title: Effect of anxiolytic and hypnotic drug prescriptions on mortality hazards: retrospective cohort study.
abstract: OBJECTIVE
  To test the hypothesis that people taking anxiolytic and hypnotic drugs are at increased risk of premature mortality, using primary care prescription records and after adjusting for a wide range of potential confounders.
  
  
  METHODS
  Retrospective cohort study.
  
  
  METHODS
  273 UK primary care practices contributing data to the General Practice Research Database.
  
  
  METHODS
  34,727 patients aged 16 years and older first prescribed anxiolytic or hypnotic drugs, or both, between 1998 and 2001, and 69,418 patients with no prescriptions for such drugs (controls) matched by age, sex, and practice. Patients were followed-up for a mean of 7.6 years (range 0.1-13.4 years).
  
  
  RESULTS
  All cause mortality ascertained from practice records.
  
  
  RESULTS
  Physical and psychiatric comorbidities and prescribing of non-study drugs were significantly more prevalent among those prescribed study drugs than among controls. The age adjusted hazard ratio for mortality during the whole follow-up period for use of any study drug in the first year after recruitment was 3.46 (95% confidence interval 3.34 to 3.59) and 3.32 (3.19 to 3.45) after adjusting for other potential confounders. Dose-response associations were found for all three classes of study drugs (benzodiazepines, Z drugs (zaleplon, zolpidem, and zopiclone), and other drugs). After excluding deaths in the first year, there were approximately four excess deaths linked to drug use per 100 people followed for an average of 7.6 years after their first prescription.
  
  
  CONCLUSIONS
  In this large cohort of patients attending UK primary care, anxiolytic and hypnotic drugs were associated with significantly increased risk of mortality over a seven year period, after adjusting for a range of potential confounders. As with all observational findings, however, these results are prone to bias arising from unmeasured and residual confounding.
authors.affiliation: Division of Mental Health and Wellbeing, Warwick Medical School, University of Warwick, Coventry, West Midlands CV4 7AL, UK.
authors.forename: Scott
authors.initials: S
authors.lastname: Weich
authors.forename: Hannah Louise
authors.initials: HL
authors.lastname: Pearce
authors.forename: Peter
authors.initials: P
authors.lastname: Croft
authors.forename: Swaran
authors.initials: S
authors.lastname: Singh
authors.forename: Ilana
authors.initials: I
authors.lastname: Crome
authors.forename: James
authors.initials: J
authors.lastname: Bashford
authors.forename: Martin
authors.initials: M
authors.lastname: Frisher
mesh_terms: D014151:Anti-Anxiety Agents / Q000009:adverse effects*; D001569:Benzodiazepines / Q000009:adverse effects; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D009026:Mortality; D055553:Prescription Drugs / Q000009:adverse effects; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D014151:Anti-Anxiety Agents; D006993:Hypnotics and Sedatives; D055553:Prescription Drugs; D001569:Benzodiazepines