Download PDF
Fortschr Neurol Psychiatr 2012; 80(3): 130-140
DOI: 10.1055/s-0031-1273223
Übersicht

© Georg Thieme Verlag KG Stuttgart · New York

Psychostimulantien und Nicht-Stimulantien in der heutigen und zukünftigen ADHS-Therapie

Stimulant and Non-Stimulant Medication in Current and Future Therapy for ADHDA. G. Franke1 , A. Konrad1 , K. Lieb1 , M. Huss2
  • 1Klinik für Psychiatrie und Psychotherapie, Universitätsmedizin Mainz
  • 2Klinik und Poliklinik für Kinder- und Jugendpsychiatrie und -psychotherapie, Universitätsmedizin Mainz
Further Information

Publication History

Publication Date:
24 May 2011 (online)

Also available at
    Permissions and Reprints

Zusammenfassung

Die gegenwärtige Pharmakotherapie der Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung (ADHS) basiert im Wesentlichen auf dem Psychostimulans Methylphenidat und in geringem Maße – nicht in Deutschland zugelassen – auf Amphetaminen. Als einziges Nicht-Stimulans ist Atomoxetin (Strattera®) als Noradrenalin-Wiederaufnahme-Hemmer zur Behandlung der ADHS zugelassen. Die Substanzen sind allerdings nur zur Pharmakotherapie der ADHS im Kindes- und Jugendalter zugelassen. Die rein symptomatische Pharmakotherapie zielt auf eine Verbesserung der drei ADHS-Kernsymptome Konzentrationsstörungen, Impulsivität und motorische Unruhe ab. Neurobiologische Korrelate der Therapieeffekte sind weiterhin nicht umfangreich aufgeklärt. Bekannt ist mittlerweile die Wirkung auf dopaminerge und noradrenerge Regelkreise. Probleme in der Anwendung der etablierten Substanzen ergeben sich durch kurze Halbwertszeiten der Psychostimulantien, dem noch nicht vollends aufgeklärten Wirkmechanismus, und der strittigen Anwendung von Stimulantien bei den noch in der Entwicklung befindlichen Kindern und Jugendlichen. Viel diskutiert, jedoch nicht hinreichend belegt ist zudem das Abhängigkeits- und Missbrauchspotenzial der Stimulantien. Die neu zur Verfügung stehenden Substanzen Lisdexamfetamin (Vyvanse®) und SPD-465 beruhen auf dem Wirkprinzip der Stimulantien. Mehrere in verschiedenen Entwicklungsstadien befindliche Substanzen weisen verschiedene andere Wirkmechanismen auf: Guanfacine/SPD-503 wirkt agonistisch am α2A-Adrenozeptor, während ABT-089 und ABT-418 vor allem als Partialagonisten am α4β2-Subtyp des nikotinischen Acetylcholinrezeptors ihre Wirkung entfalten. CX-717, -1739, -1942 und -1796 sind Agonisten am glutamatergen αAmino-3-hydroxy-5-methyl-4-isoxazol-Propion-Acid (AMPA)-Rezeptor und PF-3654746 wirkt als Antagonist am histaminergen H 3-Rezeptor. Guanfacine (Intuniv®), ein α2A-Adrenozeptor-Agonist und Lisdexamfetamin (Vyvanse®), ein über die Leber aktiviertes „Pro-Drug“ eines Amphetamins sind mittlerweile in den USA zugelassen. Die vorliegende Übersichtsarbeit fasst bewertend die etablierten und insbesondere mögliche, zukünftige symptomatische pharmakologische Therapieoptionen von Stimulantien und Nicht-Stimulantien in der ADHS-Behandlung zusammen.

Abstract

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®), 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 α2A-adrenozeptoragonist, ABT-089 and ABT-418 have partial agonistic effects to the α4β2-subtype of nicotinic acetylcholinreceptors, CX-717, -1739, -1942 and -1796 are glutamatergic α-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 α2A-adrenoceptor-agonist Guanfacine (Intuniv®) and the hepatic metabolised amphetamine prodrug Lisdexamfetamin (Vyvanse®) 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.

