Editorial: antidepressant prescriptions in children and adolescents

Editorial on the Research Topic
Antidepressant Prescriptions in Children and Adolescents

The use of antidepressants in children and adolescents has a troubled history, for almost all principles of good evidence-based medicine were violated or compromised. It is a history characterized by systematically biased research, financial conflicts of interest, and professional recklessness ( 1 – 3 ). In 2004, the Lancet Editors ( 4 ), in an article titled “ Depressing research” bluntly stated that “ The story of research into selective serotonin reuptake inhibitor (SSRI) use in childhood depression is one of confusion, manipulation, and institutional failure” (p. 1335). It is now well-established that most pediatric antidepressant trials were industry-sponsored and had serious methodological limitations; many trials remained unpublished due to unfavorable results, and those published were mostly ghost-written, selectively reported efficacy outcomes and misrepresented the true rate of treatment-emergent suicidal events ( 5 – 9 ). Drug regulators issued a suicidality warning for pediatric antidepressant use in 2003 (MHRA) and 2004 (FDA) and advised to use fluoxetine only. By consequence, some authors argued that SSRI should be reserved as a second-line option for youth with severe and resistant forms of depression ( 10 ).

However, in most countries antidepressant use has considerably increased in children and adolescent over the last 10–15 years ( 11 – 13 ), despite suicidality warnings, the serious limitations of the evidence-base ( 14 ), and ongoing controversies surrounding risks and benefits ( 15 ) as well as the placebo response ( 16 ). The aim of this special topic was thus to provide a collection of articles broadly focused on two main issues; first, on the current scientific evidence for the efficacy and safety of antidepressants, with a special emphasis on suicidality and related regulatory warnings, and, second, on recent trends in prescription rates and patterns of utilization, including antidepressant overuse, and the increasingly medicalized approach to mental health.

2. Leo J. The SSRI trials in children: disturbing implications for academic medicine. Ethical Hum Psychol Psychiatry . (2006) 8: 29–41. doi: 10. 1891/ehpp. 8. 1. 29

3. Raz A. Perspectives on the efficacy of antidepressants for child and adolescent depression. PLoS Med . (2006) 3: e9. doi: 10. 1371/journal. pmed. 0030009

4. Lancet Editors. Depressing research. Lancet.(2004) 363: 1335. doi: 10. 1016/S0140-6736(04)16080-7

5. Jureidini JN, Doecke CJ, Mansfield PR, Haby MM, Menkes DB, Tonkin AL. Efficacy and safety of antidepressants for children and adolescents. BMJ.(2004) 328: 879–83. doi: 10. 1136/bmj. 328. 7444. 879

6. Jureidini JN, McHenry LB, Mansfield PR. Clinical trials and drug promotion: selective reporting of study 329. Int J Risk Saf Med . (2008) 20: 73–81. doi: 10. 3233/JRS-2008-0426

7. Jureidini JN, Amsterdam JD, McHenry LB. The citalopram CIT-MD-18 pediatric depression trial: deconstruction of medical ghostwriting, data mischaracterisation and academic malfeasance. Int J Risk Saf Med . (2016) 28: 33–43. doi: 10. 3233/JRS-160671

8. Le Noury J, Nardo JM, Healy D, Jureidini J, Raven M, Tufanaru C, et al. Restoring Study 329: efficacy and harms of paroxetine and imipramine in treatment of major depression in adolescence. BMJ . (2015) 351: h4320. doi: 10. 1136/bmj. h4320

9. 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) 363: 1341–5. doi: 10. 1016/S0140-6736(04)16043-1

10. Cohen D. Should the use of selective serotonin reuptake inhibitors in child and adolescent depression be banned? Psychother Psychosom.(2007) 76: 5–14. doi: 10. 1159/000096360

11. Bachmann CJ, Aagaard L, Burcu M, Glaeske G, Kalverdijk LJ, Petersen I, et al. Trends and patterns of antidepressant use in children and adolescents from five western countries, 2005-2012. Eur Neuropsychopharmacol . (2016) 26: 411–9. doi: 10. 1016/j. euroneuro. 2016. 02. 001

12. John A, Marchant AL, Fone DL, McGregor JI, Dennis MS, Tan JO, et al. Recent trends in primary-care antidepressant prescribing to children and young people: an e-cohort study. Psychol Med . (2016) 46: 3315–27. doi: 10. 1017/S0033291716002099

13. Schroder C, Dorks M, Kollhorst B, Blenk T, Dittmann RW, Garbe E, et al. Outpatient antidepressant drug use in children and adolescents in Germany between 2004 and 2011. Pharmacoepidemiol Drug Saf . (2017) 26: 170–9. doi: 10. 1002/pds. 4138

14. Healy D, Le Noury J, Jureidini J. Paediatric antidepressants: benefits and risks. Int J Risk Saf Med.(2019) 30: 1–7. doi: 10. 3233/JRS-180746

15. Cipriani A, Zhou X, Del Giovane C, Hetrick SE, Qin B, Whittington C, et al. Comparative efficacy and tolerability of antidepressants for major depressive disorder in children and adolescents: a network meta-analysis. Lancet.(2016) 388: 881–90. doi: 10. 1016/S0140-6736(16)30385-3

16. Cohen D, Deniau E, Maturana A, Tanguy ML, Bodeau N, Labelle R, et al. Are child and adolescent responses to placebo higher in major depression than in anxiety disorders? A systematic review of placebo-controlled trials. PLoS ONE . (2008) 3: e2632. doi: 10. 1371/journal. pone. 0002632

17. Zhou X, Teng T, Zhang Y, Del Giovane C, Furukawa TA, Weisz JR, et al. Comparative efficacy and acceptability of antidepressants, psychotherapies, and their combination for acute treatment of children and adolescents with depressive disorder: a systematic review and network meta-analysis. Lancet Psychiatry . (2020) 7: 581–601. doi: 10. 1016/S2215-0366(20)30137-1