Methylphenidate and its isomers: Their role in the treatment of attention-deficit hyperactivity disorder using a transdermal delivery system

CNS Drugs

Volumn 20, Issue 9, 2006, Pages 713-738

  Heal, David J ^a   Pierce, David M ^b  

^a RenaSci Ltd   (United Kingdom)

^b Shire Pharmaceuticals   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

DEXMETHYLPHENIDATE; DOPAMINE UPTAKE INHIBITOR; METHYLPHENIDATE; RITALINIC ACID;

ANOREXIA; AREA UNDER THE CURVE; ATTENTION DEFICIT DISORDER; CARDIOVASCULAR FUNCTION; CLINICAL TRIAL; DECREASED APPETITE; DOSE RESPONSE; DRUG BILE LEVEL; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG DELIVERY SYSTEM; DRUG DISTRIBUTION; DRUG EFFECT; DRUG EFFICACY; DRUG ELIMINATION; DRUG FECES LEVEL; DRUG FORMULATION; DRUG HALF LIFE; DRUG INHIBITION; DRUG MECHANISM; DRUG METABOLISM; DRUG PROTEIN BINDING; DRUG RELEASE; DRUG SAFETY; DRUG STRUCTURE; DRUG TOLERABILITY; DRUG URINE LEVEL; ENANTIOSELECTIVITY; HEADACHE; HUMAN; HYPERTENSION; INSOMNIA; ISOMER; MENTAL INSTABILITY; META ANALYSIS; MOTOR DYSFUNCTION; NAUSEA; NAUSEA AND VOMITING; NONHUMAN; PRIORITY JOURNAL; RACEMIC MIXTURE; REVIEW; SOMNOLENCE; STOMACH PAIN; SUSTAINED DRUG RELEASE; SYSTEMATIC REVIEW; TACHYCARDIA; TIC; TRANSDERMAL PATCH; VOMITING;

ADMINISTRATION, CUTANEOUS; ANIMALS; ATTENTION DEFICIT DISORDER WITH HYPERACTIVITY; CENTRAL NERVOUS SYSTEM STIMULANTS; DRUG DELIVERY SYSTEMS; HUMANS; ISOMERISM; METHYLPHENIDATE;

EID: 33748532136     PISSN: 11727047     EISSN: 11727047     Source Type: Journal    
DOI: 10.2165/00023210-200620090-00002     Document Type: Review

References (141)

1. Taylor E, Sandberg S, Thorley G, et al. The epidemiology of childhood hyperactivity. Maudsley monographs no. 33. Oxford: Oxford University Press, 1991: 93-113
2. Baumgaertel A, Wolraich ML, Dietrich M. Comparison of diagnostic criteria for attention deficit disorders in a German elementary school sample. J Am Acad Child Adolesc Psychiatry 1995 May; 34 (5): 629-38
3. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC: American Psychiatric Association, 1994
4. Wolraich ML, Hannah JN, Pinnock TY, et al. Comparison of diagnostic criteria for attention-deficit hyperactivity disorder in a county-wide sample. J Am Acad Child Adolesc Psychiatry 1996 Mar; 35 (3): 319-24
5. Elia J. Drug treatment for hyperactive children: therapeutic guidelines. Drugs 1993 Nov; 46 (5): 863-71
6. Weiss G, Hechtman L, Milroy T, et al. Psychiatric status of hyperactives as adults: a controlled prospective 15-year follow-up of 63 hyperactive children. J Am Acad Child Psychiatry 1985 Mar; 24 (2): 211-20
7. Mannuzza S, Klein RG, Bessler A, et al. Adult psychiatric status Sepof hyperactive boys grown up. Am J Psychiatry 1998 Apr; 155 (4): 493-8
8. Barkley RA, Fischer M, Edelbrock CS, et al. The adolescent outcome of hyperactive children diagnosed by research criteria: I. An 8-year prospective follow-up study. J Am Acad Child Adolesc Psychiatry 1990 Jul; 29 (4): 546-57
9. Cohen P, Cohen J, Kasen S, et al. An epidemiological study of disorders in late childhood and adolescence: I. Age- and gender-specific prevalence. J Child Psychol Psychiatry 1993 Sep; 34 (6): 851-67
10. Biederman J, Faraone SV, Monuteaux MC, et al. Gender effects on attention-deficit/hyperactivity disorder in adults, revisited. Biol Psychiatry 2004 Apr 1; 55 (7): 692-700
