Skip to main content

Advertisement

SpringerLink
Log in

Ethical issues in child psychopharmacology research and practice: emphasis on preschoolers

  • Review
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Introduction

Psychoactive drug prescription for preschoolers has increased over the past decade and has been a controversial topic for those who prescribe, regulate, and research the use of psychotropics in this population. Children and adolescents are deemed vulnerable populations, at risk of being harmed by unethical or suboptimal practice and research and are in need of special protection. Historically, preschoolers have been therapeutic and research “orphans,” excluded from pharmacological studies so that the evidence base for their treatment has to be extrapolated from other ages. Within the past few decades, several ethical principles guiding pediatric psychopharmacological research have been developed. The same principles could effectively guide the treatment of these patients.

Conclusion

Further studies are needed to elucidate the safety and effectiveness of psychotropics, and sound ethical guidelines for their involvement in psychiatric research are needed. This article reviews some challenges facing mental health care providers involved in prescribing or researching the use of psychoactive drugs in preschoolers. Some of these challenges are general to medical treatment and research with children, and others are particular to child psychopharmacological treatment and research.

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

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Explore related subjects

Discover the latest articles, news and stories from top researchers in related subjects.

References

  • American Academy of Pediatrics—Committee of Drugs (1995) Guidelines for the ethical conduct of studies to evaluate drugs in pediatric populations (RE9503) 95:286–294

  • Anderson GM (2004) Peripheral and central neurochemical effects of the selective serotonin reuptake inhibitors in humans and nonhuman primates: assessing bioeffect and mechanism of action. Int J Dev Neurosci 22:397–404

    Article  PubMed  CAS  Google Scholar 

  • Ansorge MS, Zhou M, Lira A, Hen R, Gingrich JA (2004) Early-life blockade of the 5-HT transporter alters emotional behavior in adult mice. Science 306(5697):879–881 (Oct 29)

    Article  PubMed  CAS  Google Scholar 

  • Arnold LE (2002) Treatment Alternatives for attention-deficit/hyperactivity disorder. In: Jensen PS, Cooper J (eds) Attention deficit hyperactivity disorder: state of the science; best practices. Civic Research Institute, Kingston, NJ

    Google Scholar 

  • Arnold L, Stoff D, Cooke E, Cohen DJ, Wright CB, Kruesi M, Hattab J, Arnold LE (1999) Treatment alternatives for attention-deficit/hyperactivity disorder (ADHD). J Atten Disord 3:30–48

    Google Scholar 

  • Beauchamp TL, Childress JF (1994) Principles of biomedical ethics. Oxford Univ. Press, Oxford

    Google Scholar 

  • Beck J, Azari E (1998) FDA, Off-label drug use, and informed consent: debunking myths and misconceptions. Food Drug Cosmet Law J 53:71–104

    CAS  Google Scholar 

  • Bor W, Sanders M, Markie-Dadds C (2002) The effects of the Triple P Positive parenting program on preschool children with co-occurring disruptive behavior and attentional/hyperactive difficulties. J Abnorm Child Psychol 30:571–587

    Article  PubMed  Google Scholar 

  • Carrey NJ, Dursun S, Clements R, Renton K, Waschbusch D, MacMaster FP (2002) Noradrenergic and serotonergic neuroendocrine responses in prepubertal, peripubertal, and postpubertal rats pretreated with desipramine and sertraline. J Am Acad Child Adolesc Psych 41:999–1006

    Article  Google Scholar 

  • Chambers CD, Hernandez-Diaz S, Van Marter LJ, Werler MM, Louik C, Jones KL, Mitchell AA (2006) Selective serotonin-reuptake inhibitors and risk of persistent pulmonary hypertension of the newborn. New Engl J Med 354(6):579–587

    Article  PubMed  CAS  Google Scholar 

  • Chesney RW (2005) Children as clinical research subjects. J Pediatr 146:579–580 (May)

    Article  PubMed  Google Scholar 

  • Cissoko H, Swortfiguer BG, Jonville-Bera AP, Autret-Leca E (2005) Neonatal outcome after exposure to selective reuptake inhibitors late in pregnancy. Arch Pediatr 12:1081–1084

    Article  PubMed  CAS  Google Scholar 

  • Correll C, Carlson HE (2006) Endocrine and metabolic adverse effects of psychotropic medications in children and adolescents. J Am Acad Child Adolesc Psych 45(7):771–791

    Google Scholar 

  • Department of Health and Human Services–2000–Report of the Surgeon General’s Conference on Children’s Mental Health: a National Action Agenda

