Child and Adolescent Psychiatry

320 Chapter 38

before it even reaches the systemic circulation. Distribution is affected by
the relatively high proportion of extracellular fluid in young children; the
greater diversion of medication to the extracellular fluid tends to reduce
the amount in blood and brain. The blood-brain barrier is more permeable
in children than adults so drugs can get through more easily, but this easier
access to the brain may be partly offset by a higher concentration of drug-
binding proteins in the cerebrospinal fluid.

Box 38.1Relationship between the dose administered and the

effective concentration in the brain

Compliance

Absorption Blood–brain

barrier

Gut

Drug

Extracellular Blood

fluid

Brain

Clearance

Distribution

The various pharmacokinetic differences between children and adults
pull in opposite directions, with bioavailability being reduced in children
by faster clearance, slower absorption and a greater volume of distribution,
but increased by greater blood-brain permeability. The effect of rapid
hepatic clearance often dominates. As a consequence, weight-for-weight
doses for psychotropic drugs are often 50–100% higher for children than
adults.
The need for relatively high doses decreases as children get older,
dropping fairly sharply around puberty. By mid to late adolescence, drug
dosage follows adult norms.
Blood levels are useful for adjusting the dosage of some drugs, such as
tricyclics and lithium, but are unhelpful with other drugs, for example,
stimulants. Children and adolescents are very variable in their response
to medication and the dosage prescribed needs to be titrated primarily
against clinical response, seeing recommended drug dosages (and rec-
ommended blood levels) as helpful guidelines rather than rigid limits.
Because the appropriate dosage is hard to predict in advance, it is sensible
to start with a low dose and work up slowly. Once-a-day doses improve
compliance but divided doses may be needed to reduce peak and trough
effects.