11. Pelham Jr WE, Walker JL, Sturges J, et al. Comparative effects of methylphenidate on ADD girls and ADD boys. J Am Acad Child Adolesc Psychiatry 1989 Sep; 28 (5): 773-6
12. Shaffer D. Attention deficit hyperactivity disorder in adults. Am J Psychiatry 1994 May; 151 (5): 633-8
13. Hart EL, Lahey BB, Loeber R, et al. Developmental change in attention-deficit hyperactivity disorder in boys: a four-year longitudinal study. J Abnorm Child Psychol 1995 Dec; 23 (6): 729-49
14. Gittelman R, Mannuzza S, Shenker R, et al. Hyperactive boys almost grown up: I. Psychiatric status. Arch Gen Psychiatry 1985 Oct; 42 (10): 937-47
15. Huss M, Lehmkuhl U. Methylphenidate and substance abuse: a review of pharmacology, animal, and clinical studies. J Atten Disord 2002; 6 Suppl. 1: S65-71
16. Biederman J. Pharmacotherapy for attention-deficit/hyperactivity disorder (ADHD) decreases the risk for substance abuse: findings from a longitudinal follow-up of youths with and without ADHD. J Clin Psychiatry 2003; 64 Suppl. 11: 3-8
17. Mannuzza S, Klein RG, Bonagura N, et al. Hyperactive boys almost grown up: II. Status of subjects without a mental disorder. Arch Gen Psychiatry 1988 Jan; 45 (1): 13-8
18. Bymaster FP, Katner JS, Nelson DL, 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 Nov; 27 (5): 699-711
19. Panizzon L. The preparation of pyridines- and piperidine- arylacetonitriles and the alkylation products of transformations (Pt I). Helv Chim Acta 1944; 27: 1748-56
20. Meier R, Gross F, Tripod J. Ritalin, a new synthetic compound with specific central nervous system activity. Klin Wochenschr 1954 May 15; 32 (19-20): 445-50
21. Wax PM. Analeptic use in clinical toxicology: a historical appraisal. J Toxicol Clin Toxicol 1997; 35 (2): 203-9
22. Deutsch HM, Shi Q, Gruszecka-Kowalik E, et al. Synthesis and pharmacology of potential cocaine antagonists: II. Structure-activity relationship studies of aromatic ring-substituted methylphenidate analogs. J Med Chem 1996 Mar 15; 39 (6): 1201-9
23. Challman TD, Lipsky JJ. Methylphenidate: its pharmacology and uses. Mayo Clin Proc 2000 Jul; 75 (7): 711-21
24. Szporny L, Görög P. Investigations into the correlations between monoamine oxidase inhibition and other effects due to methylphenidate and its stereoisomers. Biochem Pharmacol 1961; 8: 263-8
25. Faraj BA, Israili ZH, Perel JM, et al. Metabolism and disposition of methylphenidate-14C: studies in man and animals. J Pharmacol Exp Ther 1974 Dec; 191 (3): 535-47
26. Aoyama T, Kotaki H, Iga T. Dose-dependent kinetics of methylphenidate enantiomers after oral administration of racemic methylphenidate to rats. J Pharmacobiodyn 1990 Oct; 13 (10): 647-52
27. Egger H, Bartlett F, Dreyfuss R, et al. Metabolism of methylphenidate in dog and rat. Drug Metab Dispos 1981 Sep-Oct; 9 (5): 415-23
28. National Toxicology Program. NTP toxicology and carcinogenesis studies of methylphenidate hydrochloride (CAS no. 298-59-9) in F344/N rats and B6C3F1 mice (feed studies). Natl Toxicol Program Tech Rep Ser 1995 Jul; 439: 1-299
29. Wargin W, Patrick K, Kilts C, et al. Pharmacokinetics of methylphenidate in man, rat and monkey. J Pharmacol Exp Ther 1983 Aug; 226 (2): 382-6
