Off-label antidepressant use in children and adolescents compared with young adults: extent and level of evidence

Pharmacoepidemiol Drug Saf. 2012 Sep;21(9):997-1004. doi: 10.1002/pds.3312. Epub 2012 Jul 4.

Abstract

Purpose: To estimate the degree of, and level of evidence supporting, off-label antidepressant (AD) prescribing for children and adolescents compared with young adults.

Methods: Retrospective cohort study utilizing medical and pharmacy claims data from US-managed care plans, 1997-2009.

Participants: Patients aged 5-24 years, with at least one (index) AD claim during a period of continuous enrollment.

Main outcome measures: Drug-diagnosis pairs, on the basis of medical claims within 30 days pre-index or post-index AD, were grouped as (1) Food and Drug Administration (FDA)-approved or (2) off-label with one of three evidence categories based on Micromedex®2.0: favorable, inconclusive or limited-to-none (Thomson Micromedex, Greenwood Village, CO, USA).

Results: Over the study period, 290 816 subjects met eligibility criteria: 17% 5-12 years old, 40% 13-18 years old, and 43% 19-24 years old. Sertraline was the most commonly prescribed index AD (19-23%). Psychiatrists more often prescribed the AD for children (31%) and adolescents (35%) versus young adults (17%). Only 28% of all subjects had a diagnosis consistent with an FDA-approved indication within 30 days pre-index and post-index AD. Children less than 13 years old were less likely to have had an FDA-approved indication (5-10%). Most off-label prescribing had inconclusive to no evidence supporting efficacy. The lack of evidence was especially pronounced for younger children. Trends were consistent over the study period. Increasing the time period for potential indications pre-index and post-index AD did not result in significantly reduced off-label rates.

Conclusions: Pediatric off-label AD prescribing occurs frequently without a strong evidence base, highlighting a need to generate additional evidence to ensure safe and effective use.

MeSH terms

  • Adolescent
  • Age Factors
  • Antidepressive Agents / therapeutic use*
  • Child
  • Child, Preschool
  • Cohort Studies
  • Drug Approval
  • Female
  • Humans
  • Longitudinal Studies
  • Male
  • Managed Care Programs
  • Off-Label Use / statistics & numerical data*
  • Practice Patterns, Physicians' / statistics & numerical data*
  • Retrospective Studies
  • Time Factors
  • United States
  • United States Food and Drug Administration
  • Young Adult

Substances

  • Antidepressive Agents