Comparative cardiovascular side effects of medications for attention-deficit/hyperactivity disorder: protocol of a case non-case study based on the WHO international pharmacovigilance database

Study type

• Study type:
  Non-interventional study
• Scope of the study:
  Assessment of risk minimisation measure implementation or effectiveness

  Disease epidemiology

  Drug utilisation

Non-interventional study

• Non-interventional study design:
  Other
• Non-interventional study design, other:
  Case non-case study

Study drug and medical condition

• Anatomical Therapeutic Chemical (ATC) code:
  (N06BA07) modafinil

  modafinil

  (N06BA03) metamfetamine

  metamfetamine

  (N06BA09) atomoxetine

  atomoxetine

  (N06BA02) dexamfetamine

  dexamfetamine

  (N06BA01) amfetamine

  amfetamine

  (A08AA62) bupropion and naltrexone

  bupropion and naltrexone

  (N06BA04) methylphenidate

  methylphenidate

  (C02AC02) guanfacine

  guanfacine

  (C02AC01) clonidine

  clonidine

  (N06BA11) dexmethylphenidate

  dexmethylphenidate
• Medical condition to be studied:
  Cardiac disorder
• Additional medical condition(s):
  Hypertension Cardiac Arrythmias,Torsade de pointes/QT prolongation,Heart failure,Ischemic heart disease,Central nervous system haemorrhages and cerebrovascular conditions,Cardiac valve disorders,Myocardial disorders

Population studied

• Age groups:
  • Paediatric Population (< 18 years)

    • Children (2 to < 12 years)
    • Adolescents (12 to < 18 years)
  • Adult and elderly population (≥18 years)

    • Adults (18 to < 65 years)

      • Adults (18 to < 46 years)
      • Adults (46 to < 65 years)
    • Elderly (≥ 65 years)

      • Adults (65 to < 75 years)
      • Adults (75 to < 85 years)
      • Adults (85 years and over)
• Estimated number of subjects:
  10000

Study design details

• Main study objective:
  The main objective : comparing the risk of reporting cardiovascular events among 12 medications used to treat ADHD, individually and grouped according to their major pharmacological classes.
• Outcomes:
  Risk of reporting cardiovascular events among : 1. Hypertension 2. Cardiac Arrythmias 3. Torsade de pointes/QT prolongation 4. Heart failure 5. Ischemic heart disease 6. Central nervous system haemorrhages and cerebrovascular conditions 7. Central nervous system haemorrhages and cerebrovascular conditions 8. Myocardial disorders
• Data analysis plan:
  This is a disproportionality analyses using Vigibase®, the World Health Organization's global database of Individual Case Safety Reports (ICSRs), which has included more than 30 million reports since 1967 (as of May 2022) from over 130 countries. The WHO Uppsala Monitoring Center stores these ICSRs, which are spontaneous reports of adverse drug reactions from a suspected causative agent, as reported by health professionals, consumers, or drug manufacturers. Vigibase® includes information on the patient's age, gender, medical history, and country, as well as on the medications taken, with their start and end dates. Reports are categorized according to the seriousness of the adverse drug reaction. The Medical Dictionary for Regulatory Activities (MedDRA) is used to code adverse effects