Context: The US FDA has issued an advisory warning of a possible link between antidepressant treatment for paediatric patients with major depressive disorder (MDD) and an increased risk of suicidal behaviour. A large database of paid health insurance claims for adolescents with MDD provided the opportunity to examine this possible relationship.
Objective: To examine the potential empirical link between antidepressant treatment and suicide attempts among adolescents aged 12–18 years using a community sample of managed care enrollees across the US.
Design: A retrospective longitudinal cohort using paid insurance claims for all healthcare and prescription fills for adolescents who were newly diagnosed with MDD and had at least 6 months of follow-up data. A multivariate Cox proportional hazards regression analysis was used to test the hypothesis that antidepressant use increased the risk of suicide attempt, adjusting for propensity for allocation to each treatment group and for demographic and clinical characteristics.
Setting: Managed care plans including both commercial and Medicaid plans in the east, midwest, south and western regions of the US from January 1997 to March 2003.
Participants: All adolescent insurance members aged 12–18 years at first diagnosis of MDD.
Main outcome measures: Suicide attempts as indicated by medical utilisation with International Classification of Diseases (9th edition) [ICD-9] or 10th edition (ICD-10) codes in any healthcare setting or by any covered provider.
Results: 24 119 adolescents met inclusion criteria (63% female). Crude suicide attempt rates ranged from 0.0-2.3% by index treatment group. Treatment with SSRIs (hazard ratio) [HR] = 1.59; CI 0.89, 2.82), other antidepressants (HR = 1.03; CI 0.43, 2.44), or multiple antidepressants (HR = 1.43; CI 0.70, 2.89) after index MDD diagnosis resulted in no statistically increased risk of suicide attempt. Treatment with antidepressant medication for at least 180 days (6 months) reduced the likelihood of suicide attempt compared with antidepressant treatment for <55 days (8 weeks) [HR = 0.34; CI 0.21, 0.55]. Other variables that were independently associated with greater risk of suicide attempts included female gender, severity of illness indicators, younger age at time of MDD diagnosis, and living in the midwest or west.
Conclusions: Antidepressant medication use had no statistically significant effect on the likelihood of suicide attempt in a large cohort of adolescents across the US after propensity adjustment for treatment allocation and controlling for other factors. The relationship between suicidal behaviour and antidepressant medication use is complex and requires further investigation.
Kessler RC, Berglund P, Dernier O, et al. The epidemiology of major depressive disorder: results from the national comorbidity survey replication (NCS-R). JAMA 2003; 289(23): 3095–105PubMedCrossRefGoogle Scholar
Birmaher B, Ryan ND, Williamson D, et al. Childhood and adolescent depression: a review of the past 10 years. Part I. J Am Acad Child Adolesc Psychiatry 1996; 35(11): 1427–39CrossRefGoogle Scholar
Birmaher B, Arbelaez C, Brent D. Course and outcome of child and adolescent major depressive disorder. Child Adolesc Psychiatr Clin N Am 2002; 11(3): 619–37PubMedCrossRefGoogle Scholar
Berndt E, Koran L, Finkelstein S, et al. Lost human capital from early-onset chronic depression. Am J Psychiatry 2000; 157: 940–7PubMedCrossRefGoogle Scholar
Birmaher B, Brent DA, Benson RS. Practice parameters for the assessment and treatment of children and adolescents with depressive disorders. J Am Acad Child Adolesc Psychiatry 1998; 37(10): 63S–83SCrossRefGoogle Scholar
Emslie G, Rush A, Weinberg W, et al. A double-blind, randomized, placebo-controlled trial of fluoxetine in children and adolescents with depression. Arch Gen Psychiatry 1997; 54: 1031–7PubMedCrossRefGoogle Scholar
Wagner KD, Ambrosini P, Rynn M, et al. Efficacy of sertraline in the treatment of children and adolescents with major depressive disorder: two randomized clinical Trials. JAMA 2003; 290(8): 1033–93PubMedCrossRefGoogle Scholar