30. Srinivas NR, Quinn D, Hubbard JW, et al. Stereoselective disposition of methylphenidate in children with attention-deficit disorder. J Pharmacol Exp Ther 1987 Apr; 241 (1): 300-6
31. Hubbard JW, Srinivas NR, Quinn D, et al. Enantioselective aspects of the disposition of dl-threo-methylphenidate after the administration of a sustained-release formulation to children with attention deficit-hyperactivity disorder. J Pharm Sci 1989 Nov; 78 (11): 944-7
32. Aoyama T, Kotaki H, Honda Y, et al. Kinetic analysis of enantiomers of threo-methylphenidate and its metabolite in two healthy subjects after oral administration as determined by a gas chromatographic-mass spectrometric method. J Pharm Sci 1990 Jun; 79 (6): 465-9
33. Aoyama T, Kotaki H, Sasaki T, et al. Non-linear kinetics of threo-methylphenidate enantiomers in a patient with narcolepsy and in healthy volunteers. Eur J Clin Pharmacol 1993; 44 (1): 79-84
34. Chan YP, Swanson JM, Soldin SS, et al. Methylphenidate hydrochloride given with or before breakfast: II. Effects on plasma concentration of methylphenidate and ritalinic acid. Pediatrics 1983 Jul; 72 (1): 56-9
35. Srinivas NR, Hubbard JW, Korchinski ED, et al. Enantioselective pharmacokinetics of dl-threo-methylphenidate in humans. Pharm Res 1993 Jan; 10 (1): 14-21
36. Hungund BL, Perel JM, Hurwic MJ, et al. Pharmacokinetics of methylphenidate in hyperkinetic children. Br J Clin Pharmacol 1979 Dec; 8 (6): 571-6
37. Srinivas NR, Hubbard JW, Midha KK. Enantioselective gas chromatographic assay with electron-capture detection for dl-ritalinic acid in plasma. J Chromatogr 1990 Sep 14; 530 (2): 327-36
38. Teo SK, Scheffler MR, Wu A, et al. A single-dose, two-way crossover, bioequivalence study of dexmethylphenidate HCl with and without food in healthy subjects. J Clin Pharmacol 2004 Feb; 44 (2): 173-8
39. Sun Z, Murry DJ, Sanghani SP, et al. Methylphenidate is stereoselectively hydrolyzed by human carboxylesterase CES1A1. J Pharmacol Exp Ther 2004 Aug; 310 (2): 469-76
40. Srinivas NR, Hubbard JW, Korchinski ED, et al. Stereoselective urinary pharmacokinetics of dl-threo-methylphenidate and its major metabolite in humans. J Pharm Sci 1992 Aug; 81 (8): 747-9
41. Srinivas NR, Lim HK, Hubbard JW, et al. Evidence that dogs do not model enantioselective pharmacokinetics of dl-methylphenidate in humans. J Pharm Sci 1991 Jul; 80 (7): 707-8
42. Bakhtiar R, Tse FL. Toxicokinetic assessment of methylphenidate (Ritalin [R]) in a 13-week oral (gavage) toxicity study in rats using an enantiomeric liquid chromatography/tandem mass spectrometry assay. Rapid Commun Mass Spectrom 2003; 17 (18): 2160-2
43. Teo SK, Stirling DI, Hoberman AM, et al. d-Methylphenidate and d,l-methylphenidate are not developmental toxicants in rats and rabbits. Birth Defects Res B Dev Reprod Toxicol 2003 Apr; 68 (2): 162-71
44. Bakhtiar R, Tse FL. Toxicokinetic assessment of methylphenidate (Ritalin) enantiomers in pregnant rats and rabbits. Biomed Chromatogr 2004 Jun; 18 (5): 275-81
45. Teo SK, Stirling DI, Thomas SD, et al. A 90-day oral gavage toxicity study of d-methylphenidate and d,l-methylphenidate in beagle dogs. Int J Toxicol 2003 May-Jun; 22 (3): 215-26
46. Bakhtiar R, Ramos L, Tse FL. Toxicokinetic assessment of methylphenidate (Ritalin) in a 13-week oral toxicity study in dogs. Biomed Chromatogr 2004 Jan; 18 (1): 45-50
