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ADHD: Current and Future Therapeutics

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Book cover Behavioral Neuroscience of Attention Deficit Hyperactivity Disorder and Its Treatment

Part of the book series: Current Topics in Behavioral Neurosciences ((CTBN,volume 9))

Abstract

The stimulants, amphetamine and methylphenidate, have long been the mainstay of attention-deficit hyperactivity disorder (ADHD) therapy. They are rapidly effective and are generally the first medications selected by physicians. In the development of alternative pharmacological approaches, drug candidates have been evaluated with a wide diversity of mechanisms. All of these developments have contributed real progress in the field, but there is still much room for improvement and unmet clinical need in ADHD pharmacotherapy. The availability of a wide range of compounds with a high degree of specificity for individual monoamines (dopamine and noradrenaline) and/or different pharmacological mechanisms has refined our understanding of the essential elements for optimum pharmacological effect in managing ADHD. In this chapter, we review the pharmacology of the different classes of drug used to treat ADHD and provide a neurochemical rationale, predominantly from the use of in vivo microdialysis experiments, to explain their relative efficacy and potential to elicit side effects. In addition, we will consider how predictions based on results from animal models translate into clinical outcomes. The treatment of ADHD is also described from the perspective of the physician. Finally, the new research development for drugs to treat ADHD is discussed.

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Abbreviations

CNS:

Central nervous system

COMT:

Catechol-O-methyltransferase

DAT:

Dopamine reuptake transporter

HVA:

Homovanillic acid

MAO:

Monoamine oxidase

NET:

Norepinephrine reuptake transporter

PET:

Positron emission tomography

PFC:

Prefrontal cortex

SERT:

Serotonin reuptake transporter

SHR:

Spontaneously hypertensive rat

SSRI:

Selective serotonin reuptake inhibitor

XR:

Extended release

References

  • Andersen PH (1989) The dopamine uptake inhibitor GBR 12909: selectivity and molecular mechanism of action. Eur J Pharmacol 166:493–504

    Article  PubMed  CAS  Google Scholar 

  • Andersen ML, Kessler E, Murnane KS et al (2010) Dopamine transporter-related effects of modafinil in rhesus monkeys. Psychopharmacol 210:439–448

    Article  CAS  Google Scholar 

  • Arnold LE, Wender PH, McCloskey K et al (1972) Levoamphetmaine and dextroamphetamine: comparative efficacy in the hyperkinetic syndrome. Assessment of target symptoms. Arch Gen Psychiatry 27:819–822

    Article  Google Scholar 

  • Arnsten AFT (2006) Fundamentals of attention-deficit/hyperactivity disorder: circuits and pathways. J Clin Psychiatry 67:7–12

    Article  PubMed  CAS  Google Scholar 

  • Barkley RA, DuPaul GJ, McMurray MB (1991) Attention deficit disorder with and without hyperactivity: clinical response to three dose levels of methylphenidate. Pediatrics 87:519–531

    PubMed  CAS  Google Scholar 

  • Barrickman LL, Perry PJ, Allen AJ et al (1995) Bupropion versus methylphenidate in the treatment of attention-deficit hyperactivity disorder. J Am Acad Child Adolesc Psychiatry 34:649–657

    Article  PubMed  CAS  Google Scholar 

  • Bastuji H, Jouvet M (1988) Successful treatment of idiopathic hypersomnia and narcolepsy with modafinil. Prog Neuropsychopharmacol Biol Psychiatry 12:695–700

    Article  PubMed  CAS  Google Scholar 

  • Biederman J, Swanson JM, Wigal SB et al (2005) Efficacy and safety of modafinil film-coated tablets in children and adolescents with attention-deficit/hyperactivity disorder: results of a randomized, double-blind, placebo-controlled, flexible-dose study. Pediatrics 116:e777–e784

    Article  PubMed  Google Scholar 

  • Biederman J, Melmed RD, Patel A et al (2008a) A randomized, double-blind, placebo-controlled study of guanfacine extended release in children and adolescents with attention-deficit/hyperactivity disorder. Pediatrics 121:e73–e84

    Article  PubMed  Google Scholar 

  • Biederman J, Melmed RD, Patel A et al (2008b) Long-term, open-label extension study of guanfacine extended release in children and adolescents with ADHD. CNS Spectr 13:1047–1055

