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Psychostimulants remain the mainstay in the pharmacologic management of ADHD. Methylphenidate and amphetamines are the two main options in this group. Non-stimulant options also exist-see below.

Methylphenidate apparently acts at the level of the neural synapse in dopaminergic regions of the brain to block dopamine reuptake.

The amphetamines possibly block both dopamine and norepinephrine reuptake, and may also stimulate greater release of one or both of those transmitters into the synaptic space.

About 75% of children with ADHD will respond to stimulants. There are no major differences in response among the different stimulants, and a clear failure to respond to one should generally lead to a re-evaluation of the diagnosis rather than a reflexive change from one stimulant to another.

The choice of stimulant is most frequently guided by the variations in duration of action among the different preparations. Current practice is to first try a longer-acting preparation which last 8-11 hours, but to employ their short-acting predecessors when reasons of efficacy, dosing or cost dictate. Children with congenital heart disease or hypertrophic cardiomyopathy MAY be at increased risk of sudden death when taking these medications.