47. Data on file, Noven Pharmaceuticals Inc.
48. Modi NB, Wang B, Noveck RJ, et al. Dose-proportional and stereospecific pharmacokinetics of methylphenidate delivered using an osmotic, controlled-release oral delivery system. J Clin Pharmacol 2000 Oct; 40 (10): 1141-9
49. Srinivas NR, Hubbard JW, Quinn D, et al. Enantioselective pharmacokinetics and pharmacodynamics of dl-threo-methylphenidate in children with attention deficit hyperactivity disorder. Clin Pharmacol Ther 1992 Nov; 52 (5): 561-8
50. FDA Psychopharmacologic Drugs Advisory Committee briefing document, December 2, 2005. Methylphenidate transdermal system NDA21-514 [online]. Available from URL: http://www.fda.gov/ohrms/dockets/ac/05/briefing/2005-4195 B1_01_01-Noven-Briefing-Document.pdf [Accessed 2006 Aug 28]
51. Pierce DM, Dixon CM, Wigal SB, et al. Pharmacokinetics of methylphenidate transdermal system in children with ADHD [abstract no. 4581]. Proceedings of the American Academy of Child and Adolescent Psychiatry/Canadian Academy of Child and Adolescent Psychiatry Joint Meeting; 2005 Oct 18-23; Toronto (ON)
52. Methylphenidate transdermal system [online]. Available from URL: http://www.daytrana.com [Accessed 2006 Aug 1]
53. Zhu QG, Hu JH, Zeng HW. Stereoselectivity of skin carboxylesterase metabolism. Yao Xue Xue Bao 2005; 40 (4): 322-6
54. Richelson E, Pfenning M. Blockade by antidepressants and related compounds of biogenic amine uptake into rat brain synaptosomes: most antidepressants selectively block norepinephrine uptake. Eur J Pharmacol 1984 Sep 17; 104 (3-4): 277-86
55. Andersen PH. The dopamine uptake inhibitor GBR 12909: selectivity and molecular mechanism of action. Eur J Pharmacol 1989 Aug 3; 166 (3): 493-504
56. Schweri MM, Deutsch HM, Massey AT, et al. Biochemical and behavioural characterization of novel methylphenidate analogs. J Pharmacol Exp Ther 2002 May; 301 (2): 527-35
57. Ferris RM, Tang FLM, Maxwell RA. A comparison of the capacities of isomers of amphetamine, deoxypipradrol and methylphenidate to inhibit the uptake of tritiated catecholamines 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 1972 Jun; 181 (3): 407-16
58. Patrick KS, Caldwell RW, Ferris RM, et al. Pharmacology of the enantiomers of threo-methylphenidate. J Pharmacol Exp Ther 1987 Apr; 241 (1): 152-8
59. Vickroy TW, Johnson KM. Similar dopamine-releasing effects of phencyclidine and nonamphetamine stimulants in striatal slices. J Pharmacol Exp Ther 1982 Dec; 223 (3): 669-74
60. 3H]dopamine dfrom superfused rat striatal slices: predictive value for detecting stimulant drugs of abuse. Br J Pharmacol 1996; 117: 325P
61. 3H]dopamine from brain slices suggest impaired vesicular storage of dopamine in an animal model of attention-deficit hyperactivity disorder. Behav Brain Res 1998 Jul; 94 (1): 163-71
62. Wall SC, Gu H, Rudnick G. Biogenic amine flux mediated by cloned transporters stably expressed in cultured cell lines: amphetamine specificity for inhibition and efflux. Mol Pharmacol 1995 Mar; 47 (3): 544-50
63. Hurd YL, Ungerstedt U. In vivo neurochemical profile of dopamine uptake inhibitors and releasers in rat caudate-putamen. Eur J Pharmacol 1989 Jul 18; 166 (2): 251-60
64. Butcher SP, Liptrot J, Aburthnott GW. Characterisation of methylphenidate and nomifensine induced dopamine release in rat striatum using in vivo brain microdialysis. Neurosci Lett 1991 Jan 28; 122 (2): 245-8
65. Aoyama T, Yamamoto K, Kotaki H, et al. Pharmacodynamic modeling for change of locomotor activity by methylphenidate in rats. Pharm Res 1997 Nov; 14 (11): 1601-6
