Antipsychotic polypharmacy and risk of death from natural causes in patients with schizophrenia: a population-based nested case-control study

Lone Baandrup, Christiane Gasse, Vibeke Jensen, Birte Yding Glenthøj, Merete Nordentoft, Henrik Lublin, Anders Fink-Jensen, Anne Lindhardt, Preben Bo Mortensen

100 Citations (Scopus)


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. METHOD: 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.
Original languageEnglish
JournalJournal of Clinical Psychiatry
Issue number2
Pages (from-to)103-8
Number of pages6
Publication statusPublished - 1 Feb 2010


  • Adolescent
  • Adult
  • Age Factors
  • Antipsychotic Agents
  • Benzodiazepines
  • Case-Control Studies
  • Cause of Death
  • Denmark
  • Drug Therapy, Combination
  • Female
  • Humans
  • Male
  • Middle Aged
  • Odds Ratio
  • Risk Factors
  • Schizophrenia


Dive into the research topics of 'Antipsychotic polypharmacy and risk of death from natural causes in patients with schizophrenia: a population-based nested case-control study'. Together they form a unique fingerprint.

Cite this