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Prevalence of treatment resistance and clozapine use in early intervention services

  • Stokes, Imogen1
  • Griffiths, Siân Lowri1
  • Jones, Rowena2
  • Everard, Linda2
  • Jones, Peter B.3
  • Fowler, David4
  • Hodgekins, Joanne5
  • Amos, Tim6
  • Freemantle, Nick7
  • Sharma, Vimal8
  • Marshall, Max9
  • Singh, Swaran P.10
  • Birchwood, Max11
  • Upthegrove, Rachel10
  • 1 University of Birmingham, UK
  • 2 Research and Innovation, Birmingham and Solihull Mental Health Foundation Trust, UK
  • 3 University of Cambridge, UK
  • 4 University of Sussex, UK
  • 5 University of East Anglia, UK
  • 6 University of Bristol, UK
  • 7 University College London, UK
  • 8 University of Chester, UK
  • 9 Lancashire Care NHS Foundation Trust, UK
  • 10 Birmingham Women's and Children's NHS Trust, UK
  • 11 University of Warwick, UK
Published Article
BJPsych Open
Cambridge University Press
Publication Date
Sep 07, 2020
DOI: 10.1192/bjo.2020.89
PMID: 32938513
PMCID: PMC7576650
PubMed Central


Background Treatment resistance causes significant burden in psychosis. Clozapine is the only evidence-based pharmacologic intervention available for people with treatment-resistant schizophrenia; current guidelines recommend commencement after two unsuccessful trials of standard antipsychotics. Aims This paper aims to explore the prevalence of treatment resistance and pathways to commencement of clozapine in UK early intervention in psychosis (EIP) services. Method Data were taken from the National Evaluation of the Development and Impact of Early Intervention Services study ( N = 1027) and included demographics, medication history and psychosis symptoms measured by the Positive and Negative Syndrome Scale (PANSS) at baseline, 6 months and 12 months. Prescribing patterns and pathways to clozapine were examined. We adopted a strict criterion for treatment resistance, defined as persistent elevated positive symptoms (a PANSS positive score ≥16, equating to at least two items of at least moderate severity), across three time points. Results A total of 143 (18.1%) participants met the definition of treatment resistance of having continuous positive symptoms over 12 months, despite treatment in EIP services. Sixty-one (7.7%) participants were treatment resistant and eligible for clozapine, having had two trials of standard antipsychotics; however, only 25 (2.4%) were prescribed clozapine over the 12-month study period. Treatment-resistant participants were more likely to be prescribed additional antipsychotic medication and polypharmacy, instead of clozapine. Conclusions Prevalent treatment resistance was observed in UK EIP services, but prescription of polypharmacy was much more common than clozapine. Significant delays in the commencement of clozapine may reflect a missed opportunity to promote recovery in this critical period.

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