Effect of antidepressants on suicide risk in children and adolescents
- C Scott Moreland, DO
C Scott Moreland, DO
- Clinical Assistant Professor
- Baylor College of Medicine
- Liza Bonin, PhD
Liza Bonin, PhD
- Associate Professor of Pediatrics and Psychiatry
- Baylor College of Medicine
There is concern that selective serotonin reuptake inhibitors (SSRIs) and other antidepressants may increase the risk of suicidal ideation and behavior in children, adolescents, and adults younger than 25 years [1-3]. In early 2004, the US Food and Drug Administration (FDA) in the United States asked manufacturers of a number of antidepressants to make labeling changes to include a warning about a possible increased risk of suicidal ideation or behavior, particularly at the initiation of therapy or at the time of dose changes . After further analysis, in October 2004, the FDA directed manufacturers of all antidepressants (including tricyclic antidepressants [TCAs] and monoamine oxidase inhibitors) to include a warning stating that antidepressants may increase the risk of suicidal ideation and behavior in children and adolescents .
Establishing the causal association is difficult because of the clear associations between severe depression and suicide and between severe depression and the need for antidepressant therapy. Because suicide is uncommon, it also is difficult to demonstrate the negative, which is that antidepressants do not cause suicide. Risk factors for suicidal behavior in children and adolescents are discussed separately. (See "Suicidal behavior in children and adolescents: Epidemiology and risk factors", section on 'Psychiatric disorder'.)
This topic discusses the evidence regarding antidepressants and the risk of suicide in children and adolescents. The use of antidepressants in adolescent depression is discussed separately, as is the association between antidepressants and suicide risk in adults. (See "Pediatric unipolar depression and pharmacotherapy: Choosing a medication" and "Effect of antidepressants on suicide risk in adults".)
EVIDENCE OF ASSOCIATION
Overview — Evidence for and against an association between antidepressant therapy and suicidal thoughts and/or behaviors in children, adolescents, and young adults comes from randomized trials [6-10], observational studies [11-13], and population-based studies comparing the rates of suicide and antidepressant use over time [14-18]. Each of these study designs has limitations in demonstrating a causal association [19,20]:
●Suicide is rare in randomized, controlled trials of antidepressants. Thus, individual trials typically lack the power to detect a relationship between antidepressants and suicidal ideation or behavior.To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Healy D. Lines of evidence on the risks of suicide with selective serotonin reuptake inhibitors. Psychother Psychosom 2003; 72:71.
- Whittington CJ, Kendall T, Fonagy P, et al. Selective serotonin reuptake inhibitors in childhood depression: systematic review of published versus unpublished data. Lancet 2004; 363:1341.
- Jureidini JN, Doecke CJ, Mansfield PR, et al. Efficacy and safety of antidepressants for children and adolescents. BMJ 2004; 328:879.
- US FDA. Public Health Advisory. Worsening depression and suicidality in patients being treated with antidepressant medications. March 22, 2004. www.fda.gov/cder/drug/antidepressants/AntidepressanstPHA.htm (Accessed on May 29, 2006).
- US FDA. Public Health Advisory. Suicidality in children and adolescents being treated with antidepressant medications. October 15, 2004. www.fda.gov/cder/drug/antidepressants/SSRIPHA200410.htm (Accessed on May 29, 2006).
- Khan A, Khan S, Kolts R, Brown WA. Suicide rates in clinical trials of SSRIs, other antidepressants, and placebo: analysis of FDA reports. Am J Psychiatry 2003; 160:790.
- Beasley CM Jr, Dornseif BE, Bosomworth JC, et al. Fluoxetine and suicide: a meta-analysis of controlled trials of treatment for depression. BMJ 1991; 303:685.
- 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.
- American College of Neuropsychopharmacology. Preliminary report of the Task Force on SSRIs and Suicidal Behavior in Youth. January 21, 2004. www.acnp.org (Accessed on September 13, 2007).
- Hammad TA, Laughren T, Racoosin J. Suicidality in pediatric patients treated with antidepressant drugs. Arch Gen Psychiatry 2006; 63:332.
- Fux M, Taub M, Zohar J. Emergence of depressive symptoms during treatment for panic disorder with specific 5-hydroxytryptophan reuptake inhibitors. Acta Psychiatr Scand 1993; 88:235.
- Olfson M, Marcus SC, Shaffer D. Antidepressant drug therapy and suicide in severely depressed children and adults: A case-control study. Arch Gen Psychiatry 2006; 63:865.
