Duration of prior psychotic illness and clozapine response: a retrospective observational study using electronic health records

Rowena Jones, Rachel Upthegrove, Malcolm Price, Megan Pritchard, Joht Chandan, Sophie Legge , James MacCabe

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Background: Clozapine is the gold-standard medication for treatment-resistant schizophrenia (TRS) yet its initiation is often delayed.

Objective: To examine whether earlier initiation of clozapine in TRS is associated with lower Clinical Global Impression – Severity (CGI-S) scores at 2 years.

Methods: This was a retrospective cohort study from electronic health records of patients with first adequate trial of clozapine at the South London and Maudsley mental health service between 1 January 2007 and 31 December 2016. Dates of illness onset and clozapine commencement were manually extracted from anonymised case notes. CGI-S scores were rated blind to illness duration. Ordinal logistic regression was used to describe the association between illness duration at baseline and CGI-S outcome score at 2 years, following adjustment for CGI-S start score and other key covariates.

Results: Among the 401 patients included, there was an association between illness duration and CGI-S outcome score with a 4% increase in the odds of a higher (worse) outcome CGI-S score per year of illness [adjusted odds ratio (AOR) = 1.04; 95% confidence interval (CI): 1.01–1.06]. The association between illness duration and clozapine response was most marked at less than 4 years illness duration. There were too few clozapine initiations within the first 2 years of illness to draw any conclusions about early clozapine initiation.

Conclusion: Initiation of clozapine within 2–4 years of psychotic illness onset offers the best outcome for TRS, but the advantage, if any, of earlier initiation is unclear from these data.
Original languageEnglish
Pages (from-to)1-12
Number of pages12
JournalTherapeutic advances in psychopharmacology
Publication statusPublished - 20 Jun 2022


  • clozapine
  • treatment-resistant schizophrenia
  • early intervention services


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