oa Editorial [Hot topic: Psychotropic Drugs in Child and Adolescent Psychiatry - a New Era on the Horizon (Executive Editors: Aribert Rothenberger, Manfred Gerlach and Ralf W. Dittmann)]

Frontiers in child and adolescent psychopharmacology have moved forward in different aspects. Theoretical knowledge as well as practical experience have come to a point where summarizing and rethinking about steps ahead appears timely and necessary. On the one hand, the prescription rate of psychotropic drugs in children and adolescents has increased over the past decade and has led to many objections [e.g 1, 2]. On the other hand, controlled clinical studies in minors on efficacy and safety of these compounds have improved both in quantity and quality [e.g. 3-6]. However, both processes are not yet in balance. Too many psychotropic drugs are used off-label, without regulatory approval for this young population, largely based on findings from studies in adult psychiatric patients. But there is growing awareness that this evidence cannot simply be extrapolated to children and adolescents. Hence, as a result from several recent workshops [e.g. 7, 8] and discussions with authorities in the USA (e.g. FDA) and Europe (EMEA) there is consensus about the need to intensify pediatric clinical trials not only focusing on clinical efficacy targeting disorders and symptoms (including comorbidity) but also on short-term and long-term tolerability and safety. In particular, this holds true for preschoolers; empirical literature on psychotropic drug treatment is limited and vulnerability of brain development appears to be very high in this age group [9]. Accordingly, there is first of all a want to improve study designs as well as ethical and regulatory preconditions. Koelch et al. [10] focus on ethical and legal issues in clinical research with children and adolescents in order to safeguard their rights. Their review presents the similarities and differences between US and European legislation, both regions are leading the field scientifically and from a market perspective. The authors also provide some insights in aspects of study designs favoring multimodal treatment approaches which should be as close as possible to real-life situations in treating patients. Also, they critizise research on “me-too” preparations which may not offer significant additional benefit for children and adolescents, but is consuming capacities and resources which might better be allocated to innovative projects. In order to guarantee the highest scientific standard for innovative clinical trials in children and adolescents an adequate randomization is an internationally accepted methodological tool. Henschel et al. [6] empirically studied the ethics of randomization and the concept of equipoise in publications of pediatric clinical trials for the recent years. They analyzed quality along the criteria of CONSORT and SIGN statements and came to the conclusion that “it will be a challenge for the regulatory authorities, for clinicians, the pharmaceutical industry and the public to discuss and adapt RCTs to the situation of critically ill children”. The largest psychopharmacological research activity and the best empirical evidence are available for pediatric patients with attentiondeficit/ hyperactivity disorder (ADHD). But there are still various open questions and some uncertainties might be resolved when investigating neglected issues more intensively. Chacko et al. [11] elucidate on the role of adherence in child psychiatric drug treatment and describe several potential interventions based on the Unified Theory of Behavior Change that may improve adherence in clinical trials and daily routine, since in both situations early dropouts are a great problem. Another underexplored but clinically relevant area relates to the moderating effects of age and sex, especially when developmental psychopathology along sexual maturation is considered. At least for methylphenidate it is suggested that age and sex have no or little moderating effects [5]. However, there is no clear evidence for other psychotropic compounds yet. Further, new study designs from the laboratory school protocol (LSP) may bring some progress. As Uebel et al. [12] could show even well-established procedures and questionnaires can be improved. For example, hyperactivity in ADHD is primarily considered a movementrelated dimension. Surprisingly, questionnaires seemed to mix up movement with other behaviors, but, when actigraphy was added to assess hyperactivity the two different aspects could be disentangled. The final paper directed to clinical trials is related to pharmacoeconomics, a topic that only recently gained greater importance in child and adolescent psychopharmacology [13]. So far, few respective studies exist which are mostly related to cost-effectiveness analyses along certain economical models. Hence, the author can only suggest an acceptable cost-effectiveness of medication management for ADHD since there is no such evidence for other child psychiatric disorders, i.e. more and better RCTs need to be conducted. Otherwise, third-party payers in the various health-care systems will have to decide on the allocation of resources based on poor evidence....