    PubMed  CAS  Google Scholar 

  • Bradley C (1937) Behaviour of children receiving benzedrine. Am J Psychiatry 94:577–585

    Google Scholar 

  • Buccafusco JJ, Jackson WJ, Terry AV Jr et al (1995) Improvement in performance of a delayed matching-to-sample task by monkeys following ABT-418: a novel cholinergic channel activator for memory enhancement. Psychopharmacol 120:256–266

    Article  CAS  Google Scholar 

  • Buccafusco JJ, Terry AV Jr, Decker MW et al (2007) Profile of nicotinic acetylcholine receptor agonists ABT-594 and A-582941, with differential subtype selectivity, on delayed matching accuracy by young monkeys. Biochem Pharmacol 15:1202–1211

    Article  Google Scholar 

  • Buitelaar JK, Michelson D, Danckaerts M et al (2007) A randomized, double-blind study of continuation treatment for attention-deficit/hyperactivity disorder after 1 year. Biol Psychiatry 61:694–699

    Article  PubMed  CAS  Google Scholar 

  • Bymaster FP, Katner JS, Nelson DL et al (2002) Atomoxetine increases extracellular levels of norepinephrine and dopamine in prefrontal cortex of rat: a potential mechanism for efficacy in attention deficit/hyperactivity disorder. Neuropsychopharmacol 27:699–711

    Article  CAS  Google Scholar 

  • Carboni E, Imperato A, Perezzani L et al (1989) Amphetamine, cocaine, phencyclidine and nomifensine increase extracellular dopamine concentrations preferentially in the nucleus accumbens of freely moving rats. Neurosci 28:653–661

    Article  CAS  Google Scholar 

  • Casat CD, Pleasants DZ, Van Wyck FJ (1987) A double-blind trial of bupropion in children with attention deficit disorder. Psychopharmacol Bull 23:120–122

    PubMed  CAS  Google Scholar 

  • Cass WA, Gerhardt GA (1995) In vivo assessment of dopamine uptake in rat medial prefrontal cortex: comparison with dorsal striatum and nucleus accumbens. J Neurochem 65:201–207

    Article  PubMed  CAS  Google Scholar 

  • Cheetham SC, Kulkarni RS, Rowley HL et al (2007) The SH rat model of ADHD has profoundly different catecholaminergic responses to amphetamine’s enantiomers compared with Sprague-Dawleys. Society for Neurosciences. Abstract 386.14. Available online at www.sfn.org

  • Conners CK, Casat CD, Gualtieri CT et al (1996) Bupropion hydrochloride in attention deficit disorder with hyperactivity. J Am Acad Child Adolesc Psychiatry 35:1314–1321

    Article  PubMed  CAS  Google Scholar 

  • Cooper BR, Wang CM, Cox RF et al (1994) Evidence that the acute behavioural and electrophysiological effects of bupropion (Wellbutrin) are mediated by a noradrenergic mechanism. Neuropsychopharmacol 11:133–141

    CAS  Google Scholar 

  • Daviss WB, Bentivoglio P, Racusin R et al (2001) Bupropion sustained release in adolescents with comorbid attention-deficit/hyperactivity disorder and depression. J Am Acad Child Psychiatry 40:307–314

    Article  CAS  Google Scholar 

  • de Saint Hilaire Z, Orosco M, Rouch C et al (2001) Variations in extracellular monoamines in the prefrontal cortex and medial hypothalamus after modafinil administration: a microdialysis study in rats. Neuroreport 12:3533–3537

    Article  Google Scholar 

  • Devoto P, Flore G, Longu G et al (2003) Origin of extracellular dopamine from dopamine and noradrenaline neurons in the medial prefrontal and occipital cortex. Synapse 50:200–205

    Article  PubMed  CAS  Google Scholar 

  • Durston S (2003) A review of the biological bases of ADHD: what have we learned from imaging studies? Ment Retard Dev Disabil Res Rev 9:184–195

    Article  PubMed  Google Scholar 

  • Efron D, Jarman F, Barker M (1997a) Methylphenidate versus dexamphetamine in children with attention deficit hyperactivity disorder: a double-blind, crossover trial. Pediatrics 100:E6

