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Two distinct patterns of treatment resistance: clinical predictors of treatment resistance in first-episode schizophrenia spectrum psychoses

  • J. Lally (a1) (a2) (a3), O. Ajnakina (a1), M. Di Forti (a4), A. Trotta (a1), A. Demjaha (a1), A. Kolliakou (a5), V. Mondelli (a6) (a5), T. Reis Marques (a1), C. Pariante (a6) (a5), P. Dazzan (a1) (a6), S. S. Shergil (a1) (a2) (a6), O. D. Howes (a1) (a7), A. S. David (a1) (a6), J. H. MacCabe (a1) (a2), F. Gaughran (a1) (a2) and R. M. Murray (a1) (a2)...

Clozapine remains the only evidence-based antipsychotic for treatment-resistant schizophrenia (TRS). The ability to predict which patients with their first onset of schizophrenia would subsequently meet criteria for treatment resistance (TR) could help to diminish the severe functional disability which may ensue if TR is not recognized and correctly treated.


This is a 5-year longitudinal assessment of clinical outcomes in a cohort of 246 first-episode schizophrenia spectrum patients recruited as part of the NIHR Genetics and Psychosis (GAP) study conducted in South London from 2005 to 2010. We examined the relationship between baseline demographic and clinical measures and the emergence of TR. TR status was determined from a review of electronic case records. We assessed for associations with early-, and late-onset TR, and non-TR, and differences between those TR patients treated with clozapine and those who were not.


Seventy per cent (n = 56) of TR patients, and 23% of the total study population (n = 246) were treatment resistant from illness onset. Those who met criteria for TR during the first 5 years of illness were more likely to have an early age of first contact for psychosis (<20 years) [odds ratio (OR) 2.49, 95% confidence interval (CI) 1.25–4.94] compared to those with non-TR. The relationship between an early age of first contact (<20 years) and TR was significant in patients of Black ethnicity (OR 3.71, 95% CI 1.44–9.56); and patients of male gender (OR 3.13 95% CI 1.35–7.23).


For the majority of the TR group, antipsychotic TR is present from illness onset, necessitating increased consideration for the earlier use of clozapine.

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Corresponding author
*Address for correspondence: Dr J. Lally, Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, London, UK. (Email:
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