Depression in the Paediatric Population: Current Therapeutic Context and Challenges to Innovation

Authors

  • Ana Rita Rodrigues Laboratório de Sociofarmácia e Saúde Pública / Faculdade de Farmácia, Universidade de Coimbra, Coimbra, Portugal https://orcid.org/0000-0002-6755-2980
  • Filipe Palavra Centro de Desenvolvimento da Criança – Neuropediatria / Hospital Pediátrico, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal; Laboratório de Farmacologia e Terapêutica Experimental, Instituto de Investigação Clínica e Biomédica de Coimbra (iCBR), Faculdade de Medicina, Universidade de Coimbra, Coimbra, Portugal; Centro Académico Clínico de Coimbra (CACC), Coimbra, Portugal https://orcid.org/0000-0002-2165-130X
  • Victoria Bell Laboratório de Sociofarmácia e Saúde Pública / Faculdade de Farmácia, Universidade de Coimbra, Coimbra, Portugal https://orcid.org/0000-0003-2728-9134
  • Filipa Mascarenhas-Melo Laboratório de Desenvolvimento e Tecnologias do Medicamento, Faculdade de Farmácia, Universidade de Coimbra, Coimbra, Portugal https://orcid.org/0000-0003-0786-6280
  • Luis Almeida Laboratório de Farmacologia e Terapêutica Experimental, Instituto de Investigação Clínica e Biomédica de Coimbra (iCBR), Faculdade de Medicina, Universidade de Coimbra, Coimbra, Portugal https://orcid.org/0000-0002-4861-8649
  • Francisco Veiga Laboratório de Desenvolvimento e Tecnologias do Medicamento, Faculdade de Farmácia, Universidade de Coimbra, Coimbra, Portugal https://orcid.org/0000-0002-1041-0068

DOI:

https://doi.org/10.46531/sinapse/AR/230029/2023

Keywords:

Antidepressive Agents/ therapeutic use, Child, Depression/therapy, Depressive Disorder/therapy, Depressive Disorder, Major/ drug therapy, Vortioxetine/therapeutic use

Abstract

Major depression, as a clinical condition associated with the highest rate of disability worldwide, presents very particular contours when it affects the pediatric population. The biochemical and pathophysiological changes associated with depression are naturally influenced by socioeconomic aspects and family dynamics, which contributes to great heterogeneity and variability in the symptoms expressed by children and adolescents. The COVID-19 pandemic, following the implementation of the necessary measures to mitigate the virus infection, has worsened mental illness in the general population, including the pediatric population, significantly contributing to an increase in cases of anxiety, depression and even of post-traumatic stress. This review aims to systematize the pathophysiological aspects of depression that manifests early in life, as well as its current therapeutic context, shedding some light on pharmacogenetics and the way in which multimodal drugs are designed to be used in the pediatric population. A search was conducted in the PubMed and Google Scholar databases, and only articles written in English and Portuguese published in journals indexed to the Web of Science were included in this review, as well as current guidelines for pharmacological prescription in pediatric depression. The results made it possible to compile current data on the efficacy and safety of medications used to treat this clinical situation and discuss the current paradigm of mental health in pediatrics.

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References

American Psychiatric Association. Manual diagnóstico e estatístico de transtornos mentais: DSM-5. 5th ed. Chicago: APA; 2014.

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 metaanalysis. Lancet Psychiatry. 2020; 7: 581–601. doi: 10.1016/S2215-0366(20)30137-1.

World Health Organization. Mental health. [accessed 21 Jan 2022] Available at: https://www.who.int/health-topics/mental-health#tab=tab_1 .

Maruf A Al, Greenslade A, Arnold PD, Bousman C. Antidepressant pharmacogenetics in children and young adults: A systematic review. J Affect Disord. 2019; 254: 98–108. doi:10.1016/j.jad.2019.05.025.

Thapar A, Eyre O, Patel V, Brent D. Depression in young people. Lancet. 2022; 400: 617–31. doi: 10.1016/S0140-6736(22)01012-1.