    Article  PubMed  CAS  Google Scholar 

  • Efron D, Jarman F, Barker M (1997b) Side effects of methylphenidate and dexamphetamine in children with attention deficit hyperactivity disorder: a double-blind, crossover trial. Pediatrics 100:662–666

    Article  PubMed  CAS  Google Scholar 

  • Faraone SV, Wigal SB, Hodgkins P (2007) Forecasting three-month outcomes in a laboratory school comparison of mixed amphetamine salts extended release (Adderall XR) and atomoxetine (Strattera) in school-aged children with ADHD. J Atten Disord 11:74–82

    Article  PubMed  Google Scholar 

  • Ferraro L, Fuxe K, Tanganelli S et al (2002) Differential enhancement of dialysate serotonin levels in distinct brain regions of the awake rat by modafinil: possible relevance for wakefulness and depression. J Neurosci Res 68:107–112

    Article  PubMed  CAS  Google Scholar 

  • Ferris RM, Tang FLM, Maxwell RA (1972) A comparison of the capacities of isomers of amphetamine, deoxypiprarol and methylphenidate to inhibit the uptake of tritiated catecholamine into rat cerebral cortex slices, synaptosomal preparations of rat cerebral cortex, hypothalamus and striatum and into adrenergic nerves of rabbit aorta. J Pharmacol Exp Ther 34:447–449

    Google Scholar 

  • Findling RL, Bukstein OG, Melmed RD (2008a) A randomized, double-blind, placebo-controlled, parallel-group study of methylphenidate transdermal system in pediatric patients with attention-deficit/hyperactivity disorder. J Clin Psychiatry 69:149–159

    Article  PubMed  CAS  Google Scholar 

  • Findling RL, Childress AC, Krishnan S et al (2008b) Long-term effectiveness and safety of lisdexamfetamine dimesylate in school-aged children with attention-deficit/hyperactivity disorder. CNS Spectr 13:614–620

    PubMed  Google Scholar 

  • Géranton SM, Heal DJ, Stanford SC (2003) Differences in the mechanisms that increase noradrenaline efflux after administration of d-amphetamine: a dual-probe microdialysis study in rat frontal cortex and hypothalamus. Br J Pharmacol 139:1441–1448

    Article  PubMed  Google Scholar 

  • Gerasimov MR, Franceschi M, Volkow N et al (2000) Comparison between intraperitoneal and oral methylphenidate administration: a microdialysis and locomotor activity study. J Pharm Exp Ther 295:51–57

    CAS  Google Scholar 

  • Gold LH, Balster RL (1996) Evaluation of the cocaine-like discriminative stimulus effects and reinforcing effects of modafinil. Psychopharmacol 126:286–292

    Article  CAS  Google Scholar 

  • Gross MD (1976) A comparison of dextro-amphetamine and racemic-amphetamine in the treatment of the hyperkinetic syndrome or minimal brain dysfunction. Dis Nerv Syst 37:14–16

    PubMed  CAS  Google Scholar 

  • Hammerness P, Georgiopoulos A, Doyle RL et al (2009) An open study of adjunct OROS-methylphenidate in children who are atomoxetine partial responders: II. Tolerability and pharmacokinetics. J Child Adolesc Psychopharmacol 19:493–499

    Article  PubMed  Google Scholar 

  • Hammerness P, Biederman J, Petty C, Henin A, Moore CM (2010) Brain biochemical effect of methylphenidate treatment using proton magnetic spectroscopy in youth with attention-deficit hyperactivity disorder: a controlled pilot study. CNS Neurosci Ther. Dec 8 [Epub ahead of print]

    Google Scholar 

  • Hasegawa H, Meeusen R, Sarre S et al (2005) Acute dopamine/norepinephrine reuptake inhibition increases brain and core temperature in rats. J Appl Physiol 99:1397–1401

    Article  PubMed  CAS  Google Scholar 

  • Heal DJ (2008) A method for identifying a compound for treating a disorder or condition associated with dysfunction of monoamine neurotransmission. UK Patent Application GB 2447 949

