflecting a composite measure of efficacy and tolerability. Investigators also assessed secondary outcomes such as symptom control, adverse effects, and overall functioning (National Institute of Mental Health, 2005).\u003c/p\u003e \u003cp\u003eIn Phase 1, most participants discontinued treatment before 18 months, prompting Phase 2, which included two optional pathways. The \u003cem\u003eefficacy pathway\u003c/em\u003e compared clozapine to SGAs among patients with inadequate prior response, while the \u003cem\u003etolerability pathway\u003c/em\u003e compared ziprasidone to alternative SGAs among patient\u0026rsquo;s intolerant of previous treatment (McEvoy, 2006). These phases provided valuable insights into treatment sequencing and clinical decision-making.\u003c/p\u003e \u003cp\u003eCATIE ultimately demonstrated that the studied medications were broadly comparable in effectiveness, though olanzapine yielded slightly better symptom control at the expense of significant metabolic side effects. Perphenazine, a low-cost FGA, performed similarly to the newer agents, challenging assumptions of SGA superiority. Clozapine again emerged as most effective for treatment-resistant schizophrenia (Lieberman, 2005).\u003c/p\u003e \u003cp\u003eDespite these contributions, CATIE\u0026rsquo;s generalizability to contemporary practice has been questioned due to several design and methodological factors. Several pertinent criticisms are listed below.\u003c/p\u003e \u003cp\u003e \u003col\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eThe CATIE study was a randomized clinical trial that excluded patients with various co-morbid diagnoses or treatment resistance. Individuals recruited for RCTs often represent an atypical minority as they are typically the most adherent and are more likely to meet inclusion criteria. Up to 90% of patients screened for participation in RCTs such as CATIE are ineligible due to refusal, substance abuse, suicidal or antisocial behavior, or mental or physical comorbidity, limiting applicability to general clinical practice (Hofer, 2000; Tiihonen 2017).\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eThe CATIE study did not evaluate the efficacy of long-acting injectable antipsychotics (LAIs). Adherence rates to LAIs have been noted to range from 85% to 96% and are often an option for patients (Peuskens, 2010; Heyscue 1998). Multiple studies have suggested that the use of LAIs increases time to treatment failure, first psychiatric hospitalization, re-hospitalization, and arrest (Alphs, 2015; Maestri, 2018). One study noted decreased healthcare costs if LAIs were initiated shortly after diagnosis (Munday, 2019).\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eThe CATIE study did not investigate the use of antipsychotics with partial D2-agonist action (e.g. aripiprazole) or more novel mechanisms such as M1/M4-agonism (e.g. xanomeline and trospium chloride), each of which are increasingly used today.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eThe CATIE study did not study the use of two or more antipsychotics. Some studies have suggested that antipsychotic polypharmacy is associated with a longer time to discontinuation (Weiser, 2021).\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eSeveral studies published since 2005 have shown other antipsychotics to be safer and more effective than olanzapine in treating schizophrenia. The antipsychotics studied in CATIE had mostly similar effectiveness with a modest increase in time to discontinuation with the use of olanzapine. This finding, modest as it may be, appears to have influenced the research community to use olanzapine as a \u0026lsquo;standard\u0026rsquo; with which antipsychotic efficacy can be measured. It is likewise often chosen as a first-line treatment.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eThe CATIE study did not focus on outcomes such as treatment interruptions, the need for multiple medications, arrest, incarceration, the frequency, number, or duration of psychiatric hospitalizations, increased psychiatric services to prevent hospitalization, or mortality.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003c/ol\u003e \u003c/p\u003e \u003cp\u003eWhile these limitations highlight challenges in applying CATIE findings directly to modern clinical settings, the study\u0026rsquo;s impact on antipsychotic research, mental health policy, and psychiatric education remains substantial. Subsequent analyses have called for integrating CATIE-derived evidence into state mental health programs and residency training curricula. Medicaid and other public health systems continue to reference CATIE in formulary development, although this reliance has been questioned for potentially limiting access to lower-cost, equally effective FGAs.\u003c/p\u003e \u003cp\u003eTo better understand how CATIE findings continue to shape practice and training, this study examined their role in U.S. psychiatry residency education and state-level policy implementation.\u003c/p\u003e"},{"header":"2. Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Ethical Considerations\u003c/h2\u003e \u003cp\u003eThe study protocol was reviewed and approved by the University of Nevada, Las Vegas Institutional Review Board (IRB#: UNLV-2023-464) and granted an exemption under Category 2 on April 23, 2025. All procedures complied with institutional and federal guidelines for research involving human participants. Participation was voluntary, and completion of the online survey indicated informed consent. No financial or other incentives were provided.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Data Security and Confidentiality\u003c/h2\u003e \u003cp\u003eAll study procedures adhered to applicable data privacy laws and institutional policies. The web-based survey was administered via Qualtrics (Provo, UT), which maintains industry-standard data encryption and secure access protocols. The platform did not store or share identifiable information beyond the initial data collection. Email addresses used to prevent duplicate responses were deleted immediately after data verification and were not exported outside the Qualtrics environment. Survey results were accessible only to authorized members of the research team through secure login via Okta identity authentication.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3 Participants\u003c/h2\u003e \u003cp\u003eThis cross-sectional mixed-methods study surveyed two key stakeholder groups: (1) members of the Medical Directors Council of the National Association of State Mental Health Program Directors (NASMHPD) and (2) directors of U.S.-based psychiatry residency training programs. These participants were purposefully selected for their leadership roles in clinical psychiatry and psychiatric education, as well as their capacity to provide insight into how major research findings influence both policy and training. Email distribution lists were obtained directly from organizational leaders and verified for accuracy. A standardized recruitment email described the study objectives, provided a secure Qualtrics survey link, and informed recipients that participation was voluntary. Reminder emails were sent approximately one month after the initial invitation. The survey remained open for two months, during which 80 total responses were received; after response rates plateaued, data collection was closed for analysis.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4 Survey Instrument\u003c/h2\u003e \u003cp\u003eParticipants accessed the survey link after reviewing the consent statement. The survey consisted of a brief instrument containing two multiple-choice items and one optional open-ended question. The closed-ended questions captured whether the CATIE study was taught in psychiatry residency programs and whether its findings influenced state treatment protocols or formulary decisions. The open-ended item allowed participants to provide additional comments or perspectives regarding the educational or clinical relevance of the CATIE trial (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The survey items were adapted by the research team and reviewed by two content experts in psychiatric education and policy for clarity and face validity. A brief pilot test with three faculty members ensured accessibility and comprehension. The finalized survey was distributed electronically via Qualtrics, a platform familiar to most academic and clinical professionals.\u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e lists the questions that were asked of the residency program directors and NASMHPD medical directors, respectively. Bold text was used to highlight key phrases and appeared to participants as it does below.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSurvey Questions Administered to Psychiatry Residency Program Directors and State Medical Directors\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"1\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eFor US-based psychiatric residency program directors\u003c/span\u003e\u003c/p\u003e \u003cp\u003eWhich of the following best describes your program\u0026rsquo;s current practice of utilizing the CATIE study in psychiatric resident education?\u003c/p\u003e \u003cp\u003e1. Our program educates the residents about the CATIE study because of its historical significance in understanding the effectiveness of treatment interventions available for treatment of schizophrenia in early 2000s.\u003c/p\u003e \u003cp\u003e2. Our program educates residents about the CATIE study because of its clinical significance in understanding the effectiveness of treatment interventions for schizophrenia.\u003c/p\u003e \u003cp\u003e3. Our program does not routinely review CATIE study as part of resident training.