Schlüsselwörter

ADHS - Therapie - Pharmaka - Stimulantien - Neuentwicklungen

Keywords

ADHD - therapy - drugs - stimulants - developments

Literatur

  • 1 Barkley R A. Adolescents with attention-deficit/hyperactivity disorder: an overview of empirically based treatments.  J Psychiatr Pract. 2004;  10 (1) 39-56
    Search in Google Scholar
  • 2 Still G. The Goulstonian lectures on some abnormal psychical conditions in children, Lecture I, II, III.  Lancet. 1902;  1 1008-1012, 1077 – 1082, 1163 – 1168
    Search in Google Scholar
  • 3 Polanczyk G, Lima M S, Horta B L et al. The worldwide prevalence of ADHD: a systematic review and metaregression analysis.  Am J Psychiatry. 2007;  164 (6) 942-948
    Search in Google Scholar
  • 4 Goldman L S, Genel de M, Bezman R J et al. Diagnosis and treatment of attention-deficit/hyperactivity disorder in children and adolescents. Council on Scientific Affairs, American Medical Association.  Jama. 1998;  279 (14) 1100-1107
    Search in Google Scholar
  • 5 Huss M, Holling H, Kurth B M et al. How often are German children and adolescents diagnosed with ADHD? Prevalence based on the judgment of health care professionals: results of the German health and examination survey (KiGGS).  Eur Child Adolesc Psychiatry. 2008;  17 (Suppl 1) 52-58
    Search in Google Scholar
  • 6 Taylor E, Dopfner M, Sergeant J et al. European clinical guidelines for hyperkinetic disorder – first upgrade.  Eur Child Adolesc Psychiatry. 2004;  13 (Suppl 1) 17-30
    Search in Google Scholar
  • 7 Barbaresi W J, Katusic S K, Colligan R C et al. How common is attention-deficit/hyperactivity disorder? Incidence in a population-based birth cohort in Rochester, Minn.  Arch Pediatr Adolesc Med. 2002;  156 (3) 217-224
    Search in Google Scholar
  • 8 Polanczyk G, Jensen P. Epidemiologic considerations in attention deficit hyperactivity disorder: a review and update.  Child Adolesc Psychiatr Clin N Am. 2008;  17 (2) 245-260, vii
    Search in Google Scholar
  • 9 Faraone S V, Biederman J, Spencer T et al. Attention-deficit/hyperactivity disorder in adults: an overview.  Biol Psychiatry. 2000;  48 (1) 9-20
    Search in Google Scholar
  • 10 Fayyad J, De Graaf R, Kessler R et al. Cross-national prevalence and correlates of adult attention-deficit hyperactivity disorder.  Br J Psychiatry. 2007;  190 402-409
    Search in Google Scholar
  • 11 Spencer T J, Biederman J, Wilens T E et al. Overview and neurobiology of attention-deficit/hyperactivity disorder.  J Clin Psychiatry. 2002;  63 (Suppl 12) 3-9
    Search in Google Scholar
  • 12 Faraone S V, Perlis R H, Doyle A E et al. Molecular genetics of attention-deficit/hyperactivity disorder.  Biol Psychiatry. 2005;  57 (11) 1313-1323
    Search in Google Scholar
  • 13 Seidman L J, Valera E M, Makris N. Structural brain imaging of attention-deficit/hyperactivity disorder.  Biol Psychiatry. 2005;  57 (11) 1263-1272
    Search in Google Scholar
  • 14 Viggiano D, Grammatikopoulos G, Sadile A G. A morphometric evidence for a hyperfunctioning mesolimbic system in an animal model of ADHD.  Behav Brain Res. 2002;  130 (1 – 2) 181-189
    Search in Google Scholar
  • 15 Hüther G, Brandl Y, Leuzinger-Bohleber M. ADHS – Frühprävention statt Medikalisierung. Theorie, Forschung, Kontroversen. Göttingen: Vandenhoeck und Ruprecht; 2006
    Search in Google Scholar
  • 16 Zametkin A J, Rapoport J L. Noradrenergic hypothesis of attention deficit disorder with hyperactivity: a critical review. In: Meltzer H Y, (Ed.) Psychopharmacology: The Third Generation of Progress.. New York: Raven Press; 1987: 837-842
    Search in Google Scholar
  • 17 Valera E M, Faraone S V, Murray K E et al. Meta-analysis of structural imaging findings in attention-deficit/hyperactivity disorder.  Biol Psychiatry. 2007;  61 (12) 1361-1369
    Search in Google Scholar