Emslie G, Heiligenstein J, Wagner K, 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: 1205–15PubMedCrossRefGoogle Scholar
Keller M, Ryan N, Strober M, et al. Efficacy of paroxetine in the treatment of adolescent major depression: a randomized, controlled trial. J Am Acad Child Adolesc Psychiatry 2001; 40: 762–72PubMedCrossRefGoogle Scholar
Varley C. Psychopharmocological treatment of major depressive disorder in children and adolescents. JAMA 2003; 290(8): 1091–3PubMedCrossRefGoogle Scholar
Brent D, Birmaher B. British warning on SSRIs questioned. J Am Acad Child Adolesc Psychiatry 2004; 43(4): 379–80PubMedCrossRefGoogle Scholar
Hazell P, O’Connell D, Heathcote D, et al. Efficacy of tricyclic drugs in treating child and adolescent depression: a meta-analysis. BMJ 1995; 310: 897–901PubMedCrossRefGoogle Scholar
Shireman T, Olson BM, Dewan NA. Patterns of antidepressant use among children and adolescents. Psychiatr Serv (Chic) 2002; 53(11): 1444–50CrossRefGoogle Scholar
McCombs JS, Nichol MB, Stimmel GL, et al. The cost of antidepressant drug therapy failure: a study of antidepressant use patterns in a Medicaid population. J Clin Psychiatry 1990; 51 Suppl.: 60–9PubMedGoogle Scholar
McCombs JS, Nichol MB, Stimmel GL. The role of SSRI antidepressants for treating depressed patients in the California Medicaid (Medi-Cal) program. Value Health 1999; 2(4): 269–80PubMedCrossRefGoogle Scholar
Hoagwood K, Burns BJ, Kiser L, et al. Evidence-based practice in child and adolescent mental health services. Psychiatr Serv (Chic) 2001; 52(9): 1179–89CrossRefGoogle Scholar
New Freedom Commission on Mental Health. Achieving the promise: transforming mental health care in America. Final report. Rockville, MD: DHHS; 2003. Pub. No. SMA-03-3832Google Scholar
Horesh N, Orbach I, Gothelf D, et al. Comparison of the suicidal behavior of adolescent inpatients with borderline personality disorder and major depression. J Nerv Ment Dis 2003; 191(9): 582–8PubMedCrossRefGoogle Scholar
Zametkin AJ, Atler MR, Yemeni T. Suicide in teenagers: assessment, management, and prevention. JAMA 2001; 286(24): 3120–5PubMedCrossRefGoogle Scholar
Russell M, Taylor D, Cummins G, et al. Use of managed care claims data in the risk assessment of venous thromboembolism in outpatients. Am J Manag Care 2002; 8(1 Suppl.): S3–9PubMedGoogle Scholar
Valuck R. Treatment of depression with citalopram, fluoxetine, paroxetine, sertraline, and venlafaxine in managed care. Part 1: drug selection, dosing, and utilization. Drug Benefit Trends 2002; 14(7): 23–30Google Scholar
Valuck R. Treatment of depression with citalopram, fluoxetine, paroxetine, sertraline, and venlafaxine in managed care. Part 2: patient comorbidities and coprescribed therapies. Drug Benefit Trends 2002; 14(8): 33–40Google Scholar
World Health Organization. ICD-9: international statistical classification of diseases and relation health problems. 9th rev. Geneva: World Health Organization, 1978Google Scholar
World Health Organization. ICD-10: international statistical classification of diseases and relation health problems. 10th rev. Geneva: World Health Organization, 1994Google Scholar
O’Carroll PW, Potter LB. Suicide contagion and the reporting of suicide: recommendations from a national workshop. Morb Mortal Wkly Rep 1994; 43(RR-6): 9–18Google Scholar
American Psychiatric Association. Diagnostic and statistical manual of mental disorders (DSM-IV). 4th ed. Washington, DC: American Psychiatric Association, 1994Google Scholar
Martin A, Van Hoof T, Stubbe D, et al. Multiple psychotropic pharmacotherapy among child and adolescent enrollees in Connecticut Medicaid managed care. Psychiatric Services 2003; 54(1): 72–7PubMedCrossRefGoogle Scholar
Malone D, Billups S, Valuck R, et al. Development of a chronic disease indicator score using a Veterans Affairs Medical Center medication database. J Clin Epidemiol 1999; 52: 551–7PubMedCrossRefGoogle Scholar
