title: Comparative effectiveness of risperidone long-acting injectable vs first-generation antipsychotic long-acting injectables in schizophrenia: results from a nationwide, retrospective inception cohort study.
abstract: OBJECTIVE
  To compare in a generalizable sample/setting objective outcomes in patients receiving first-generation antipsychotic long-acting injectables (FGA-LAIs) or risperidone-LAI (RIS-LAI).
  
  
  METHODS
  Nationwide, retrospective inception cohort study of adults with International Classification of Diseases-10 schizophrenia using Danish registers from 1995 to 2009 comparing outcomes between clinician's/patient's choice treatment with FGA-LAIs or RIS-LAI. Primary outcome was time to psychiatric hospitalization using Cox-regression adjusting for relevant covariates. Secondary outcomes included time to all-cause discontinuation and psychiatric hospitalization in patients without LAI possession gap >28 days, and number of bed-days after psychiatric hospitalization.
  
  
  RESULTS
  Among 4532 patients followed for 2700 patient-years, 2078 received RIS-LAI and 2454 received FGA-LAIs (zuclopenthixol decanoate = 52.2%, perphenazine decanoate = 37.2%, haloperidol decanoate = 5.0%, flupenthixol decanoate = 4.4%, fluphenazine decanoate = 1.3%). RIS-LAI was similar to FGA-LAIs regarding time to hospitalization (RIS-LAI = 246.2±323.7 days vs FGA-LAIs = 276.6±383.3 days; HR = 0.95, 95% confidence interval (CI) = 0.87-1.03, P = 0.199) and time to all-cause discontinuation (RIS-LAI = 245.8±324.0 days vs FGA-LAIs = 287.0±390.9 days; HR = 0.93, 95% CI = 0.86-1.02, P = 0.116). Similarly, in patients without LAI discontinuation, RIS-LAI and FGA-LAIs did not differ regarding time to hospitalization (RIS-LAI = 175.0±268.1 days vs FGA-LAIs = 210.7±325.3 days; HR = 0.95, 95% CI = 0.86-1.04, P = 0.254). Finally, duration of hospitalization was also similar (incidence rate ratio = 0.97, 95% CI = 0.78-1.19, P = 0.744). Results were unchanged when analyzing only patients treated after introduction of RIS-LAI.
  
  
  CONCLUSIONS
  In this nationwide cohort study, RIS-LAI was not superior to FGA-LAIs regarding time to psychiatric hospitalization, all-cause discontinuation, and duration of hospitalization. Given the cost of hospitalization and second-generation antipsychotic (SGA)-LAIs, these findings require consideration when making treatment choices, but also need to be balanced with the individual relevance of adverse effects/patient centered outcomes. In future, head-to-head trials and additional nationwide database studies including other SGA-LAIs is needed.
authors.affiliation: Department of Clinical Medicine, Aalborg University, Aalborg, Denmark; Aalborg University Hospital, Psychiatry, Aalborg, Denmark; jin@rn.dk.
authors.forename: Jimmi
authors.initials: J
authors.lastname: Nielsen
authors.affiliation: Aalborg University Hospital, Psychiatry, Aalborg, Denmark;
authors.forename: Signe O W
authors.initials: SO
authors.lastname: Jensen
authors.affiliation: Aalborg University Hospital, Psychiatry, Aalborg, Denmark;
authors.forename: Rasmus B
authors.initials: RB
authors.lastname: Friis
authors.affiliation: Aalborg University Hospital, Psychiatry, Aalborg, Denmark;
authors.forename: Jan B
authors.initials: JB
authors.lastname: Valentin
authors.affiliation: The Zucker Hillside Hospital, Department of Psychiatry, North Shore-Long Island Jewish Health System, Glen Oaks, NY; Hofstra North Shore LIJ School of Medicine, Hempstead, NY.
authors.forename: Christoph U
authors.initials: CU
authors.lastname: Correll
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D003651:Decanoates / Q000008:administration & dosage / Q000494:pharmacology*; D003692:Delayed-Action Preparations; D003718:Denmark; D005260:Female; D005500:Follow-Up Studies; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D007267:Injections; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D012042:Registries; D012189:Retrospective Studies; D018967:Risperidone / Q000008:administration & dosage / Q000494:pharmacology*; D012559:Schizophrenia / Q000188:drug therapy*; D013997:Time Factors
chemical_list: D014150:Antipsychotic Agents; D003651:Decanoates; D003692:Delayed-Action Preparations; D018967:Risperidone
keywords: all-cause discontinuation; cohort study; first-generation antipsychotics; hospitalization; long-acting injectable; risperidone; schizophrenia