title: Risk of pneumonia associated with incident benzodiazepine use among community-dwelling adults with Alzheimer disease.
abstract: BACKGROUND
  Knowledge regarding whether benzodiazepines and similarly acting non-benzodiazepines (Z-drugs) are associated with an increased risk of pneumonia among older adults is lacking. We sought to investigate this association among community-dwelling adults with Alzheimer disease, a condition in which both sedative/hypnotic use and pneumonia are common.
  
  
  METHODS
  We obtained data on all community-dwelling adults with a recent diagnosis of Alzheimer disease in Finland (2005-2011) from the Medication use and Alzheimer disease (MEDALZ) cohort, which incorporates national registry data on prescriptions, reimbursement, hospital discharges and causes of death. Incident users of benzodiazepines and Z-drugs were identified using a 1-year washout period and matched with nonusers using propensity scores. The association with hospital admission or death due to pneumonia was analyzed with the Cox proportional hazards model and adjusted for use of other psychotropic drugs in a time-dependent manner.
  
  
  RESULTS
  Among 49 484 eligible participants with Alzheimer disease, 5232 taking benzodiazepines and 3269 taking Z-drugs were matched 1:1 with those not taking these drugs. Collectively, use of benzodiazepines and Z-drugs was associated with an increased risk of pneumonia (adjusted hazard ratio [HR] 1.22, 95% confidence interval [CI] 1.05-1.42). When analyzed separately, benzodiazepine use was significantly associated with an increased risk of pneumonia (adjusted HR 1.28, 95% CI 1.07-1.54), whereas Z-drug use was not (adjusted HR 1.10, 95% CI 0.84-1.44). The risk of pneumonia was greatest within the first 30 days of benzodiazepine use (HR 2.09, 95% CI 1.26-3.48).
  