  • 18 Castellanos F X, Lee P P, Sharp W et al. Developmental trajectories of brain volume abnormalities in children and adolescents with attention-deficit/hyperactivity disorder.  Jama. 2002;  288 (14) 1740-1748
    Search in Google Scholar
  • 19 Wilens T E. Effects of methylphenidate on the catecholaminergic system in attention-deficit/hyperactivity disorder.  J Clin Psychopharmacol. 2008;  28 (3 Suppl 2) S46-S53
    Search in Google Scholar
  • 20 Jensen V, Rinholm J E, Johansen T J et al. N-methyl-D-aspartate receptor subunit dysfunction at hippocampal glutamatergic synapses in an animal model of attention-deficit/hyperactivity disorder.  Neuroscience. 2009;  158 (1) 353-364
    Search in Google Scholar
  • 21 Renner T J, Gerlach M, Romanos M et al. Neurobiology of attention-deficit hyperactivity disorder.  Nervenarzt. 2008;  79 (7) 771-781
    Search in Google Scholar
  • 22 Beijsterveldt C E, Middeldorp C M, Slof-Op’t Landt M C et al. Influence of Candidate Genes on Attention Problems in Children: A Longitudinal Study.  Behav Genet. 2010;  41 155-164
    Search in Google Scholar
  • 23 Schuchardt J P, Huss van M, Stauss-Grabo M et al. Significance of long-chain polyunsaturated fatty acids (PUFAs) for the development and behaviour of children.  Eur J Pediatr. 2010;  169 (2) 149-164
    Search in Google Scholar
  • 24 Transler C, Eilander A, Mitchell S et al. The impact of polyunsaturated fatty acids in reducing child attention deficit and hyperactivity disorders.  J Atten Disord. 2010;  14 (3) 232-246
    Search in Google Scholar
  • 25 Gemeinsamer Bundesausschuss (G-BA) .Zusammenfassende Dokumentation zum Beschluss des Gemeinsamen Bundesausschusses über eine Änderung der Arzneimittel-Richtlinie: Anlage III Nummer 44 – Stimulantien. Berlin; 16.9.2010
    Search in Google Scholar
  • 26 Wilens T E, Adler L A, Adams J et al. Misuse and diversion of stimulants prescribed for ADHD: a systematic review of the literature.  J Am Acad Child Adolesc Psychiatry. 2008;  47 (1) 21-31
    Search in Google Scholar
  • 27 Bukstein O. Substance abuse in patients with attention-deficit/hyperactivity disorder.  Medscape J Med. 2008;  10 (1) 24
    Search in Google Scholar
  • 28 Kollins S H. A qualitative review of issues arising in the use of psycho-stimulant medications in patients with ADHD and co-morbid substance use disorders.  Curr Med Res Opin. 2008;  24 (5) 1345-1357
    Search in Google Scholar
  • 29 Yamamoto B K, Moszczynska A, Gudelsky G A. Amphetamine toxicities: classical and emerging mechanisms.  Ann N Y Acad Sci. 2010;  1187 101-121
    Search in Google Scholar
  • 30 Advokat C. Update on amphetamine neurotoxicity and its relevance to the treatment of ADHD.  J Atten Disord. 2007;  11 (1) 8-16
    Search in Google Scholar
  • 31 Cadet J L, Krasnova I N, Jayanthi S et al. Neurotoxicity of substituted amphetamines: molecular and cellular mechanisms.  Neurotox Res. 2007;  11 (3 – 4) 183-202
    Search in Google Scholar
  • 32 Shaw P, Sharp W S, Morrison M et al. Psychostimulant treatment and the developing cortex in attention deficit hyperactivity disorder.  Am J Psychiatry. 2009;  166 (1) 58-63
    Search in Google Scholar
  • 33 Gould M S, Walsh B T, Munfakh J L et al. Sudden death and use of stimulant medications in youths.  Am J Psychiatry. 2009;  166 (9) 992-1001
    Search in Google Scholar
  • 34 Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM) .Methylphenidat-haltige Arzneimittel: Artikel 31 – Verfahren nach Entscheidung der Kommission der Europäischen Gemeinschaft (27.5.2009, Brüssel, Belgien). Bonn 23.6.2009
  • 35 Prince J. Catecholamine dysfunction in attention-deficit/hyperactivity disorder: an update.  J Clin Psychopharmacol. 2008;  28 (3 Suppl 2) S39-S45
    Search in Google Scholar
  • 36 Oades R D, Sadile A G, Sagvolden T et al. The control of responsiveness in ADHD by catecholamines: evidence for dopaminergic, noradrenergic and interactive roles.  Dev Sci. 2005;  8 (2) 122-131
    Search in Google Scholar
