Off-label use of neuroleptics and antidepressants and risks of psychostimulant use in ADHD patients during childhood and adolescents (OLUNAR)

Study type

• Study topic:
  Disease /health condition

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

  Drug utilisation
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

  Cross-sectional

Study drug and medical condition

• Anatomical Therapeutic Chemical (ATC) code:
  (N05A) ANTIPSYCHOTICS

  ANTIPSYCHOTICS

  (N06A) ANTIDEPRESSANTS

  ANTIDEPRESSANTS

  (N06BA04) methylphenidate

  methylphenidate
• Medical condition to be studied:
  Completed suicide

  Cardiovascular disorder

  Cerebrovascular disorder

  Neuroleptic malignant syndrome

  Extrapyramidal disorder

  Ischaemic stroke

  Myocardial infarction

  Angina pectoris

  Cardiomyopathy

  Death

Population studied

• Short description of the study population:
  Children and adolescents with attention deficit and hyperactivity disorder (ADHD) who use antidepressant (ATDs) and antipsychotic(AP) drugs.
• Age groups:
  Preterm newborn infants (0 – 27 days)

  Term newborn infants (0 – 27 days)

  Infants and toddlers (28 days – 23 months)

  Children (2 to < 12 years)

  Adolescents (12 to < 18 years)
• Special population of interest:
  Other
• Special population of interest, other:
  Attention deficit and hyperactivity disorder (ADHD) patients
• Estimated number of subjects:
  2000000

Study design details

• Main study objective:
  The objectives are to examine the extent of off-label use of antidepressant(ATDs) and antipsychotic(AP) drugs in children and adolescents and to estimate the risk of specific adverse events associated with off-label use of these drugs. Also, we evaluate the cardio- and cerebrovascular risks of methylphenidate use compared to nonuse for the treatment of children and adolescents with ADHD in Germany
• Outcomes:
  Risks and side effects, including Drug-induced obesity, Hyperglycemia, Diabetes mellitus, Hyperprolactinemia, Malignant neuroleptic syndrome, Drug-induced parkinsonism, Drug-induced dystonia / tardive Dyskinesia, Drug-induced tremor, Poisoning by psychotropic drugs, Myocardial infarction, Stroke, Bradycardia / Tachycardia, Cardiomyopathy, Heart failure, Suicide risk, All-cause mortality, in the second part of the study (methylphenidate in children with ADHD): cardiac arrhythmia, angina pectoris, cardiomyopathy and all-cause mortality
• Data analysis plan:
  In both study parts, prevalence and incidence rates of the considered medications will be determined.First part: for the antipsychotic cohort, the primary analysis will be a Cox regression analysis estimating the adjusted hazard ratio (HR) for metabolic and endocrine adverse effects in off-label users vs. on-label users. For the antidepressant cohort, the primary analysis will be a Cox regression analysis estimating the adjusted HR for cardio- and cerebrovascular side effects in off-label users vs. on-label users.Second part: a time-dependent Cox proportional hazard model will be used to estimate the adjusted hazard ratio for major cardio-cerebrovascular events in current MPH use vs. nonuse.

Documents

Study publications

Schröder C, Dörks M, Kollhorst B, Blenk T, Dittmann RW, Garbe E, Riedel O. Outp…

Schröder, C., Dörks, M., Kollhorst, B. et al. Outpatient antipsychotic drug use…