    Google Scholar 

  • Heal DJ, Cheetham SC, Prow MR et al (1998) A comparison of the effects on central 5-HT function of sibutramine hydrochloride and other weight-modifying agents. Br J Pharmacol 125:301–308

    Article  PubMed  CAS  Google Scholar 

  • Heal DJ, Smith SL, Kulkarni RS et al (2008) New perspectives from microdialysis studies in freely-moving, spontaneously hypertensive rats on the pharmacology of drugs for the treatment of ADHD. Pharmacol Biochem Behav 90:184–197

    Article  PubMed  CAS  Google Scholar 

  • Heal DJ, Cheetham SC, Smith SL (2009) The neuropharmacology of ADHD drugs in vivo: insights on efficacy and safety. Neuropharmacol 57:608–618

    Article  CAS  Google Scholar 

  • Hitri A, Venable D, Nguyen HQ et al (1991) Characteristics of [3H]GBR 12935 binding in the human and rat frontal cortex. J Neurochem 56:1663–1672

    Article  PubMed  CAS  Google Scholar 

  • Hurd YL, Ungerstedt U (1989) Ca2+ dependence of the amphetamine, nomifensine, and Lu 19-005 effect on in vivo dopamine transmission. Eur J Pharmacol 166:261–269

    Article  PubMed  CAS  Google Scholar 

  • Ihalainen JA, Tanila H (2002) In vivo regulation of dopamine and noradrenaline release by α2A-adrenoceptors in the mouse prefrontal cortex. Eur J Neurosci 15:1789–1794

    Article  PubMed  Google Scholar 

  • Jasinski DR (2000) An evaluation of the abuse potential of modafinil using methylphenidate as a reference. J Psychopharmacol 14:53–60

    Article  PubMed  CAS  Google Scholar 

  • Jasinski DR, Faries DE, Moore RJ et al (2008) Abuse liability assessment of atomoxetine in a drug-abusing population. Drug Alcohol Depend 95:140–146

    Article  PubMed  CAS  Google Scholar 

  • Jenner P, Zeng BY, Smith LA et al (2000) Antiparkinsonian and neuroprotective effects of modafinil in the mptp-treated common marmoset. Exp Brain Res 133:178–188

    Article  PubMed  CAS  Google Scholar 

  • Kaiser S, Wonnacott S (2000) α-Bungarotoxin-sensitive nicotonic receptors indirectly modulate [3H]dopamine release in rat striatal slices via glutamate release. Mol Pharmacol 58:312–318

    PubMed  CAS  Google Scholar 

  • Kelsey DK, Sumner CR, Casat CD et al (2004) Once-daily atomoxetine treatment for children with attention-deficit/hyperactivity disorder, including an assessment of evening and morning behavior: a double-blind, placebo-controlled trial. Pediatrics 114:e1–e8

    Article  PubMed  Google Scholar 

  • Kuczenski R, Segal DS (1997) Effects of methylphenidate on extracellular dopamine, serotonin, and norepinephrine: comparison with amphetamine. J Neurochem 68:2032–2037

    Article  PubMed  CAS  Google Scholar 

  • Kuczenski R, Segal DS, Cho AK et al (1995) Hippocampus norepinephrine, caudate dopamine and serotonin, and behavioral responses to the stereoisomers of amphetamine and methamphetamine. J Neurosci 15:1308–1317

    PubMed  CAS  Google Scholar 

  • Lehola M, Kellaway L, Russell VA (2004) NMDA receptor function in the prefrontal cortex of a rat model for attention-deficit hyperactivity disorder. Metab Brain Dis 19:35–42

    Article  Google Scholar 

  • Li SX, Perry KW, Wong DT (2002) Influence of fluoxetine on the ability of bupropion to modulate extracellular dopamine and norepinephrine concentration in three mesocorticolimbic areas of rats. Neuropharmacol 42:181–190

    Article  CAS  Google Scholar 

  • Madras BK, Xie Z, Lin Z et al (2006) Modafinil occupies dopamine and norepinephrine transporters in vivo and modulates the transporters and trace amine activity in vitro. J Pharmacol Exp Ther 319:561–569

    Article  PubMed  CAS  Google Scholar 

  • Mantle TJ, Tipton KF, Garrett NJ (1976) Inhibition of monoamine oxidase by amphetamine and related compounds. Biochem Pharmacol 25:2073–2077