- Barbui C, Esposito E, Cipriani A. Selective serotonin reuptake inhibitors and risk of suicide: a systematic review of observational studies. CMAJ 2009; 180:291.
- Hall WD, Mant A, Mitchell PB, et al. Association between antidepressant prescribing and suicide in Australia, 1991-2000: trend analysis. BMJ 2003; 326:1008.
- Olfson M, Shaffer D, Marcus SC, Greenberg T. Relationship between antidepressant medication treatment and suicide in adolescents. Arch Gen Psychiatry 2003; 60:978.
- Carlsten A, Waern M, Ekedahl A, Ranstam J. Antidepressant medication and suicide in Sweden. Pharmacoepidemiol Drug Saf 2001; 10:525.
- Isacsson G, Holmgren P, Druid H, Bergman U. The utilization of antidepressants--a key issue in the prevention of suicide: an analysis of 5281 suicides in Sweden during the period 1992-1994. Acta Psychiatr Scand 1997; 96:94.
- Gibbons RD, Hur K, Bhaumik DK, Mann JJ. The relationship between antidepressant medication use and rate of suicide. Arch Gen Psychiatry 2005; 62:165.
- Vitiello B, Swedo S. Antidepressant medications in children. N Engl J Med 2004; 350:1489.
- Friedman RA, Leon AC. Expanding the black box - depression, antidepressants, and the risk of suicide. N Engl J Med 2007; 356:2343.
- Gunnell D, Ashby D. Antidepressants and suicide: what is the balance of benefit and harm. BMJ 2004; 329:34.
- Rappaport N, Prince JB, Bostic JQ, Association of Medical School Pediatric Department Chairs, Inc. Lost in the black box: juvenile depression, suicide, and the FDA's black box. J Pediatr 2005; 147:719.
- Gibbons RD, Coca Perraillon M, Hur K, et al. Antidepressant treatment and suicide attempts and self-inflicted injury in children and adolescents. Pharmacoepidemiol Drug Saf 2015; 24:208.
- American Academy of Child and Adolescent Psychiatry. Supplementary talking points for child and adolescent psychiatrists regarding the FDA black box warning on the use of antidepressants for pediatric patients. November 2004. www.aacap.org/announcements/psychiatricmeds.htm (Accessed on June 29, 2006).
- Jick H, Kaye JA, Jick SS. Antidepressants and the risk of suicidal behaviors. JAMA 2004; 292:338.
- Bridge JA, Iyengar S, Salary CB, et al. Clinical response and risk for reported suicidal ideation and suicide attempts in pediatric antidepressant treatment: a meta-analysis of randomized controlled trials. JAMA 2007; 297:1683.
- Hetrick SE, McKenzie JE, Cox GR, et al. Newer generation antidepressants for depressive disorders in children and adolescents. Cochrane Database Syst Rev 2012; 11:CD004851.
- Gibbons RD, Brown CH, Hur K, et al. Suicidal thoughts and behavior with antidepressant treatment: reanalysis of the randomized placebo-controlled studies of fluoxetine and venlafaxine. Arch Gen Psychiatry 2012; 69:580.
- Cipriani A, Zhou X, Del Giovane C, et al. Comparative efficacy and tolerability of antidepressants for major depressive disorder in children and adolescents: a network meta-analysis. Lancet 2016; 388:881.
- March JS, Silva S, Petrycki S, et al. The Treatment for Adolescents With Depression Study (TADS): long-term effectiveness and safety outcomes. Arch Gen Psychiatry 2007; 64:1132.
- Emslie G, Kratochvil C, Vitiello B, et al. Treatment for Adolescents with Depression Study (TADS): safety results. J Am Acad Child Adolesc Psychiatry 2006; 45:1440.
- Lu CY, Zhang F, Lakoma MD, et al. Changes in antidepressant use by young people and suicidal behavior after FDA warnings and media coverage: quasi-experimental study. BMJ 2014; 348:g3596.
- Schneeweiss S, Patrick AR, Solomon DH, et al. Comparative safety of antidepressant agents for children and adolescents regarding suicidal acts. Pediatrics 2010; 125:876.
- Cooper WO, Callahan ST, Shintani A, et al. Antidepressants and suicide attempts in children. Pediatrics 2014; 133:204.
- Miller M, Swanson SA, Azrael D, et al. Antidepressant dose, age, and the risk of deliberate self-harm. JAMA Intern Med 2014; 174:899.