\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eFor medical directors, members of National Association of State Mental Health Program Directors (NASMHPD) Medical Directors Council\u003c/span\u003e\u003c/p\u003e \u003cp\u003ePlease select the response that best describes your state mental health program\u0026rsquo;s current practice of utilizing the CATIE study in formulating treatment recommendations:\u003c/p\u003e \u003cp\u003e1. Our state mental health treatment programs \u003cb\u003erely on the findings of the CATIE study\u003c/b\u003e to determine treatment protocols and/or formulary options for treatment of patients with schizophrenia.\u003c/p\u003e \u003cp\u003e2. Our state mental health treatment programs \u003cb\u003edo not rely on the findings of the CATIE study\u003c/b\u003e to determine treatment protocols and/or formulary options for treatment of patients with schizophrenia.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e2.3 Data Analysis\u003c/h2\u003e \u003cp\u003eQuantitative data were analyzed descriptively to summarize response frequencies and proportions for each survey item. Responses from psychiatry residency program directors and state medical directors were examined separately to allow comparison between educational and policy perspectives. Categorical variables were summarized as counts and percentages. Qualitative data from open-ended responses were analyzed using a conventional content analysis approach. Two members of the research team independently reviewed and coded all free-text comments to identify recurring ideas and sentiments regarding the CATIE study. Codes were grouped into themes that reflected participants\u0026rsquo; perceptions of CATIE\u0026rsquo;s clinical, educational, and policy relevance. Each response was further classified by sentiment (positive, negative, or neutral). Coding discrepancies were discussed and resolved through consensus to enhance reliability. This mixed-methods analytic strategy allowed integration of quantitative findings with qualitative insights to determine whether the CATIE study was being taught in psychiatric residency programs, why it is being taught in residency programs, and whether it is being used to influence policy decision-making at state mental health treatment programs. We were also interested to survey for any other general trends that might have emerged from participants\u0026rsquo; responses.\u003c/p\u003e \u003c/div\u003e"},{"header":"3. Results","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e3.1 Participants\u003c/h2\u003e \u003cp\u003eSeventy-five completed responses were analyzed. Sixty-four responses were from residency program directors (80%) while 16 responses were from NASMHPD medical directors (20%). Four residency program directors and one NASMHPD medical director did not complete the survey and their responses were not included in the analysis. The survey was sent to 104 NASMHPD medical directors yielding a response rate of roughly 15%, nearly double the average response rate reported in seven NASMHPD surveys distributed from October to December of 2025 (average 8%, range 2.9\u0026ndash;23%). We were unable to determine the response rate of residency program directors due to limitations on access to the recruitment email list.\u003c/p\u003e \u003cp\u003eResponse rates to each question are listed in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, and Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e below.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe optional free-response question collected 23 responses. Free responses were then read and roughly categorized into expressing either positive sentiment toward the CATIE trial, negative sentiment, or not expressing an opinion.\u003c/p\u003e \u003cp\u003eEleven respondents expressed positive sentiment. Some notable comments are listed below:\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003e \u003cem\u003eThe lack of compliance 18 months later is always surprising to residents and is important for them to understand. It also is one of the largest studies with multiple sites and demonstrated no meaningful difference between typical and atypical as far as efficacy goes, but also shows clozapine seems to work best. It\u0026rsquo;s still referenced often today.\u003c/em\u003e \u003c/p\u003e\u003cp\u003eThe CATIE finding regarding olanzapine's superiority in managing symptoms has been upheld in both the 2019 (oral) and 2022 (oral and LAI) systematic reviews and network metaanalyses of antipsychotic medications, both published in The Lancet.\u003c/p\u003e\u003cp\u003eIt's a great example of an effectiveness study, in comparison to clinical trials (efficacy studies). It's also a great example of how, mostly, most antipsychotics don't separate out well from each other in terms of effectiveness.\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e \u003cp\u003eTwo respondents expressed negative sentiment:\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eCATIE is flawed because the drugs were not tried at equipotent D2 dosages. Side effects are different among the different agents and clozapine is a different animal. It does not work through D2 and has different efficacy.\u003c/p\u003e\u003cp\u003eIt's a dated study and does not include newer therapeutic options.