66. 11C]d-threo and l-threo-methylphenidate in the human and baboon brain. Psychopharmacology (Berl) 1997 May; 131 (1): 71-8
67. Kuczenski R, Segal DS. Effects of methylphenidate on extracellular dopamine, serotonin, and norepinephrine: comparison with amphetamine. J Neurochem 1997 May; 68 (5): 2032-7
68. Kuczenski R, Segal DS. Dynamic changes in sensitivity occur during the acute response to cocaine and methylphenidate. Psychopharmacology (Berl) 1999 Nov; 147 (1): 96-103
69. Segal DS, Kuczenski R. Escalating dose-binge treatment with methylphenidate: role of serotonin in the emergent behavioural profile. J Pharmacol Exp Ther 1999 Oct; 291 (1): 19-30
70. Kulkarni RS, Rowley HL, Cheetham SC, et al. Differential effects of d- and l-threo-methylphenidate on extracellular levels of dopamine in the striatum and noradrenaline in the frontal cortex: a dual-probe microdialysis study in freely-moving spontaneously hypertensive rats. In: Di Chiara G, Carboni E, Valentini V, et al., editors. Monitoring molecules in neuroscience: proceedings of the 11th International Conference on In Vivo Methods. Cagliari: University of Cagliari, 2006: 499-501
71. Kuczenski R, Segal DS. Exposure of adolescent rats to oral methylphenidate: preferential effects on extracellular norepinephrine and absence of sensitization and cross-sensitization to methamphetamine. J Neurosci 2002 Aug 15; 22 (16): 7264-71
72. During MJ, Bean AJ, Roth RH. Effects of CNS stimulants on the in vivo release of the colocalized transmitters, dopamine and neurotensin, from rat prefrontal cortex. Neurosci Lett 1992 Jun 8; 140 (1): 129-33
73. Aoyama T, Kotaki H, Sawada Y, et al. Pharmacokinetics and pharmacodynamics of methylphenidate enantiomers in rats. Psychopharmacology (Berl) 1996 Sep; 127 (2): 117-22
74. Shaywitz BA, Yager RD, Klopper JH. Selective brain dopamine depletion in developing rats: an experimental model of minimal brain dysfunction. Science 1976 Jan 23; 191 (4224): 305-8
75. Erinoff L, MacPhail RC, Heller A, et al. Age-dependent effects of 6-hydroxydopamine on locomotor activity in rat. Brain Res 1979 Mar 23; 164: 195-205
76. Concannon JT, Braughler JM, Schechter MD. The development of brain biogenic amines, cyclic nucleotides and hyperactivity in 6-OHDA-treated rat pups. Pharmacol Biochem Behav 1983 Apr; 18 (4): 477-82
77. Luthman J, Fredriksson A, Lewander T, et al. Effects of dfrom amphetamine and methylphenidate on hyperactivity produced by neonatal 6-hydroxydopamine treatment. Psychopharmacology (Berl) 1989; 99 (4): 550-7
78. Davids E, Zhang K, Tarazi FI, et al. Stereoselective effects of methylphenidate on motor hyperactivity in juvenile rats induced by neonatal 6-hydroxydopamine lesioning. Psychopharmacology (Berl) 2002 Feb; 160 (1): 92-8
79. Davids E, Zhang K, Kula NS, et al. Effects of norepinephrine and serotonin transporter inhibitors on hyperactivity induced by neonatal 6-hydroxydopamine lesioning in rats. J Pharmacol Exp Ther 2002 Jun; 301 (3): 1097-102
80. Teo SK, Stirling DI, Thomas SD, et al. Neurobehavioral effects of racemic threo-methylphenidate and its d- and l-enantiomers in rats. Pharmacol Biochem Behav 2003 Feb; 74 (3): 747-54
81. Moser VC, McCormick JP, Creason JP, et al. Comparison of chlordimeform and carbaryl using a functional observational battery. Fundam Appl Toxicol 1988 Aug; 11 (2): 189-206
82. Eckerman DA, Moy SS, Perkins AN, et al. Enantioselective behavioral effects of threo-methylphenidate in rats. Pharmacol Biochem Behav 1991 Dec; 40 (4): 875-80
