Dosing of Selective Serotonin Reuptake Inhibitors Among Children and Adults Before and After the FDA Black-Box Warning

Psychiatr Serv. 2016 Mar;67(3):302-9. doi: 10.1176/ Epub 2015 Nov 16.


Objective: Prior research evaluated various effects of the 2004 black-box warning by the U.S. Food and Drug Administration (FDA) on the risk of suicidality among children associated with use of antidepressants, but the warning's effect on dosing of antidepressants has not been evaluated. This study estimated whether the initial antidepressant dose prescribed decreased and the proportion of patients who augmented the dose on the second fill increased following the 2004 warning and its 2007 expansion to young adults.

Methods: The study utilized the LifeLink Health Plan Claims Database. The study cohort consisted of commercially insured children (ages 5-17), young adults (18-24), and adults (25-64) who initiated a selective serotonin reuptake inhibitor (SSRI) (citalopram, fluoxetine, paroxetine, or sertraline) from January 1, 2000, to December 31, 2009. Dose per day was determined by days' supply, strength, and quantity dispensed. Initiation with a low dose and augmentation of >1 mg/day on the second prescription before and after the 2004 warning were considered.

Results: Of 51,948 children who initiated an SSRI, 15% initiated with a low dose before the 2004 warning compared with 31% after the warning; there was a smaller change among young adults (6 percentage points) and adults (3 percentage points). The overall increase in dose augmentations among children and young adults was driven by the increase in patients initiating with a low dose.

Conclusions: The proportion of commercially insured children initiating an SSRI with a low dose was higher after the 2004 FDA warning on the risk of suicidality among children, suggesting improved prescribing practices surrounding SSRI dosing among children.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antidepressive Agents / administration & dosage*
  • Child
  • Child, Preschool
  • Citalopram / therapeutic use
  • Cohort Studies
  • Databases, Factual
  • Depression / drug therapy*
  • Dose-Response Relationship, Drug
  • Drug Labeling / standards*
  • Drug Prescriptions
  • Female
  • Fluoxetine / therapeutic use
  • Humans
  • Male
  • Middle Aged
  • Paroxetine / adverse effects*
  • Paroxetine / therapeutic use
  • Practice Guidelines as Topic
  • Psychiatric Status Rating Scales
  • Serotonin Uptake Inhibitors / administration & dosage*
  • Sertraline / therapeutic use
  • Severity of Illness Index
  • Suicide, Attempted / statistics & numerical data*
  • United States
  • United States Food and Drug Administration
  • Young Adult


  • Antidepressive Agents
  • Serotonin Uptake Inhibitors
  • Fluoxetine
  • Citalopram
  • Paroxetine
  • Sertraline