title: Atypical Antipsychotics and the Risks of Acute Kidney Injury and Related Outcomes Among Older Adults: A Replication Analysis and an Evaluation of Adapted Confounding Control Strategies.
abstract: A recently published analysis of population-based claims data from Ontario, Canada reported higher risks of acute kidney injury (AKI) and related outcomes among older adults who were new users of atypical antipsychotics (AAPs) compared with unexposed patients. In light of these findings, the objective of the current study was to further investigate the risks of AKI and related outcomes among older adults receiving AAPs.
  
  
  
  A replication of the previously published analysis was performed using the US Truven MarketScan Medicare Supplemental database (MDCR) among patients aged 65 years and older. Compared with non-users of AAPs, the study compared the risk of AKI and related outcomes with users of AAPs (quetiapine, risperidone, olanzapine, aripiprazole, or paliperidone) using a 1-to-1 propensity score matched analysis. In addition, we performed adapted analyses that: (1) included all covariates used to fit propensity score models in outcome models; and (2) required patients to have a diagnosis of schizophrenia, bipolar disorder, or major depression and a healthcare visit within 90 days prior to the index date.
  
  
  
  AKI effect estimates [as odds ratios (ORs) with 95% confidence intervals (CIs)] were significantly elevated in our MDCR replication analyses (OR 1.45, 95% CI 1.32-1.60); however, in adapted analyses, associations were not significant (OR 0.91, 95% CI 0.78-1.07)). In analyses of AKI and related outcomes, results were mostly consistent between the previously published and the MDCR replication analyses. The primary change that attenuated associations in adapted analyses was the requirement for patients to have a mental health condition and a healthcare visit prior to the index date.
  
  
  
  The MDCR analysis yielded similar results when the methodology of the previously published analysis was replicated, but, in adapted analyses, we did not find significantly higher risks of AKI and related outcomes. The contrast of results between our replication and adapted analyses may be due to the analytic approach used to compare patients (and potential confounding by indication). Further research is warranted to evaluate these associations, while also examining methods to account for differences in older adults who do and do not use these medications.
authors.affiliation: Janssen Research & Development, LLC, Global Research and Development Epidemiology, 1125 Trenton Harbourton Road, Rm K30205, Titusville, NJ, 08560, USA.
authors.forename: Patrick B
authors.initials: PB
authors.lastname: Ryan
authors.affiliation: Janssen Research & Development, LLC, Global Research and Development Epidemiology, 1125 Trenton Harbourton Road, Rm K30205, Titusville, NJ, 08560, USA.
authors.forename: Martijn J
authors.initials: MJ
authors.lastname: Schuemie
authors.affiliation: Janssen Research & Development, LLC, Global Research and Development Epidemiology, 1125 Trenton Harbourton Road, Rm K30205, Titusville, NJ, 08560, USA. dramchar@ITS.JNJ.com.
authors.forename: Darmendra
authors.initials: D
authors.lastname: Ramcharran
authors.affiliation: Janssen Research & Development, LLC, Global Research and Development Epidemiology, 1125 Trenton Harbourton Road, Rm K30205, Titusville, NJ, 08560, USA.
authors.forename: Paul E
authors.initials: PE
authors.lastname: Stang
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced*; D000368:Aged; D000369:Aged, 80 and over; D014150:Antipsychotic Agents / Q000009:adverse effects*; D001569:Benzodiazepines / Q000009:adverse effects; D001714:Bipolar Disorder / Q000188:drug therapy; D003865:Major Depressive Disorder / Q000188:drug therapy; D005260:Female; D006801:Humans; D008297:Male; D000077152:Olanzapine; D000069348:Quetiapine Fumarate / Q000009:adverse effects; D018967:Risperidone / Q000009:adverse effects; D012559:Schizophrenia / Q000188:drug therapy
chemical_list: D014150:Antipsychotic Agents; D001569:Benzodiazepines; D000069348:Quetiapine Fumarate; D018967:Risperidone; D000077152:Olanzapine