Journal of Adolescent Health
Volume 36, Issue 1 , Pages 92-93, January 2005

Suicidality in adolescents being treated with antidepressant medications and the black box label: Position paper of the Society for Adolescent Medicine

  • James Lock, M.D., Ph.D.

      Affiliations

    • Department of Psychiatry and Behavioral Medicine, Stanford University School of Medicine, Stanford, California, USA
    • ,
  • Leslie R. Walker, M.D. (FSAM)

      Affiliations

    • Department of Pediatrics, Adolescent Medicine, Georgetown University Hospital, Washington, DC, USA
    • ,
  • Vaughn I. Rickert, Psy.D. (FSAM)

      Affiliations

    • Heilbrunn Department of Population and Family Health, Mailman School of Public Health at Columbia University, New York, New York, USA
    • ,
  • Debra K. Katzman, M.D. (FSAM)

      Affiliations

    • Division of Adolescent Medicine, Department of Paediatrics, The Eating Disorder Program, The Hospital for Sick Children and University of Toronto, Toronto, Ontario, Canada

Article Outline

 

Recent attention has focused on the use of antidepressant medications in the treatment of depression in children and adolescents. The United States (U.S.) Food and Drug Administration (FDA) has required manufacturers to include a “black box” warning label on antidepressants that alerts health care providers and consumers to an increased risk of suicidal thinking and behavior in children and adolescents being treated with these medications (FDA Public Health Advisory: Suicidality in Children and Adolescents Being Treated with Antidepressant Medications. Oct. 15, 2004 available at http://www.fda.gov/cder/drug/antidepressants/SSRIPHA200410.htm). This warning has prompted further discussion of the relative risks and benefits of use of antidepressants in children and adolescents [1]. The Society for Adolescent Medicine issues this statement to urge a balanced approach to the treatment of depression in adolescents, a serious and prevalent problem for this age group.

Depressive disorders are relatively common among adolescents, with a point prevalence of 3–8% [2]. This disorder is chronic, with an average episode in a clinical setting lasting around 8 months. Adolescent depression is also highly recurrent, with up to 75% having a recurrence in 5 years [3]. Evidence suggests that an adolescent with untreated major depression is likely to experience a lifelong course of maladjustment, potentially including the development of substance abuse, significant weight gain, personality disorders, poor school performance and impaired relationships with peers and family [4], [5]. Depression is the condition most closely associated with significant suicidal thoughts, attempts, and suicide completions, the latter of which is the third leading cause of death in adolescents [6]. Given both the short-term and long-term health implications of depression among adolescents, it is critical that effective treatments be offered to depressed adolescents.

Effective treatments for adolescents with major depressive disorder include psychotherapy and antidepressant medications. In one study, a combination of psychotherapy and antidepressant medication was the most efficacious, but antidepressant medication alone conveyed almost as much benefit as did the combined treatment [7]. The strongest support for efficacy in adolescents with depression is for fluoxetine. In all three trials, fluoxetine showed superiority to placebo [7], [8], [9].

Recently, the FDA required that a black box label be placed on all antidepressant medications warning prospective health care providers and consumers of an increased risk for suicidal thinking and behavior in children and adolescents with major depressive disorder when taking these types of medications [10]. The FDA concluded from their analyses of all pooled pediatric trials (both published and unpublished) that a greater risk of suicidality exists during the first few months of treatment for those receiving antidepressant medications [11]. The average risk of suicidality among children and adolescents on antidepressants was 4%, twice the placebo risk of 2% [1]. There were no suicides among the subjects included in the analysis [10].

In the context of the FDA warning, an unfortunate outcome of such labeling may be to discourage the appropriate use of antidepressants among adolescents who would benefit from them. Certainly it is important to balance the appropriate concern for the safety of medications with the risk of adverse events. The data supporting the effectiveness of selective serotonin reuptake inhibitors for adolescents with major depressive disorder, particularly for fluoxetine, is compelling despite an increased rate of suicidal thoughts and behaviors [1], [12]. Given the response rate to the antidepressant medication compared to placebo (61% vs. 35%, respectively) and the low rate of suicidality, many more adolescents will benefit from the drug than become suicidal [7]. Although antidepressant treatment carries risks, untreated depression has potentially greater risks [4].

