title: Design and protocol for the Focusing on Clozapine Unresponsive Symptoms (FOCUS) trial: a randomised controlled trial.
abstract: For around a third of people with a diagnosis of schizophrenia, the condition proves to respond poorly to treatment with many typical and atypical antipsychotics. This is commonly referred to as treatment-resistant schizophrenia. Clozapine is the only antipsychotic with convincing efficacy for people whose symptoms are considered treatment-resistant to antipsychotic medication. However, 30-40 % of such conditions will have an insufficient response to the drug. Cognitive behavioural therapy has been shown to be an effective treatment for schizophrenia when delivered in combination with antipsychotic medication, with several meta-analyses showing robust support for this approach. However, the evidence for the effectiveness of cognitive behavioural therapy for people with a schizophrenia diagnosis whose symptoms are treatment-resistant to antipsychotic medication is limited. There is a clinical and economic need to evaluate treatments to improve outcomes for people with such conditions.
  
  
  
  A parallel group, prospective randomised, open, blinded evaluation of outcomes design will be used to compare a standardised cognitive behavioural therapy intervention added to treatment as usual versus treatment as usual alone (the comparator group) for individuals with a diagnosis of schizophrenia for whom an adequate trial of clozapine has either not been possible due to tolerability problems or was not associated with a sufficient therapeutic response. The trial will be conducted across five sites in the United Kingdom.
  
  
  
  The recruitment target of 485 was achieved, with a final recruitment total of 487. This trial is the largest definitive, pragmatic clinical and cost-effectiveness trial of cognitive behavioural therapy for people with schizophrenia whose symptoms have failed to show an adequate response to clozapine treatment. Using a prognostic risk model, baseline information will be used to explore whether there are identifiable subgroups for which the treatment effect is greatest.
  
  
  
  Current Controlled Trials ISRCTN99672552 . Registered 29(th) November 2012.
authors: The Psychosis Research Unit, Department of Psychology, Greater Manchester West Mental Health NHS Foundation Trust, Prestwich, M25 3BL, UK.|Department of Psychology, University of Manchester, Zochonis Building, Manchester, M13 9PL, UK.
authors: Melissa
authors: M
authors: Pyle
authors: Centre for Healthcare Randomised Trials, Health Services Research Unit, University of Aberdeen, 3rd Floor Health Sciences Building, Aberdeen, AB25 2ZD, UK.
authors: John
authors: J
authors: Norrie
authors: Department of Clinical Psychology, University of Edinburgh. Medical School, Teviot Place, Edinburgh, EHY8 9AG, UK. m.schwannauer@ed.ac.uk.
authors: Matthias
authors: 0000-0002-4683-2596
authors: M
authors: Schwannauer
authors: University Department of Psychiatry, University of Southampton, Academic Centre, College Keep 4 - 12 Terminus Terrace, Southampton, SO14 3DT, UK.
authors: David
authors: D
authors: Kingdon
authors: Institute of Health and Wellbeing, University of Glasgow, Gartnavel Royal Hospital, 1055 Great Western Road, Glasgow, G12 0XH, UK.
authors: Andrew
authors: A
authors: Gumley
authors: Academic Psychiatry, Northumberland, Tyne and Wear NHS Foundation Trust, Centre for Aging and Vitality, Newcastle General Hospital, Westgate Road, Newcastle upon Tyne, NE4 6BE, UK.
authors: Douglas
authors: D
authors: Turkington
authors: The Psychosis Research Unit, Department of Psychology, Greater Manchester West Mental Health NHS Foundation Trust, Prestwich, M25 3BL, UK.|Department of Psychology, University of Manchester, Zochonis Building, Manchester, M13 9PL, UK.
authors: Rory
authors: R
authors: Byrne
authors: Institute of Health and Wellbeing, University of Glasgow, Gartnavel Royal Hospital, 1055 Great Western Road, Glasgow, G12 0XH, UK.
authors: Suzy
authors: S
authors: Syrett
authors: Centre for Healthcare Randomised Trials, Health Services Research Unit, University of Aberdeen, 3rd Floor Health Sciences Building, Aberdeen, AB25 2ZD, UK.
authors: Graeme
authors: G
authors: MacLennan
authors: School of Psychology, Newcastle University, 4th Floor, Ridley Building 1, Queen Victoria Road, Newcastle Upon Tyne, NE1 7RU, UK.
authors: Robert
authors: R
authors: Dudley
authors: Institute of Health and Wellbeing, University of Glasgow, Gartnavel Royal Hospital, 1055 Great Western Road, Glasgow, G12 0XH, UK.
authors: Hamish J
authors: HJ
authors: McLeod
authors: Department of Clinical Psychology, University of Edinburgh. Medical School, Teviot Place, Edinburgh, EHY8 9AG, UK.
authors: Helen
authors: H
authors: Griffiths
authors: The Psychosis Research Unit, Department of Psychology, Greater Manchester West Mental Health NHS Foundation Trust, Prestwich, M25 3BL, UK.
authors: Samantha
authors: S
authors: Bowe
authors: Centre for Mental Health, Imperial College London, Charing Cross Campus, St Dunstans Road, London, W6 8RP, UK.
authors: Thomas R E
authors: TR
authors: Barnes
authors: The Psychosis Research Unit, Department of Psychology, Greater Manchester West Mental Health NHS Foundation Trust, Prestwich, M25 3BL, UK.|Institute of Psychology, Health and Society, University of Liverpool, Waterhouse Building, Block B, 2nd Floor, Liverpool, L69 3BX, UK.
authors: Paul
authors: P
authors: French
authors: Department of Clinical Psychology, University of Edinburgh. Medical School, Teviot Place, Edinburgh, EHY8 9AG, UK.
authors: Paul
authors: P
authors: Hutton
authors: Department of Psychology, University of Manchester, Zochonis Building, Manchester, M13 9PL, UK.
authors: Linda
authors: L
authors: Davies
authors: The Psychosis Research Unit, Department of Psychology, Greater Manchester West Mental Health NHS Foundation Trust, Prestwich, M25 3BL, UK.|Department of Psychology, University of Manchester, Zochonis Building, Manchester, M13 9PL, UK.
authors: Anthony P
authors: AP
authors: Morrison
mesh_terms: D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use; D002985:Clinical Protocols; D003024:Clozapine / Q000627:therapeutic use*; D015928:Cognitive Behavioral Therapy; D003131:Combined Modality Therapy / Q000379:methods; D003362:Cost-Benefit Analysis; D004311:Double-Blind Method; D004351:Drug Resistance / Q000187:drug effects*; D005260:Female; D006801:Humans; D008297:Male; D019057:Quality-Adjusted Life Years; D012559:Schizophrenia / Q000188:drug therapy*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D003024:Clozapine
keywords: Clozapine-resistant; Cognitive behavioural therapy; Psychosis; Randomised controlled trial; Schizophrenia