title: Sustained Use of Benzodiazepines and Escalation to High Doses in a Canadian Population.
abstract: "Antibenzodiazepine" campaigns have been conducted worldwide to limit the prescribing of these drugs because of concerns about inappropriate use and addiction. The causal relationship between long-term use and escalation to high doses has not been proven. This study assessed the extent of dose escalation among individuals who were long-term users of benzodiazepines or Z-hypnotics.
  
  
  
  A population-based study was conducted in the Canadian province of Manitoba using administrative health databases. Sustained use was defined as continuous use for at least two years (N=12,598). Dose escalation, measured in diazepam milligram equivalents (DMEs) per day and observed at six-month intervals, was assessed by using latent-class trajectory analysis. Characteristics of individuals with sustained use were described.
  
  
  
  The analysis revealed four distinct groups. Two groups (<8% of the cohort) showed escalation to high doses (over 40 DMEs). More than 55% of high-dose escalators were in the 0- to 44-year age group, 75% lived in urban areas, and approximately 75% had a diagnosis of depression. Clonazepam was the drug most commonly involved with dose escalation; among individuals escalating to doses higher than 60 DMEs, 91% were using clonazepam. Rates of "doctor shopping" and "pharmacy hopping" were higher among younger adults, compared with older adults. Younger adults also had higher rates of concomitant antidepressant therapy.
  
  
  
  A limited segment of a population that received benzodiazepine prescriptions was classified as sustained users, and a small proportion of that group escalated to doses higher than those recommended by product monographs and clinical guidelines.
authors.affiliation: Dr. Alessi-Severini and Dr. Collins are with the College of Pharmacy, and Dr. Bolton, Dr. Enns, and Dr. Sareen are with the Department of Psychiatry, College of Medicine, all in the Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada (e-mail: alessise@cc.umanitoba.ca ). Dr. Alessi-Severini is also with the Manitoba Centre for Health Policy, Winnipeg, where Mr. Dahl and Dr. Chateau are affiliated. Dr. Bolton, Dr. Enns, Dr. Chateau, and Dr. Sareen are also with the Department of Community Health, College of Medicine, Faculty of Health Sciences, University of Manitoba.
authors.forename: Silvia
authors.initials: S
authors.lastname: Alessi-Severini
authors.affiliation: Dr. Alessi-Severini and Dr. Collins are with the College of Pharmacy, and Dr. Bolton, Dr. Enns, and Dr. Sareen are with the Department of Psychiatry, College of Medicine, all in the Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada (e-mail: alessise@cc.umanitoba.ca ). Dr. Alessi-Severini is also with the Manitoba Centre for Health Policy, Winnipeg, where Mr. Dahl and Dr. Chateau are affiliated. Dr. Bolton, Dr. Enns, Dr. Chateau, and Dr. Sareen are also with the Department of Community Health, College of Medicine, Faculty of Health Sciences, University of Manitoba.
authors.forename: James M
authors.initials: JM
authors.lastname: Bolton
authors.affiliation: Dr. Alessi-Severini and Dr. Collins are with the College of Pharmacy, and Dr. Bolton, Dr. Enns, and Dr. Sareen are with the Department of Psychiatry, College of Medicine, all in the Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada (e-mail: alessise@cc.umanitoba.ca ). Dr. Alessi-Severini is also with the Manitoba Centre for Health Policy, Winnipeg, where Mr. Dahl and Dr. Chateau are affiliated. Dr. Bolton, Dr. Enns, Dr. Chateau, and Dr. Sareen are also with the Department of Community Health, College of Medicine, Faculty of Health Sciences, University of Manitoba.
authors.forename: Murray W
authors.initials: MW
authors.lastname: Enns
authors.affiliation: Dr. Alessi-Severini and Dr. Collins are with the College of Pharmacy, and Dr. Bolton, Dr. Enns, and Dr. Sareen are with the Department of Psychiatry, College of Medicine, all in the Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada (e-mail: alessise@cc.umanitoba.ca ). Dr. Alessi-Severini is also with the Manitoba Centre for Health Policy, Winnipeg, where Mr. Dahl and Dr. Chateau are affiliated. Dr. Bolton, Dr. Enns, Dr. Chateau, and Dr. Sareen are also with the Department of Community Health, College of Medicine, Faculty of Health Sciences, University of Manitoba.
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Dahl
authors.affiliation: Dr. Alessi-Severini and Dr. Collins are with the College of Pharmacy, and Dr. Bolton, Dr. Enns, and Dr. Sareen are with the Department of Psychiatry, College of Medicine, all in the Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada (e-mail: alessise@cc.umanitoba.ca ). Dr. Alessi-Severini is also with the Manitoba Centre for Health Policy, Winnipeg, where Mr. Dahl and Dr. Chateau are affiliated. Dr. Bolton, Dr. Enns, Dr. Chateau, and Dr. Sareen are also with the Department of Community Health, College of Medicine, Faculty of Health Sciences, University of Manitoba.
authors.forename: Daniel
authors.initials: D
authors.lastname: Chateau
authors.affiliation: Dr. Alessi-Severini and Dr. Collins are with the College of Pharmacy, and Dr. Bolton, Dr. Enns, and Dr. Sareen are with the Department of Psychiatry, College of Medicine, all in the Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada (e-mail: alessise@cc.umanitoba.ca ). Dr. Alessi-Severini is also with the Manitoba Centre for Health Policy, Winnipeg, where Mr. Dahl and Dr. Chateau are affiliated. Dr. Bolton, Dr. Enns, Dr. Chateau, and Dr. Sareen are also with the Department of Community Health, College of Medicine, Faculty of Health Sciences, University of Manitoba.
authors.forename: David M
authors.initials: DM
authors.lastname: Collins
authors.affiliation: Dr. Alessi-Severini and Dr. Collins are with the College of Pharmacy, and Dr. Bolton, Dr. Enns, and Dr. Sareen are with the Department of Psychiatry, College of Medicine, all in the Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada (e-mail: alessise@cc.umanitoba.ca ). Dr. Alessi-Severini is also with the Manitoba Centre for Health Policy, Winnipeg, where Mr. Dahl and Dr. Chateau are affiliated. Dr. Bolton, Dr. Enns, Dr. Chateau, and Dr. Sareen are also with the Department of Community Health, College of Medicine, Faculty of Health Sciences, University of Manitoba.
authors.forename: Jitender
authors.initials: J
authors.lastname: Sareen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001569:Benzodiazepines / Q000008:administration & dosage*; D002648:Child; D002675:Child, Preschool; D002998:Clonazepam / Q000008:administration & dosage*; D015331:Cohort Studies; D003863:Depression / Q000188:drug therapy* / Q000453:epidemiology; D011307:Drug Prescriptions / Q000706:statistics & numerical data*; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage*; D007223:Infant; D008297:Male; D008350:Manitoba / Q000453:epidemiology; D008875:Middle Aged; D055815:Young Adult
chemical_list: D006993:Hypnotics and Sedatives; D001569:Benzodiazepines; D002998:Clonazepam