title: Cumulative dosages of antipsychotic drugs are associated with increased mortality rate in patients with Alzheimer's dementia.
abstract: We wished to investigate the effects of cumulative dosages of antipsychotic drug in Alzheimer's dementia, when controlling for known risk factors, including current antipsychotic exposure, on all-cause mortality.
  
  
  
  We utilized a nationwide, population-based, retrospective cohort study design with mortality as outcome in individual patients diagnosed with Alzheimer's dementia.
  
  
  
  We included a total of 45 894 patients and followed them for 3 803 996 person-years in total, presenting 27 894 deaths in the study population. Cumulative antipsychotic exposure increased mortality: more than 0 Daily Defined Dosage (DDDs) but less than 90: HR 2.20, 95% CI (2.14-2.27), P < 0.001; more than or equal to 90 DDDs but less than 365: HR 1.81, 95% CI (1.74-1.89), P < 0.001; more than or equal to 365 DDDs but less than 730: HR 1.38, 95% CI (1.428-1.49), P < 0.001; and more than or equal to 730 DDDs: HR 1.06, 95% CI (0.95-1.18), P = 0.322, when controlling for proxy markers of severity, somatic and mental comorbid disorders.
  
  
  
  In this nationwide cohort study of 45 894 patients diagnosed with Alzheimer's dementia, we found that cumulative dosages of antipsychotic drugs were associated with increased mortality rates.
authors.affiliation: Department of Psychiatry, Unit for Psychiatric Research, Aalborg University Hospital, Aalborg, Denmark. ren@rn.dk.|Department of Clinical Medicine, Aalborg University, Aalborg, Denmark. ren@rn.dk.
authors.forename: R E
authors.initials: RE
authors.lastname: Nielsen
authors.affiliation: Department of Psychiatry, Institute of Clinical Health, University of Southern Denmark, Odense, Region of Southern Denmark, Denmark.
authors.forename: A
authors.initials: A
authors.lastname: Lolk
authors.affiliation: Department of Psychiatry, Unit for Psychiatric Research, Aalborg University Hospital, Aalborg, Denmark.
authors.forename: J B
authors.initials: JB
authors.lastname: Valentin
authors.affiliation: Department of Psychiatry, Institute of Clinical Health, University of Southern Denmark, Odense, Region of Southern Denmark, Denmark.
authors.forename: K
authors.initials: K
authors.lastname: Andersen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000401:mortality* / Q000523:psychology; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D003704:Dementia / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality*; D003718:Denmark; D005260:Female; D006801:Humans; D008297:Male; D011569:Psychiatric Status Rating Scales; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D014150:Antipsychotic Agents
keywords: Alzheimer; antipsychotics; mortality; pharmacoepidemiology