Clinical correlates of early onset antipsychotic treatment resistance

Daniela Fonseca de Freitas, Deborah Agbedjro, Giouliana Kadra-Scalzo, Emma Francis, Isobel Ridler, Megan Pritchard, Hitesh Shetty, Aviv Segev, Cecilia Casetta, Sophie E. Smart, Anna Morris, Johnny Downs, Søren Rahn Christensen, Nikolaj Bak, Bruce J. Kinon, Daniel Stahl, Richard D. Hayes, James H. MacCabe

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Background: There is evidence of heterogeneity within treatment-resistant schizophrenia (TRS), with some people not responding to antipsychotic treatment from illness onset and others becoming treatment-resistant after an initial response period. These groups may have different aetiologies.

Aim: This study investigates sociodemographic and clinical correlates of early onset of TRS.

Method: Employing a retrospective cohort design, we do a secondary analysis of data from a cohort of people with TRS attending the South London and Maudsley. Regression analyses were conducted to identify the correlates of the length of treatment to TRS. Predictors included the following: gender, age, ethnicity, problems with positive symptoms, problems with activities of daily living, psychiatric comorbidities, involuntary hospitalisation and treatment with long-acting injectable antipsychotics.

Results: In a cohort of 164 people with TRS (60% were men), the median length of treatment to TRS was 3 years and 8 months. We observed no cut-off on the length of treatment until TRS presentation differentiating between early and late TRS (i.e. no bimodal distribution). Having mild to very severe problems with hallucinations and delusions at the treatment start was associated with earlier TRS (~19 months earlier). In sensitivity analyses, including only complete cases (subject to selection bias), treatment with a long-acting injectable antipsychotic was additionally associated with later TRS (~15 months later).

Conclusion: Our findings do not support a clear separation between early and late TRS but rather a continuum of the length of treatment before TRS onset. Having mild to very severe problems with positive symptoms at treatment start predicts earlier onset of TRS.
Original languageEnglish
Pages (from-to)1226-1233
Number of pages8
JournalJournal of Psychopharmacology
Issue number11
Early online date21 Oct 2022
Publication statusPublished - 1 Nov 2022


  • Psychotic disorders
  • antipsychotic agents
  • clozapine
  • schizophrenia
  • treatment refractory

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