Child psychopharmacology: how much have we progressed?

Since its inception, pediatric psychopharmacology has been a point of clinical interest as well as concern. While a constant attempt has been made to find the “magic pill” for psychiatric disorders, concerns regarding safety have often overshadowed new drug development. However, with double blind randomized placebo controlled trials becoming the norm, pediatric psychopharmacology has come of age to certain extent. Rapoport reviews the evolution, current practices and future of child psychopharmacology. However, there are other important issues relevant to clinical practice across the world that we would like to discuss briefly.

To begin with, a large part of pediatric psychopharmacological literature comes from the US and European countries. Most drug trials are on homogenous populations of Caucasian individuals, often to the exclusion of other ethnic and cultural groups. However, studies have shown that different ethnic groups metabolize drugs differently, and hence safety and efficacy in one group cannot be easily generalized to the other 1,2. This is especially important given that a huge population of today's children reside in Asia and Africa. Ideally, in the future, we should design large scale multicentric or multicountry trials to generate data which can be applicable to children and adolescents throughout the world. Additionally, diagnostic criteria for various psychiatric disorders have been developed in the Western world and may not be valid in their entirety in other populations. Even in the Western world, diagnostic criteria for most severe and common mental illness are developed for adult populations. Researchers and clinicians often apply adult criteria to children and adolescents, which is at times not appropriate. For example, evidence shows that childhood depression has phenomenological differences from adult depression. Until we develop sufficient culture as well as age based evidence, child psychiatrists must tread with caution while making decisions regarding prescription.

Next, even in a homogenous population, most of the psychopharmacological evidence is for a particular disorder and for a particular age group. Evidence of efficacy for one diagnosis does not imply efficacy for other related diagnoses. Additionally, the available evidence should not be taken as applicable across all ages during the childhood and adolescence, as the current level of evidence based on randomized controlled trials is limited to certain age groups. For example, the US Food and Drug Administration has approved the use of stimulants for children above 6 years only, based on randomized controlled trial data 3. In contrast, available data suggest that in certain cases stimulants are used in children as young as 2 years 4. It must be remembered that organ systems (including and especially the central nervous system) in children are in a state of constant development and any form of pharmacology may impact this. Safety data that are available for most drugs do not extend beyond 6 months to 1 year, with studies that follow up participants for 2 years being labeled as “long term”. While constraints of the investigators and the study itself are understandable, the clinician needs to remember that we just do not have enough information about how a particular drug will impact a child as he/she grows towards adulthood.

Evidence is accumulating that, like in adults, second generation antipsychotics cause significant weight gain and dyslipidemia in children and adolescents 5. Cardiovascular diseases are the most common cause of mortality and morbidity worldwide, and lack of long-term surveillance data on cardiometabolic side effects in those receiving antipsychotics is an important limitation of current evidence. The increase in the prevalence of obesity, diabetes mellitus and cardiovascular events in younger age groups may significantly impact on the health expenditures in the years to come.

Additionally, the growing practice to use different agents for various symptoms rather than treating disorders leads to polypharmacy, further adding to the safety conundrum. As pointed out by Rapoport, polypharmacy and off-label use of medications must be strongly discouraged.

One issue which is not discussed by Rapoport is the dearth of research on the attitudes of patients and their parents (who are often the decision makers) toward use of medications, both for short and long term. Some studies suggest that parents are usually fearful of administering psychotropics to their children and often prefer psychological treatments over pharmacological agents 6. Medication compliance rates in patients with disorders like attention-deficit/hyperkinetic disorder vary from 56 to 75% 7 and attitudes towards medication certainly contribute to reduce adherence to treatment. Hence, the clinician should not ignore the need to assess patients' and caregivers' attitudes and concerns. Clinicians should work with them to clarify possible erroneous beliefs and misconceptions associated with use of medications in childhood and adolescence.

Finally, a problem that plagues almost all of psychopharmacology, and particularly child psychopharmacology, is that, while we have a great deal of efficacy data, true real-world effectiveness data are sorely missing.

Despite all these problems, the future of pediatric psychopharmacology seems bright. With the recognition of financial conflicts of interests and increased governmental funding to test various psychotropics for different conditions in children and adolescents, we can soon expect to have much better quality data from neutral sources which can streng-then the confidence of use of medications in children and adolescents. Further, with the development of psychiatric pharmacogenomics, we can hope that we will soon be able to develop more targeted drugs and understand genetic variations which influence treatment response, thus moving from empirical selection of medications to personalized medicine in true sense.