\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e \u003cp\u003eTen left comments that were neither positive nor negative, often commenting simply whether or not the CATIE trial is used at a given program. One other notable response is listed below:\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eAfter the CATIE findings were published, our state agency developed and published practice guidelines for the state psychiatric hospitals and community mental health programs. However, support for these was not continued and no current treatment protocols for antipsychotics are supported by the state other than the evidence-based guidelines available, such as by the APA.\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e \u003cp\u003eProviders from at least 20 states participated in the survey and response rates roughly estimate nationwide population trends. States such as New York, California, and Florida had 2\u0026ndash;3 respondents each, whereas North Dakota, Kentucky, Ohio, New Mexico, and others with similar population density had roughly one respondent each. Apart from a relative under-representation of states in the US south (i.e. Texas, Mississippi, Alabama), responses came from a fairly representative cross-section of US-based providers. These results suggest that the survey respondents\u0026rsquo; range of views about the CATIE trial may be roughly generalizable to nationwide trends.\u003c/p\u003e \u003c/div\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eThe survey results highlighted several notable trends. Participants voiced diverse opinions about the utility of the CATIE study, its reasons for being taught, and the ways in which it is used. This appears to capture the fact that the CATIE study remains a topic of discussion among professionals and suggests that our survey reached a variety of leaders in US academic and clinical programs.\u003c/p\u003e \u003cp\u003eAlthough 57% of residency program directors stated that they teach the CATIE trial due to its clinical significance, 80% of NASMHPD medical directors indicated that they do \u003cem\u003enot\u003c/em\u003e use the findings of the CATIE study to determine treatment protocols or formulary treatment options. This may suggest that some residency program directors overestimate the use of CATIE results in clinical practice. Alternatively, and perhaps more likely, this result may highlight differences between psychiatric practice in academic settings and state psychiatric institutions. These institutions vary widely in their patient populations, resource availability, and institutional goals among other factors, which may at least partly explain how some of these differences arise.\u003c/p\u003e \u003cp\u003e32% of residency program directors reported teaching the CATIE trial due to historical significance, and 12% responded that they do not routinely teach the CATIE trial to residents. This suggests that nearly half of participating residency directors do not see the CATIE trial as particularly meaningful in clinical practice.\u003c/p\u003e \u003cp\u003eSeveral respondents endorsed strengths of the CATIE trial beyond what was immediately reported in the study. Residency program directors tend to agree that it remains a landmark study, and it is frequently utilized as an example to teach study design, to train critical reading skills, and to discuss the possible utility of other antipsychotics such as clozapine and long-acting injectable formulations. Respondents also note the importance of phase 2 of the trial, in which patients who failed to achieve symptomatic relief in phase 1 often had marked reduction in symptoms of schizophrenia when switched to clozapine.\u003c/p\u003e \u003cp\u003eA particular strength of this study is that the questionnaire was brief, accessible, and gathered a sizable number of responses. The optional free-response question was particularly popular among respondents highlighting apparent interest in discussing the CATIE trial still today. The results of this study are limited in that responses were gathered from roughly half of the states and may have appealed to respondents naturally involved in academic discussions. It is difficult to assess whether the opinions expressed apply to providers in private practice, for example. Future studies may consider surveying opinions more broadly.\u003c/p\u003e \u003cp\u003eOur results suggest that psychiatric providers nationwide continue to hold a variety of opinions regarding the CATIE study. Respondents remain particularly concerned that the study did not investigate the use of LAIs, that it did not compare the effectiveness of FGAs or SGAs to clozapine, and that the trial is not entirely generalizable despite the investigators\u0026rsquo; best efforts. It should also be noted that academic metrics used to investigate the clinical efficacy of antipsychotic medications (i.e. measuring reductions in PANSS scores) may provide a narrow view of these medications\u0026rsquo; overall efficacy. State providers and hospital administrators remain interested in outcomes such as patient readmission rates, lengths of stay, frequency of arrests, and the total costs of health care rather than the price of a given antipsychotic. Institutional differences-of-interest are again highlighted by these survey results and remain relevant when discussing CATIE today.