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Clinical predictors of antipsychotic treatment resistance: Development and internal validation of a prognostic prediction model by the STRATA-G consortium

Smart, Sophie E. ORCID:, Agbedjro, Deborah, Pardinas, Antonio F. ORCID:, Ajnakina, Olesya, Alameda, Luis, Andreassen, Ole A., Barnes, Thomas R.E., Berardi, Domenico, Camporesi, Sara, Cleusix, Martine, Conus, Philippe, Crespo-Facorro, Benedicto, D'Andrea, Giuseppe, Demjaha, Arsime, Di Forti, Marta, Do, Kim, Doody, Gillian, Eap, Chin B., Ferchiou, Aziz, Guidi, Lorenzo, Homman, Lina, Jenni, Raoul, Joyce, Eileen, Kassoumeri, Laura, Lastrina, Ornella, Melle, Ingrid, Morgan, Craig, O'Neill, Francis A., Pignon, Baptiste, Restellini, Romeo, Richard, Jean-Romain, Simonsen, Carmen, ?paniel, Filip, Szöke, Andrei, Tarricone, Ilaria, Tortelli, Andrea, Üçok, Alp, Vázquez-Bourgon, Javier, Murray, Robin M., Walters, James T.R. ORCID:, Stahl, Daniel and MacCabe, James H. 2022. Clinical predictors of antipsychotic treatment resistance: Development and internal validation of a prognostic prediction model by the STRATA-G consortium. Schizophrenia Research 250 , pp. 1-9. 10.1016/j.schres.2022.09.009

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IntroductionOur aim was to, firstly, identify characteristics at first-episode of psychosis that are associated with later antipsychotic treatment resistance (TR) and, secondly, to develop a parsimonious prediction model for TR.MethodsWe combined data from ten prospective, first-episode psychosis cohorts from across Europe and categorised patients as TR or non-treatment resistant (NTR) after a mean follow up of 4.18 years (s.d. = 3.20) for secondary data analysis. We identified a list of potential predictors from clinical and demographic data recorded at first-episode. These potential predictors were entered in two models: a multivariable logistic regression to identify which were independently associated with TR and a penalised logistic regression, which performed variable selection, to produce a parsimonious prediction model. This model was internally validated using a 5-fold, 50-repeat cross-validation optimism-correction.ResultsOur sample consisted of N = 2216 participants of which 385 (17 %) developed TR. Younger age of psychosis onset and fewer years in education were independently associated with increased odds of developing TR. The prediction model selected 7 out of 17 variables that, when combined, could quantify the risk of being TR better than chance. These included age of onset, years in education, gender, BMI, relationship status, alcohol use, and positive symptoms. The optimism-corrected area under the curve was 0.59 (accuracy = 64 %, sensitivity = 48 %, and specificity = 76 %).ImplicationsOur findings show that treatment resistance can be predicted, at first-episode of psychosis. Pending a model update and external validation, we demonstrate the potential value of prediction models for TR.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Publisher: Elsevier
ISSN: 0920-9964
Funders: MRC
Date of First Compliant Deposit: 1 November 2022
Date of Acceptance: 4 September 2022
Last Modified: 15 Jun 2023 18:03

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