83. Barkley RA, Grodzinsky G, DuPaul GJ. Frontal lobe functions in attention deficit disorder with and without hyperactivity: a review and research report. J Abnorm Child Psychol 1992 Apr; 20 (2): 163-88
84. Drewe EA. Go - no go learning after frontal lobe lesions in humans. Cortex 1975 Mar; 11 (1): 8-16
85. Pelham WE, Aronoff HR, Midlam JK, et al. A comparison of ritalin and adderall: efficacy and time-course in children with attention-deficit/ hyperactivity disorder. Pediatrics 1999 Apr; 103 (4): E43
86. Pelham WE, Gnagy EM, Chronis AM, et al. A comparison of morning-only and morning/late afternoon Adderall to morning-only, twice-daily, and three times-daily methylphenidate in children with attention-deficit/hyperactivity disorder. Pediatrics 1999 Dec; 104 (6): 1300-11
87. Pelham Jr WE, Greenslade KE, Vodde-Hamilton M, et al. 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 1990 Aug; 86 (2): 226-37
88. Efron D, Jarman F, Barker M. Methylphenidate versus dexamphetamine in children with attention deficit hyperactivity disorder: a double-blind, crossover trial. Pediatrics 1997 Dec; 100 (6): E6
89. Winsberg BG, Press M, Bialer I, et al. Dextroamphetamine and methylphenidate in the treatment of hyperactive-aggressive children. Pediatrics 1974 Feb; 53 (2): 236-41
90. Borcherding BG, Keysor CS, Cooper TB, et al. Differential effects of methylphenidate and dextroamphetamine on the motor activity level of hyperactive children. Neuropsychopharmacology 1989 Dec; 2 (4): 255-63
91. Elia J, Borcherding BG, Rapoport JL, et al. Methylphenidate and dextroamphetamine treatments of hyperactivity: are there true nonresponders? Psychiatry Res 1991 Feb; 36 (2): 141-55
92. Wilens TE, Biederman J. The stimulants. Psychiatr Clin North Am 1992 Mar; 15 (1): 191-222
93. Spencer T, Biederman J, Wilens T, et al. Pharmacotherapy of attention-deficit hyperactivity disorder across the life cycle. J Am Acad Child Adolesc Psychiatry 1996 Apr; 35 (4): 409-32
94. Elia J, Ambrosini PJ, Rapoport JL. Treatment of attention-deficit- hyperactivity disorder. N Engl J Med 1999 Mar 11; 340 (10): 780-8
95. Schachter HM, 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 Nov 27; 165 (11): 1475-88
96. Quinn D, Wigal S, Swanson J, et al. 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 2004 Nov; 43 (11): 1422-9
97. Wigal S, Swanson JM, Feifel D, et al. A double-blind, placebo-controlled trial of dexmethylphenidate hydrochloride and d,l-threo-methylphenidate hydrochloride in children with attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry 2004 Nov; 43 (11): 1406-14
98. Greenhill LL, Swanson JM, Vitiello B, et al. Impairment and deportment responses to different methylphenidate doses in children with ADHD: the MTA titration trial. J Am Acad Child Adolesc Psychiatry 2001 Feb; 40 (2): 180-7
99. Wolraich ML, Greenhill LL, Pelham W, et al. Randomized, controlled trial of OROS methylphenidate once a day in children with attention-deficit/ hyperactivity disorder. Pediatrics 2001 Oct; 108 (4): 883-92
100. Stein MA, Sarampote CS, Waldman ID, et al. A dose-response study of OROS methylphenidate in children with attention-deficit/hyperactivity disorder. Pediatrics 2003 Nov; 112 (5): E404
101. Silva R, Muniz R, Pestreich LK, et al. Efficacy of two long-acting methylphenidate formulations in children with attention-deficit/hyperactivity disorder in a laboratory classroom setting. J Child Adolesc Psychopharmacol 2005 Aug; 15 (4): 637-54
102. Lim HK, Hubbard JW, Midha KK. Development of enantioselective gas chromatographic quantitation assay for dl-threo-methylphenidate in biological fluids. J Chromatogr 1986 May 28; 378 (1): 109-23
