2398 Current Pharmaceutical Design, 2010, 16, 2398-2406 1381-6128/10 $55.00+.00 © 2010 Bentham Science Publishers Ltd. Safeguarding Children’s Rights in Psychopharmacological Research: Ethical and Legal Issues Michael Kölch 1, *, Andrea G. Ludolph 1 , Paul L. Plener 1 , Heiner Fangerau 2 , Benedetto Vitiello 3 and Joerg M. Fegert 1 1 Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital of Ulm, Germany, 2 Institute for the History, Philosophy and Ethics of Medicine, Ulm University; Germany, 3 Child and Adolescent Treatment and Preventive Intervention Research Branch, National Institute of Mental Health, USA Abstract: Objective: Research on psychopharmacological treatment in children and adolescents is the subject of ongoing ethical discus- sion, as minors with mental disorders constitute a vulnerable patient group. Considering the important legislative changes in pediatric re- search over the past decade in both the US and Western Europe, there is a need to review recent developments in this area. Method: Based on a systematic literature review, a hermeneutical analysis focusing the main issues of ethics in child and adolescent psy- chopharmacology is provided. Legal and regulatory aspects of psychopharmacological research in children are compared between the US and Europe. Relevant issues were informed assent and consent to research participation, minimal risk and burden of research, ethics of pharmacogenetics, research on “me-too” medications, and justice in global research. Additionally, the concern about undue influence of financial interests in research is also addressed. Conclusion: Incentives for the conduct of clinical trials with children comparable to those contained in US legislation are now provided in the EU. Research to develop “me-too” preparations may have no significant benefit for children, but can cause research burden and de- tract from clinically more important projects by utilizing limited investigator time and patient resources. Thus far, pharmacogenetic stud- ies may bring more individualized treatment approaches into child psychiatry but they remain at present a promise for the future. Finally, the issues of avoiding undue influence from funders and conflicts of interest remain a prominent concern which can be solved by declar- ing conflicts and publishing all results of studies extensively. Keywords: Ethics, psychopharmacology, research, children and adolescents. INTRODUCTION Both psychopharmacological treatment and research can pose substantial ethical concerns [1]. As psychopharmacological treat- ment in children involves an intervention on a developing, rapidly growing brain, the risk–to-benefit ratio of a medication needs to be favorable. Unfortunately for many pharmacological substances used in children and adolescents, safety and efficacy have not been ade- quately studied [2-4]. Child and adolescent psychiatric disorders are caused mostly multiple factors and treated with complex interven- tions, therefore the question whether solely medication trials are appropriate to test efficacy and effectiveness in child populations remains disputed, or whether studies which investigate multimodal treatments should be conducted [5]. A paucity of medications li- censed for use in children is accompanied by a high rate of ‘off- label’ use and an urgent need to inform caregivers about the license status of medication [6-10]. Shearer and Bermingham reasoned by the fact of off-label use of antidepressants in pediatric population and the lack of long terms studies that ”prescribing practices in the paediatric population ought to be severely restricted” and others critize presciptions of psychotropic drug to children in general [11, 12]. Among the historical reasons for the lack of licensed medica- tions for children are the small size of the pediatric market, with marginal profits for pharmaceutical companies, and ethical and legal barriers, because children are a vulnerable population which cannot provide undisputed consent to research participation. Parents are reluctant to involve their children in clinical medication trials [13]. The participation of children in decision-making about joining a research project may help to justify research in this vulnerable population; however, the problem of how to guarantee their proper *Address correspondence to this author at the Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital of Ulm, Steinhövelstr.5, 89075 Ulm, Germany; Tel: +49 073150061601; Fax: +49 073150061602; E-mail: michael.koelch@uniklinik-ulm.de participation in decisions is unresolved. Additional factors which negatively impact the feasibility of clinical trials in children are the difficulty of recruiting and retaining adequate numbers of patients in randomized trials and the small pool of researchers in child psy- chopharmacology[14]. In conclusion, pediatric psychopharmacology continues to gen- erate ethical debates. This review will present the similarities and differences between US and European legislation on research with children, as these areas are the world’s largest markets for pharma- cotherapeutics, even though they are not always the areas where most clinical trials are conducted. The ethical consequences result- ing from the legislation for research projects with children will be discussed and foreseeable developments in research, such as phar- macogenetics and individualized medicine, will be analyzed with regards to ethical and legal requirements. METHOD A literature search was performed in PubMed (Index Medicus) to detect key articles on ethical and legal aspects in psychopharma- cological research. Since several studies have shown that the Index Medicus has a US-American bias regarding ethical literature this research was backed by further documents available from German library resources [15]. Literature published between 2000 and 2010 was searched using various terms (“ethics child adolescent psycho- pharmacology”, “ethics child adolescent psychopharmacotherapy”, “ethics child adolescent pharmacology”) (date of search: January 13 2010). The term “ethics child adolescent psychopharmacology” yielded 16 results. Ten of the papers were reviews, one was a publi- cation in Spanish. The term “ethics child adolescent psychopharma- cotherapy” yielded only one result which was already included in the results of the former search term. The term “ethics child adoles- cent pharmacology” yielded 189 results. Only results related to psychopharmacological research and published in English were