What's next for developmental psychiatry?

J. Rapoport provides an accurate and thoughtful overview of the history and current state of pediatric psychopharmacology. Since Bradley's report in 1937 concerning the use of benzedrine in children with behavior problems 1, pediatric psychopharmacology has been with us. However, psychoanalytically oriented psychotherapy was the generally preferred treatment for children and adolescents in the USA until the late 1970s, when things began to change. By 2002, with the publication of the first edition of Pediatric Psychopharmacology 2 and the advent of Journal of Pediatric Psychopharmacology, the use of psychoactive medications in children had become main stream in the USA, although remaining problematic for large segments of the general population in Europe and other areas of the world, including South America. There is no doubt that for many children the use of psychoactive drugs has been beneficial. So, from my perspective, pediatric psychopharmacology is here to stay. Rapoport summarizes many of these advances. Sadly, however, there are many children for whom the benefits are modest at best. We need new agents, but the pharmaceutical industry has become cautious. For the most part they are content to develop analogs of successful compounds. How many derivatives of stimulant medications are on the market, to say nothing of the serotonin reuptake inhibitors and antipsychotics? As noted by Rapoport, attempts at “repurposing” of existing compounds initially developed for other indications also make sense. Here, it is of interest to recall that antipsychotics were first developed by surgeons to potentiate the effects of anesthetics and analgesics, and cycloserine was initially used as an antibiotic to treat tuberculosis. A significant portion of my research and clinical practice is focused on Tourette's syndrome (TS), where we do not have ideal agents (efficacious with minimal side effects). Consequently, we are in the midst of trying a number of agents, some of which are novel and others have been in development for other indications. For example, recent genetic findings indicating a role for central histamergic pathways 3,4 have led to the development of a clinical trial for histamine H3 receptor antagonists, using an agent first developed for the treatment of obesity. We are also evaluating the evidence base for the use of nutritional supplements. Caution is warranted here as well. Once nutritional companies recognize the commercial potential of their products, financial as well as clinical pressure will likely drive the development of ever more aggressively marketed products. More importantly, we need to develop and sustain efforts to build on the strengths and interests of children and adolescents with behavioral and emotional difficulties and find ways to take advantage of advances in developmental neuroscience to enhance their cognitive and emotional development. This echoes the recent forum in World Psychiatry on “Positive mental health: models and clinical implications” 5. When seeing a new case in our clinic, I frequently ask the parents “to brag” about their child and indicate what his/her favorite activities are and what skills he/she is developing. In the case of TS, engaging in activities that require focused attention and motor control, e.g., playing a musical instrument or practicing a martial art, markedly diminishes motor and vocal tics 6. Consequently, encouraging parents to build on those interests and the child's innate abilities can be a path to a more positive future. For example, success in sports activities can enhance a child's physical fitness, self esteem and social connectedness. This, along with the extensive animal literature indicating that exercise enhances neural development, including the survival, growth and differentiation of neurons, synaptogenesis and myelination, provides a strong rationale to evaluate interventions including regular physical exercise programs 7. Building on the work of Klingberg and associates, there is also a growing body of evidence that computer games focused on working memory and other cognitive capacities can reduce inattentive symptoms in young children with attention-deficit/hyperactivity disorder (ADHD) as well as enhance fluid intelligence in typically developing preschoolers 8,9. It is too early to tell how efficacious will be more advanced cognitive training programs designed to expand the horizon beyond working memory to include other cognitive skills (e.g., sustained attention, inhibitory control, cognitive flexibility, category formation, pattern recognition and inductive thinking), synergistically combined with aerobic sports activities designed to enhance the same cognitive abilities. Such trials are currently underway. One other neuroscience based intervention, neurofeedback, also shows promise for ADHD, but further evidence is required to guide its use 10,11. It is possible that such interventions will emerge as adjunctive, if not possible alternatives, to pharmacological treatment options 12. Time will tell, but there is a real possibility that they will have positive effects on neurodevelopment as well as the subjective well-being of children and adolescents. In closing let me briefly point to areas of concern. First, with the advent of pediatric psychopharmacology we have seen a shift away from viewing the “whole child” and his/her strengths and weaknesses across various domains and contexts to a greater attention to his/her “symptoms”. This has led to a reification of diagnostic entities and comorbidities. Our diagnostic classification systems are far from perfect. Each child is unique and not simply a child with ADHD or TS or autism spectrum disorder or obsessive-compulsive disorder. Often the boundaries between specific disorders are indistinct, at best. Next, this refocusing on diagnosis and the successes of pediatric psychopharmacology have led many programs to train developmental psychiatrists to become essentially experts in “medication management” rather than clinicians for the whole child and his/her family. Last but not least, as noted by Rapoport, many psychopharmacological agents have undesirable side effects. Most of the acute and initially appearing adverse effects are reasonably well known, but in many instances the long-term effects of these agents on neurodevelopment have not been a major focus of research. For example, a recent systematic review clearly indicates that a substantial proportion of children and youth with depressive (11.2%) and anxiety (13.8%) disorders being treated with antidepressants experience behavioral side effects including excessive arousal activation 13. These rates are 3- to 10-times higher than seen during treatment with a placebo. There are also data from the Danish registries suggesting that for a subset of children the use of high doses of psychostimulants may have long-term adverse effects on cardiac function 14. Another area of concern is the use of psychotropic agents during gestation and their long-term effects on the fetus' neurodevelopment. Animal models may help to clarify these risks but the ethical dilemmas faced by the treating clinician will remain 15.