103. Volkow ND, Wang GJ, Fowler JS, et al. Dopamine transporter occupancies in the human brain induced by therapeutic doses of oral methylphenidate. Am J Psychiatry 1998 Oct; 155 (10): 1325-31
104. 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 Nov; 108 (5): E83
105. Spencer T, Heiligenstein JH, Biederman J, et al. Results from two proof-of-concept, placebo-controlled studies of atomoxetine in children with attention-deficit/hyperactivity disorder. J Clin Psychiatry 2002 Dec; 63 (12): 1140-7
106. Barrickman LL, Perry PJ, Allen AJ, et al. Bupropion versus methylphenidate in the treatment of attention-deficit hyperactivity disorder. J Am Acad Child Adolesc Psychiatry 1995 May; 34 (5): 649-57
107. Michelson D, Allen AJ, Busner J, et al. Once-daily atomoxetine treatment for children and adolescents with attention deficit hyperactivity disorder: a randomized, placebo-controlled study. Am J Psychiatry 2002 Nov; 159 (11): 1896-901
108. Kelsey DK, Sumner CR, Casat CD, et al. 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 2004 Jul; 114 (1): E1-8
109. Wilens TE, Spencer TJ, Biederman J, et al. A controlled clinical trial of bupropion for attention deficit hyperactivity disorder in adults. Am J Psychiatry 2001 Feb; 158 (2): 282-8
110. Kuperman S, Perry PJ, Gaffney GR, et al. Bupropion SR vs methylphenidate vs placebo for attention deficit hyperactivity disorder in adults. Ann Clin Psychiatry 2001 Sep; 13 (3): 129-34
111. Efron D, Jarman F, Barker M. Side-effects of methylphenidate and dexamphetamine in children with attention deficit hyperactivity disorder: a double-blind, crossover trial. Pediatrics 1997 Oct; 100 (4): 662-6
112. Rapport MD, Moffitt C. Attention deficit/hyperactivity disorder and methylphenidate: a review of height/weight, cardiovascular, and somatic complaint side effects. Clin Psychol Rev 2002 Nov; 22 (8): 1107-31
113. Biederman J, Heiligenstein JH, Faries DE, et al. Efficacy of atomoxetine versus placebo in school-age girls with attention-deficit/hyperactivity disorder. Atomoxetine ADHD study group. Pediatrics 2002 Dec; 110 (6): E75
114. Bouffard R, Hechtman L, Minde K, et al. The efficacy of two different dosages of methylphenidate in treating adults with attention-deficit hyperactivity disorder. Can J Psychiatry 2003 Sep; 48 (8): 546-54
115. Klorman R, Brumaghim JT, Fitzpatrick PA, et al. Clinical effects of a controlled trial of methylphenidate on adolescents with attention deficit disorder. J Am Acad Child Adolesc Psychiatry 1990 Sep; 29 (5): 702-9
116. 1-adrenoceptor function: effects of acute and repeated administration of antidepressant drugs and electroconvulsive shock. Neuropharmacology 1984 Nov; 23 (11): 1241-51
117. 2-adrenoceptor and dopamine D1 receptor actions: relevance to therapeutic effects in attention deficit hyperactivity disorder. Behav Brain Funct 2005 Apr 22; 1 (1): 2
118. Oades RD, Sadile AG, Sagvolden T, et al. The control of responsiveness in ADHD by catecholamines: evidence for dopaminergic, noradrenergic and interactive roles. Dev Sci 2005 Mar; 8 (2): 122-31
119. Barkley RA, McMurray MB, Edelbrock CS, et al. Side-effects of methylphenidate in children with attention deficit hyperactivity disorder: a systemic, placebo-controlled evaluation. Pedate diatrics 1990 Aug; 86 (2): 184-92
120. Ahmann PA, Waltonen SJ, Olson KA, et al. Placebo-controlled evaluation of ritalin side-effects. Pediatrics 1993 Jun; 91 (6): 1101-6
