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

doi:http://dx.doi.org/10.4088/JCP.08m04818yel

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

86 Citations (Scopus)

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. 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 language	English
Journal	Journal of Clinical Psychiatry
Volume	71
Issue number	2
Pages (from-to)	103-8
Number of pages	6
ISSN	0160-6689
DOIs	https://doi.org/10.4088/JCP.08m04818yel
Publication status	Published - 1 Feb 2010

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Baandrup, L., Gasse, C., Jensen, V., Glenthøj, B. Y., Nordentoft, M., Lublin, H., Fink-Jensen, A., Lindhardt, A., & Mortensen, P. B. (2010). Antipsychotic polypharmacy and risk of death from natural causes in patients with schizophrenia: a population-based nested case-control study. Journal of Clinical Psychiatry, 71(2), 103-8. https://doi.org/10.4088/JCP.08m04818yel

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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. 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.",

author = "Lone Baandrup and Christiane Gasse and Vibeke Jensen and Glenth{\o}j, {Birte Yding} and Merete Nordentoft and Henrik Lublin and Anders Fink-Jensen and Anne Lindhardt and Mortensen, {Preben Bo}",

year = "2010",

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doi = "http://dx.doi.org/10.4088/JCP.08m04818yel",

language = "English",

volume = "71",

pages = "103--8",

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T1 - Antipsychotic polypharmacy and risk of death from natural causes in patients with schizophrenia: a population-based nested case-control study

AU - Baandrup, Lone

AU - Gasse, Christiane

AU - Jensen, Vibeke

AU - Glenthøj, Birte Yding

AU - Nordentoft, Merete

AU - Lublin, Henrik

AU - Fink-Jensen, Anders

AU - Lindhardt, Anne

AU - Mortensen, Preben Bo

PY - 2010/2/1

Y1 - 2010/2/1

N2 - 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.

AB - 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.

U2 - http://dx.doi.org/10.4088/JCP.08m04818yel

DO - http://dx.doi.org/10.4088/JCP.08m04818yel

M3 - Journal article

SN - 0160-6689

VL - 71

SP - 103

EP - 108

JO - Journal of Clinical Psychiatry

JF - Journal of Clinical Psychiatry

IS - 2

ER -

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

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