\u003c/p\u003e"},{"header":"5. Conclusion","content":"\u003cp\u003eWe conducted a brief survey assessing opinions of the CATIE study among psychiatry residency program directors and state psychiatric program directors. The results generally reaffirmed that CATIE remains a topic of interest among psychiatric providers and that opinions of the study remain varied. Particular differences of opinion were seen between residency program directors and NASMHPD medical directors, highlighting likely differences in institutional aims. We hope that the results of this survey encourage further discussion about the CATIE trial and additional research into its use in clinical practice.\u003c/p\u003e \u003cp\u003eThe survey results reveal an evolving relationship between the CATIE study and its role in psychiatric education and clinical practice. While many residency program directors continue to teach CATIE for its clinical and historical significance, its practical influence on treatment decisions appears limited particularly in state psychiatric systems. This divergence underscores the differing priorities and constraints between academic and institutional settings, where factors such as patient acuity, resource availability, and administrative goals shape how evidence is applied.\u003c/p\u003e \u003cp\u003eThe findings also highlight the enduring educational value of the CATIE trial. Despite its limitations it remains a useful tool for teaching study design, critical appraisal, and the nuanced application of antipsychotic treatment strategies, including the use of clozapine and long-acting injectable antipsychotics. These insights suggest that while CATIE retains relevance, future research and training should increasingly reflect the broader clinical realities and evolving pharmacologic landscape of psychiatric care.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eNo funding was received for the publication of this article. The authors have no competing interests to disclose. The study protocol was reviewed and approved by the University of Nevada, Las Vegas Institutional Review Board (IRB#: UNLV-2023-464) and granted an exemption under Category 2 on April 23, 2025. All procedures complied with institutional and federal guidelines for research involving human participants. Participation was voluntary, and completion of the online survey indicated informed consent. No financial or other incentives were provided. Informed consent was obtained from all individual participants included in the study. All participants consented to the submission of collected responses for publication. All data remains available to members of the research team via Qualtrics survey tool and may be shared at readers\u0026rsquo; request if appropriate.\u003c/p\u003e\n\u003cp\u003eLeon Ravin developed study design and contributed to writing manuscript. Cole Edwards and Alexander Lin assisted in developing study design, facilitating data collection, and writing manuscript.\u003c/p\u003e\n\u003ch2\u003eFunding\u003c/h2\u003e\n\u003cp\u003eNo funding was received for the publication of this article.\u003c/p\u003e\n\u003ch3\u003eCompeting Interests\u003c/h3\u003e\n\u003cp\u003eThe authors have no competing interests to disclose.\u003c/p\u003e\n\u003ch3\u003eEthics approval\u003c/h3\u003e\n\u003cp\u003eThe study protocol was reviewed and approved by the University of Nevada, Las Vegas Institutional Review Board (IRB#: UNLV-2023-464) and granted an exemption under Category 2 on April 23, 2025. All procedures complied with institutional and federal guidelines for research involving human participants. Participation was voluntary, and completion of the online survey indicated informed consent. No financial or other incentives were provided.\u003c/p\u003e\n\u003ch3\u003eConsent to participate\u003c/h3\u003e\n\u003cp\u003eInformed consent was obtained from all individual participants included in the study.\u003c/p\u003e\n\u003ch3\u003eConsent to publish\u003c/h3\u003e\n\u003cp\u003eAll participants consented to the submission of collected responses for publication.\u003c/p\u003e\n\u003ch3\u003eData availability\u003c/h3\u003e\n\u003cp\u003eAll data remains available to members of the research team via Qualtrics survey tool and may be shared at readers\u0026rsquo; request if appropriate.\u003c/p\u003e\n\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\n\u003cp\u003eLR developed study design and contributed to writing manuscript. CE and AL assisted in developing study design, facilitating data collection, and writing manuscript.\u003c/p\u003e\n\u003ch2\u003eData Availability\u003c/h2\u003e\n\u003cp\u003eAll data remains available to members of the research team via Qualtrics survey tool and may be shared at readers\u0026rsquo; request if appropriate.