title: Antipsychotic polypharmacy and risk of death from natural causes in patients with schizophrenia: a population-based nested case-control study.
abstract: OBJECTIVE
  Concomitant prescription of more than 1 antipsychotic agent (antipsychotic polypharmacy) in the treatment of schizophrenia is prevalent, although monotherapy is generally recommended. Mortality from natural causes is markedly increased in schizophrenia, and the role of polypharmacy remains controversial. The objective was to investigate if antipsychotic polypharmacy is associated with the excess mortality from natural causes among patients with schizophrenia.
  
  
  METHODS
  A population-based nested case-control study was conducted using patient data from January 1, 1996, to December 31, 2005, obtained from central Danish registers. From the study population of 27,633 patients with ICD-8- and ICD-10-diagnosed schizophrenia or other mainly nonaffective psychoses, aged 18-53 years, we identified 193 cases who died of natural causes within a 2-year period and 1,937 age- and sex-matched controls. Current drug use was defined as at least 1 prescription filled within 90 days before the date of death or the index date. The data were analyzed by conditional logistic regression.
  
  
  RESULTS
  Risk of natural death did not increase with the number of concurrently used antipsychotic agents compared with antipsychotic monotherapy (no antipsychotics: adjusted odds ratio [OR] = 1.48 [95% CI, 0.89-2.46]; 2 antipsychotics: OR = 0.91 [95% CI, 0.61-1.36]; 3 or more antipsychotics: OR = 1.16 [95% CI, 0.68-2.00]). Current use of benzodiazepine derivatives with long elimination half-lives (more than 24 hours) was associated with increased risk of natural death in patients with schizophrenia treated with antipsychotics (OR = 1.78 [95% CI, 1.25-2.52]).
  
  
  CONCLUSIONS
  Antipsychotic polypharmacy did not contribute to the excess mortality from natural causes in middle-aged patients with schizophrenia. The detected increased risk of death associated with benzodiazepines with long elimination half-lives calls for further clarification.
authors.affiliation: Centre for Neuropsychiatric Schizophrenia Research, Psychiatric Centre Glostrup, Copenhagen University Hospital, Glostrup, Nordre Ringvej 29-67, DK-2600 Glostrup, Denmark. lone.baandrup@cnsr.dk
authors.forename: Lone
authors.initials: L
authors.lastname: Baandrup
authors.forename: Christiane
authors.initials: C
authors.lastname: Gasse
authors.forename: Vibeke D
authors.initials: VD
authors.lastname: Jensen
authors.forename: Birte Y
authors.initials: BY
authors.lastname: Glenthoj
authors.forename: Merete
authors.initials: M
authors.lastname: Nordentoft
authors.forename: Henrik
authors.initials: H
authors.lastname: Lublin
authors.forename: Anders
authors.initials: A
authors.lastname: Fink-Jensen
authors.forename: Anne
authors.initials: A
authors.lastname: Lindhardt
authors.forename: Preben B
authors.initials: PB
authors.lastname: Mortensen
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D001569:Benzodiazepines / Q000009:adverse effects; D016022:Case-Control Studies; D002423:Cause of Death / Q000639:trends*; D003718:Denmark; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D012307:Risk Factors; D012559:Schizophrenia / Q000188:drug therapy / Q000401:mortality*
chemical_list: D014150:Antipsychotic Agents; D001569:Benzodiazepines