title: Clozapine use reduced psychiatric hospitalization and emergency room visits in patients with bipolar disorder independent of improved treatment regularity in a three-year follow-up period.
abstract: OBJECTIVE
  The efficacy of clozapine in bipolar disorder remains to be systemically examined. In the current study, we sought to disentangle the effect of clozapine from that of improved treatment regularity and to compare the effect of clozapine with the effect of regular treatment for bipolar disorder by exploring the complete 10-year clozapine prescription data from a Taiwanese total population health claims database.
  
  
  METHODS
  In the period between 2000 and 2009, 3,874 (3.3%) out of the 117,785 patients identified as having bipolar disorder in a Taiwanese total population health claims database were ever prescribed clozapine. Among them, 920 patients with bipolar disorder who had good pre-clozapine medication compliance and received at least two clozapine prescriptions were further categorized according to their clozapine medication possession ratio (MPR) as regular users (MPR ≥ 0.8; n = 476) and irregular users (MPR < 0.8; n = 444). Using a mirror-image design, we compared the numbers of emergency room (ER) visits, hospitalizations and hospital days, and the average durations of a single hospitalization during the pre- and post-clozapine mirror periods with a follow-up time of up to three years, controlling for time-variant course confounders.
  
  
  RESULTS
  The patterns of change in outcome indices from the pre-clozapine period to the post-clozapine period differed significantly between the two clozapine-user groups. Clinical outcome indices improved only in regular users, while they deteriorated in irregular users. Over the three-year follow-up period, the irregular users consistently had a higher adjusted risk for increased numbers of ER visits [odds ratio (OR): 2.06-2.43], hospitalizations (OR: 2.52-3.22), and total hospital days (OR: 2.42-2.91) when compared to the regular users. Thus, effects of clozapine were consistently demonstrated in one- to three-year mirror comparison periods.
  
  
  CONCLUSIONS
  Clozapine, when used with high treatment regularity (MPR > 0.8), was effective in reducing the numbers of ER visits, hospitalizations, and total hospital days in patients with bipolar disorder with previous frequent hospitalizations and ER visits despite regular pre-clozapine treatment for bipolar disorder. However, high early attrition and suboptimal treatment compliance need to be rectified in order to optimize the outcome of clozapine treatment in bipolar disorders.
authors.affiliation: Department of Psychiatry, Far Eastern Memorial Hospital, New Taipei City, Taiwan.|Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.
authors.forename: Chi-Shin
authors.initials: CS
authors.lastname: Wu
authors.affiliation: Center for Neuropsychiatric Research, National Health Research Institutes, Miaoli, Taiwan.
authors.forename: Sheng-Chang
authors.initials: SC
authors.lastname: Wang
authors.affiliation: Centre for Addiction and Mental Health, Toronto, ON, Canada.|Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
authors.forename: Shi-Kai
authors.initials: SK
authors.lastname: Liu
mesh_terms: D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D003024:Clozapine / Q000627:therapeutic use*; D004636:Emergency Service, Hospital / Q000706:statistics & numerical data*; D005260:Female; D005500:Follow-Up Studies; D006760:Hospitalization / Q000706:statistics & numerical data*; D006801:Humans; D007902:Length of Stay / Q000706:statistics & numerical data; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D013624:Taiwan; D014600:Utilization Review
chemical_list: D014150:Antipsychotic Agents; D003024:Clozapine
keywords: bipolar disorder; clozapine; hospitalization; medication possession ratio (MPR); treatment regularity