The importance of therapeutic drug monitoring in child and adolescent psychiatry

Objective: Drug treatment of children and adolescent is disadvantaged by lack of evidenced based efficacy and safety for many indications. For that reason, many psychoactive drugs in children and adolescent are not approved for use until now. Because pharmacokinetics and pharmacodynamics properties of children and adolescent are different from adults, and these properties change during development, therapeutic drug monitoring (TDM) is recommended in these groups. However, there is still lack of sufficient studies to illustrate age and indication specific therapeutic ranges of serum or plasma concentrations in these groups. The aim of this study is to investigate relationship between doses of various psychoactive drugs and plasma concentrations in children and adolescents with attention deficit hyperactivity disorder ADHD, and to review TDM in the literature.

Materials and Methods: The literature on TDM in children and adolescent with psychiatric disorders was reviewed. The study group was consisted of children and adolescents with ADHD. Plasma methylphenidate and other psychoactive drug concentrations of children and adolescents with ADHD were determined by using high-pressure liquid chromatography coupled to mass spectrometry (LC-MS/MS). The relationship between drug dose and plasma drug concentration of children and adolescents was determined by using Pearson correlation test. The effect of other drugs on methylphenidate plasma level was also tested. In addition, the effect of age, sex, and body mass index on plasma concentration of drugs at usual therapeutic doses was investigated.

Results: TDM may be a valuable tool for qualification of serum or plasma concentrations of drugs for optimal dose, and to illustrate uncertain drug adherence, non-response at therapeutic doses, tolerability problems, and drug-drug interactions. Because drug treatments of psychiatric disorders take a long time, TDM may ensure lower risk for toxicity and cost effective treatment. According to Arbeitsgemeinschasft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP) Consensus Guidelines, TDM is strongly recommended for the typical antipsychotics (e.g. haloperidol, perphenazine and şuphenazine), atypical antipsychotics (e.g. amisulpride, clozapine, olanzapine, and risperidone), mood stabilizing or antimanic drugs (e.g. lithium, valproic acid, and carbamazepine), and most tricyclic antidepressants. Typical indications for measuring plasma concentrations of psychoactive drugs may include dose optimization after initial prescription or after dose change, drugs that TDM is mandatory for safety reasons (e.g. lithium), suspected complete or partial non-adherence (non-compliance) to medication, lack of clinical improvement under recommended doses, adverse effects and clinical improvement under recommended doses, combination treatment with a drug known for its interaction potential or suspected drug interaction, relapse prevention under maintenance treatment, recurrence under adequate doses, presence of a genetic particularity concerning drug metabolism (genetic deficiency, gene multiplication), pregnant or breast feeding patients, children and adolescents patients, elderly patients, individuals with intellectual disabilities, patients with pharmacokinetically relevant comorbidities (hepatic or renal insufficiency, cardiovascular disease), forensic patients, problems occurring after switching from an original preparation to a generic form (and vice versa), and TDM in pharmacovigilance programs (Hiemke et al 2011).

Conclusions: Limited studies are investigated relationship between clinical doses and plasma levels of psychoactive drugs in children and adolescents with psychiatric disorders. More studies are needed to use evidence based usage of TDM in children and adolescents with psychiatric disorders.