Skip to main content
Log in

Antidepressant Drugs and the Risk of Suicide in Children and Adolescents

  • Current Opinion
  • Published:
Pediatric Drugs Aims and scope Submit manuscript

Abstract

Government agencies have issued warnings about the use of antidepressant medications in children, adolescents, and young adults since 2003. The statements warn that such medications may cause de novo ‘suicidality’ in some people. This review explores the data on the treatment of depression that led to these warnings and subsequent data that are relevant to the warnings. It also addresses the effectiveness of antidepressant treatment in general and the relationship of suicide rates to antidepressant treatment. It concludes that the decisions for the ‘black box’ warnings were based on biased data and invalid assumptions. Furthermore, the decisions were unsupported by the observational data regarding suicide in young people that existed in 2003. The following recommendations would seem to follow from these observations. First, drug authorities should re-evaluate the basis for their imposed warnings on antidepressant medicines, and analyze the actual public health consequences the warnings have had. In the absence of substantial evidence supporting the warnings, they should be removed. Second, physicians and other providers with prescription privileges should continue to be educated regarding the importance of aggressively treating depression in young people, using antidepressants when indicated. Third, physicians and other professionals who treat depressed young people must always be aware of the risk of suicide (albeit quite low) and observe them closely for any signs of increased risk of suicide. This is necessary regardless of the type of treatment being provided.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Mann J, Emslie G, Baldessarini R, et al. ACNP task force report on SSRIs and suicidal behavior in youth. Neuropsychopharmacology. 2006;31:473–92.

    Article  CAS  PubMed  Google Scholar 

  2. Busch SH, Frank RG, Leslie DL, et al. Antidepressants and suicide risk: how did specific information in FDA safety warnings affect treatment patterns? Psychiatr Serv. 2010;61:11–6.

    PubMed Central  PubMed  Google Scholar 

  3. Isacsson G, Boëthius G, Bergman U. Low level of antidepressant prescription for people who later commit suicide: 15 years of experience from a population-based drug database in Sweden. Acta Psychiatr Scand. 1992;85:444–8.

    Article  CAS  PubMed  Google Scholar 

  4. Isacsson G. Suicide prevention—a medical breakthrough? Acta Psychiatr Scand. 2000;102:113–7.

    Article  CAS  PubMed  Google Scholar 

  5. Isacsson G, Holmgren A, Osby U, Ahlner J. Decrease in suicide among the individuals treated with antidepressants: a controlled study of antidepressants in suicide, Sweden 1995–2005. Acta Psychiatr Scand. 2009;120:37–44.

    Article  CAS  PubMed  Google Scholar 

  6. Simon GE, Savarino J, Operskalski B, Wang PS. Suicide risk during antidepressant treatment. Am J Psychiatry. 2006;163:41–7.

    Article  PubMed  Google Scholar 

  7. Busch S, Golberstein E, Meara E. The FDA and ABCS: The unintended consequences of antidepressant warning on human capital. NBER Working Paper Series. 2011. p. 1–48.

  8. Brent DA. Antidepressants and pediatric depression—the risk of doing nothing. N Engl J Med. 2004;14(351):1598–601.

    Google Scholar 

  9. Jellinek MS, Snyder JB. Depression and suicide in children and adolescents. Pediatr Rev/Am Acad Pediatr. 1998;19:255–64.

    Article  CAS  Google Scholar 

  10. Merikangas KR, He JP, Burstein M, et al. Lifetime prevalence of mental disorders in U.S. adolescents: results from the National Comorbidity Survey Replication-Adolescent Supplement (NCS-A). J Am Acad Child Adolesc Psychiatry. 2010;49:980–9.

    Article  PubMed Central  PubMed  Google Scholar 

  11. Whittington CJ, Kendall T, Fonagy P, Cottrell D, Cotgrove A, Boddington E. Selective serotonin reuptake inhibitors in childhood depression: systematic review of published versus unpublished data. Lancet. 2004;24(363):1341–5.

    Article  Google Scholar 

  12. von Knorring AL, Olsson GI, Thomsen PH, Lemming OM, Hulten A. A randomized, double-blind, placebo-controlled study of citalopram in adolescents with major depressive disorder. J Clin Psychopharmacol. 2006;26:311–5.

    Article  Google Scholar 

  13. Wagner KD, Jonas J, Findling RL, Ventura D, Saikali K. A double-blind, randomized, placebo-controlled trial of escitalopram in the treatment of pediatric depression. J Am Acad Child Adolesc Psychiatry. 2006;45:280–8.

    Article  PubMed  Google Scholar 

  14. Moreno C, Arango C, Parellada M, Shaffer D, Bird H. Antidepressants in child and adolescent depression: where are the bugs? Acta Psychiatr Scand. 2007;115:184–95.

