title: Predictors of Nonhospitalization and Functional Response in Clozapine Treatment: A Nationwide, Population-Based Cohort Study.
abstract: BACKGROUND
  Clozapine remains the only evidence-based treatment for treatment-resistant schizophrenia, and prediction of clozapine response is important in developing stratified treatment. We studied potential predictors of clozapine response, applying functional assessments as well as service use.
  
  
  METHODS
  We performed a nationwide cohort study among all individuals diagnosed with schizophrenia in Denmark after 1995 (age, ≥18 years) who initiated clozapine treatment between 2004 and 2011 with a Global Assessment of Functioning (GAF-F) score registered at clozapine initiation. During up to 2-year follow-up, clinical response was defined as (a) no further hospitalization with schizophrenia or (b) improvement in GAF-F score (moderate improvement: increase, ≥10; substantial improvement: increase, ≥20; and GAF-F, ≥50). We performed Cox regression analysis and report adjusted hazard rate ratios (HRRs; 95% confidence intervals [95% CIs]).
  
  
  RESULTS
  Among 502 clozapine users with a registered GAF-F score, 232 (46.2%) remained out of hospital, 96 (19.1%) achieved moderate functional improvement, and 29 (5.8%) substantial functional improvement. Of all potential predictors, voluntary status at clozapine initiation showed borderline statistical significance with nonhospitalization (HRR, 1.61; 95% CI, 0.97-2.67). Regarding functional improvement, living with a partner was the strongest predictor with an almost threefold increased HRR (2.78; 95% CI, 1.07-7.23). Female sex was only nonsignificantly associated with functional improvement, whereas the chance of substantial improvement decreased by 15% (HRR, 0.85; 95% CI, 0.72-1.00) for each year delay in clozapine initiation among females.
  
  
  CONCLUSIONS
  Living with a partner was the strongest predictor of functioning after clozapine initiation in this study. Although potentially indicating better premorbid functioning, this finding stresses the need and importance of social support during the course of the treatment independent of clinical factors.
authors.affiliation: From the *National Centre for Register-based Research; †CRESTAR, Aarhus University, Aarhus, Denmark; ‡Psychosis Research Unit, Aarhus University Hospital, Risskov, Denmark; §Institute of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, School of Medicine, Cardiff University, Cardiff; ∥Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, United Kingdom; ¶Centre for Integrated Register-Based Research at Aarhus University (CIRRAU); and #iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark.
authors.forename: Ole
authors.initials: O
authors.lastname: Köhler-Forsberg
authors.forename: Henriette T
authors.initials: HT
authors.lastname: Horsdal
authors.forename: Sophie E
authors.initials: SE
authors.lastname: Legge
authors.forename: James H
authors.initials: JH
authors.lastname: MacCabe
authors.forename: Christiane
authors.initials: C
authors.lastname: Gasse
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D003024:Clozapine / Q000627:therapeutic use*; D015331:Cohort Studies; D003718:Denmark / Q000453:epidemiology; D005260:Female; D006760:Hospitalization / Q000706:statistics & numerical data*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care / Q000706:statistics & numerical data*; D012042:Registries / Q000706:statistics & numerical data*; D012559:Schizophrenia / Q000188:drug therapy* / Q000453:epidemiology; D012944:Social Support; D018454:Spouses / Q000706:statistics & numerical data*; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D003024:Clozapine