To this end, the Society for Adolescent Medicine strongly supports the appropriate use of antidepressant medications in the treatment of adolescents with depression despite the risks. It is important to minimize potential risks and the Society for Adolescent Medicine endorses the following guidelines for clinical practice in the context of the FDA warning:

1.The initiation and continued use of antidepressant medications for adolescents is appropriate when clinically warranted. Importantly, suicide risk appears highest at the beginning of a depressive episode, so expeditious treatment or referral is crucial [13].

2.Health care providers considering the use of antidepressants in adolescents for any clinical use must balance the risk of increased suicidality with the clinical need.

3.Health care providers must inform and educate families, caregivers and adolescents about the benefits and risks of antidepressant medications, and the availability of alternative treatments, namely, psychotherapy. Collaborative treatment decisions are best made among the adolescent, family and provider.

4.The use of antidepressant medications must be closely monitored by the health care provider, family and caregiver for emergent suicidality, hostility, agitation, mania or unusual changes in behavior, especially within the first few months of treatment, as well as when the dosage is adjusted.

5.If suicidal thoughts or behaviors increase, decreasing or discontinuing the medications should be considered [14].

6.Further clinical trials and long-term follow-up studies must be conducted in order to provide further evidence on the rates of sucidiality and other side effects of antidepressant medications in the treatment of adolescents with depression.

Back to Article Outline

References 

  1. Brent DA . Antidepressants and pediatric depression-the risk of doing nothing . N Engl J Med . 2004;351:1598–1601
  2. Lewinsohn PM , Hops H , Roberts RE , Seeley JR , Andrews JA . Adolescent psychopathology: I. Prevalence and incidence of depression and other DSM-III-R disorders in high school students . J Abnorm Psychol . 1993;102:133–144
  3. Kovacs M . Presentation and course of major depressive disorder during childhood and later years of the life span . J Am Acad Child Adolesc Psychiatry . 1996;35:705–715
  4. Lewinsohn PM , Rohde P , Seeley JR , Klein DN , Gotlib IH . Natural course of adolescent major depressive disorder in a community sample (predictors of recurrence in young adults) . Am J Psychiatry . 2000;157:1584–1591
  5. National Institute of Mental Health . Depression in children and adolescents (a fact sheet for physicians) . 2004; www.nimh.nih.gov/publicat/depchildresfact.cfm. Accessed March 8
  6. Brent DA . Assessment and treatment of the youthful suicidal patient . Ann N Y Acad Sci . 2001;932:106–128
  7. March J , Silva S , Petrycki S , et al.   Fluoxetine, cognitive-behavioral therapy, and their combination for adolescents with depression (Treatment for Adolescents with Depression Study (TADS) randomized controlled trial) . JAMA . 2004;292:807–820
  8. Emslie GJ , Rush AJ , Weinberg WA , et al.   A double-blind, randomized placebo-controlled trial of fluoxetine in children and adolescents with depression . Arch Gen Psychiatry . 1997;54:1031–1037
  9. Emslie GJ , Heiligenstein JH , Wagner KD , et al.   Fluoxetine treatment for prevention of relapse of depression in children and adolescents (a double-blind, placebo-controlled study) . J Am Acad Child Adolesc Psychiatry . 2002;41:1205–1215
  10. FDA launches a multi-pronged strategy to strengthen safeguards for children treatment with antidepressants medications, U.S. Food and Drug Administration, FDA News, October 15, 2004. www.fda.gov/bbs/topics/news/2004/NEW01124.html Accessed November 11, 2004.
  11. Newman TB . A black-box warning for antidepressants in children? . N Engl J Med . 2004;351:1595–1598
  12. Brent DA , Birmaher B . Adolescent depression . N Engl J Med . 2000;347:667–671
  13. Zametkin AJ , Alter MR , Yemini T . Suicide in teenagers (assessment, management, and prevention) . JAMA . 2001;286:3120–3125
  14. Sarles RM . Joint meeting of the Psychopharmacologic Drugs Advisory Committee and the Pediatric Advisory Committee. Academy of Child and Adolescent Psychiatry . 2004; http://www.aacap.org/Announcements/AACAP_Comment.html. Accessed September 28

 The guidance in this Position Paper does not indicate an exclusive course of treatment or serve as a standard of medical care. Variations, taking into account individual circumstances, may be appropriate.

PII: S1054-139X(04)00394-5

doi:10.1016/j.jadohealth.2004.11.125

Journal of Adolescent Health
Volume 36, Issue 1 , Pages 92-93, January 2005

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