  • 37 Kostrzewa R M, Kostrzewa J P, Kostrzewa R A et al. Pharmacological models of ADHD.  J Neural Transm. 2008;  115 (2) 287-298
    Search in Google Scholar
  • 38 Greenhill L L, Pliszka S, Dulcan M K et al. Practice parameter for the use of stimulant medications in the treatment of children, adolescents, and adults.  J Am Acad Child Adolesc Psychiatry. 2002;  41 (2 Suppl) 26S-49S
    Search in Google Scholar
  • 39 Swanson J M, Gupta S, Williams L et al. Efficacy of a new pattern of delivery of methylphenidate for the treatment of ADHD: effects on activity level in the classroom and on the playground.  J Am Acad Child Adolesc Psychiatry. 2002;  41 (11) 1306-1314
    Search in Google Scholar
  • 40 Schachter H M, Pham B, King J et al. How efficacious and safe is short-acting methylphenidate for the treatment of attention-deficit disorder in children and adolescents? A meta-analysis.  Cmaj. 2001;  165 (11) 1475-1488
    Search in Google Scholar
  • 41 Faraone S V, Spencer T, Aleardi M et al. Meta-analysis of the efficacy of methylphenidate for treating adult attention-deficit/hyperactivity disorder.  J Clin Psychopharmacol. 2004;  24 (1) 24-29
    Search in Google Scholar
  • 42 Koesters M, Becker T, Kilian R et al. Limits of meta-analysis: methylphenidate in the treatment of adult attention-deficit hyperactivity disorder.  J Psychopharmacol. 2009;  23 (7) 733-744
    Search in Google Scholar
  • 43 Brams M, Muniz R, Childress A et al. A randomized, double-blind, crossover study of once-daily dexmethylphenidate in children with attention-deficit hyperactivity disorder: rapid onset of effect.  CNS Drugs. 2008;  22 (8) 693-704
    Search in Google Scholar
  • 44 Rosler M, Fischer R, Ammer R et al. A randomised, placebo-controlled, 24-week, study of low-dose extended-release methylphenidate in adults with attention-deficit/hyperactivity disorder.  Eur Arch Psychiatry Clin Neurosci. 2009;  259 (2) 120-129
    Search in Google Scholar
  • 45 Wilens T E. The nature of the relationship between attention-deficit/hyperactivity disorder and substance use.  J Clin Psychiatry. 2007;  68 (Suppl 11) 4-8
    Search in Google Scholar
  • 46 Wilens T E, Adamson J, Monuteaux M C et al. Effect of prior stimulant treatment for attention-deficit/hyperactivity disorder on subsequent risk for cigarette smoking and alcohol and drug use disorders in adolescents.  Arch Pediatr Adolesc Med. 2008;  162 (10) 916-921
    Search in Google Scholar
  • 47 Biederman J, Monuteaux M C, Spencer T et al. Stimulant therapy and risk for subsequent substance use disorders in male adults with ADHD: a naturalistic controlled 10-year follow-up study.  Am J Psychiatry. 2008;  165 (5) 597-603
    Search in Google Scholar
  • 48 Barkley R A, Fischer M, Smallish L et al. Does the treatment of attention-deficit/hyperactivity disorder with stimulants contribute to drug use/abuse? A 13-year prospective study.  Pediatrics. 2003;  111 (1) 97-109
    Search in Google Scholar
  • 49 Poulin C. From attention-deficit/hyperactivity disorder to medical stimulant use to the diversion of prescribed stimulants to non-medical stimulant use: connecting the dots.  Addiction. 2007;  102 (5) 740-751
    Search in Google Scholar
  • 50 Fuller R W, Hemrick-Luecke S K. Further studies on the long-term depletion of striatal dopamine in iprindole-treated rats by amphetamine.  Neuropharmacology. 1982;  21 (5) 433-438
    Search in Google Scholar
  • 51 U. S. Food and Drug Administration (FDA) .Issues Safety Communication about an Ongoing Review of Medications Used in Children with ADHD. FDA news release. Rockville, Maryland; 15.6.2009
    Search in Google Scholar
  • 52 Vetter V L, Elia J, Erickson C et al. Cardiovascular monitoring of children and adolescents with heart disease receiving medications for attention deficit/hyperactivity disorder (corrected): a scientific statement from the American Heart Association Council on Cardiovascular Disease in the Young Congenital Cardiac Defects Committee and the Council on Cardiovascular Nursing.  Circulation. 2008;  117 (18) 2407-2423
