Attention Deficit Hyperactivity Disorder

Attention-Deficit/Hyperactivity disorder (ADHD) is a ‘lifespan’ neurodevelopmental disorder, which typically manifest early in development, characterized by impaired levels of inattention, disorganization, and/or hyperactivity-impulsivity. These features are pervasive across multiple settings and cause substantial functional impairment of personal, social, academic, or occupational functioning. Dysregulation in cortico-striato-thalamo-cortical circuits is considered the neurobiological underpinning of ADHD and based on two main mechanisms: the altered tuning of dopamine and norepinephrine signaling in the prefrontal cortex, which impairs processing stimuli, leading to inattention and hyperactivity; insufficient dopamine signaling in the basal ganglia, which impairs reward processes, leading to impulsivity. Drug therapies for ADHD should restore the physiological signaling of noradrenaline and dopamine in the pre-frontal cortex, and allow dopamine phasic signaling in the accumbens. The mechanism of action of stimulants (methylphenidate and amphetamine) and non-stimulants (atomoxetine, guanfacine and clonidine) treatment is discussed in detail, both in term of pharmacodynamics and pharmacokinetics. A special focus is placed on therapeutic value and limitations of each drug. New drug developments must take into account the long-term effectiveness and focus on other issues including low adherence, adverse effects and non-tolerability, especially when comorbid diagnoses are present. Some innovative drugs may be promising as add-on or stand-alone treatments for ADHD.