    Article  CAS  PubMed  Google Scholar 

  15. 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;18(292):807–20.

    Google Scholar 

  16. 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;54:1031–7.

    Article  CAS  PubMed  Google Scholar 

  17. Emslie GJ, Heiligenstein JH, Wagner KD, et al. Fluoxetine for acute treatment of depression in children and adolescents: a placebo-controlled, randomized clinical trial. J Am Acad Child Adolesc Psychiatry. 2002;41:1205–15.

    Article  PubMed  Google Scholar 

  18. Gibbons RD, Hur K, Brown CH, Davis JM, Mann JJ. Benefits from antidepressants: synthesis of 6-week patient-level outcomes from double-blind placebo-controlled randomized trials of fluoxetine and venlafaxine. Arch Gen Psychiatry. 2012;5(69):572–9.

    Google Scholar 

  19. Duff G. Safety of Seroxat (paroxetine) in children and adolescents under 18 years—contraindication in the treatment of depressive illness. In: MHRA, editor. Message from professor G Duff, Chairman of Committee on Safety of Medicines; 2003.

  20. Barry CL, Busch SH. News coverage of FDA warnings on pediatric antidepressant use and suicidality. Pediatrics. 2010;125:88–95.

    Article  PubMed Central  PubMed  Google Scholar 

  21. Hammad A. Review and evaluation of clinical data. FDA; 2004 [updated 2004; cited 2013 Oct 17]. http://www.fda.gov/ohrms/dockets/ac/04/briefing/2004-4065b1-10-tab08-hammads-review.pdf.

  22. Isacsson G, Rich CL. Antidepressant drug use and suicide prevention. Int Rev Psychiatry. 2005;17:153–62.

    Article  PubMed  Google Scholar 

  23. Ludwig J, Marcotte DE. Anti-depressants, suicide, and drug regulation. J Policy Anal Manag. 2005;24:249–72.

    Article  Google Scholar 

  24. Isacsson G, Holmgren P, Ahlner J. Selective serotonin reuptake inhibitor antidepressants and the risk of suicide: a controlled forensic database study of 14,857 suicides. Acta Psychiatr Scand. 2005;111:286–90.

    Article  CAS  PubMed  Google Scholar 

  25. Centers for Disease Control and Prevention (CDC). 2013 [updated 2013; cited 2013 Oct 17]. http://www.cdc.gov/injury/wisqars/facts.html.

  26. Olfson M, Shaffer D, Marcus SC, Greenberg T. Relationship between antidepressant medication treatment and suicide in adolescents. Arch Gen Psychiatry. 2003;60:978–82.

    Article  PubMed  Google Scholar 

  27. Gibbons RD, Hur K, Bhaumik DK, Mann JJ. The relationship between antidepressant prescription rates and rate of early adolescent suicide. Am J Psychiatry. 2006;2006(163):1898–904.

    Article  Google Scholar 

  28. Leon AC, Marzuk PM, Tardiff K, Bucciarelli A, Markham Piper T, Galea S. Antidepressants and youth suicide in New York City, 1999–2002. J Am Acad Child Adolesc Psychiatry. 2006;45:1054–8.

    Article  PubMed  Google Scholar 

  29. Moskos M, Olson L, Halbern S, Keller T, Gray D. Utah youth suicide study: psychological autopsy. Suicide Life Threat Behav. 2005;35:536–46.

    Article  PubMed  Google Scholar 

  30. Sondergard L, Kvist K, Andersen PK, Kessing LV. Do antidepressants precipitate youth suicide? A nationwide pharmacoepidemiological study. Eur Child Adolesc Psychiatry. 2006;15:232–40.

    Article  PubMed  Google Scholar 

  31. Dudley M, Goldney R, Hadzi-Pavlovic D. Are adolescents dying by suicide taking SSRI antidepressants? A review of observational studies. Australas Psychiatry. 2010;18:242–5.

    Article  PubMed  Google Scholar 

  32. Gibbons RD, Brown CH, Hur K, et al. Early evidence on the effects of regulators’ suicidality warnings on SSRI prescriptions and suicide in children and adolescents. Am J Psychiatry. 2007;164:1356–63.

    Article  PubMed  Google Scholar 

  33. Grunbaum JA, Kann L, Kinchen SA, et al. Youth risk behavior surveillance—United States, 2001. J Sch Health. 2002;72:313–28.

    Article  PubMed  Google Scholar 

  34. Weisberg HI, Hayden VC, Pontes VP. Selection criteria and generalizability within the counterfactual framework: explaining the paradox of antidepressant-induced suicidality? Clin Trials. 2009;6:109–18.

