Prevalence of treatment resistance and clozapine use in early intervention services

Research output: Contribution to journalArticlepeer-review


  • Imogen Stokes
  • Rowena Jones
  • Linda Everard
  • Peter B Jones
  • David Fowler
  • Joanne Hodgekins
  • Tim Amos
  • Nick Freemantle
  • Vimal Sharma
  • Max Marshall
  • Swaran P Singh
  • Max Birchwood

External organisations

  • Birmingham and Solihull Mental Health NHS Foundation Trust
  • University of Sussex
  • University of East Anglia
  • University Hospitals Bristol NHS Foundation Trust
  • Cheshire and Wirral Partnership NHS Foundation Trust
  • Lancashire Care NHS Foundation Trust
  • Birmingham Early Intervention Service
  • University of Warwick
  • University of Chester


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.


Original languageEnglish
Article numbere107
JournalBritish Journal of Psychiatry Open
Issue number5
Publication statusPublished - 17 Sep 2020


  • Treatment resistance, schizophrenia, clozapine, early psychosis, early intervention