title: The cost of relapse for patients with a manic/mixed episode of bipolar disorder in the EMBLEM study.
abstract: BACKGROUND
  Bipolar disorder (BD) is characterized by episodes of mania and depression. The debilitating symptoms during an acute episode require intensive treatment, frequently leading to inpatient psychiatric care, which places significant demands on health and social care systems and incurs substantial costs. However, no study to date has estimated the economic impact of relapse.
  
  
  OBJECTIVE
  To estimate the direct costs associated with relapse in the treatment of BD following an acute manic or mixed episode over a 21-month follow-up period in routine clinical practice in Europe, using data from a large, prospective, observational study.
  
  
  METHODS
  EMBLEM was a prospective, observational study on the outcomes of patients with a manic/mixed episode of BD conducted in 14 European countries. Patients eligible for analysis were those enrolled in the 21-month maintenance phase of the study, following the 3-month acute phase. Relapse was defined as achieving any one of the following criteria: (i) at least a one-point increase in Clinical Global Impression - Bipolar Disorder (CGI-BP) overall score from the previous visit, with a final rating of > or =4; (ii) inpatient admission for an acute episode of BD; or (iii) psychiatrists' confirmation of relapse. Data on healthcare resource use were recorded retrospectively for the four respective periods (3-6, 6-12, 12-18 and 18-24 month visits). Multivariate analyses were performed to compare the cost of resource use (inpatient stay, day care, psychiatrist visits and medication) for those who relapsed during the 21-month maintenance phase and those who never relapsed. A sensitivity analysis was also conducted to examine the 6-month costs during relapse. The analyses were adjusted for patient characteristics and took account of non-Normality of the cost data by using a log link function. UK unit costs were applied to resource use. The analysis was repeated after multiple imputation for missing data. All costs were presented as year 2007/08 values.
  
  
  RESULTS
  A total of 1379 patients completed all visits during the maintenance phase and were eligible for inclusion in the present analysis. Of these, over half (54.3%) experienced relapse during this period. A total of 792 patients without any missing data were eventually included in the final cost model. Costs incurred by patients who relapsed during the 21-month maintenance phase were approximately double those incurred by patients who never relapsed (pounds sterling 9140 vs pounds sterling 4457; p < 0.05). Of the cost difference, 80.3% was accounted for by inpatient stay. Estimates on the economic impact were higher (pounds sterling 11,781 vs pounds sterling 4789; p < 0.05) in the additional analysis with imputed missing data. The impact of relapse was even greater in the 6-month cost comparison. The average 6-month costs for patients who relapsed were found to be about three times higher than for those who did not relapse (pounds sterling 4083 vs pounds sterling 1298; p < 0.05).
  
  
  CONCLUSIONS
  Our findings confirm the significant economic impact of relapse in BD patients after an acute manic or mixed episode, even when considering direct costs only. Such costs were dominated by inpatient stay. Nevertheless, the use of UK unit costs requires caution when interpreting this costing in the context of a specific country, as resource use and the associated costs will differ by country.
authors.affiliation: Personal Social Services Research Unit, London School of Economics and Political Science, London, UK. j.hong@lse.ac.uk
authors.forename: Jihyung
authors.initials: J
authors.lastname: Hong
authors.forename: Catherine
authors.initials: C
authors.lastname: Reed
authors.forename: Diego
authors.initials: D
authors.lastname: Novick
authors.forename: Josep Maria
authors.initials: JM
authors.lastname: Haro
authors.forename: Frank
authors.initials: F
authors.lastname: Windmeijer
authors.forename: Martin
authors.initials: M
authors.lastname: Knapp
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000191:economics* / Q000517:prevention & control*; D003365:Costs and Cost Analysis; D005060:Europe; D005260:Female; D005500:Follow-Up Studies; D017048:Health Care Costs; D006801:Humans; D008297:Male; D018803:Models, Economic; D015999:Multivariate Analysis; D011446:Prospective Studies; D055502:Secondary Prevention; D012959:Socioeconomic Factors; D016896:Treatment Outcome
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