    Article  PubMed  CAS  Google Scholar 

  • Medhurst AD, Atkins AR, Beresford IJ et al (2007) GSK189254, a novel H3 receptor antagonist that binds to histamine H3 receptors in Alzheimer’s disease brain and improves cognitive performance in preclinical models. J Pharmacol Exp Ther 321:1032–1045

    Article  PubMed  CAS  Google Scholar 

  • Michelson D, Faries D, Wernicke J et al (2001) Atomoxetine in the treatment of children and adolescents with attention-deficit/hyperactivity disorder: a randomized, placebo-controlled, dose-response study. Pediatrics 108:E83–E92

    Article  PubMed  CAS  Google Scholar 

  • Michelson D, Adler L, Spencer S (2003) Atomoxetine in adults with ADHD: two randomized placebo-controlled studies. Biol Psychiatry 53:112–120

    Article  PubMed  CAS  Google Scholar 

  • Miller L, Griffith J (1983) A comparison of bupropion, dextroamphetamine, and placebo in mixed-substance abusers. Psychopharmacol 80:199–205

    Article  CAS  Google Scholar 

  • Minzenberg MJ, Carter CS (2008) Modafinil: a review of neurochemical actions and effects on cognition. Neuropsychopharmacol 33:1477–1502

    Article  CAS  Google Scholar 

  • Morón JA, Brockington A, Wise RA et al (2002) Dopamine uptake through the norepinephrine transporter in brain regions with low levels of the dopamine transporter: evidence from knock-out mouse lines. J Neurosci 22:389–395

    PubMed  Google Scholar 

  • Murillo-Rodríguez E, Haro R, Palomero-Rivero M et al (2007) Modafinil enhances extracellular levels of dopamine in the nucleus accumbens and increases wakefulness in rats. Behav Brain Res 176:353–357

    Article  PubMed  Google Scholar 

  • Newcorn JH, Kratochvil CJ, Allen AJ et al (2008) Atomoxetine and osmotically released methylphenidate for the treatment of attention deficit hyperactivity disorder: acute comparison and differential response. Am J Psychiatry 165:721–730

    Article  PubMed  Google Scholar 

  • Nomikos GG, Damsma G, Wenkstern D et al (1990) In vivo characterization of locally applied dopamine uptake inhibitors by striatal microdialysis. Synapse 6:106–112

    Article  PubMed  CAS  Google Scholar 

  • Pelham WE, Greenslade KE, Vodde-Hamilton M et al (1990) Relative efficacy of long-acting stimulants on children with attention deficit-hyperactivity disorder: a comparison of standard methylphenidate, sustained-release methylphenidate, sustained-release dextroamphetamine, and pemoline. Pediatrics 86:226–237

    PubMed  Google Scholar 

  • Pelham WE, Aronoff HR, Midlam JK et al (1999) A comparison of Ritalin and Adderall: efficacy and time-course in children with attention-deficit/hyperactivity disorder. Pediatrics 103:e43

    Article  PubMed  CAS  Google Scholar 

  • Pozzi L, Invernizzi R, Cervo L et al (1994) Evidence that extracellular concentration of dopamine are regulated by noradrenergic neurons in the frontal cortex of rats. J Neurochem 63:195–200

    Article  PubMed  CAS  Google Scholar 

  • Pum M, Carey RJ, Huston JP et al (2007) Dissociating effects of cocaine and d-amphetamine on dopamine and serotonin in the perirhinal, entorhinal, and prefrontal cortex of freely moving rats. Psychopharmacol 193:375–390

    Article  CAS  Google Scholar 

  • Quinn D, Wigal S, Swanson J et al (2004) Comparative pharmacodynamics and plasma concentrations of d-threo-methylphenidate hydrochloride after single doses of d-threo-methylphenidate hydrochloride and d, l-threo-methylphenidate hydrochloride in a double-blind, placebo-controlled, crossover laboratory school study in children with attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry 43:1422–1429

    Article  PubMed  Google Scholar 

  • Richelson E, Pfenning M (1984) Blockade by antidepressants and related compounds of biogenic amine uptake into rat brain synaptosomes: most antidepressants selectively block norepinephrine uptake. Eur J Pharmacol 104:277–286

