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

Sophie E. Smart*, Deborah Agbedjro, Antonio F. Pardiñas, Olesya Ajnakina, Luis Alameda, Ole A. Andreassen, Thomas R.E. Barnes, Domenico Berardi, Sara Camporesi, Martine Cleusix, Philippe Conus, Benedicto Crespo-Facorro, Giuseppe D'Andrea, Arsime Demjaha, Marta Di Forti, Kim Do, Gillian Doody, Chin B. Eap, Aziz Ferchiou, Lorenzo GuidiLina Homman, Raoul Jenni, Eileen Joyce, Laura Kassoumeri, Ornella Lastrina, Ingrid Melle, Craig Morgan, Francis A. O'Neill, Baptiste Pignon, Romeo Restellini, Jean Romain Richard, Carmen Simonsen, Filip Španiel, Andrei Szöke, Ilaria Tarricone, Andrea Tortelli, Alp Üçok, Javier Vázquez-Bourgon, Robin M. Murray, James T.R. Walters, Daniel Stahl, James H. MacCabe

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)
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Introduction: Our 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. Methods: We 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. Results: Our 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 %). Implications: Our 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.

Original languageEnglish
Pages (from-to)1-9
Number of pages9
JournalSchizophrenia Research
Publication statusPublished - Dec 2022


  • First episode psychosis
  • Machine learning
  • Prediction modelling
  • Prospective longitudinal cohort
  • Stratification
  • Treatment resistant schizophrenia


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