ebook_ADHD2019

86 Rohde, Buitelaar, Gerlach & Faraone mine, an amphetamine pro-drug, which has an extended duration of action due to the prodrug mechanism, is a more recent addition to the ADHD medications and is now licensed in several parts of the world. Three non-stimulant medications are licensed for treating ADHD. Atomoxetine, and extended release formulations of guanfacine and clonidine. The extended release formulations of guanfacine and clonidine are the only medications with a specific indication within their license for co-administration alongside the stimulants. UNDERSTANDING HOW ADHD MEDICATIONS WORK AND HOW TO USE THEM EFFECTIVELY Having a good understanding of psychopharmacology in relation to the neuros- cience of the brain, neural circuitries, attention networks, receptors and neuro- transmitters can significantly enhance the effective drug management of ADHD. This is particularly the case in the presence of comorbid conditions, which for ADHD is the rule than the exception. The reasons are fourfold: 1 The actions of dopamine (DA) and/or noradrenaline (NA) (sometimes ter- med ‘norepinephrine (NE)’ interchangeably) and the medication dose-res- ponse relationships in ADHD do not follow a linear relationship; in fact, they often track in an inverted-U shape curve (see Figure 5.1). 11 2 Individuals vary considerably regarding the actual dosage required for opti- mal drug response, duration of action, frequency of dosing and tendency to experience rebound effect (i.e. symptoms more intense than baseline) when a medication starts to wear off. Importantly for the stimulants, the clinical effects vary between individuals, independent of a patient’s weight; and are different from many other medications used within paediatric populations. 3 The presence of comorbidities such as anxiety, depression and autism spec- trum disorder can influence the side-effect profiles of medications; and how a given dosage of drug impacts on the therapeutic window, within which treatment responses become optimal. 4 Some children require combination treatment instead of monotherapy in order to gain full control over their problems. These may include a com- bination of inattention, hyperactivity, impulsivity, emotional dysregulation, mood, anxiety and tics. A prudent and judicious selection of appropriate agents to yield a combination therapy (instead of uninformed polypharma- cy) is predicated upon sound knowledge of psychopharmacology. All currently licensed ADHD medications are thought to act, at least in part, through their impact on DA and/or NA. Both DA and NA are key modulators of the key brain circuits that support attention, reward processing, and activity