Risk of suicide attempt and suicide associated with benzodiazepine: a nationwide case crossover study (R.SUB)

Study type

• Study topic:
  Human medicinal product

  Disease /health condition
• Study type:
  Non-interventional study
• Scope of the study:
  Assessment of risk minimisation measure implementation or effectiveness
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Other
• Non-interventional study design, other:
  Case-crossover

Study drug and medical condition

• Anatomical Therapeutic Chemical (ATC) code:
  (N05BA) Benzodiazepine derivatives

  Benzodiazepine derivatives

  (N05CD) Benzodiazepine derivatives

  Benzodiazepine derivatives

  (N05CF) Benzodiazepine related drugs

  Benzodiazepine related drugs
• Medical condition to be studied:
  Suicide attempt

  Completed suicide

Population studied

• Short description of the study population:
  Patients ≥16 years , with hospitalised suicide attempt or suicide between 2013 and 2016, and at least one benzodiazepine dispensing within the 120 days before their act.
• Age groups:
  • Adult and elderly population (≥18 years)

    • Adults (18 to < 65 years)

      • Adults (18 to < 46 years)
• Estimated number of subjects:
  70000

Study design details

• Main study objective:
  This study aimed at estimating the risk of suicide attempt and suicide death associated with recent exposure to benzodiazepines in patients with or without recent psychiatric history using methods minimizing confounding factors.
• Outcomes:
  Suicide attempts as hospitalisation with hospital discharge codes for intentional self-harm. Suicide deaths identified through the causes-of-death registry as those with intentional self-harm codes as well.
• Data analysis plan:
  The suicidal outcomes were hospitalised suicide attempts and suicide, identified through the hospital discharge and causes-of-death registry, using ICD-10 codes X60-X84. Patients were considered exposed to benzodiazepines within one of the studied periods of interest (risk/reference) if they have been reimbursed for at least one dispensing of a benzodiazepine during this period. Conditional logistic regression models were used to estimate the crude and adjusted odds ratios (OR) of suicidal behaviours associated with benzodiazepine over the risk period compared with the reference periods. Models were adjusted for time-varying confounders (other psychotropics). Sensitivity analyses concerned: varying lengths of risk and reference periods, performing another CCO analysis using cyamemazine as a negative control with similar risk of indication bias, performing a case-case-time-control model to examine whether the main CCO analysis was confounded by a time trend in benzodiazepine use.