Hertz MF, Barrios LC. Adolescent mental health, COVID-19, and the value of school-community partnerships. Inj Prev. 2021; 27: 85–6. doi: 10.1136/injuryprev-2020-044050.

Walter HJ, Abright AR, Bukstein OG, Diamond J, Keable H, Ripperger-Suhler J et al. Clinical practice guideline for the assessment and treatment of children and adolescents with major and persistent depressive disorders. J Am Acad Child Adolesc Psychiatry. 2023; 62: 479–502. doi: 10.1016/j.jaac.2022.10.001.

Singh S, Roy D, Sinha K, Parveen S, Sharma G, Joshi G. Impact of COVID-19 and lockdown on mental health of children and adolescents: A narrative review with recommendations. Psychiatry Res. 2020; 293. doi:10.1016/j.psychres.2020.113429.

World Health Organization. Mental Health: a state of wellbeig. https://www.who.int/features/factfiles/mental_health/en/

World Health Organization. Suicide worldwide in 2019: Global Health Estimates. Geneve: WHO; 2021.

World Health Organization. Mental disorders. [accessed 21 Jan 2022] Available at: https://www.who.int/en/newsroom/fact-sheets/detail/mental-disorders

Malhi GS, Mann JJ. Depression. Lancet. 2018; 392: 2299312. doi: 10.1016/S0140-6736(18)31948-2.

Fu Z, Brouwer M, Kennis M, Williams A, Cuijpers P, Bockting C. Psychological factors for the onset of depression: A meta-analysis of prospective studies. BMJ Open. 2021;11. doi:10.1136/bmjopen-2021-050129.

Schmitgen MM, Depping MS, Bach C, Wolf ND, Kubera KM, Vasic N et al. Aberrant cortical neurodevelopment in major depressive disorder. J Affect Disord. 2019; 243: 3407. doi: 10.1016/j.jad.2018.09.021.

Gray JP, Müller VI, Eickhoff SB, Fox PT. Multimodal abnormalities of brain structure and function in major depressive disorder: A meta-analysis of neuroimaging studies. Am J Psychiatry. 2020; 177: 422–34. doi: 10.1176/appi.ajp.2019.19050560.

Buch AM, Liston C. Dissecting diagnostic heterogeneity in depression by integrating neuroimaging and genetics. Neuropsychopharmacology. 2021; 46: 156–75. doi: 10.1038/s41386-020-00789-3.

Johnson SE, Lawrence D, Perales F, Baxter J, Zubrick SR. Prevalence of mental disorders among children and adolescents of parents with self-reported mental health problems. Community Ment Health J. 2018; 54: 884–97. doi: 10.1007/s10597-017-0217-5.

World Health Organization. Depression and Other Common Mental Disorders: Global Health Estimates. Geneve: WHO; 2017.

World Health Organization. Fact Sheets on Depression. [accessed 21 Jan 2022] Available at: https://www.who.int/news-room/fact-sheets/detail/depression

de Almeida JMC. A saúde mental dos portugueses. Lisboa: Fundação Francisco Manuel dos Santos; 2018.

World Health Organization. Adolescent mental health. [accessed 21 Jan 2022] Available at: https://www.who.int/news-room/fact-sheets/detail/adolescent-mental-

World Health Organization. 10 Facts on Mental Health. 10 Facts on Mental Health. [accessed 21 Jan 2022] Available at: https://www.who.int/features/factfiles/mental_health/mental_health_facts/en/

Silk JS, Price RB, Rosen D, Ryan ND, Forbes EE, Siegle GJ et al. A longitudinal follow-up study examining adolescent depressive symptoms as a function of prior anxiety treatment. J Am Acad Child Adolesc Psychiatry. 2019; 58: 359–67. doi: 10.1016/j.jaac.2018.10.012.

Bernaras E, Jaureguizar J, Garaigordobil M. Child and adolescent depression: A review of theories, evaluation instruments, prevention programs, and treatments. Front Psychol 2019; 10. doi:10.3389/fpsyg.2019.00543.

Hetrick SE, McKenzie JE, Cox GR, Simmons MB, Merry SN. Newer generation antidepressants for depressive disorders in children and adolescents. Cochrane Database Syst Rev. 2012;11:CD004851. doi: 10.1002/14651858.CD004851.pub3.