    Article  PubMed  CAS  Google Scholar 

  • Rush CR, Kelly TH, Hays LR et al (2002) Acute behavioral and physiological effects of modafinil in drug abusers. Behav Pharmacol 13:105–115

    Article  PubMed  CAS  Google Scholar 

  • Russell VA (2003) Dopamine hypofunction possibly results from a defect in glutamate stimulated release of dopamine in the nucleus accumbens shell of a rat model for attention deficit hyperactivity disorder – the spontaneously hypertensive rat. Neurosci Biobehav Rev 27:671–682

    Article  PubMed  CAS  Google Scholar 

  • Sagvolden T, Metzger MA, Schiørbeck HK et al (1992) The spontaneously hypertensive rat (SHR) as an animal model of childhood hyperactivity (ADHD): changed reactivity to reinforcers and to psychomotor stimulants. Behav Neural Biol 58:103–112

    Article  PubMed  CAS  Google Scholar 

  • Sallee FR, Lyne A, Wigal T et al (2009) Long-term safety and efficacy of guanfacine extended release in children and adolescents with attention-deficit/hyperactivity disorder. J Child Adolesc Psychopharmacol 19:215–226

    Article  PubMed  Google Scholar 

  • Scahill L, Chappell PB, Kim YS (2001) A placebo-controlled study of guanfacine in the treatment of children with tic disorders and attention deficit hyperactivity disorder. Am J Psychiatry 158:1067–1074

    Article  PubMed  CAS  Google Scholar 

  • Sharman DF (1966) Changes in the metabolism of 3, 4-dihydroxyphenylethylamine (dopamine) in the striatum of the mouse induced by drugs. Br J Pharmacol Chemother 28:158–163

    Google Scholar 

  • Sharples CGV, Kaiser S, Soliakov L et al (2000) UB-165: a novel nicotinic agonist with subtype selectivity implicates the α4/β2* subtype in the modulation of dopamine release from rat striatal synaptosomes. J Neurosci 20:2783–2791

    PubMed  CAS  Google Scholar 

  • Sidhpura N, Redfern P, Rowley H et al (2007) Comparison of the effects of bupropion and nicotine on locomotor activation and dopamine release in vivo. Biochem Pharmacol 74:1292–1298

    Article  PubMed  CAS  Google Scholar 

  • Smith RC, Davis JM (1977) Comparative effects of d-amphetamine, l-amphetamine, and methylphenidate on mood in man. Psychopharmacol 53:1–12

    Article  CAS  Google Scholar 

  • Sofuoglu M, Hill K, Kosten T et al (2009) Atomoxetine attenuates dextroamphetamine effects in humans. Am J Drug Alcohol Abuse 35:412–416

    Article  PubMed  Google Scholar 

  • Stocking EM, Letavic MA (2008) Histamine H3 antagonists as wake-promoting and pro-cognitive agents. Curr Top Med Chem 8:988–1002

    Article  PubMed  CAS  Google Scholar 

  • Sulzer D, Rayport S (1990) Amphetamine and other psychostimulants reduce pH gradients in midbrain dopaminergic neurons and chromaffin granules: a mechanism of action. Neuron 5:797–808

    Article  PubMed  CAS  Google Scholar 

  • Tani Y, Saito K, Tsuneyoshi A et al (1997) Nicotinic acetylcholine receptor (nACh-R) agonist-induced changes in brain monoamine turnover in mice. Psychopharmacol 129:225–232

    Article  CAS  Google Scholar 

  • Uhlén S, Porter AC, Neubig RR (1994) The novel alpha-2 adrenergic radioligand [3H]-MK912 is alpha-2C selective among human alpha-2A, alpha-2B and alpha-2C adrenoceptors. J Pharmacol Exp Ther 271:1558–1565

    PubMed  Google Scholar 

  • Volkow ND, Fowler JS, Logan J et al (2009) Effects of modafinil on dopamine and dopamine transporters in the male human brain: clinical implications. J Am Med Assoc 301:1148–1154

