Antidepressant Regulatory Warnings, Prescription Patterns, Suicidality and Other Aggressive Behaviors in Major Depressive Disorder and Anxiety Disorders

Psychiatr Q. 2016 Jun;87(2):329-42. doi: 10.1007/s11126-015-9389-8.


In 2004 the Food and Drug Administration issued a warning on the risk of suicidality in children and adolescents receiving antidepressants. This was followed by reports of changes in antidepressant prescription patterns, suicidality and other aggressive behaviors, but debate is continuing regarding the nature and magnitude of these changes. We examined a large physician database for impact of the warning on antidepressant prescriptions, suicidality and other aggressive behaviors in major depressive disorder (MDD) and anxiety disorders in adult and pediatric patients. We analyzed electronic database covering over 100,000 patients, treated in Pre- (before 2003) and Post- (after 2004) warning periods. We compared strength of the association between the measures and the time period with two tests. Multivariate logistic regression analyses were performed to ascertain the unique effect of each parameter. Of 10,089 MDD (61.0 %) and anxiety disorders (39.0 %) patients, 65.2 % received antidepressant prescription and 16.1 % were pediatric patients. In post-warning period, there was a greater reduction in adult versus pediatric antidepressant prescription rates. Logistic modeling showed greater likelihood of antidepressant prescription in MDD as compared with anxiety disorders in post-warning period. Pediatric patients were more likely than adults to receive fluoxetine during the post-warning period. There was an overall reduction in suicidality and other aggressive behaviors in the post-warning period. Regulatory warnings may have had an impact on antidepressant benefit/risk assessment and consequent utilization, therapeutic effects, and adverse events. Our observations suggest that psychiatrists may heed regulatory warnings, but may also exert professional independence and discrimination in their application.

Keywords: Aggressive behaviors; Antidepressant; Anxiety disorders; Black box warning; Depression; Prescription patterns; Suicidality.

Publication types

  • Comparative Study

MeSH terms

  • Adolescent
  • Adult
  • Aggression / drug effects*
  • Antidepressive Agents / adverse effects*
  • Antidepressive Agents / therapeutic use
  • Anxiety Disorders / drug therapy*
  • Anxiety Disorders / psychology*
  • Child
  • Databases, Factual
  • Depressive Disorder, Major / drug therapy
  • Drug Labeling*
  • Female
  • Humans
  • Male
  • Practice Patterns, Physicians' / trends*
  • Suicide*
  • United States
  • United States Food and Drug Administration
  • Young Adult


  • Antidepressive Agents