Valuck R, Williams S, MacArthur M, et al. A retrospective cohort study of correlates of response to pharmacologic therapy for hyperlipidemia in members of a managed care organization. Clin Ther 2003; 25: 2936–57PubMedCrossRefGoogle Scholar
Rey M, Schulz P, Costa C, et al. Guidelines for the dosage of neuroleptics: I. Chloropromazine equivalents of orally administered neuroleptics. Int Clin Psychiatry 1989; 4: 95–104Google Scholar
Rijcken C, Monster T, Brouwers J, et al. Chlorpromazine equivalents versus defined daily doses: how to compare anti-psychotic drug doses? J Clin Psychopharmacology 2003; 23(6): 657–9CrossRefGoogle Scholar
Asburn M, Lipman A. Management of pain in the cancer patient. Anesth Analg 1994; 79(3): 612–4CrossRefGoogle Scholar
Steiner J, Prochazka A. The assessment of refill compliance using pharmacy records: methods, validity, and applications. J Clin Epidemiol 1997; 50: 105–16PubMedCrossRefGoogle Scholar
Current Procedural Terminology. 4th ed. Chicago (IL): American Medical Association, 2000Google Scholar
Wang J, Donnan P. Propensity score methods in drug safety studies: practice, strengths, and limitations. Pharmacoepidemiol Drug Saf 2001; 10: 341–4PubMedCrossRefGoogle Scholar
Cox DR. Regression models and life tables. J R Stat Soc 1972; 34: 187–202Google Scholar
Crown W, Treglia M, Meneades L, et al. Long-term costs of treatment for depression: impact of drug selection and guideline adherence. Value Health 2001; 4(4): 295–307PubMedGoogle Scholar
SAS Language [computer program]. Version 8.1. Cary (NC): SAS Institute, 2000Google Scholar
Wong I, Besag F, Santosh P, et al. Use of selective serotonin reuptake inhibitors in children and adolescents. Drug Saf 2004; 27(13): 991–1000PubMedCrossRefGoogle Scholar
Cook TD, Campbell DT. Quasi-experimentation: design and analysis issues for field settings. Chicago (IL): Rand McNally, 1979Google Scholar
Vorstman J, Lahuis B, Buitelaar JK. SSRIs associated with behavioral activation and suicidal ideation. J Am Acad Child Adolesc Psychiatry 2001; 40(12): 1364–5PubMedCrossRefGoogle Scholar
American Psychiatric Association, et al. Practice guideline for the treatment of patients with major depressive disorder (revision). Am J Psychiatry 2000; 157(4): 1–45Google Scholar
Goldstein B, Goodnick P. Selective serotonin reuptake inhibitors in the treatment of affective disorders: III. Tolerability, safety and pharmacoeconomics. J Psychopharmacol 1998; 12Suppl. B: S57AGoogle Scholar
Aguglia E, Casacchia M, Cassano G, et al. Double-blind study of the efficacy and safety of sertraline versus fluoxetine in major depression. Int Clin Psychopharmacol 1993; 8(3): 197–202PubMedCrossRefGoogle Scholar
Montgomery SA, Huusom AK. Escitalopram is at least as effective as venlafaxine XR in the treatment of depression and is better tolerated [poster]. 15th Congress of the European College of Neuropsychopharmacology; 2002 Oct 5–9; BarcelonaGoogle Scholar
Bielski R, Ventura D, Chang C. A double-blind comparison of escitalopram with venlafaxine XR in the treatment of major depressive disorder [poster]. 16th Congress of the European College of Neuropsychopharmacology; 2003 Sep 20–24; PragueGoogle Scholar
Valuck R. Selective serotonin reuptake inhibitors: a class review. Pharmacy and Therapeutics. 2004; 29(4): 234–43Google Scholar
Schlesselman J. Sample size requirements in cohort and case-control studies of disease. Am J Epidemiol 1974; 99: 381–4PubMedGoogle Scholar
Spettell C, Wall T, Allison J, et al. Identifying physician-recognized depression from administrative data: consequences for quality measurement. Health Serv Res 2003; 38(4): 1081–102PubMedCrossRefGoogle Scholar
Rost K, Smith R, Matthews D, et al. The deliberate misdiagnosis of major depression in primary care. Arch Fam Med 1994; 3(4): 333–7PubMedCrossRefGoogle Scholar
Hirschfeld R, Keller M, Panico S, et al. The National Depressive and Manic-Depressive Association consensus statement on the undertreatment of depression. JAMA 1997; 277(4): 333–40PubMedCrossRefGoogle Scholar
Lemelin J, Hotz S, Swensen R, et al. Depression in primary care: why do we miss the diagnosis? Can Fam Physician 1994; 40: 104–8PubMedGoogle Scholar