A review of the rationale and clinical utilization of α2- Adrenoceptor agonists for the treatment of attention-deficit/hyperactivity and related disorders

Journal of Child and Adolescent Psychopharmacology

Volumn 23, Issue 5, 2013, Pages 308-319

  Sallee, Floyd ^a   Connor, Daniel F ^b   Newcorn, Jeffrey H ^c  

^a UNIVERSITY OF CINCINNATI COLLEGE OF MEDICINE   (United States)

^b UNIVERSITY OF CONNECTICUT SCHOOL OF MEDICINE   (United States)

^c MOUNT SINAI SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMPHETAMINE; CLONIDINE; CYTOCHROME P450 3A4; GUANFACINE; METHYLPHENIDATE; PLACEBO;

ANXIETY DISORDER; AREA UNDER THE CURVE; ATTENTION DEFICIT DISORDER; BLOOD PRESSURE; BRAIN REGION; CARDIOVASCULAR EFFECT; CLINICAL PRACTICE; CONDUCT DISORDER; CROSS REACTION; DISEASE PREDISPOSITION; DRUG BIOAVAILABILITY; DRUG CLEARANCE; DRUG DOSE TITRATION; DRUG EFFICACY; DRUG ELIMINATION; DRUG METABOLISM; DRUG RELEASE; DRUG SAFETY; DRUG TOLERABILITY; EVENING DOSAGE; FATIGUE; FOOD AND DRUG ADMINISTRATION; GILLES DE LA TOURETTE SYNDROME; HALF LIFE TIME; HEADACHE; HUMAN; HYPERSOMNIA; HYPERTENSION; INSOMNIA; LIQUID CHROMATOGRAPHY; MASS SPECTROMETRY; MAXIMUM PLASMA CONCENTRATION; MEDICAL HISTORY; MEDLINE; META ANALYSIS; MONOTHERAPY; MORNING DOSAGE; MULTICENTER STUDY (TOPIC); OUTCOME ASSESSMENT; POSITRON EMISSION TOMOGRAPHY; PRACTICE GUIDELINE; PULSE RATE; QUESTIONNAIRE; RADIOIMMUNOASSAY; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; SEDATION; SIDE EFFECT; SOMNOLENCE; TASK PERFORMANCE; TIC;

ADRENERGIC ALPHA-2 RECEPTOR AGONISTS; ANIMALS; ATTENTION DEFICIT DISORDER WITH HYPERACTIVITY; CLONIDINE; DELAYED-ACTION PREPARATIONS; DRUG APPROVAL; DRUG DESIGN; GUANFACINE; HUMANS; RANDOMIZED CONTROLLED TRIALS AS TOPIC; UNITED STATES; UNITED STATES FOOD AND DRUG ADMINISTRATION;

EID: 84879400277     PISSN: 10445463     EISSN: 15578992     Source Type: Journal    
DOI: 10.1089/cap.2013.0028     Document Type: Review

References (103)