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eOnline article (Sept. 2005). Questions and Answers about the NIMH Clinical Antipsychotic Trials of Intervention Effectiveness Study (Catie) - Phase 1 Results. \u003cem\u003eNational Institute of Mental Health\u003c/em\u003e, U.S. Department of Health and Human Services. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e\u003c/span\u003e\u003cspan address=\"http://www.nimh.nih.gov/funding/clinical-research/practical/catie/phase1results\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJournal article Heyscue, B. E., Levin, G. M., \u0026amp; Merrick, J. P. (1998). Compliance with depot antipsychotic medication by patients attending outpatient clinics. \u003cem\u003ePsychiatr Serv.\u003c/em\u003e ;49(9):1232-4. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1176/ps.49.9.1232\u003c/span\u003e\u003cspan address=\"10.1176/ps.49.9.1232\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 9735970.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJournal article Hofer, A., Hummer, M., Huber, R., Kurz, M., Walch, T., \u0026amp; Fleischhacker, W. W. (2000). Selection bias in clinical trials with antipsychotics. \u003cem\u003eJ Clin Psychopharmacol\u003c/em\u003e. ;20(6):699\u0026ndash;702. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/00004714-200012000-00019\u003c/span\u003e\u003cspan address=\"10.1097/00004714-200012000-00019\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 11106145.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJournal, L., Alphs, M. D., Carmela Benson, P. D., Kimberly Cheshire-Kinney, M. S. M. S. H. P., Jean-Pierre, B. A., Lindenmayer, M. D., Lian Mao, P. D., Stephen, C., \u0026amp; Rodriguez, M. S. (2015). Lynn Starr, MD Real-World Outcomes of Paliperidone Palmitate Compared to Daily Oral Antipsychotic Therapy in Schizophrenia. A Randomized, Open-Label, Review Board-Blinded 15-Month Study. \u003cem\u003eJournal Of Clinical Psychiatry\u003c/em\u003e, \u003cem\u003e76\u003c/em\u003e(5), 554\u0026ndash;561.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJournal article Lieberman, J. A., Stroup, T. S., McEvoy, J. P., Swartz, M. S., Rosenheck, R. A., Perkins, D. O., Keefe, R. S., Davis, S. M., Davis, C. E., Lebowitz, B. D., Severe, J., \u0026amp; Hsiao, J. K. (2005). Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Investigators. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. \u003cem\u003eN Engl J Med.\u003c/em\u003e ;353(12):1209-23. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1056/NEJMoa051688\u003c/span\u003e\u003cspan address=\"10.1056/NEJMoa051688\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Epub 2005 Sep 19. Erratum in: \u003cem\u003eN Engl J Med.\u003c/em\u003e 2010;363(11):1092-3. PMID: 16172203.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJournal article Maestri, T. J., Mican, L. M., Rozea, H., \u0026amp; Barner, J. C. (2018). Do Long-Acting Injectable Antipsychotics Prevent or Delay Hospital Readmission? \u003cem\u003ePsychopharmacology Bulletin\u003c/em\u003e, \u003cem\u003e48\u003c/em\u003e(3), 8\u0026ndash;15.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJournal article McEvoy, J. P., Lieberman, J. A., Stroup, T. S., Davis, S. M., Meltzer, H. Y., Rosenheck, R. A., Swartz, M. S., Perkins, D. O., Keefe, R. S., Davis, C. E., Severe, J., \u0026amp; Hsiao, J. K. (2006). CATIE Investigators. Effectiveness of clozapine versus olanzapine, quetiapine, and risperidone in patients with chronic schizophrenia who did not respond to prior atypical antipsychotic treatment. \u003cem\u003eAm J Psychiatry.\u003c/em\u003e ;163(4):600\u0026thinsp;\u0026ndash;\u0026thinsp;10. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1176/ajp.2006.163.4.600\u003c/span\u003e\u003cspan address=\"10.1176/ajp.2006.163.4.600\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 16585434.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJournal article Munday, J., Greene, M., Chang, E., Hartry, A., Yan, T., \u0026amp; Broder, M. S. (2019). Early initiation of long-acting injectable antipsychotic treatment is associated with lower hospitalization rates and healthcare costs in patients with schizophrenia: real-world evidence from US claims data. \u003cem\u003eCurrent Medical Research And Opinion\u003c/em\u003e, \u003cem\u003e35\u003c/em\u003e(7), 1231\u0026ndash;1239. Epub 2019 Jan 31. PMID: 30649965.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJournal article Peuskens, J., Olivares, J. M., Pecenak, J., Tuma, I., Bij de Weg, H., Eriksson, L., Resseler, S., Akhras, K., \u0026amp; Jacobs, A. (2010). Treatment retention with risperidone long-acting injection: 24-month results from the Electronic Schizophrenia Treatment Adherence Registry (e-STAR) in six countries. \u003cem\u003eCurr Med Res Opin.\u003c/em\u003e ;26(3):501-9. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1185/03007990903488670\u003c/span\u003e\u003cspan address=\"10.1185/03007990903488670\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 20014981.