Pharmacokinetics

All stimulants, despite very different half lives, reach their maximal therapeutic effects during the absorption phase of their kinetic curve. This timing parallels the release of neurotransmitters into synaptic clefts suggesting that alteration in neurotransmitter levels in critical tracts is the mechanism by which these drugs exert their effects. This phenomenon may also explain why long acting preparations of stimulant medications have failed to provide the same clinical benefits as the shorter acting preparations (16).

The time course of effectiveness for tricyclic antidepressants (TCAs) in improving symptoms of depression and AD/HD is quite different. There is a well documented lag in improvement of depression when treating with TCAs felt to be due to time required for receptor down-regulation. However, maximal symptomatic improvement in AD/HD can be seen within days of starting therapy with TCAs. A different mechanism of action must be postulated and is likely to be related to neurotransmitter release in the CNS (15, 22).