    Search in Google Scholar
  • 53 Faraone S V, Biederman J, Roe C. Comparative efficacy of Adderall and methylphenidate in attention-deficit/hyperactivity disorder: a meta-analysis.  J Clin Psychopharmacol. 2002;  22 (5) 468-473
    Search in Google Scholar
  • 54 Bymaster F P, Katner J S, Nelson D L et al. Atomoxetine increases extracellular levels of norepinephrine and dopamine in prefrontal cortex of rat: a potential mechanism for efficacy in attention deficit/hyperactivity disorder.  Neuropsychopharmacology. 2002;  27 (5) 699-711
    Search in Google Scholar
  • 55 Swanson C J, Perry K W, Koch-Krueger S et al. Effect of the attention deficit/hyperactivity disorder drug atomoxetine on extracellular concentrations of norepinephrine and dopamine in several brain regions of the rat.  Neuropharmacology. 2006;  50 (6) 755-760
    Search in Google Scholar
  • 56 Newman L A, Darling J, McGaughy J. Atomoxetine reverses attentional deficits produced by noradrenergic deafferentation of medial prefrontal cortex.  Psychopharmacology. 2008;  200 (1) 39-50
    Search in Google Scholar
  • 57 Michelson D, Faries D, Wernicke J et al. Atomoxetine in the treatment of children and adolescents with attention-deficit/hyperactivity disorder: a randomized, placebo-controlled, dose-response study.  Pediatrics. 2001;  108 (5) E83
    Search in Google Scholar
  • 58 Kratochvil C J, Heiligenstein J H, Dittmann R et al. Atomoxetine and methylphenidate treatment in children with ADHD: a prospective, randomized, open-label trial.  J Am Acad Child Adolesc Psychiatry. 2002;  41 (7) 776-784
    Search in Google Scholar
  • 59 Michelson D, Adler L, Spencer T et al. Atomoxetine in adults with ADHD: two randomized, placebo-controlled studies.  Biol Psychiatry. 2003;  53 (2) 112-120
    Search in Google Scholar
  • 60 Adler L A, Spencer T J, Milton D R et al. Long-term, open-label study of the safety and efficacy of atomoxetine in adults with attention-deficit/hyperactivity disorder: an interim analysis.  J Clin Psychiatry. 2005;  66 (3) 294-299
    Search in Google Scholar
  • 61 Adler L A, Spencer T J, Williams D W et al. Long-term, open-label safety and efficacy of atomoxetine in adults with ADHD: final report of a 4-year study.  J Atten Disord. 2008;  12 (3) 248-253
    Search in Google Scholar
  • 62 Adler L A, Spencer T, Brown T E et al. Once-daily atomoxetine for adult attention-deficit/hyperactivity disorder: a 6-month, double-blind trial.  J Clin Psychopharmacol. 2009;  29 (1) 44-50
    Search in Google Scholar
  • 63 Jasinski D R, Faries D E, Moore R J et al. Abuse liability assessment of atomoxetine in a drug-abusing population.  Drug Alcohol Depend. 2008;  95 (1 – 2) 140-146
    Search in Google Scholar
  • 64 Heil S H, Holmes H W, Bickel W K et al. Comparison of the subjective, physiological, and psychomotor effects of atomoxetine and methylphenidate in light drug users.  Drug Alcohol Depend. 2002;  67 (2) 149-156
    Search in Google Scholar
  • 65 Bangs M E, Tauscher-Wisniewski S, Polzer J et al. Meta-analysis of suicide-related behavior events in patients treated with atomoxetine.  J Am Acad Child Adolesc Psychiatry. 2008;  47 (2) 209-218
    Search in Google Scholar
  • 66 U. S. Food and Drug Administration (FDA) .Sicherheitshinweis am 29.05.2005: Public Health Advisory Suicidal Thinking in Children and Adolescents Being Treated With Strattera (Atomoxetine). Rockville, Maryland; 2005
    Search in Google Scholar
  • 67 Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM) .Pressemitteilung vom 29.9.2005: 18 / 05 Strattera: Warnhinweis auf suizidales Verhalten bei Kindern mit ADHS angeordnet. Bonn; 29.9.2005
    Search in Google Scholar
  • 68 Wang Y, Zheng Y, Du Y et al. Atomoxetine versus methylphenidate in paediatric outpatients with attention deficit hyperactivity disorder: a randomized, double-blind comparison trial.  Aust N Z J Psychiatry. 2007;  41 (3) 222-230