  • Deveaugh-Geiss J, March J, Shapiro M, Andreason P, Emslie G, Ford L, Greenhill L, Murphy D, Prentice E, Roberts R, Silva S, Swanson JM, Van Zwieten-Boot B, Vitiello B, Wagner KD, Mangum B (2006) Child and adolescent psychopharmacology in the New Millenium: a workshop for academia, industry, and government. J Am Acad Child Adolesc Psych 45(3):261–270

    Article  Google Scholar 

  • FDA (2001) FDA ignores Helsinki Declaration’s new thinking on placebo trials. FDA week, Feb 9

  • Food and Drug Administration (1997) Modernization act of 1997. 21 USC 321

  • Gordon B, Prentice E, Anderson J (2000) Conflict between research design and minimization of risks in pediatric research. IRB 22(3):1–6

    Article  PubMed  CAS  Google Scholar 

  • Grady C (2005) Payment of clinical research subjects. J Clin Invest 115(7):1681–1687 (July 2005)

    Article  PubMed  CAS  Google Scholar 

  • Greenhill L, Jensen P, Abikoff H, Blumer JL, DeVeaugh-Geiss J, Fisher C, Hoagwood K, Kratochvil CJ, Lahey B, Laughren T, Leckman J, Petti TA, Pope K, Shaffer D, Vitiello B, Zeanah, C (2003) Developing strategies for psychopharmacological studies in preschool children. J Am Acad Child Adolesc Psych 42:406–414 (April)

    Google Scholar 

  • Jensen PS (1998) Ethical and pragmatic issues in the use of psychotropic agents in young children. Can J Psychiatry 43:585–588

    PubMed  CAS  Google Scholar 

  • Kazdin AE, Wassell G (2000) Therapeutic changes in children, parents, and families resulting from treatment of children with conduct problems. J Am Acad Child Adolesc Psych 39:414–420

    Article  CAS  Google Scholar 

  • Keenan K, Wakschlag LS (1998) More than the terrible twos: the nature and severity of behavior problems in clinic-referred preschool children. J Abnorm Child Psychol 28(1):33–46

    Article  Google Scholar 

  • Kollins SH, Greenhill L (2006) Evidence base for the use of stimulant medication in preschool children with ADHD. Infants Young Child 19(2):132–141

    Google Scholar 

  • Kopelman LM (2004) Minimal risk as an international ethical standard in research. J Med Philos 29(3):351–378

    Article  PubMed  Google Scholar 

  • Kratochvil CJ, Vitiello B, Walkup J, Emslie G, Waslick BD, Weller EB, Burke WJ, March JS (2006) Selective serotonin reuptake inhibitors in pediatric depression: Is the balance between benefits and risks favorable? J Child Adolesc Psychopharmacol 16(1/2):11–24

    Article  PubMed  Google Scholar 

  • Kwan P, Brodie MJ (2001) Neuropsychological effects of epilepsy and antiepileptic drugs. Lancet 357:216–222

    Article  PubMed  CAS  Google Scholar 

  • Lahey BB, Pelham WE, Stein MA, Loney J, Trapani C, Nugent K, Kipp H, Schmidt E et al (1998) Validity of DSM-IV attention-deficit/hyperactivity disorder for younger children. J Am Acad Child Adolesc Psych 37(7):695–702

    Article  CAS  Google Scholar 

  • Lehrman NS, Sharav VH (1997) Ethical problems in psychiatric research. J Mental Health Adm 24:227–250

    CAS  Google Scholar 

  • March J, Beiderman J, Wolkow R, Safferman A, Mardekian J, Cook E, Cutler N, Dominquez R, Feruson J, Muller B, Riesenberg R, Rosenthal R, Sallee F, Wagner K, Steiner H (1998) Sertraline in children and adolescents with obsessive–compulsive disorder: a multicenter randomized controlled trial. J Am Med Assoc 280(20):1752–1756

    Article  CAS  Google Scholar 

  • March J, Kratochvil C, Clarke G, Beardslee W, Derivan A, Emslie G, Green E, Heiligenstein J, Hinshaw S, Hoagwood K, Jensen P et al (2004) AACAP 2002 research forum: placebo and alternatives to placebo in randomized controlled trials in pediatric psychopharmacology. J Am Acad Child Adolesc Psych 43(8):1046–1056 (August)

    Article  Google Scholar 

  • Martin A, Young C, Leckman JF, Mukonoweshuro C, Rosenheck R, Leslie D (2004) Age effects on antidepressant-induced manic conversion. Arch Pediatr Adolesc Med 158(8):773–780

    Article  PubMed  Google Scholar 

  • Minde K (1998) The use of psychotropic medications in preschoolers: some recent developments. Can J Psychiatry 43:571–575

