title: Real-world risk of diabetes with antipsychotic use in older New Zealanders: a case-crossover study.
abstract: OBJECTIVE
  The primary aim was to examine and compare the increased risk of incident diabetes associated with second-generation antipsychotics (SGAs) and first-generation antipsychotics (FGAs), with and without adjusting for potential confounding factors. The secondary aim was to recalculate the relative risks of diabetes onset using a semi-symmetric bidirectional case-crossover (SSBC) design to adjust for time-trend bias.
  
  
  METHODS
  Prescription records (2005-2015) of antipsychotics were sourced from New Zealand Pharmaceutical Collections. The first-time diabetes diagnosis was extracted from the National Minimal Dataset. Relative risks (RRs) of diabetes onset were calculated using conditional logistic regression. Time-trend bias was corrected by recalculating the RR using a SSBC design.
  
  
  RESULTS
  Among 645 individuals, the risk of diabetes onset is higher in SGA users (ARR = 8.72, 95% CI = [5.57, 13.67]) compared to FGA users (ARR = 5.68, 95% CI = [3.43, 9.39]). The increased risk of diabetes onset associated with quetiapine is higher (ARR = 7.47, 95% CI = [4.10, 13.62]), compared to haloperidol (ARR = 5.05, 95% CI = [2.91, 8.75]). However, the increased risk of diabetes onset associated with olanzapine (ARR = 2.27, 95% CI = [0.86, 5.98]) is insignificant after adjusting for concomitant use of effect modifiers and other antipsychotic drugs.
  
  
  CONCLUSIONS
  The results support that the magnitude of the risk of diabetes is higher with SGA use compared with FGA use, and the risk is higher when co-prescribed. Confounding by indication and time-varying confounders such as body mass index could bias the risk of onset of diabetes. Marginal structural models could provide more precise estimates of the risk of onset of diabetes following exposure to antipsychotics.
authors.affiliation: School of Pharmacy, University of Otago, PO Box 56, Dunedin, 9054, New Zealand. prasad.nishtala@otago.ac.nz.
authors.forename: Prasad S
authors.identifier: http://orcid.org/0000-0002-4155-8540
authors.initials: PS
authors.lastname: Nishtala
authors.affiliation: School of Pharmacy, University of Otago, PO Box 56, Dunedin, 9054, New Zealand.
authors.forename: Te-Yuan
authors.initials: TY
authors.lastname: Chyou
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014150:Antipsychotic Agents / Q000009:adverse effects*; D003920:Diabetes Mellitus / Q000139:chemically induced* / Q000453:epidemiology; D005260:Female; D006220:Haloperidol / Q000009:adverse effects; D006801:Humans; D008297:Male; D009520:New Zealand / Q000453:epidemiology; D000069348:Quetiapine Fumarate / Q000009:adverse effects; D012306:Risk
chemical_list: D014150:Antipsychotic Agents; D000069348:Quetiapine Fumarate; D006220:Haloperidol
keywords: Antipsychotic agents; Case-crossover; Diabetes mellitus; Older people; Pharmacoepidemiology