  
  CONCLUSIONS
  Benzodiazepine use was associated with an increased risk of pneumonia among patients with Alzheimer disease. Risk of pneumonia should be considered when weighing the benefits and risks of benzodiazepines in this population.
authors.affiliation: Kuopio Research Centre of Geriatric Care (Taipale, Koponen, Lavikainen, Hartikainen); School of Pharmacy (Taipale, Tolppanen, Koponen, Lavikainen, Hartikainen); Department of Forensic Psychiatry (Taipale, Tanskanen, Tiihonen), Niuvanniemi Hospital; Institute of Clinical Medicine (Sund); Research Centre for Comparative Effectiveness and Patient Safety (RECEPS) (Tolppanen), University of Eastern Finland, Kuopio, Finland; Department of Clinical Neuroscience (Tanskanen, Tiihonen), Karolinska Institutet, Stockholm, Sweden; National Institute for Health and Welfare (Tanskanen), Helsinki, Finland; Department of Pharmacology (Lavikainen), Drug Development and Therapeutics, University of Turku, Turku, Finland; Department of Social Research (Sund), Centre for Research Methods, University of Helsinki, Helsinki, Finland; Department of Psychiatry (Hartikainen), Kuopio University Hospital, Kuopio, Finland heidi.taipale@uef.fi.
authors.forename: Heidi
authors.initials: H
authors.lastname: Taipale
authors.affiliation: Kuopio Research Centre of Geriatric Care (Taipale, Koponen, Lavikainen, Hartikainen); School of Pharmacy (Taipale, Tolppanen, Koponen, Lavikainen, Hartikainen); Department of Forensic Psychiatry (Taipale, Tanskanen, Tiihonen), Niuvanniemi Hospital; Institute of Clinical Medicine (Sund); Research Centre for Comparative Effectiveness and Patient Safety (RECEPS) (Tolppanen), University of Eastern Finland, Kuopio, Finland; Department of Clinical Neuroscience (Tanskanen, Tiihonen), Karolinska Institutet, Stockholm, Sweden; National Institute for Health and Welfare (Tanskanen), Helsinki, Finland; Department of Pharmacology (Lavikainen), Drug Development and Therapeutics, University of Turku, Turku, Finland; Department of Social Research (Sund), Centre for Research Methods, University of Helsinki, Helsinki, Finland; Department of Psychiatry (Hartikainen), Kuopio University Hospital, Kuopio, Finland.
authors.forename: Anna-Maija
authors.initials: AM
authors.lastname: Tolppanen
authors.affiliation: Kuopio Research Centre of Geriatric Care (Taipale, Koponen, Lavikainen, Hartikainen); School of Pharmacy (Taipale, Tolppanen, Koponen, Lavikainen, Hartikainen); Department of Forensic Psychiatry (Taipale, Tanskanen, Tiihonen), Niuvanniemi Hospital; Institute of Clinical Medicine (Sund); Research Centre for Comparative Effectiveness and Patient Safety (RECEPS) (Tolppanen), University of Eastern Finland, Kuopio, Finland; Department of Clinical Neuroscience (Tanskanen, Tiihonen), Karolinska Institutet, Stockholm, Sweden; National Institute for Health and Welfare (Tanskanen), Helsinki, Finland; Department of Pharmacology (Lavikainen), Drug Development and Therapeutics, University of Turku, Turku, Finland; Department of Social Research (Sund), Centre for Research Methods, University of Helsinki, Helsinki, Finland; Department of Psychiatry (Hartikainen), Kuopio University Hospital, Kuopio, Finland.
authors.forename: Marjaana
authors.initials: M
authors.lastname: Koponen
authors.affiliation: Kuopio Research Centre of Geriatric Care (Taipale, Koponen, Lavikainen, Hartikainen); School of Pharmacy (Taipale, Tolppanen, Koponen, Lavikainen, Hartikainen); Department of Forensic Psychiatry (Taipale, Tanskanen, Tiihonen), Niuvanniemi Hospital; Institute of Clinical Medicine (Sund); Research Centre for Comparative Effectiveness and Patient Safety (RECEPS) (Tolppanen), University of Eastern Finland, Kuopio, Finland; Department of Clinical Neuroscience (Tanskanen, Tiihonen), Karolinska Institutet, Stockholm, Sweden; National Institute for Health and Welfare (Tanskanen), Helsinki, Finland; Department of Pharmacology (Lavikainen), Drug Development and Therapeutics, University of Turku, Turku, Finland; Department of Social Research (Sund), Centre for Research Methods, University of Helsinki, Helsinki, Finland; Department of Psychiatry (Hartikainen), Kuopio University Hospital, Kuopio, Finland.
authors.forename: Antti
authors.initials: A
authors.lastname: Tanskanen
authors.affiliation: Kuopio Research Centre of Geriatric Care (Taipale, Koponen, Lavikainen, Hartikainen); School of Pharmacy (Taipale, Tolppanen, Koponen, Lavikainen, Hartikainen); Department of Forensic Psychiatry (Taipale, Tanskanen, Tiihonen), Niuvanniemi Hospital; Institute of Clinical Medicine (Sund); Research Centre for Comparative Effectiveness and Patient Safety (RECEPS) (Tolppanen), University of Eastern Finland, Kuopio, Finland; Department of Clinical Neuroscience (Tanskanen, Tiihonen), Karolinska Institutet, Stockholm, Sweden; National Institute for Health and Welfare (Tanskanen), Helsinki, Finland; Department of Pharmacology (Lavikainen), Drug Development and Therapeutics, University of Turku, Turku, Finland; Department of Social Research (Sund), Centre for Research Methods, University of Helsinki, Helsinki, Finland; Department of Psychiatry (Hartikainen), Kuopio University Hospital, Kuopio, Finland.
authors.forename: Piia
authors.initials: P
authors.lastname: Lavikainen
authors.affiliation: Kuopio Research Centre of Geriatric Care (Taipale, Koponen, Lavikainen, Hartikainen); School of Pharmacy (Taipale, Tolppanen, Koponen, Lavikainen, Hartikainen); Department of Forensic Psychiatry (Taipale, Tanskanen, Tiihonen), Niuvanniemi Hospital; Institute of Clinical Medicine (Sund); Research Centre for Comparative Effectiveness and Patient Safety (RECEPS) (Tolppanen), University of Eastern Finland, Kuopio, Finland; Department of Clinical Neuroscience (Tanskanen, Tiihonen), Karolinska Institutet, Stockholm, Sweden; National Institute for Health and Welfare (Tanskanen), Helsinki, Finland; Department of Pharmacology (Lavikainen), Drug Development and Therapeutics, University of Turku, Turku, Finland; Department of Social Research (Sund), Centre for Research Methods, University of Helsinki, Helsinki, Finland; Department of Psychiatry (Hartikainen), Kuopio University Hospital, Kuopio, Finland.
authors.forename: Reijo
authors.initials: R
authors.lastname: Sund
authors.affiliation: Kuopio Research Centre of Geriatric Care (Taipale, Koponen, Lavikainen, Hartikainen); School of Pharmacy (Taipale, Tolppanen, Koponen, Lavikainen, Hartikainen); Department of Forensic Psychiatry (Taipale, Tanskanen, Tiihonen), Niuvanniemi Hospital; Institute of Clinical Medicine (Sund); Research Centre for Comparative Effectiveness and Patient Safety (RECEPS) (Tolppanen), University of Eastern Finland, Kuopio, Finland; Department of Clinical Neuroscience (Tanskanen, Tiihonen), Karolinska Institutet, Stockholm, Sweden; National Institute for Health and Welfare (Tanskanen), Helsinki, Finland; Department of Pharmacology (Lavikainen), Drug Development and Therapeutics, University of Turku, Turku, Finland; Department of Social Research (Sund), Centre for Research Methods, University of Helsinki, Helsinki, Finland; Department of Psychiatry (Hartikainen), Kuopio University Hospital, Kuopio, Finland.
authors.forename: Jari
authors.initials: J
authors.lastname: Tiihonen
authors.affiliation: Kuopio Research Centre of Geriatric Care (Taipale, Koponen, Lavikainen, Hartikainen); School of Pharmacy (Taipale, Tolppanen, Koponen, Lavikainen, Hartikainen); Department of Forensic Psychiatry (Taipale, Tanskanen, Tiihonen), Niuvanniemi Hospital; Institute of Clinical Medicine (Sund); Research Centre for Comparative Effectiveness and Patient Safety (RECEPS) (Tolppanen), University of Eastern Finland, Kuopio, Finland; Department of Clinical Neuroscience (Tanskanen, Tiihonen), Karolinska Institutet, Stockholm, Sweden; National Institute for Health and Welfare (Tanskanen), Helsinki, Finland; Department of Pharmacology (Lavikainen), Drug Development and Therapeutics, University of Turku, Turku, Finland; Department of Social Research (Sund), Centre for Research Methods, University of Helsinki, Helsinki, Finland; Department of Psychiatry (Hartikainen), Kuopio University Hospital, Kuopio, Finland.
authors.forename: Sirpa
authors.initials: S
authors.lastname: Hartikainen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy*; D001569:Benzodiazepines / Q000009:adverse effects*; D015897:Comorbidity; D005260:Female; D005387:Finland; D006801:Humans; D006993:Hypnotics and Sedatives / Q000009:adverse effects*; D016015:Logistic Models; D008297:Male; D010351:Patient Discharge; D011014:Pneumonia / Q000453:epidemiology*; D016016:Proportional Hazards Models; D012042:Registries; D012307:Risk Factors
chemical_list: D006993:Hypnotics and Sedatives; D001569:Benzodiazepines