title: Reasons for discontinuing clozapine: A cohort study of patients commencing treatment.
abstract: Clozapine is uniquely effective in the management of treatment-resistant schizophrenia (TRS). However, a substantial proportion of patients discontinue treatment and this carries a poor prognosis.
  
  
  
  We investigated the risk factors, reasons and timing of clozapine discontinuation in a two-year retrospective cohort study of 316 patients with TRS receiving their first course of clozapine. Reasons for discontinuation of clozapine and duration of treatment were obtained from case notes and Cox regression was employed to test the association of baseline clinical factors with clozapine discontinuation.
  
  
  
  A total of 142 (45%) patients discontinued clozapine within two years. By studying the reasons for discontinuations due to a patient decision, we found that adverse drug reactions (ADRs) accounted for over half of clozapine discontinuations. Sedation was the most common ADR cited as a reason for discontinuation and the risk of discontinuation due to ADRs was highest in the first few months of clozapine treatment. High levels of deprivation in the neighbourhood where the patient lived were associated with increased risk of clozapine discontinuation (HR=2.12, 95% CI 1.30-3.47).
  
  
  
  Living in a deprived neighbourhood was strongly associated with clozapine discontinuation. Clinical management to reduce the burden of ADRs in the first few months of treatment may have a significant impact and help more patients experience the benefits of clozapine treatment.
authors.affiliation: Division of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, School of Medicine, Cardiff University, Cardiff, UK.
authors.forename: Sophie E
authors.initials: SE
authors.lastname: Legge
authors.affiliation: Division of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, School of Medicine, Cardiff University, Cardiff, UK.
authors.forename: Marian
authors.initials: M
authors.lastname: Hamshere
authors.affiliation: Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Hayes
authors.affiliation: Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK.
authors.forename: Johnny
authors.initials: J
authors.lastname: Downs
authors.affiliation: Division of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, School of Medicine, Cardiff University, Cardiff, UK.
authors.forename: Michael C
authors.initials: MC
authors.lastname: O'Donovan
authors.affiliation: Division of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, School of Medicine, Cardiff University, Cardiff, UK.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Owen
authors.affiliation: Division of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, School of Medicine, Cardiff University, Cardiff, UK. Electronic address: WaltersJT@Cardiff.ac.uk.
authors.forename: James T R
authors.initials: JTR
authors.lastname: Walters
authors.affiliation: Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK; Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK.
authors.forename: James H
authors.initials: JH
authors.lastname: MacCabe
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D003024:Clozapine / Q000009:adverse effects* / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008131:London; D008297:Male; D008875:Middle Aged; D010352:Patient Dropouts; D016016:Proportional Hazards Models; D011618:Psychotic Disorders / Q000188:drug therapy / Q000453:epidemiology; D012042:Registries; D012189:Retrospective Studies; D012307:Risk Factors; D012559:Schizophrenia / Q000188:drug therapy / Q000453:epidemiology; D013997:Time Factors; D028761:Withholding Treatment; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D003024:Clozapine
keywords: Cessation; Clozapine; Discontinuation; Schizophrenia; Treatment-resistant schizophrenia