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.

Centre for Public Health Institute of Clinical Sciences Queens University Belfast Belfast UK

Centro de Investigacion en Red Salud Mental Santander Spain; Department of Medicine and Psychiatry School of Medicine University of Cantabria Santander Spain

Centro de Investigacion en Red Salud Mental Sevilla Spain; Department of Psychiatry Hospital Universitario Virgen del Rocio IBiS Universidad de Sevilla Spain

Department of Applied Neuroscience and Neuroimaging National Institute of Mental Health Klecany Czechia; Department of Psychiatry and Medical Psychology 3rd Faculty of Medicine Charles University Prague Czechia

Department of Biomedical and Neuro motor Sciences Psychiatry Unit Alma Mater Studiorum Università di Bologna Bologna Italy

Department of Biostatistics and Health Informatics Institute of Psychiatry Psychology and Neuroscience King's College London London UK

Department of Biostatistics and Health Informatics Institute of Psychiatry Psychology and Neuroscience King's College London London UK; Department of Behavioural Science and Health Institute of Epidemiology and Health Care University College London London UK

Department of Clinical and Movement Neuroscience UCL Queen Square Institute of Neurology University College London London UK

Department of Medical and Surgical Sciences Bologna Transcultural Psychosomatic Team Alma Mater Studiorum University of Bologna Bologna Italy

Department of Medical Education University of Nottingham Faculty of Medicine and Health Sciences Nottingham UK

Department of Psychosis Studies Institute of Psychiatry Psychology and Neuroscience King's College London London UK

Department of Psychosis Studies Institute of Psychiatry Psychology and Neuroscience King's College London London UK; Centro de Investigacion en Red Salud Mental Lausanne Switzerland

Department of Psychosis Studies Institute of Psychiatry Psychology and Neuroscience King's College London London UK; South London and Maudsley NHS Foundation Trust London UK

Disability Research Division Department of Behavioural Sciences and Learning Linköping University Linköping Sweden

Division of Psychiatry Imperial College London UK

Health Service and Population Research King's College London London UK; Centre for Society and Mental Health King's College London London UK

Istanbul University Istanbul Faculty of Medicine Department of Psychiatry Istanbul Turkey

MRC Centre for Neuropsychiatric Genetics and Genomics Division of Psychological Medicine and Clinical Neurosciences Cardiff University Cardiff UK

MRC Centre for Neuropsychiatric Genetics and Genomics Division of Psychological Medicine and Clinical Neurosciences Cardiff University Cardiff UK; Department of Psychosis Studies Institute of Psychiatry Psychology and Neuroscience King's College London London UK

Norwegian Centre for Mental Disorders Research Division of Mental Health and Addiction Oslo University Hospital Norway

Norwegian Centre for Mental Disorders Research Institute of Clinical Medicine University of Oslo Oslo Norway; Division of Mental Health and Addiction Oslo University Hospital Oslo Norway

Social Genetics and Developmental Psychiatry Institute of Psychiatry Psychology and Neuroscience King's College London London UK; South London and Maudsley NHS Foundation Trust London UK

TIPP Lausanne Switzerland

Unit for Research in Schizophrenia Center for Psychiatric Neuroscience Department of Psychiatry Lausanne University Hospital Lausanne Switzerland

Unit of Pharmacogenetics and Clinical Psychopharmacology Centre for Psychiatric Neuroscience Department of Psychiatry Lausanne University Hospital University of Lausanne Prilly Switzerland; School of Pharmaceutical Sciences University of Geneva University of Lausanne Geneva Switzerland; Center for Research and Innovation in Clinical Pharmaceutical Sciences University of Lausanne Switzerland; Institute of Pharmaceutical Sciences of Western Switzerland University of Geneva University of Lausanne

Univ Paris Est Creteil INSERM IMRB Translational Neuropsychiatry Fondation FondaMental Creteil France

Univ Paris Est Creteil INSERM IMRB Translational Neuropsychiatry Fondation FondaMental Creteil France; AP HP Hôpitaux Universitaires H Mondor DMU IMPACT FHU ADAPT Creteil France

Univ Paris Est Creteil INSERM IMRB Translational Neuropsychiatry Fondation FondaMental Creteil France; Groupe Hospitalier Universitaire Psychiatrie Neurosciences Paris Pôle Psychiatrie Précarité Paris France

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