Effects of Food and Drug Administration Warnings on Antidepressant Use in a National Sample

Arch Gen Psychiatry. 2008 Jan;65(1):94-101. doi: 10.1001/archgenpsychiatry.2007.5.


Context: In June 2003, the Food and Drug Administration (FDA) recommended that paroxetine hydrochloride not be used to treat young people because of potential increased risk of suicidal behavior, and in October 2004, the FDA issued a black box warning concerning all antidepressants for youth.

Objective: To characterize associations between these warnings and antidepressant use.

Design: Interrupted time series analyses of trends in antidepressant use were performed with Medco pharmacy and enrollment data stratified by patient age, sex, antidepressant type, and specialty of the prescribing physician across 3 study periods: prewarning (May 1, 2002 to June 19, 2003), paroxetine warning (June 20, 2003 to October 15, 2004), and black box warning (October 16, 2004 to December 31, 2005).

Main outcome measures: The rate of antidepressant use, annualized percentage change in rate of antidepressant use, and difference in trend of antidepressant use between consecutive study periods.

Results: During the prewarning study period, there was a 36.0% per year (P < .001) increase in total youth (aged 6-17 years) antidepressant use, which was followed by decreases of -0.8% per year (P = .85) and -9.6% per year (P = .21) during the paroxetine and black box warning study periods, respectively. The difference in trends between the prewarning and paroxetine warning periods was significant (P < .001). Youth paroxetine use also significantly increased during the prewarning study period (30.0% per year; P < .001) before significantly declining during the paroxetine warning study period (-44.2% per year; P < .001), which was also a significant between-period difference in trends (P < .001). Changes in antidepressant use were less pronounced in adults than in youth. For adults 65 years and older, overall antidepressant use significantly increased (8.1% per year; P < .001) during the black box study period. Changes in the pattern of antidepressant use varied little by patient sex.

Conclusions: The paroxetine and black box warnings had modest and relatively targeted effects on the intended populations. These changes, which were greatest for youth, were broadly consistent with the FDA warnings and the scientific literature.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Aged
  • Antidepressive Agents / adverse effects*
  • Antidepressive Agents / therapeutic use*
  • Child
  • Drug Labeling*
  • Drug Prescriptions / statistics & numerical data
  • Female
  • Health Surveys
  • Humans
  • Male
  • Middle Aged
  • Paroxetine / adverse effects
  • Paroxetine / therapeutic use
  • Practice Patterns, Physicians' / statistics & numerical data*
  • Sex Factors
  • Suicide, Attempted
  • United States
  • United States Food and Drug Administration*


  • Antidepressive Agents
  • Paroxetine