Van Dijk MT, Murphy E, Posner JE, Talati A, Weissman MM. Association of multigenerational family history of depression with lifetime depressive and other psychiatric disorders in children: results from the Adolescent Brain Cognitive Development (ABCD) Study. JAMA Psychiatry. 2021; 78:778–87. doi: 10.1001/jamapsychiatry.2021.0350.

Hankin BL, Young JF, Gallop R, Garber J. Cognitive and Interpersonal Vulnerabilities to Adolescent Depression: Classification of Risk Profiles for a Personalized Prevention Approach. J Abnorm Child Psychol. 2018; 46: 1521–33. doi: 10.1007/s10802-018-0401-2.

Jaffee SR, Sligo JL, McAnally HM, Bolton AE, Baxter JM, Hancox RJ. Early-onset and recurrent depression in parents increases risk of intergenerational transmission to adolescent offspring. J Child Psychol Psychiatry. 2021; 62: 979–88. doi: 10.1111/jcpp.13356.

Slomian J, Honvo G, Emonts P, Reginster JY, Bruyère O. Consequences of maternal postpartum depression: A systematic review of maternal and infant outcomes. Womens Health. 2019; 15. doi:10.1177/1745506519844044.

Carballo JJ, Llorente C, Kehrmann L, Flamarique I, Zuddas A, Purper-Ouakil D et al. Psychosocial risk factors for suicidality in children and adolescents. Eur Child Adolesc Psychiatry. 2020; 29: 759–76. doi: 10.1007/s00787-018-01270-9.

Rey JM, Bella-Awusah TT, Liu J, Professor of Psychiatry F. Depression in Children and Adolescents. IACAPAP Textbook of Child and Adolescent Mental Health 2015. Chicago: IACAPAP; 2015.

Asselmann E, Wittchen HU, Lieb R, Beesdo-Baum K. Sociodemographic, clinical, and functional long-term outcomes in adolescents and young adults with mental disorders. Acta Psychiatr Scand. 2018; 137: 6–17. doi: 10.1111/acps.12792.

Avenevoli S, Swendsen J, He JP, Burstein M, Merikangas KR. Major depression in the national comorbidity surveyadolescent supplement: prevalence, correlates, and treatment. J Am Acad Child Adolesc Psychiatry. 2015; 54: 37-44.e2. doi: 10.1016/j.jaac.2014.10.010.

Ames ME, Leadbeater BJ. Depressive symptom trajectories and physical health: Persistence of problems from adolescence to young adulthood. J Affect Disord. 2018; 240: 121–9. doi: 10.1016/j.jad.2018.07.001.

Food & Drug Administration. Depression Medicines. 2019. [accessed 21 Jan 2022] Available at: https://www.fda.gov/consumers/free-publications-women/depression-medicines

Agência Europeia de Medicamentos. European Medicines Agency adopts a positive opinion for the use of Prozac in the treatment of children and adolescents suffering from depression. London:EMA; 2006.

Direção-Geral da Saúde. Norma DGS: Prescrição de Antidepressivos Médicos do Sistema Nacional de Saúde. Lisbon: DGS; 2011.

Infarmed - Autoridade Nacional do Medicamento e Produtos de Saúde IP. Resumo das Características do Medicamento - Citalopram. 2021. [accessed 21 Jan 2022] Available at: https://extranet.infarmed.pt/INFOMED-fo/pesquisa-avancada.xhtml

Infarmed - Autoridade Nacional do Medicamento e Produtos de Saúde IP. Resumo das Características do Medicamento - Sertralina. 2022. [accessed 21 Jan 2022] Available at: https://extranet.infarmed.pt/INFOMED-fo/pesquisa-avancada.xhtml

Infarmed - Autoridade Nacional do Medicamento e Produtos de Saúde IP. Resumo das Características do Medicamento - Paroxetina. 2019. [accessed 21 Jan 2022] Available at: https://extranet.infarmed.pt/INFOMED-fo/pesquisa-avancada.xhtml