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJournal article Tiihonen, J., Haukka, J., Taylor, M., Haddad, P. M., Patel, M. X., \u0026amp; Korhonen, P. (2011). A nationwide cohort study of oral and depot antipsychotics after first hospitalization for schizophrenia. Am J Psychiatry. ;168(6):603-9. doi: 10.1176/appi.ajp.2011.10081224. Epub 2011 Mar 1. Erratum in: \u003cem\u003eAm J Psychiatry.\u003c/em\u003e 2012;169(2):223. PMID: 21362741.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJournal article Tiihonen, J., Mittendorfer-Rutz, E., Majak, M., et al. (2017). Real-World Effectiveness of Antipsychotic Treatments in a Nationwide Cohort of 29 823 Patients With Schizophrenia. \u003cem\u003eJAMA Psychiatry\u003c/em\u003e, \u003cem\u003e74\u003c/em\u003e(7), 686\u0026ndash;693. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1001/jamapsychiatry.2017.1322\u003c/span\u003e\u003cspan address=\"10.1001/jamapsychiatry.2017.1322\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJournal article Weiser, M., Davis, J. M., Brown, C. H., Slade, E. P., Fang, L. J., Medoff, D. R., Buchanan, R. W., Levi, L., Davidson, M., \u0026amp; Kreyenbuhl, J. (2021). Differences in Antipsychotic Treatment Discontinuation Among Veterans With Schizophrenia in the U.S. Department of Veterans Affairs. \u003cem\u003eAm J Psychiatry.\u003c/em\u003e ;178(10):932\u0026ndash;940. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1176/appi.ajp.2020.20111657\u003c/span\u003e\u003cspan address=\"10.1176/appi.ajp.2020.20111657\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Epub 2021 Jul 14. PMID: 34256606.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"CATIE, antipsychotic, attitudes, survey","lastPublishedDoi":"10.21203/rs.3.rs-8770465/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8770465/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective:\u003c/h2\u003e \u003cp\u003eThe Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study has had a lasting impact on the treatment of schizophrenia, yet its current role in psychiatric education and treatment policy remains unclear. This study aimed to assess how the CATIE trial is taught in U.S. psychiatry residency programs and whether its findings influence state-level treatment protocols.\u003c/p\u003e\u003ch2\u003eMethods:\u003c/h2\u003e \u003cp\u003eA cross-sectional mixed-methods survey was distributed to U.S. psychiatry residency program directors and members of the National Association of State Mental Health Program Directors (NASMHPD) Medical Directors Council. The survey included closed-ended and open-ended questions assessing the educational and policy relevance of the CATIE study. Quantitative data were summarized descriptively, and qualitative responses were analyzed thematically and categorized by sentiment. Participation was voluntary and anonymous, and institutional review board exemption was obtained.\u003c/p\u003e\u003ch2\u003eResults:\u003c/h2\u003e \u003cp\u003eA total of 75 responses were analyzed, including 60 psychiatry residency program directors and 15 NASMHPD medical directors. Among residency directors, 57% reported teaching the CATIE study for its clinical significance, 32% for its historical relevance, and 12% did not routinely include it in training. In contrast, 80% of state medical directors reported that CATIE findings no longer inform treatment protocols or formulary decisions. Qualitative responses highlighted CATIE\u0026rsquo;s continued educational value for teaching study design, clinical decision-making, and the evolution of antipsychotic therapy, while also noting concerns regarding generalizability. These findings underscore a widening gap between academic instruction and policy application of psychiatric evidence.\u003c/p\u003e\u003ch2\u003eConclusions:\u003c/h2\u003e \u003cp\u003eThe CATIE study continues to serve as a valuable educational tool in psychiatric training, yet its influence on state-level clinical policy appears limited. These findings highlight a divergence between academic and institutional priorities and suggest a need for updated research that reflects contemporary clinical realities and pharmacologic advancements.\u003c/p\u003e","manuscriptTitle":"The Legacy Impact of the CATIE Study on Healthcare Policy and Psychiatric Resident Education: A Cross-Sectional Mixed-methods Survey of U.S. Psychiatry Residency and State Medical Directors","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-05 19:12:09","doi":"10.21203/rs.3.rs-8770465/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"536ea68b-d5f6-4d01-aee4-f7431addb5c2","owner":[],"postedDate":"February 5th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-04-22T12:09:21+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-05 19:12:09","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8770465","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8770465","identity":"rs-8770465","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}