    PubMed  CAS  Google Scholar 

  • Misri S, Reebye P, Kendrick K, Carter D, Ryan D, Grunau RE, Oberlander TF (2006) Internalizing behaviors in 4-year-old children exposed in utero to psychotropic medications. Am J Psychiatr 163(6):1026–1032 (June)

    Article  PubMed  Google Scholar 

  • National Archives and Records Administration (1991) 45 Code of Federal Regulations (CFR). Subtitle A, part 46, Subpart D

  • National Archives and Records Administration (1998) 21 CFR parts 201, 312, 314, and 601—FDA. Pediatric patients regulations requiring manufacturers to assess the safety and effectiveness of new drugs and biological products; proposed rule (DOCKET no. 97N-0165) RIN 0910-AB20

  • National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research (1979) The Belmont report: ethical principles and guidelines for the protection of human subjects of research. Fed Regist 44(76):23192–23197

    Google Scholar 

  • National Institutes of Health (1998) Policy and guidelines on the inclusion of children as participants in research involving human subjects, March

  • NIMH (2000a) NIMH research forum. Recommended strategies for developing and implementing psychopharmacologic studies in preschool children. American academy of child and adolescent psychiatry 47th annual meeting, Oct. 25, 2000. Jointly sponsored by National Institute of Mental Health

  • NIMH (2000b) NIMH Workshop on Long-Term Drug Safety (Research Units in Pediatric Psychopharmacology, RUPP)—Sept. 25. NIMH Neurosciences Center, Rockville, MD

    Google Scholar 

  • Nulman I, Rovet J, Stewart DE, Wolpin J, Gardner HA, Theis JGW, Kulin N, Koren G (1997) Neurodevelopment of children exposed in utero to antidepressant drugs. N Engl J Med 336:258–262

    Article  PubMed  CAS  Google Scholar 

  • Nulman I, Rovet J, Stewart DE, Wolpin J, Pace-Asciak P, Shuhaiber S, Koren G (2002) Child development following exposure to tricyclic antidepressants or fluoxetine throughout fetal life: a prospective, controlled study. Am J Psychiatry 159:1889–1895

    Article  PubMed  Google Scholar 

  • Olfson M, Shaffer D, Marcus SC, Greenberg T (2003) Relationship between antidepressant medication treatment and suicide in adolescents. Arch Gen Psychiatry 60:978–982

    Article  PubMed  Google Scholar 

  • Reid MJ, Webster-Stratton C, Baydar N (2004) Halting the development of conduct problems in head start children: the effects of parent training. J Clin Child Adolesc Psychol 33(2):279–291 (June)

    Article  PubMed  Google Scholar 

  • Riddle M, Reeve E, Yaryura-Tobias J, Yang H et al (2001) Fluvoxamine for children and adolescents with obsessive compulsive disorder: a randomized controlled multicenter trial. J Am Acad Child Adolesc Psych 40(2):222–229

    Article  CAS  Google Scholar 

  • Roberts LW, Roberts B (1999) Psychiatric research ethics: an overview of evolving guidelines and current ethical dilemmas in the study of mental illness. Biol Psychiatry 46:1025–1038

    Article  PubMed  CAS  Google Scholar 

  • Roberts LW, Warner TD, Brody JL (2000) Perspectives of patients with schizophrenia and psychiatrists regarding ethically important aspects of research participation. Am J Psychiatry 157:67–74

    PubMed  CAS  Google Scholar 

  • Shah S, Whittle A, Wilfond B, Gensler G, Wendler D (2004) Research in children: assessing risks and benefits. Pediatr Res 56(2):165–166

    Article  Google Scholar 

  • Shaw DS, Dishion TJ, Supplee L, Gardner F, Arnds K (2006) Randomized trial of a family-centered approach to the prevention of early conduct problems: 2-year effects of the family check-up in early childhood. J Consult Clin Psychol 74(1):1–9 (Feb)

    Article  PubMed  Google Scholar 

  • Sivojelezova A, Shuhaiber S, Sarkissian L, Einarson A, Koren G (2005) Citalopram use in pregnancy: prospective comparative evaluation of pregnancy and fetal outcome. Am J Obstet Gynecol 193:2004–2009

    Article  PubMed  CAS  Google Scholar 

  • Solyom AE, Moreno JD (2005) Protection of children and adolescents in psychiatric research: an unfinished business. HEC Forum 17(3):210–226

    Google Scholar 

  • Streyhorn JM, Weidman CS (1989) Reduction of attention deficit and internalizing symptoms in preschoolers through parent–child interaction training. J Am Acad Child Adolesc Psych 28:888–896

