Psychopharmacology of ADHD in pediatrics: current advances and issues

Neuropsychiatric Disease and Treatment downloaded from https://www.dovepress.com/ by 37.59.46.207 on 13-Jul-2018 For personal use only. REVIEW Psychopharmacology of ADHD in pediatrics: current advances and issues Donald E Greydanus Ahsan Nazeer Dilip R Patel Michigan State University College of Human Medicine, Michigan State University/Kalamazoo Center for Medical Studies, Kalamazoo, MI, USA Abstract: Attention deficit hyperactivity disorder (ADHD) is a neurobehavioral developmental disorder found in 3% to 8% of children and adolescents. An important part of ADHD management is psychopharmacology, which includes stimulants, norepinephrine reuptake inhibitors, alpha-2 agonists, and antidepressants. Medications with the best evidence-based support for ADHD management are the stimulants methylphenidate and amphetamine. A number of newer, long-acting stimulants are now available and a number of new medications are considered that are under current research. Keywords: ADHD, methylphenidate, amphetamine, norepinephrine reuptake inhibitors, alpha-2 agonists, antidepressants Introduction Attention deficit hyperactivity disorder (ADHD) is a neurobehavioral developmental disorder with neurotransmitter dysfunction of the noradrenergic, dopaminergic, and serotonergic systems. It is present in 3% to 8% of children and adolescents and has characteristics of inattentiveness with or without impulsivity.1–6 A thorough history and physical examination is necessary to make this diagnosis.7–9 Management includes providing appropriate psychological therapy, insuring proper school placement, and, if necessary, judicious use of anti-ADHD medications.1,2 This report summarizes current concepts in ADHD psychopharmacology specifically the use of stimulants, alpha-2 agonists, and anti-depressants. Other medications under research are also considered. Stimulant medications Research in the 20th century revealed that stimulant medications were useful in improving attentional dysfunction in children and adolescents.10 Indeed, hundreds of studies conducted over the past 60+ years have consistently demonstrated the effectiveness of stimulant medications in improving attention dysfunction associated with ADHD in children, adolescents, and adults.11–20 Research notes improvement in concentration ability in 75% to 95% of those with ADHD on stimulants. The success of this pharmacologic approach has resulted in increasing use of stimulants for ADHD with 6% of pediatric patients 5 to 15 years of age being placed on stimulant medication in the United States.21,22 Correspondence: Donald E Greydanus Professor, Pediatrics and Human Development, Michigan State University College of Human Medicine, Pediatrics Program Director, Michigan State University/Kalamazoo Center for Medical Studies, Kalamazoo, MI 49008-1284, USA Tel +269-337-6450 Fax +269-337-6474 Email Methylphenidate General considerations MPH (methylphenidate) has been available in the United States since the late 1950s and has become the most common stimulant medication used to treat ADHD because of its beneficial effect on problems with concentration. Its pharmacologic effects are based on selective binding of the presynaptic dopamine transporter in the central Neuropsychiatric Disease and Treatment 2009:5 171–181 171 © 2009 Greydanus et al, publisher and licensee Dove Medical Press Ltd. This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited. Powered by TCPDF (www.tcpdf.org) Neuropsychiatric Disease and Treatment downloaded from https://www.dovepress.com/ by 37.59.46.207 on 13-Jul-2018 For personal use only. Greydanus et al nervous system (particularly the striatal and prefrontal areas) that result in a rise in extracellular dopamine in the central nervous system (CNS).14,20,23 Table 1 lists medications used to treat ADHD that have evidence-based research and notes their dosages and common side effects. MPH is a schedule II medication produced in short-acting and long-acting oral formulations (Table 2). Short-acting MPH is marketed as Ritalin® (and other brand names) or its generic version and after oral ingestion, pharmacologic action is noted in 30 to 45 minutes that peaks in 1 to 2 hours, and fades away over 3 to 5 hours. This short acting formulation requires one to three doses a day as desired by the child or adolescent to improve attentional dysfunction. One should not exceed a single dose over 20 mg or a daily dosage over 60 to 80 mg while the patient is titrated to the dosage regimen best suited for him or her. MPH preparations After the development of MPH as a short-acting stimulant, a longer-acting product became available, Ritalin SR®. It comes as a 20 mg sustained released tablet that results in a release of about 7 mg of short-acting MPH over several hours. Since Ritalin SR® only comes in a 20 mg tablet and unpredictable gastrointestinal absorption is noted in half of its users, pharmaceutical companies launched a search for additional MPH products, mostly those with a longeracting effect. Table 2 lists these newer longer-acting MPH products while Table 3 notes reasons for failure of benefit from psychostimulant medications.1,6,11–19 Though there has been intense advertising by the manufacturers of these newer products that one is better than another or that longacting formulations are “better” than short-acting, there is no neutral scientific evidence to sustain such statements. A trial and error method is necessary to determine what specific product or products are best for a specific child or adolescent with ADHD. Some of these newer products are discussed below. An MPH patch (Daytrana®) was released in June 2006 and allows effect for up to 12 hours; it is applied in the morning and removed in the afternoon or evening, providing Table 1 Medications with research support for use in attention disorders Medication Daily dose (mg/kg) schedule Common untoward effects 0.3–2.0 (10–80 mg/day) in 2–4 divided doses Insomnia, decreased appetite, abdominal pain, headache, depression, loss of weight, rebound symptoms, decreased velocity versus growth delay. See text Magnesium pemoline 0.5–3.0 (37.5–131.25 mg/day) In 1–2 divided doses Same as methylphenidate + possible liver toxicity (new FDA Black Box warning) Dextroamphetamine 0.1–1.5 (5–80 mg/day) in 2–4 divided doses Same as methylphenidate but more depression Stimulants Methylphenidate Antidepressants Tricyclic antidepressants imipramine desipramine nortriptyline Bupropion Alpha-2 agonists Clonidine Guanfacine Norepinephrine reuptake inhibitors Atomoxetine Anticholinergic effects, others. See text 1–5 1–5 0.5–3 3–6 (50–300 mg/day) in 2–3 divided doses Insomnia, irritability, drug-induced seizures (with doses ⬎6 mg/kg) Contraindicated in bulimic patients 3–10 μg/kg (0.05–0.4 mg/day) in 2–4 divided doses Sedation (very frequent), depression, dry mouth, rebound hypertension, hypotension (rare), confusion (w (...truncated)