Infarmed - Autoridade Nacional do Medicamento e Produtos de Saúde IP. Resumo das Características do Medicamento - Escitalopram. 2020. [accessed 21 Jan 2022] Available at: https://extranet.infarmed.pt/INFOMED-fo/pesquisa-avancada.xhtml

Infarmed - Autoridade Nacional do Medicamento e Produtos de Saúde IP. Resumo das Características do Medicamento - Fluvoxamina. 2021. [accessed 21 Jan 2022] Available at: https://extranet.infarmed.pt/INFOMED-fo/pesquisa-avancada.xhtml

Infarmed - Autoridade Nacional do Medicamento e Produtos de Saúde IP. Resumo das Características do Medicamento - Fluoxetina. 2021. [accessed 21 Jan 2022] Available at: https://extranet.infarmed.pt/INFOMED-fo/pesquisa-avancada.xhtml

Dwyer JB, Stringaris A, Brent DA, Bloch MH. Annual Research Review: Defining and treating pediatric treatment-resistant depression. J Child Psychol Psychiatry. 2020; 61:312–32. doi: 10.1111/jcpp.13202.

Bezchlibnyk-Butler KZ, Virani AS. Clinical handbook of psychotropic drugs for children and adolescents. Berlin: Hogrefe & Huber Publishers; 2004.

Spielmans GI, Spence-Sing T, Parry P. Duty to Warn: Antidepressant Black Box Suicidality Warning Is Empirically Justified. Front Psychiatry. 2020; 11. doi:10.3389/fpsyt.2020.00018.

Beurel E, Toups M, Nemeroff CB. The bidirectional relationship of depression and inflammation: double trouble. Neuron. 2020; 107: 234–56. doi: 10.1016/j.neuron.2020.06.002.

Schramm E, Klein DN, Elsaesser M, Furukawa TA, Domschke K. Review of dysthymia and persistent depressive disorder: history, correlates, and clinical implications. Lancet Psychiatry. 2020; 7: 801–12. doi: 10.1016/S2215-0366(20)30099-7.

Conradi HJ, Ormel J, De Jonge P. Presence of individual (residual) symptoms during depressive episodes and periods of remission: A 3-year prospective study. Psychol Med. 2011; 41: 1165–74. doi: 10.1017/S0033291710001911.

Andersen SL, Navalta CP. Annual research review: New frontiers in developmental neuropharmacology: Can long-term therapeutic effects of drugs be optimized through carefully timed early intervention? J Child Psychol Psychiatry. 2011;52: 476–503. doi: 10.1111/j.1469-7610.2011.02376.x.

Brunello N, Mendlewicz J, Leonard B, Montgomery S, Craig Nelson J, Paykel E, et al. The role of noradrenaline and selective noradrenaline reuptake inhibition in depression. Eur Neuropsychopharmacol. 2002; 12: 461–75. doi: 10.1016/s0924-977x(02)00057-3.

Andersen SL. Trajectories of brain development: Point of vulnerability or window of opportunity? In: Neuroscience and Biobehavioral Reviews. Amsterdam: Elsevier; 2003. p. 3–18.

Planchez B, Surget A, Belzung C. Animal models of major depression: drawbacks and challenges. J Neural Transm. 2019; 126: 1383–408. doi: 10.1007/s00702-019-02084-y.

Thapar A, Collishaw S, Pine DS, Thapar AK. Depression in adolescence. Lancet 2012; 379: 1056–67. doi: 10.1016/S0140-6736(11)60871-4.

Bradley P, Shiekh M, Mehra V, Vrbicky K, Layle S, Olson MC, et al. Improved efficacy with targeted pharmacogenetic-guided treatment of patients with depression and anxiety: A randomized clinical trial demonstrating clinical utility. J Psychiatr Res. 2018; 96: 100–7. doi: 10.1016/j.jpsychires.2017.09.024.

Hicks JK, Sangkuhl K, Swen JJ, Ellingrod VL, Müller DJ, Shimoda K, et al. Clinical pharmacogenetics implementation consortium guideline (CPIC) for CYP2D6 and CYP2C19 genotypes and dosing of tricyclic antidepressants: 2016 update. Clin Pharmacol Ther. 2017; 102: 37–44. doi: 10.1002/cpt.597.

