Pediatric Pharmacology

Pediatric patients have very different pharmacokinetic and pharmacodynamic profiles compared to adults. When considering psychotropic medication for a child or adolescent, be cautious about extrapolating from adult studies or practices. Always remember, children are not small adults!

Children tend to have higher rates of metabolism and elimination than adults.[1] As a result, children generally require higher weight-adjusted doses of most medications to achieve similar blood levels as adults.[2] The volume of distribution is also increased for most psychotropic medications. However, pharmacokinetics is hard to predict in children, and thus a 'start low and go slow' approach is important.[3]

Pharmacodynamic Differences in Children

Absorption Oral absorption is generally similar in older infants and children compared to adults.[4]
Distribution (Body Fat) Proportion of body fat is the highest in the first year of life, followed by a steady decrease during early/middle childhood, until an increase occurs pre-pubertally. A lower proportion of body fat leads to a smaller volume of distribution, while a higher proportion of body fat leads to a larger volume of distribution. For example, most psychotropic medications (antidepressants and antipsychotics) are lipophilic. The lower proportion of body fat in middle childhood results in a smaller volume of distribution, and thus higher plasma drug concentrations
Distribution (Body Water) Proportion of body water(total and extracellular) is high in infancy and decreases with age. For drugs primarily distributed in body water (e.g. - lithium), the higher proportion of body water in childhood results in a larger volume of distribution, and thus lower plasma drug concentrations.
Metabolism Phase I: CYP450 enzyme activity develops in the fetal period and infancy, and increases in childhood to above adult levels, and then declines after puberty to adult levels. The greater CYP450 activity during childhood results in lower plasma drug concentrations (other factors being equal and adjusting the dose for weight)
Phase II: Glucuronide formation reaches adult levels by age 3-4 years; thereafter the efficiency of phase II reactions does not vary with age
Elimination GFR is much lower in newborns, but reaches adult values by age 6-12 months. Children have lower absolute clearance than adults because of their smaller body size, but evidence is mixed on whether children have higher weight-adjusted clearance compared to adults.[5]

The central nervous system undergoes substantial developmental change during childhood, adolescence, and even in early adulthood. These developmental changes in neurotransmitter systems can cause unique therapeutic and adverse effects.

Pharmacodynamics of Neurotransmitters Systems in Children

Neurotransmitter System Implications
Dopamine Children and adolescents appear to have an increased risk of dystonic reactions with antipsychotics
Serotonin Prepubertal children appear to have an increased risk of activating side effects (i.e. - paradoxical reactions) from SSRIs
Noradrenergic Immaturity of the noradrenergic pathways explains in part why tricyclic antidepressants are less effective for depression in children and adolescents than in adults
See main article: Paradoxical Reactions

Overall, the evidence for efficacy in pediatric psychopharmacology is strongest for stimulants, intermediate for SSRIs and antipsychotics, and weak for lithium and anticonvulsants. Although evidence for short-term efficacy maybe strong for a few medications in children and adolescents, the evidence supporting the long-term use of pharmacotherapy is sparse. It is also important to note that most paediatric studies (as in adults) of psychotropic medications are funded by the pharmaceutical industry.

Children and adolescents may experience adverse effects that adults do not experience, for example:

  • Enuresis with risperidone[6]
  • Cardiac effects of medications
    • Monitoring is indicated when using tricyclic antidepressants, lithium, and antipsychotics in children
  • Stimulants and growth (height and weight)
  • Hyperprolactinemia caused by antipsychotics may affect sexual development and bone density
  • Priapism with stimulants
  • Cognitive side effects and sedation can interfere with learning and academic performance
  • Weight gain can have a negative influence on a child or adolescent’s fragile self-esteem