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Objective: The proportion of children and adolescents having psychiatric disorders increases and treatment options are developed. Pharmacological intervention is an important option to treat psychiatric disorders of childhood and adolescence. Clinicians generally decide a drug according to the information about the patient’s illness process, target symptoms, and family medication experiences within the context of their experience, subspecialty practice guidelines, and results of pharmaceutical trials. Although this approach is effective for many patients, significant number of patients develops serious side effects/adverse events or does not respond sufficiently to psychotropic drugs given. Because there is significant inter-individual variability among children and adolescents on the clinical response (i.e., improvement of symptoms and occurrence of side effects/adverse events) to the same psychotropic drug. Also, the clinical response to the same agent may differ through time, because the affinity, functional capacity, and expression of the targets (enzymes, transporters etc.) of medications vary along development. This variability in individual response to psychotropic drug partly depends on well-known and easily assessable factors like age, sex, liver and renal function, co-medication, heterogeneity in the disease. Moreover, inherited variants in pharmacokinetics (which are related to absorption, distribution, metabolism and excretion) and pharmacodynamics (which are related to receptors and enzymes involved in the mechanism of action) components that are under genetic control affect to some extent the clinical response to a psychotropic drug. The inşuence of genetic factors on clinical response (drug efficacy and side effects/adverse events) is defined as pharmacokinetics/pharmacogenomics. Pharmacogenetics is focused on pharmacological consequences of a single gene mutation, whereas pharmacogenomics tries to simultaneously consider numerous genes and their mutual interaction. Over the past few years, pharmacogenetic tests have been applied to clinical psychiatric practice. Aim of this presentation is to review the literature of the pharmacokinetic, pharmacodynamic and pharmacogenetic approach in the field of child and adolescent psychiatry, and to discuss the findings.
Materials and Methods: The literature of the pharmacokinetic, pharmacodynamic and pharmacogenetic approach in the field of child and adolescent psychiatry was searched via PubMed and Google Academic, and reviewed.
Results: By searching the literature, few studies that evaluated pharmacokinetic, pharmacodynamic and pharmacogenetic approach in the field of child and adolescent psychiatry have been found while most psychiatric pharmacokinetic, pharmacodynamic and pharmacogenetic studies have focused on the adult population. Psychiatric pharmacogenetic approach is divided into two primary categories: pharmacokinetic approach (including metabolic enzymes, for example the cytochrome P-450 enzyme system); and pharmacodynamic approach (including genes that effect neuronal function, for example the dopamine transporter and receptor genes). Many of these psychiatric pharmacogenetic target genes have also been studied in relation to their inşuence on disease vulnerability. The majority of the studies focused on pharmacogenetic approach of psychiatric disorders in children and adolescents were associated with response to psychotropic drugs like methylphenidate, atomoxetine and SSRIs. Cytochrome P-450 enzymes are the most commonly tested genes in pharmacogenetic practice, especially in adult population. Pharmacogenetics has arrived in clinical psychiatric practice with a test those genotypes for two cytochrome P450 2D6 and 2C19 genes.
Conclusions: Relatively few studies on pharmacokinetic, pharmacodynamic and pharmacogenetic approach in the field of child and adolescent psychiatry have been performed to date. Currently available pharmacokinetic, pharmacodynamic and pharmacogenetic technology offers patients and prescribers an opportunity to move closer to the ultimate goal of truly individualized prescriptions. Pharmacokinetic, pharmacodynamic or pharmacogenetic testing may be suggested when a patient or their family is reporting minimal response to typically therapeutic doses in two or more unsuccessful medication, or if there is a clear report of significant side effects. In fact, while pharmacogenetic tests focused on pharmacokinetic genes are in clinical practice especially in non-psychiatric field, those focused on pharmacodynamic genes are far from ready for clinical application. In recent several years, pharmacogenetic testing has become far more cost-effective. As the cost of pharmacogenetic testing decreases, it will become more applicable in clinical psychiatric practice for children and adolescents. Probably in the next decades, pharmacogenetic testing will routinely be ordered to guide the selection and dosing of psychotropic medications. In conclusion, considering the significant burden associated with psychiatric disorders in children and adolescents, and the necessity to identify effective (with high efficacy and low side effects) pharmacological interventions, the field of pharmacokinetics, pharmacodynamics and pharmacogenetics of childhood psychiatric disorders will be further developed.