    Article  Google Scholar 

  • Twomey JG (2000) Ethical implications of pediatric drug research policy initiatives. IRB pp 2–7 (March–April)

  • US FDA (2004a) Public health advisory. Worsening depression and suicidality in patients being treated with antidepressant medications. March 22, 2004. Available at http://www.fda.gov/cder/drug/antidepressants/AntidepressanstPHA.htm

  • US FDA (2004b) Public health advisory. Suicidality in children and adolescents being treated with antidepressant medications. October 15, 2004. Available at http://www.fda.gov/cder/drug/antidepressants/SSRIPHA200410.htm

  • Vitiello B (1998) Pediatric psychopharmacology and the interaction between drugs and the developing brain. Can J Psychiatry 43:582–584

    PubMed  CAS  Google Scholar 

  • Vitiello B (2001a) Long term effects of stimulant medications on the brain: possible relevance to the treatment of attention deficit hyperactivity disorder. J Child Adolesc Psychopharmacol 11:25–34

    Article  PubMed  CAS  Google Scholar 

  • Vitiello B (2001b) Psychopharmacology for young children: clinical needs and research opportunities. Pediatrics 108:983–989

    Article  PubMed  CAS  Google Scholar 

  • Vitiello B (2003) Ethical considerations in psychopharmacological research involving children and adolescents. Psychopharmacology 171:86–91

    Article  PubMed  CAS  Google Scholar 

  • Wadman M (1998) Ethical protection for subjects could stifle psychiatric research. Nature 394:713 (Aug. 20)

    Article  PubMed  CAS  Google Scholar 

  • Wasserman GA, Miller LS (1998) The prevention of serious and violent juvenile offending. In: Loeber R, Farrington DP (eds) Serious and violent juvenile offenders: Risk factors and successful interventions. Sage, Thousand Oaks, CA, pp 197–247

    Google Scholar 

  • Webster-Stratton C, Reid MJ, Hammond M (2004) Treating children with early-onset conduct problems: intervention outcomes for parent, child, and teacher training. J Clin Child Adolesc Psychol 33(1):105–124 (March)

    Article  PubMed  Google Scholar 

  • Wegerer V, Moll GH, Bagli M, Rothenberger A, Ruther E, Huether G (1999) Persistently increased density of serotonin transporters in the frontal cortex of rats treated with fluoxetine during early juvenile life. J Child Adolesc Psychopharmacol 9:13–24

    Article  PubMed  CAS  Google Scholar 

  • World Medical Association (1964) Declaration of Helsinki IV, 18th world medical assembly. Amended Hong Kong, Sept 1989. Council for international organizations of medical sciences (CIOMS). Geneva 1993

  • World Medical Association (2000) Declaration of Helsinki, ethical principles for medical research involving human subjects, adopted by the 52nd World Medical Association General Assembly, Edinburgh, Scotland, October

  • World Medical Association (2001) Declaration of Helsinki, note of clarification on placebo-controlled trials. World Medical Association, Newsletter, October

  • Yan EG, Munir KM (2004) Regulatory and ethical principles in research involving children and individuals with developmental disabilities. Ethics Behav 14(1)

  • Young SN, Annable L (1997) The use of placebos in psychiatry: a response to the draft document prepared by the tri-council working group. A position paper of the Canadian College of Neuropsychopharmacology. J Psychiatry Neurosci 21:354–359

    Google Scholar 

Download references

Acknowledgement

Table 2 and portions of text were reproduced or updated with permission from: Arnold, LE. Turn-of-the-century ethical issues in child psychiatric research. Current Psychiatry Reports 3:109–114, 2001 copyright 2001, “Current Science Or Current Medicine” publisher, Philadelphia.

Author information

Authors and Affiliations

  1. Department of Psychiatry, Ohio State University, 1670 Upham Drive, Columbus, OH, 43210, USA

    Lacramioara Spetie & L. Eugene Arnold

Authors
  1. Lacramioara Spetie
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. L. Eugene Arnold
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lacramioara Spetie.

Additional information

Adapted from: Arnold, LE. Turn-of-the-century ethical issues in child psychiatric research. Current Psychiatry Reports 3:109–114; 2001, copyright 2001, “Current Science or Current Medicine” publisher; Philadelphia.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Spetie, L., Arnold, L.E. Ethical issues in child psychopharmacology research and practice: emphasis on preschoolers. Psychopharmacology 191, 15–26 (2007). https://doi.org/10.1007/s00213-006-0685-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-006-0685-8

Keywords

Search

Navigation