Stahl SM. Modes and nodes explain the mechanism of action of vortioxetine, a multimodal agent (MMA): Enhancing serotonin release by combining serotonin (5HT) transporter inhibition with actions at 5HT receptors (5HT1A, 5HT1B, 5HT1D, 5HT7 receptors). CNS Spectr. 2015; 20: 93–97.

Autoridade Nacional Do Medicamento E Produtos De Saúde I.P. Resumo das Características do Medicamento - Vortioxetina. [accessed 21 Jan 2022] Available at: https://www.ema.europa.eu/en/documents/product-information/brintellix-epar-product-information_pt.pdf

Hetrick SE, McKenzie JE, Bailey AP, Sharma V, Moller CI, Badcock PB, et al. New generation antidepressants for depression in children and adolescents: a network meta-analysis. Cochrane Database Syst Rev. 2021;5:CD013674. doi: 10.1002/14651858.CD013674.pub2.

Meherali S, Punjani N, Louie-Poon S, Rahim KA, Das JK, Salam RA, et al. Mental health of children and adolescents amidst covid-19 and past pandemics: A rapid systematic review. Int J Environ Res Public Health. 2021; 18. doi:10.3390/ijerph18073432.

Nearchou F, Hennessy E, Flinn C, Niland R, Subramaniam SS. Exploring the impact of covid-19 on mental health outcomes in children and adolescents: A systematic review. Int J Environ Res Public Health. 2020; 17: 8479. doi: 10.3390/ijerph17228479.

Racine N, McArthur BA, Cooke JE, Eirich R, Zhu J, Madigan S. Global prevalence of depressive and anxiety symptoms in children and adolescents during COVID-19: a meta-analysis. JAMA Pediatr. 2021; 175: 1142–50. doi: 10.1001/jamapediatrics.2021.2482.

Ma L, Mazidi M, Li K, Li Y, Chen S, Kirwan R, et al. Prevalence of mental health problems among children and adolescents during the COVID-19 pandemic: A systematic review and meta-analysis. J Affect Disord. 2021;293:78-89. doi: 10.1016/j.jad.2021.06.021.

Rabeea SA, Merchant HA, Khan MU, Kow CS, Hasan SS. Surging trends in prescriptions and costs of antidepressants in England amid COVID-19. Daru. 2021;29:217-21. doi:10.1007/s40199-021-00390-z.

Chua KP, Volerman A, Conti RM. Prescription Drug Dispensing to US Children During the COVID-19 Pandemic. Pediatrics. 2021; 148. doi:10.1542/peds.2021-049972.

Findling RL, Delbello MP, Zuddas A, Emslie GJ, Ettrup A, Petersen ML, et al. Vortioxetine for major depressive disorder in adolescents: 12-week randomized, placebo-controlled, fluoxetine-referenced, fixed-dose study. J Am Acad Child Adolesc Psychiatry. 2022; 61: 1106–18. doi: 10.1016/j.jaac.2022.01.004.

Jones EAK, Mitra AK, Bhuiyan AR. Impact of covid-19 on mental health in adolescents: A systematic review. Int J Environ Res Public Health. 2021; 18: 2470. doi: 10.3390/ijerph18052470.

Marques de Miranda D, da Silva Athanasio B, Sena Oliveira AC, Simões-e-Silva AC. How is COVID-19 pandemic impacting mental health of children and adolescents? Int J Disaster Risk Reduct. 2020; 51. doi:10.1016/j.ijdrr.2020.101845.

Published

2024-01-27

How to Cite

1.
Rodrigues AR, Palavra F, Bell V, Mascarenhas-Melo F, Almeida L, Veiga F. Depression in the Paediatric Population: Current Therapeutic Context and Challenges to Innovation. Sinapse [Internet]. 2024 Jan. 27 [cited 2024 Apr. 30];23(4):198-206. Available from: https://sinapse.pt/index.php/journal/article/view/4

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