Franke_2012_Fortschr.Neurol.Psychiatr_80_130

The current pharmacotherapy for attention-deficit hyperactivity disorder (ADHD) is mainly based on the stimulant methylphenidate and to a small extent on amphetamines which are not approved in Germany. The only approved non-stimulant so far is atomoxetin (Strattera(R)), a norepinephrine reuptake inhibitor. There is no approved pharmacotherapy for adults. The aim of the available medication is a reduction of impulsivity, hyperactivity, and attention deficits. Neurobiological correlates of these effects are still not fully understood, however, a functional implication of dopaminergic and noradrenergic systems is known. To date there is no disease-modifying therapy. The currently available substances have limitations due to the short half-life of stimulants, the unknown pathomechanisms, and the use of stimulants in developing brains with possible long-term side-effects. Moreover, the abuse potential of stimulants is still controversially discussed. The recently developed Lisdexamfetamin and SPD-465 have stimulant effects, too. A number of different developmental substances in preclinical and clinical phases show other mechanisms: SPD-503 represents an alpha(2)A-adrenozeptoragonist, ABT-089 and ABT-418 have partial agonistic effects to the alpha(4)beta(2)-subtype of nicotinic acetylcholinreceptors, CX-717, -1739, -1942 and -1796 are glutamatergic alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-receptor agonists and PF-3 654 746 exhibits antagonistic properties to histaminergic H(3)-receptors. The alpha(2)A-adrenoceptor-agonist Guanfacine (Intuniv(R)) and the hepatic metabolised amphetamine prodrug Lisdexamfetamin (Vyvanse(R)) are yet approved for ADHD treatment in the USA. The aim of this review is to summarise established pharmacological treatment options and the stage of development of upcoming symptomatic stimulant and non-stimulant substances in ADHD therapy.