    Search in Google Scholar
  • 69 Newcorn J H, Kratochvil C J, Allen A J et al. Atomoxetine and osmotically released methylphenidate for the treatment of attention deficit hyperactivity disorder: acute comparison and differential response.  Am J Psychiatry. 2008;  165 (6) 721-730
    Search in Google Scholar
  • 70 Carlson G A, Dunn D, Kelsey D et al. A pilot study for augmenting atomoxetine with methylphenidate: safety of concomitant therapy in children with attention-deficit/hyperactivity disorder.  Child Adolesc Psychiatry Ment Health. 2007;  1 (1) 10
    Search in Google Scholar
  • 71 Adler L A, Reingold L S, Morrill M S et al. Combination pharmacotherapy for adult ADHD.  Curr Psychiatry Rep. 2006;  8 (5) 409-415
    Search in Google Scholar
  • 72 Buitelaar J K, Gaag R J, Swaab-Barneveld van der H et al. Pindolol and methylphenidate in children with attention-deficit hyperactivity disorder. Clinical efficacy and side-effects.  J Child Psychol Psychiatry. 1996;  37 (5) 587-595
    Search in Google Scholar
  • 73 Arnold L E, Lindsay R L, Lopez F A et al. Treating attention-deficit/hyperactivity disorder with a stimulant transdermal patch: the clinical art.  Pediatrics. 2007;  120 (5) 1100-1106
    Search in Google Scholar
  • 74 Findling R L, Bukstein O G, Melmed R D et al. A randomized, double-blind, placebo-controlled, parallel-group study of methylphenidate transdermal system in pediatric patients with attention-deficit/hyperactivity disorder.  J Clin Psychiatry. 2008;  69 (1) 149-159
    Search in Google Scholar
  • 75 Shire .Press Release. Shire withdraws European Application for DAYTRANA™ (methylphenidate transdermal system). Jersey; 16.3.2009
    Search in Google Scholar
  • 76 Mattingly G. Lisdexamfetamine dimesylate: a prodrug stimulant for the treatment of ADHD in children and adults.  CNS Spectr. 2010;  15 (5) 315-325
    Search in Google Scholar
  • 77 Pennick M. Absorption of lisdexamfetamine dimesylate and its enzymatic conversion to d-amphetamine.  Neuropsychiatr Dis Treat. 24;  6 317-327
    Search in Google Scholar
  • 78 Blick S K, Keating G M. Lisdexamfetamine.  Paediatr Drugs. 2007;  9 (2) 129-135 ; discussion 136 – 138
    Search in Google Scholar
  • 79 Biederman J, Krishnan S, Zhang Y et al. Efficacy and tolerability of lisdexamfetamine dimesylate (NRP-104) in children with attention-deficit/hyperactivity disorder: a phase III, multicenter, randomized, double-blind, forced-dose, parallel-group study.  Clin Ther. 2007;  29 (3) 450-463
    Search in Google Scholar
  • 80 Biederman J, Boellner S W, Childress A et al. Lisdexamfetamine dimesylate and mixed amphetamine salts extended-release in children with ADHD: a double-blind, placebo-controlled, crossover analog classroom study.  Biol Psychiatry. 2007;  62 (9) 970-976
    Search in Google Scholar
  • 81 Shire .Mündliche Mitteilung der Firma am 10.9.2009. 
  • 82 Goodman D W, Surman C BH. New Research on Adult and Pediatric ADHD – Extended Duration Long-acting Amphetamine: SPD465. Medscape Today; 28.June.2007
    Search in Google Scholar
  • 83 Spencer T J, Adler L A, Weisler R H et al. Triple-bead mixed amphetamine salts (SPD465), a novel, enhanced extended-release amphetamine formulation for the treatment of adults with ADHD: a randomized, double-blind, multicenter, placebo-controlled study.  J Clin Psychiatry. 2008;  69 (9) 1437-1448
    Search in Google Scholar
  • 84 Spencer T J, Landgraf J M, Adler L A et al. Attention-deficit/hyperactivity disorder-specific quality of life with triple-bead mixed amphetamine salts (SPD465) in adults: results of a randomized, double-blind, placebo-controlled study.  J Clin Psychiatry. 2008;  69 (11) 1766-1775
    Search in Google Scholar
  • 85 Jarvis B, Figgitt D P. Memantine.  Drugs Aging. 2003;  20 (6) 465-476 ; discussion 477 – 478
    Search in Google Scholar