    Article  CAS  Google Scholar 

  • Wang Y, Zheng Y, Du Y et al (2007) Atomoxetine versus methylphenidate in paediatric outpatients with attention deficit hyperactivity disorder: a randomized, double-blind comparison trial. Aust NZ J Psychiatry 41:222–230

    Article  CAS  Google Scholar 

  • Wigal SB, McGough JJ, McCracken JT et al (2005) A laboratory school comparison of mixed amphetamine salts extended release (Adderal XR®) and atomoxetine (Strattera®) in school-aged children with attention deficit/hyperactivity disorder. J Atten Disord 9:275–289

    Article  PubMed  Google Scholar 

  • Wigal SB, Biederman J, Swanson JM et al (2006) Efficacy and safety of modafinil film-coated tablets in children and adolescents with or without prior stimulant treatment for attention-deficit/hyperactivity disorder: pooled analysis of 3 randomized, double-blind, placebo-controlled studies. Prim Care Companion J Clin Psychiatry 8:352–360

    PubMed  Google Scholar 

  • Wilens TE, Biederman J, Spencer TJ et al (1999) A pilot controlled clinical trial of ABT-418, a cholinergic agonist, in the treatment of adults with attention deficit hyperactivity disorder. Am J Psychiatry 156:1931–1937

    PubMed  CAS  Google Scholar 

  • Wilens TE, Spencer TJ, Biederman J et al (2001) A controlled clinical trial of bupropion for attention deficit hyperactivity disorder in adults. Am J Psychiatry 158:282–288

    Article  PubMed  CAS  Google Scholar 

  • Wilens TE, Haight BR, Horrigan JP et al (2005) Bupropion XL in adults with attention-deficit/hyperactivity disorder: a randomized, placebo-controlled study. Biol Psychiatry 57:793–801

    Article  PubMed  CAS  Google Scholar 

  • Wilens TE, Verlinden MH, Adler LA et al (2006) ABT-089, a neuronal nicotinic receptor partial agonist, for the treatment of attention-deficit/hyperactivity disorder in adults: results of a pilot study. Biol Psychiatry 59:1065–1070

    Article  PubMed  CAS  Google Scholar 

  • Wilens TE, Hammerness P, Utzinger L et al (2009) An open study of adjunct OROS-methylphenidate in children and adolescents who are atomoxetine partial responders: I. Effectiveness. J Child Adolesc Psychopharmacol 19:485–492

    Article  PubMed  Google Scholar 

  • Wisor JP, Nishino S, Sora I et al (2001) Dopaminergic role in stimulant-induced wakefulness. J Neurosci 21:1787–1794

    PubMed  CAS  Google Scholar 

  • Wolraich ML, Greenhill LL, Pelham W et al (2001) Randomized, controlled trial of OROS methylphenidate once a day in children with attention-deficit/hyperactivity disorder. Pediatrics 108:883–892

    Article  PubMed  CAS  Google Scholar 

  • Zolkowska D, Jain R, Rothman RB et al (2009) Evidence for the involvement of dopamine transporters in behavioral stimulant effects of modafinil. J Pharmacol Exp Ther 329:738–746

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. RenaSci Consultancy Ltd, BioCity, Nottingham, NG1 1GF, UK

    David J. Heal & Sharon L. Smith

  2. University Hospitals Case Medical Center, Case Western Reserve University School of Medicine, Cleveland, Ohio, 44106-2205, USA

    Robert L. Findling

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  1. David J. Heal
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  2. Sharon L. Smith
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  3. Robert L. Findling
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Correspondence to David J. Heal .

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  1. , Dept of Neurosci, Physiol & Pharmacol, University College London, Gower Street, London, WC1E6BT, United Kingdom

    Clare Stanford

  2. , Human Development & Applied Psychology, The Ontario Institute for Studies in Edu, Bloor Street West 252, Toronto, M5S1V6, Canada

    Rosemary Tannock

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Heal, D.J., Smith, S.L., Findling, R.L. (2011). ADHD: Current and Future Therapeutics. In: Stanford, C., Tannock, R. (eds) Behavioral Neuroscience of Attention Deficit Hyperactivity Disorder and Its Treatment. Current Topics in Behavioral Neurosciences, vol 9. Springer, Berlin, Heidelberg. https://doi.org/10.1007/7854_2011_125

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