Antipsychotic treatment resistance in first-episode psychosis: prevalence, subtypes and predictors

A Demjaha*, J M Lappin, D Stahl, M X Patel, J H MacCabe, O D Howes, Margaret Heslin, U A Reininghaus, K Donoghue, B Lomas, M Charalambides, A Onyejiaka, P Fearon, P Jones, G Doody, C Morgan, P Dazzan, R M Murray

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

193 Citations (Scopus)
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BACKGROUND: We examined longitudinally the course and predictors of treatment resistance in a large cohort of first-episode psychosis (FEP) patients from initiation of antipsychotic treatment. We hypothesized that antipsychotic treatment resistance is: (a) present at illness onset; and (b) differentially associated with clinical and demographic factors.

METHOD: The study sample comprised 323 FEP patients who were studied at first contact and at 10-year follow-up. We collated clinical information on severity of symptoms, antipsychotic medication and treatment adherence during the follow-up period to determine the presence, course and predictors of treatment resistance.

RESULTS: From the 23% of the patients, who were treatment resistant, 84% were treatment resistant from illness onset. Multivariable regression analysis revealed that diagnosis of schizophrenia, negative symptoms, younger age at onset, and longer duration of untreated psychosis predicted treatment resistance from illness onset.

CONCLUSIONS: The striking majority of treatment-resistant patients do not respond to first-line antipsychotic treatment even at time of FEP. Clinicians must be alert to this subgroup of patients and consider clozapine treatment as early as possible during the first presentation of psychosis.

Original languageEnglish
Pages (from-to)1981-1989
Number of pages9
JournalPsychological Medicine
Issue number11
Early online date11 Apr 2017
Publication statusPublished - Aug 2017


  • Clozapine
  • First-Episode- Psychosis
  • Schizophrenia
  • Treatment-Resistant
  • Treatment-Response


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