    Article  PubMed  Google Scholar 

  35. Libby AM, Brent DA, Morrato EH, Orton HD, Allen R, Valuck RJ. Decline in treatment of pediatric depression after FDA advisory on risk of suicidality with SSRIs. Am J Psychiatry. 2007;164:884–91.

    Article  PubMed  Google Scholar 

  36. Libby AM, Orton HD, Valuck RJ. Persisting decline in depression treatment after FDA warnings. Arch Gen Psychiatry. 2009;66:633–9.

    Article  PubMed  Google Scholar 

  37. Nemeroff CB, Kalali A, Keller MB, et al. Impact of publicity concerning pediatric suicidality data on physician practice patterns in the United States. Arch Gen Psychiatry. 2007;64:466–72.

    Article  PubMed  Google Scholar 

  38. Olfson M, Marcus SC, Druss BG. Effects of Food and Drug Administration warnings on antidepressant use in a national sample. Arch Gen Psychiatry. 2008;65:94–101.

    Article  PubMed  Google Scholar 

  39. Tournier M, Greenfield B, Galbaud du Fort G, et al. Patterns of antidepressant use in Quebec children and adolescents: trends and predictors. Psychiatry Res. 2010;179:57–63.

    Article  PubMed  Google Scholar 

  40. Dean AJ, Hendy A, McGuire T. Antidepressants in children and adolescents—changes in utilisation after safety warnings. Pharmacoepidemiol Drug Saf. 2007;16:1048–53.

    Article  PubMed  Google Scholar 

  41. Isacsson G, Ahlner J. Antidepressants and the risk of suicide in young persons—prescription trends and toxicological analyses. Acta Psychiatr Scand. e-published ahead of print. Open access: http://onlinelibrary.wiley.com/doi/10.1111/acps.12160/pdf. Accepted 17 June 2013.

  42. Wheeler BW, Gunnell D, Metcalfe C, Stephens P, Martin RM. The population impact on incidence of suicide and non-fatal self harm of regulatory action against the use of selective serotonin reuptake inhibitors in under 18 s in the United Kingdom: ecological study. BMJ. 2008;8(336):542–5.

    Article  Google Scholar 

  43. Murray ML, Thompson M, Santosh PJ, Wong IC. Effects of the Committee on Safety of Medicines advice on antidepressant prescribing to children and adolescents in the UK. Drug Saf Int J Med Toxicol Drug Exp. 2005;28:1151–7.

    Article  CAS  Google Scholar 

  44. Wijlaars LP, Nazareth I, Petersen I. Trends in depression and antidepressant prescribing in children and adolescents: a cohort study in The Health Improvement Network (THIN). PLoS One. 2012;7:e33181.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  45. Bridge JA, Greenhouse JB, Weldon AH, Campo JV, Kelleher KJ. Suicide trends among youths aged 10 to 19 years in the United States, 1996–2005. JAMA. 2008;300:1025–6.

    Article  CAS  PubMed  Google Scholar 

  46. Katz LY, Kozyrskyj AL, Prior HJ, Enns MW, Cox BJ, Sareen J. Effect of regulatory warnings on antidepressant prescription rates, use of health services and outcomes among children, adolescents and young adults. CMAJ. 2008;8(178):1005–11.

    Article  Google Scholar 

  47. Vitiello B, Silva SG, Rohde P, et al. Suicidal events in the treatment for adolescents with depression study (TADS). J Clin Psychiatry. 2009;70:741–7.

    Article  PubMed Central  PubMed  Google Scholar 

  48. Gibbons RD, Brown CH, Hur K, Davis JM, Mann JJ. Suicidal thoughts and behavior with antidepressant treatment: reanalysis of the randomized placebo-controlled studies of fluoxetine and venlafaxine. Arch Gen Psychiatry. 2012;9(69):580–7.

    Article  Google Scholar 

  49. Teicher MH, Glod C, Cole JO. Emergence of intense suicidal preoccupation during fluoxetine treatment. Am J Psychiatry. 1990;147:207–10.

    CAS  PubMed  Google Scholar 

  50. Busch S, Golberstein E, Meara E. The FDA and ABCs: The unintended consequences of antidepressant warnings on human capital. NBER Working Paper Series. 2011. p. 1–48.

  51. Leon AC. The revised black box warning for antidepressants sets a public health experiment in motion. J Clin Psychiatry. 2007;68:1139–41.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

Neither Göran Isacsson nor Charles L. Rich has any conflicts of interest. Göran Isacsson was funded by the Karolinska Institutet funds (ALF). No other funding were used to prepare the review.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Göran Isacsson.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Isacsson, G., Rich, C.L. Antidepressant Drugs and the Risk of Suicide in Children and Adolescents. Pediatr Drugs 16, 115–122 (2014). https://doi.org/10.1007/s40272-013-0061-1

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40272-013-0061-1

Keywords

Navigation