  • 86 Findling R L, McNamara N K, Stansbrey R J et al. A pilot evaluation of the safety, tolerability, pharmacokinetics, and effectiveness of memantine in pediatric patients with attention-deficit/hyperactivity disorder combined type.  J Child Adolesc Psychopharmacol. 2007;  17 (1) 19-33
    Search in Google Scholar
  • 87 Minzenberg M J, Carter C S. Modafinil: a review of neurochemical actions and effects on cognition.  Neuropsychopharmacology. 2008;  33 (7) 1477-1502
    Search in Google Scholar
  • 88 Biederman J, Pliszka S R. Modafinil improves symptoms of attention-deficit/hyperactivity disorder across subtypes in children and adolescents.  J Pediatr. 2008;  152 (3) 394-399
    Search in Google Scholar
  • 89 Rugino T A, Samsock T C. Modafinil in children with attention-deficit hyperactivity disorder.  Pediatr Neurol. 2003;  29 (2) 136-142
    Search in Google Scholar
  • 90 Taylor F B, Russo J. Efficacy of modafinil compared to dextroamphetamine for the treatment of attention deficit hyperactivity disorder in adults.  J Child Adolesc Psychopharmacol. 2000;  10 (4) 311-320
    Search in Google Scholar
  • 91 Rugino T. A review of modafinil film-coated tablets for attention-deficit/hyperactivity disorder in children and adolescents.  Neuropsychiatr Dis Treat. 2007;  3 (3) 293-301
    Search in Google Scholar
  • 92 Arnsten A F, Contant T A. Alpha-2 adrenergic agonists decrease distractibility in aged monkeys performing the delayed response task.  Psychopharmacology. 1992;  108 (1 – 2) 159-169
    Search in Google Scholar
  • 93 Steere J C, Arnsten A F. The alpha-2A noradrenergic receptor agonist guanfacine improves visual object discrimination reversal performance in aged rhesus monkeys.  Behav Neurosci. 1997;  111 (5) 883-891
    Search in Google Scholar
  • 94 Sagvolden T. The alpha-2A adrenoceptor agonist guanfacine improves sustained attention and reduces overactivity and impulsiveness in an animal model of Attention-Deficit/Hyperactivity Disorder (ADHD).  Behav Brain Funct. 2006;  2 41
    Search in Google Scholar
  • 95 Arnsten A F, Steere J C, Hunt R D. The contribution of alpha 2-noradrenergic mechanisms of prefrontal cortical cognitive function. Potential significance for attention-deficit hyperactivity disorder.  Arch Gen Psychiatry. 1996;  53 (5) 448-455
    Search in Google Scholar
  • 96 Boellner S W, Pennick M, Fiske K et al. Pharmacokinetics of a guanfacine extended-release formulation in children and adolescents with attention-deficit-hyperactivity disorder.  Pharmacotherapy. 2007;  27 (9) 1253-1262
    Search in Google Scholar
  • 97 Biederman J, Melmed R D, Patel A et al. A randomized, double-blind, placebo-controlled study of guanfacine extended release in children and adolescents with attention-deficit/hyperactivity disorder.  Pediatrics. 2008;  121 (1) e73-84
    Search in Google Scholar
  • 98 Connor D F, Rubin J. Guanfacine extended release in the treatment of attention deficit hyperactivity disorder in children and adolescents.  Drugs Today. 2010;  46 (5) 299-314
    Search in Google Scholar
  • 99 Decker M W, Bannon A W, Curzon P et al. ABT-089 (2-methyl-3-[2-(S)-pyrrolidinylmethoxy]pyridine dihydrochloride): II. A novel cholinergic channel modulator with effects on cognitive performance in rats and monkeys.  J Pharmacol Exp Ther. 1997;  283 (1) 247-258
    Search in Google Scholar
  • 100 Wilens T E, Verlinden M H, Adler L A et al. 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. 2006;  59 (11) 1065-1070
    Search in Google Scholar
  • 101 Prendergast M A, Jackson W J, Terry Jr A V et al. Central nicotinic receptor agonists ABT-418, ABT-089, and (-)-nicotine reduce distractibility in adult monkeys.  Psychopharmacology. 1998;  136 (1) 50-58
    Search in Google Scholar
  • 102 Wilens T E, Biederman J, Spencer T J et al. A pilot controlled clinical trial of ABT-418, a cholinergic agonist, in the treatment of adults with attention deficit hyperactivity disorder.  Am J Psychiatry. 1999;  156 (12) 1931-1937