- Brent DA, Gibbons R. Initial dose of antidepressant and suicidal behavior in youth: start low, go slow. JAMA Intern Med 2014; 174:909.
- Labeling change request letter for antidepressant medications. www.fda.gov/cder/drug/antidepressants/SSRIlabelChange.htm (Accessed on June 29, 2006).
- US Food and Drug Administration. Center for Drug Evaluation and Research. Antidepressant use in children, adolescents, and adults. www.fda.gov/cder/drug/antidepressants/default.htm (Accessed on May 02, 2007).
- FDA Revised Talk Paper: FDA Proposes new warnings about suicidal thinking, behavior in young adults who take antidepressant medications. May 2, 2007. www.fda.gov/bbs/topics/NEWS/2007/NEW01624.html (Accessed on July 26, 2008).
- FDA proposed medication guide: about using antidepressants in children for teenagers. www.fda.gov/cder/drug/antidepressants/SSRIMedicationGuide.htm (Accessed on June 29, 2006).
- Selective serotonin reuptake inhibitors (SSRIs): Overview of regulatory status and CSM advice relating to major depressive disorder (MDD) in children and adolescents including a summary of available safety and efficacy data. www.mhra.gov.uk (Accessed on June 29, 2006).
- Mann JJ, Emslie G, Baldessarini RJ, et al. ACNP Task Force report on SSRIs and suicidal behavior in youth. Neuropsychopharmacology 2006; 31:473.
- 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.
- Leon AC, Marzuk PM, Tardiff K, Teres JJ. Paroxetine, other antidepressants, and youth suicide in New York City: 1993 through 1998. J Clin Psychiatry 2004; 65:915.
- Simon GE, Savarino J, Operskalski B, Wang PS. Suicide risk during antidepressant treatment. Am J Psychiatry 2006; 163:41.
- Valuck RJ, Libby AM, Sills MR, et al. Antidepressant treatment and risk of suicide attempt by adolescents with major depressive disorder: a propensity-adjusted retrospective cohort study. CNS Drugs 2004; 18:1119.
- Birmaher B, Brent D, AACAP Work Group on Quality Issues, et al. Practice parameter for the assessment and treatment of children and adolescents with depressive disorders. J Am Acad Child Adolesc Psychiatry 2007; 46:1503.
- Brent D, Emslie G, Clarke G, et al. Switching to another SSRI or to venlafaxine with or without cognitive behavioral therapy for adolescents with SSRI-resistant depression: the TORDIA randomized controlled trial. JAMA 2008; 299:901.
- Lock J, Walker LR, Rickert VI, et al. Suicidality in adolescents being treated with antidepressant medications and the black box label: position paper of the Society for Adolescent Medicine. J Adolesc Health 2005; 36:92.
- Libby AM, Brent DA, Morrato EH, et al. Decline in treatment of pediatric depression after FDA advisory on risk of suicidality with SSRIs. Am J Psychiatry 2007; 164:884.
- 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.
- Libby AM, Orton HD, Valuck RJ. Persisting decline in depression treatment after FDA warnings. Arch Gen Psychiatry 2009; 66:633.
- Mittal M, Harrison DL, Miller MJ, Brahm NC. National antidepressant prescribing in children and adolescents with mental health disorders after an FDA boxed warning. Res Social Adm Pharm 2014; 10:781.
- Clarke G, Dickerson J, Gullion CM, DeBar LL. Trends in youth antidepressant dispensing and refill limits, 2000 through 2009. J Child Adolesc Psychopharmacol 2012; 22:11.
- Centers for Disease Control and Prevention (CDC). Suicide trends among youths and young adults aged 10-24 years--United States, 1990-2004. MMWR Morb Mortal Wkly Rep 2007; 56:905.
- Hamilton BE, Miniño AM, Martin JA, et al. Annual summary of vital statistics: 2005. Pediatrics 2007; 119:345.
- 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.
- Katz LY, Kozyrskyj AL, Prior HJ, et al. Effect of regulatory warnings on antidepressant prescription rates, use of health services and outcomes among children, adolescents and young adults. CMAJ 2008; 178:1005.
- Mosholder AD, Pamer CA. Postmarketing surveillance of suicidal adverse events with pediatric use of antidepressants. J Child Adolesc Psychopharmacol 2006; 16:33.
- National Mental Health Information Center, Center for Mental Health Services. Children and Mental Health Fast Facts, 2000. mentalhealth.samhsa.gov/publications/allpubs/fastfact5/default.asp (Accessed on July 25, 2008).