121. Dorrego MF, Canevaro L, Kuzis G, et al. A randomized, double-blind, crossover study of methylphenidate and lithium in adults with attention-deficit/hyperactivity disorder: preliminary findings. J Neuropsychiatry Clin Neurosci 2002; 14 (3): 289-95
122. Silva R, Tilker HA, Cecil JT, et al. Open-label study of dexmethylphenidate hydrochloride in children and adolescents with attention deficit hyperactivity disorder. J Child Adolesc Psychopharmacol 2004; 14 (4): 555-63
123. Arnold LE, Lindsay RL, Conners CK, et al. A double-blind, placebo-controlled withdrawal trial of dexmethylphenidate hydrochloride in children with attention deficit hyperactivity disorder. J Child Adolesc Psychopharmacol 2004; 14 (4): 542-54
124. Keating GM, Figgitt DP. Dexmethylphenidate. Drugs 2002; 62 (13): 1899-904
125. Rush CR, Baker RW. Behavioral pharmacological similarities between methylphenidate and cocaine in cocaine abusers. Exp Clin Psychopharmacol 2001; 9: 59-73
126. Golden GS. Gilles de la Tourette's syndrome following methylphenidate administration. Dev Med Child Neurol 1974 Feb; 16 (1): 76-8
127. Golden GS. The effect of central nervous system stimulants on Tourette syndrome. Ann Neurol 1977 Jul; 2 (1): 69-70
128. Lowe TL, Cohen DJ, Detlor J, et al. Stimulant medications precipitate Tourette's syndrome. JAMA 1982 Mar 26; 247 (12): 1729-31
129. Costall B, Naylor RJ. The involvement of dopaminergic systems with the stereotyped behaviour patterns induced by methylphenidate. J Pharm Pharmacol 1974 Jan; 26 (1): 30-3
130. Kelly PH, Seviour PW, Iversen SD. Amphetamine and apomorphine responses in the rat following 6-OHDA lesions of the nucleus accumbens septi and corpus striatum. Brain Res 1975 Sep 5; 94 (3): 507-22
131. Morpurgo C. Aggressive behavior induced by large doses of 2-(2,6-dichlorphenylamino)-2-imidazoline hydrochloride (ST 155) in mice. Eur J Pharmacol 1968 Jul; 3 (4): 374-7
132. Razzak A, Fujiwara M, Ueki S. Automutilation induced by clonidine in mice. Eur J Pharmacol 1975 Feb; 30 (2): 356-9
133. Donnelly M, Rapoport JL, Potter WZ, et al. Fenfluramine and dextroamphetamine treatment of childhood hyperactivity: clinical and biochemical findings. Arch Gen Psychiatry 1989 Mar; 46 (3): 205-12
134. Law SF, Schachar RJ. Do typical clinical doses of methylphenidate cause tics in children treated for attention-deficit hyperactivity disorder? J Am Acad Child Adolesc Psychiatry 1999 Aug; 38 (8): 944-51
135. Borcherding BG, Keysor CS, Rapoport JL, et al. Motor/vocal tics and compulsive behaviors on stimulant drugs: is there a common vulnerability? Psychiatry Res 1990 Jul; 33 (1): 83-94
136. Gadow KD, Sverd J, Sprafkin J, et al. Efficacy of methylphenidate for attention-deficit hyperactivity disorder in children with tic disorder. Arch Gen Psychiatry 1995 Jun; 52 (6): 444-55
137. Gadow KD, Nolan E, Sprafkin J, et al. School observations of children with attention-deficit hyperactivity disorder and comorbid tic disorder: effects of methylphenidate treatment. J Dev Behav Pediatr 1995 Jun; 16 (3): 167-76
138. Lipkin PH, Goldstein IJ, Adesman AR. Tics and dyskinesias associated with stimulant treatment in attention-deficit hyperactivity disorder. Arch Pediatr Adolesc Med 1994 Aug; 148 (8): 859-61
139. Erenberg G, Cruse RP, Rothner AD. Gilles de la Tourette's syndrome: effects of stimulant drugs. Neurology 1985 Sep; 35 (9): 1346-8
140. Spencer TJ, Biederman J, Wilens TE, et al. Novel treatments for attention-deficit/hyperactivity disorder in children. J Clin Psychiatry 2002; 63 Suppl. 12: 16-22
141. Pliszka SR. Non-stimulant treatment of attention-deficit/hyperactivity disorder. CNS Spectr 2003 Apr; 8 (4): 253-8