    Search in Google Scholar
  • 103 Wilens T E, Decker M W. Neuronal nicotinic receptor agonists for the treatment of attention-deficit/hyperactivity disorder: focus on cognition.  Biochem Pharmacol. 2007;  74 (8) 1212-1223
    Search in Google Scholar
  • 104 Rueter L E, Anderson D J, Briggs C A et al. ABT-089: pharmacological properties of a neuronal nicotinic acetylcholine receptor agonist for the potential treatment of cognitive disorders.  CNS Drug Rev. 2004;  10 (2) 167-182
    Search in Google Scholar
  • 105 Lynch G. Glutamate-based therapeutic approaches: ampakines.  Curr Opin Pharmacol. 2006;  6 (1) 82-88
    Search in Google Scholar
  • 106 Cortex Pharmaceuticals .Clinical Developments and Products/Programs. Meltzer H Y Psychopharmacology: The Third Generation of Progress.. Irvine, CA; 9.15.2009
    Search in Google Scholar
  • 107 Chen J R, Hsu S F, Hsu C D et al. Dietary patterns and blood fatty acid composition in children with attention-deficit hyperactivity disorder in Taiwan.  J Nutr Biochem. 2004;  15 (8) 467-472
    Search in Google Scholar
  • 108 Mitchell E A, Aman M G, Turbott S H et al. Clinical characteristics and serum essential fatty acid levels in hyperactive children.  Clin Pediatr. 1987;  26 (8) 406-411
    Search in Google Scholar
  • 109 Stevens L J, Zentall S S, Abate M L et al. Omega-3 fatty acids in boys with behavior, learning, and health problems.  Physiol Behav. 1996;  59 (4 – 5) 915-920
    Search in Google Scholar
  • 110 Stevens L J, Zentall S S, Deck J L et al. Essential fatty acid metabolism in boys with attention-deficit hyperactivity disorder.  Am J Clin Nutr. 1995;  62 (4) 761-768
    Search in Google Scholar
  • 111 Colter A L, Cutler C, Meckling K A. Fatty acid status and behavioural symptoms of attention deficit hyperactivity disorder in adolescents: a case-control study.  Nutr J. 2008;  7 8
    Search in Google Scholar
  • 112 Belanger S A, Vanasse M, Spahis S et al. Omega-3 fatty acid treatment of children with attention-deficit hyperactivity disorder: A randomized, double-blind, placebo-controlled study.  Paediatr Child Health. 2009;  14 (2) 89-98
    Search in Google Scholar
  • 113 Johnson M, Ostlund S, Fransson G et al. Omega-3 /omega-6 fatty acids for attention deficit hyperactivity disorder: a randomized placebo-controlled trial in children and adolescents.  J Atten Disord. 2009;  12 (5) 394-401
    Search in Google Scholar
  • 114 Bradley C. The behavior of children receiving benzedrine.  Am J Psychiatry. 1937;  94 577-585
    Search in Google Scholar
  • 115 Huss M, Lehmkuhl U. Methylphenidate and substance abuse: a review of pharmacology, animal, and clinical studies.  J Atten Disord. 2002;  6 (Suppl 1) S65-S71
    Search in Google Scholar
  • 116 Francis P T. Glutamatergic approaches to the treatment of cognitive and behavioural symptoms of Alzheimer’s disease.  Neurodegener Dis. 2008;  5 (3 – 4) 241-243
    Search in Google Scholar
  • 117 Scheffler R M, Hinshaw S P, Modrek S et al. The global market for ADHD medications.  Health Aff. 2007;  26 (2) 450-457
    Search in Google Scholar
  • 118 Fritze J, Schmauss M. Off-label use: the case of methylphenidate (Ritalin).  Nervenarzt. 2002;  73 (12) 1210-1212
    Search in Google Scholar
  • 119 Deutsche Gesellschaft für Kinder- und Jugendpsychiatrie und Psychotherapie .Leitlinien zur Diagnostik und Therapie von psychischen Störungen im Säuglings-, Kindes- und Jugendalter. 3. Aufl. Köln: Deutscher Ärzte Verlag; 2007
    Search in Google Scholar
  • 120 Greenhill L L, Pliszka S, Dulcan M K et al. Summary of the practice parameter for the use of stimulant medications in the treatment of children, adolescents, and adults.  J Am Acad Child Adolesc Psychiatry. 2001;  40 (11) 1352-1355
    Search in Google Scholar

Dr. Dr. Andreas Günter Franke, M.A.

Klinik für Psychiatrie und Psychotherapie, Universitätsmedizin Mainz

Untere Zahlbacher Str. 8

55131 Mainz

Email: afranke@uni-mainz.de