title: Atypical antipsychotics and hyperglycemic emergencies: multicentre, retrospective cohort study of administrative data.
abstract: OBJECTIVE
  To evaluate the relationship between initiation of atypical antipsychotic agents and the risk of hyperglycemic emergencies.
  
  
  METHODS
  We conducted a multicentre retrospective cohort study using administrative health data from 7 Canadian provinces and the UK Clinical Practice Research Datalink. Hospitalizations for hyperglycemic emergencies (hyperglycemia, diabetic ketoacidosis, hyperosmolar hyperglycemic state) were compared between new users of risperidone (reference), and new users of olanzapine, other atypical antipsychotics, and typical antipsychotics. We used propensity scores with inverse probability of treatment weighting and proportional hazard models to estimate the site-specific hazard ratios of hyperglycemic emergencies in the year following drug initiation separately for adults under and over age 66 years. Site-level results were pooled using meta-analytic methods.
  
  
  RESULTS
  Among 725,489 patients, 55% were aged 66+years; 5% of younger and 19% of older patients had pre-existing diabetes. Hyperglycemic emergencies were rare (1-2 per 1000 person years), but more frequent in patients with pre-existing diabetes (6-12 per 1000 person years). We did not find a significant difference in risk of hyperglycemic emergencies with initiation of olanzapine versus risperidone; however heterogeneity existed between sites. The risk of an event was significantly lower with other atypical (99% quetiapine) compared to risperidone use in older patients [adjusted hazard ratio, 95% confidence interval (CI): 0.69, 0.53-0.90].
  
  
  CONCLUSIONS
  Risk for hyperglycemic emergencies is low after initiation of antipsychotics, but patients with pre-existing diabetes may be at greater risk. The risk appeared lower with the use of quetiapine in older patients, but the clinical significance of the findings requires further study.
authors.affiliation: Institute for Clinical Evaluative Sciences, G1 06, 2075 Bayview Ave, Toronto, ON M4N 3M5, Canada; Women's College Hospital, Women's College Research Institute, Department of Medicine, University of Toronto, 790 Bay St, Toronto, ON M5G 1N8, Canada. Electronic address: Lorraine.Lipscombe@wchospital.ca.
authors.forename: Lorraine L
authors.initials: LL
authors.lastname: Lipscombe
authors.affiliation: Institute for Clinical Evaluative Sciences, G1 06, 2075 Bayview Ave, Toronto, ON M4N 3M5, Canada.
authors.forename: Peter C
authors.initials: PC
authors.lastname: Austin
authors.affiliation: Faculty of Pharmacy, Apotex Centre, University of Manitoba, Winnipeg, MB R3E 0T5, Canada; Manitoba Centre for Health Policy, 408-727 McDermot Ave, Winnipeg, MB R3E 3P5, Canada.
authors.forename: Silvia
authors.initials: S
authors.lastname: Alessi-Severini
authors.affiliation: College of Pharmacy & Nutrition, University of Saskatchewan, 110 Science Place, Saskatoon, SK S7N 5C9, Canada.
authors.forename: David F
authors.initials: DF
authors.lastname: Blackburn
authors.affiliation: Faculty of Pharmacy, Université de Montréal, 2940 Chemin de Polytechnique, Montreal, QC H3T 1J4, Canada.
authors.forename: Lucie
authors.initials: L
authors.lastname: Blais
authors.affiliation: Alberta Health Services, 10301 Southport Lane SW, Calgary, AB T2W 1S7, Canada.
authors.forename: Lauren
authors.initials: L
authors.lastname: Bresee
authors.affiliation: Division of Clinical Epidemiology, McGill University, Ross Pavillion, 687 avenue des Pins Ouest, Montreal, QC H3A 1A1, Canada; Lady Davis Research Institute at the Jewish General Hospital, 3755 Côte Ste-Catherine Road, Montreal, QC H3T 1E2, Canada.
authors.forename: Kristian B
authors.initials: KB
authors.lastname: Filion
authors.affiliation: Department of Anesthesiology, Pharmacology, & Therapeutics, University of British Columbia, 217-2176 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kawasumi
authors.affiliation: Institute for Clinical Evaluative Sciences, G1 06, 2075 Bayview Ave, Toronto, ON M4N 3M5, Canada; Centre for Addiction and Mental Health, 250 College St, Toronto, ON M5T 1R8, Canada.
authors.forename: Paul
authors.initials: P
authors.lastname: Kurdyak
authors.affiliation: Departments of Epidemiology, Biostatistics, and Occupational Health, and of Pediatrics, McGill University, Purvis Hall, 1020 Pine Ave. West, Montreal, QC H3A 1A2, Canada.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Platt
authors.affiliation: Department of Community Health and Epidemiology, Dalhousie University, 5790 University Ave, Halifax, NS B3H 1V7, Canada; School of Kinesiology and Health Science, York University, 341-4700 Keele St, Toronto, ON M3J 1P3, Canada.
authors.forename: Hala
authors.initials: H
authors.lastname: Tamim
authors.affiliation: Institute for Clinical Evaluative Sciences, G1 06, 2075 Bayview Ave, Toronto, ON M4N 3M5, Canada.
authors.forename: J Michael
authors.initials: JM
authors.lastname: Paterson
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001569:Benzodiazepines / Q000009:adverse effects / Q000627:therapeutic use; D048909:Diabetes Complications / Q000453:epidemiology; D005260:Female; D006801:Humans; D006943:Hyperglycemia / Q000139:chemically induced* / Q000453:epidemiology*; D008297:Male; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D000077152:Olanzapine; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012306:Risk; D018967:Risperidone / Q000009:adverse effects / Q000627:therapeutic use; D012559:Schizophrenia / Q000188:drug therapy* / Q000453:epidemiology*; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D001569:Benzodiazepines; D018967:Risperidone; D000077152:Olanzapine
keywords: Antipsychotics; Database research; Diabetes; Drug side effects; Epidemiology; Hyperglycemic emergencies; Psychosis