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

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.
Competing Interests: Declaration of competing interest The Authors declare no Competing Non-Financial Interests but the following Competing Financial Interests: J.T.R.W. is an investigator on a grant from Takeda Pharmaceuticals Ltd. to Cardiff University, for a project unrelated to the work presented here. S.E.S. is employed on this grant. M.D.F. has received a fee for educational seminars from Lundbeck and Janssen. O.A.A. is a consultant to HealthLytix and has received speakers honorarium from Lundbeck and Sunovion. T.R.E.B. has been a member of an advisory board for Gedeon Richter. C.B.E. received honoraria for conferences from Forum pour la formation médicale, Janssen-Cilag, Lundbeck, Otsuka, Sandoz, Servier, Sunovion, Sysmex Suisse AG, Takeda, Vifor-Pharma, and Zeller in the past 3 years. B.C.F. has received honoraria for participation as a consultant and/or as a speaker at educational events from ADAMED, Mylan, Angelini, Janssen Johnson & Johnson, Lundbeck, and Otsuka Pharmaceuticals. R.M.M. has received payments for non-promotional lectures from Janssen, Otsuka, Sunovian, and Lundbeck. J.H.M. has received research funding from H Lundbeck.
(Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)