Retrospective registry study evaluating the safety of melatonin use in children and adolescents with attention deficit hyperactivity disorder (ADHD) in Sweden (Safety of melatonin in children with ADHD)

Study type

• Study topic:
  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Safety study (incl. comparative)

Study drug and medical condition

• Name of medicine:
  MELATONIN
• Study drug International non-proprietary name (INN) or common name:
  MELATONIN
• Anatomical Therapeutic Chemical (ATC) code:
  (N05CH01) melatonin

  melatonin
• Medical condition to be studied:
  Attention deficit hyperactivity disorder

Population studied

• Short description of the study population:
  Swedish prescription register showed in 2020 that 56.435 individuals that had been prescribed ADHD medication, the study expect the number to be fewer than this.
• Age groups:
  Children (2 to < 12 years)

  Adolescents (12 to < 18 years)
• Estimated number of subjects:
  56435

Study design details

• Main study objective:
  The primary objective is to determine whether long-term treatment of melatonin (≥30 days) influences height development in children and adolescence with ADHD. As secondary reference PC PAL standard national Swedish growth chart will be used, which describes the growth in relation to chronological age.
• Outcomes:
  Growth velocity. It is not possible to access data on sexual maturation as it is not available , the growth velocity is the only possible outcome of this study.
• Data analysis plan:
  Data measurements will be unevenly spaced, occur at different ages for different subjects, and there may be missing. Participants with fewer than two height measurements will be further analysed for missing data by comparing the two groups with and without registered measurements. For the primary endpoint, height growth, a linear approach will be used to approximate the growth velocity. Analysis of height growth will be performed with a random coefficients model using PROC MIXED in SAS® where a separate regression line, i.e., intercept and slope, is fitted for each subject. The basic model will include age, subject group, and subject group*age as fixed effects and subject and subject*age as random effects. As a secondary reference the digital tool PC PAL will be used for comparison. Unmeasured confounders will be handled in a complementary analysis with the use of an instrumental variable. Sensitivity analyses of height growth will be performed.