1. American Psychiatric Association: Attention-deficit and disruptive behavior disorders. In: Diagnostic and Statistical Manual of Mental Disorders, 4th ed., text revision. Washington, DC: American Psychiatric Association; 2000, pp 85-93.
2. Arndts D: New aspects of the clinical pharmacology of clonidine. Chest 83:397-400, 1983. (Pubitemid 13153337)
3. Arndts D, Stahle H, Struck CJ: A newly developed precise and sensitive radioimmunoassay for clonidine. Arzneimittelforschung 29: 532-538, 1979. (Pubitemid 9137281)
4. Arnsten AF, Cai JX, Goldman-Rakic PS: The alpha-2 adrenergic agonist guanfacine improves memory in aged monkeys without sedative or hypotensive side effects: Evidence for alpha-2 receptor subtypes. J Neurosci 8:4287-4298, 1988. (Pubitemid 19017410)
5. Arnsten AF, Contant TA: Alpha-2 adrenergic agonists decrease distractibility in aged monkeys performing the delayed response task. Psychopharmacology (Berl ) 108:159-169, 1992.
6. Arnsten AF, Dudley AG: Methylphenidate improves prefrontal cortical cognitive function through alpha2 adrenoceptor and dopamine D1 receptor actions: Relevance to therapeutic effects in Attention Deficit Hyperactivity Disorder. Behav Brain Funct 1:2, 2005.
7. Arnsten AF, Scahill L, Findling RL: alpha2-Adrenergic receptor agonists for the treatment of attention-deficit/hyperactivity disorder: emerging concepts from new data. J Child Adolesc Psychopharmacol 17:393-406, 2007.
8. Aston-Jones G, Cohen JD: Adaptive gain and the role of the locus coeruleus-norepinephrine system in optimal performance. J Comp Neurol 493:99-110, 2005. (Pubitemid 41637975)
9. Barbaresi WJ, Katusic SK, Colligan RC, Weaver AL, Leibson CL, Jacobsen SJ: Long-term stimulant medication treatment of attention-deficit/hyperactivity disorder: Results from a populationbased study. J Dev Behav Pediatr 27:1-10, 2006. (Pubitemid 44315107)
10. Berridge CW, Waterhouse BD: The locus coeruleus-noradrenergic system: modulation of behavioral state and state-dependent cognitive processes. Brain Res Brain Res Rev 42:33-84, 2003. (Pubitemid 36369264)
11. Biederman J, Faraone SV: Attention-deficit hyperactivity disorder. Lancet 366:237-248, 2005. (Pubitemid 40981053)
12. Biederman J, Melmed RD, Patel A, McBurnett K, Donahue J, Lyne A: Long-term, open-label extension study of guanfacine extended release in children and adolescents with ADHD. CNS Spectr 13:1047-1055, 2008a.
13. Biederman J, Melmed RD, Patel A, McBurnett K, Konow J, Lyne A, Scherer N: A randomized, double-blind, placebo-controlled study of guanfacine extended release in children and adolescents with attention-deficit/hyperactivity disorder. Pediatrics 121:e73-e84, 2008b.
14. Biederman J, Newcorn J, Sprich S: Comorbidity of attention deficit hyperactivity disorder with conduct, depressive, anxiety, and other disorders. Am J Psychiatry 148:564-577, 1991.
15. Boellner SW, Pennick M, Fiske K, Lyne A, Shojaei A: Pharmacokinetics of a guanfacine extended-release formulation in children and adolescents with attention-deficit-hyperactivity disorder. Pharmacotherapy 27:1253-1262, 2007. (Pubitemid 47339123)
16. Brady KT, Gray KM, Tolliver BK: Cognitive enhancers in the treatment of substance use disorders: clinical evidence. Pharmacol Biochem Behav 99:285-294, 2011.
17. Buchanan ML, Easterling TR, Carr DB, Shen DD, Risler LJ, Nelson WL, Mattison DR, Hebert MF: Clonidine pharmacokinetics in pregnancy. Drug Metab Dispos 37:702-705, 2009.
18. Carchman SH, Crowe JT, Jr., Wright GJ: The bioavailability and pharmacokinetics of guanfacine after oral and intravenous administration to healthy volunteers. J Clin Pharmacol 27:762-767, 1987.
19. Catapres [package insert]. Ridgefield CT: Boehringer Ingelheim Pharmaceuticals Inc.; 2010.
20. Centers for Disease Control and Prevention: Increasing prevalence of parent-reported attention-deficit/hyperactivity disorder among children-United States, 2003 and 2007. MMWR Morb Mortal Wkly Rep 59:1439-1443, 2010.
21. Chappell PB, Riddle MA, Scahill L, Lynch KA, Schultz R, Arnsten A, Leckman JF, Cohen DJ: Guanfacine treatment of comorbid attention-deficit hyperactivity disorder and Tourette's syndrome: Preliminary clinical experience. J Am Acad Child Adolesc Psychiatry 34:1140-1146, 1995.
22. Childress AC: Guanfacine extended release as adjunctive therapy to psychostimulants in children and adolescents with attention-deficit/ hyperactivity disorder. Adv Ther 29:385-400, 2012.
23. Connor DF, Findling RL, Kollins SH, Sallee F, Lopez FA, Lyne A, Tremblay G: Effects of guanfacine extended release on oppositional symptoms in children aged 6-12 years with attention-deficit hyperactivity disorder and oppositional symptoms: A randomized, double-blind, placebo-controlled trial. CNS Drugs 24:755-768, 2010.
24. Connor DF, Fletcher KE, Swanson JM: A meta-analysis of clonidine for symptoms of attention-deficit hyperactivity disorder. J Am Acad Child Adolesc Psychiatry 38:1551-1559, 1999.
25. Connor DF, Grasso DJ, Slivinsky MD, Pearson GS, Banga A: An open-label study of guanfacine extended release for traumatic stress related symptoms in children and adolescents (In press). J Child Adolesc Psychopharmacol 23:244-251, 2013.
26. Coull JT, Buchel C, Friston KJ, Frith CD: Noradrenergically mediated plasticity in a human attentional neuronal network. Neuroimage 10:705-715, 1999. (Pubitemid 30026764)
27. Coull JT, Nobre AC, Frith CD: The noradrenergic alpha2 agonist clonidine modulates behavioural and neuroanatomical correlates of human attentional orienting and alerting. Cereb Cortex 11:73-84, 2001. (Pubitemid 32064177)
28. Cunningham FE, Baughman VL, Peters J, Laurito CE: Comparative pharmacokinetics of oral versus sublingual clonidine. J Clin Anesth 6:430-433, 1994. (Pubitemid 24302213)
29. Darda S, Forster HJ, Sthle H: Metabolic degradation of clonidine [in German; author's translation]. Arzneimittelforschung 28:255-259, 1978. (Pubitemid 8264281)
30. Davies DS, Wing AM, Reid JL, Neill DM, Tippett P, Dollery CT: Pharmacokinetics and concentration-effect relationships of intervenous and oral clonidine. Clin Pharmacol Ther 21:593-601, 1977. (Pubitemid 8098143)
31. Daviss WB, Patel NC, Robb AS, McDermott MP, Bukstein OG, Pelham WE, Jr., Palumbo D, Harris P, Sallee FR: Clonidine for attention-deficit/hyperactivity disorder: II. ECG changes and adverse events analysis. J Am Acad Child Adolesc Psychiatry 47: 189-198, 2008. (Pubitemid 351158787)
32. Elia J, Ambrosini PJ, Rapoport JL: Treatment of attention- deficithyperactivity disorder. N Engl J Med 340:780-788, 1999.
33. Faraone SV, Buitelaar J: Comparing the efficacy of stimulants for ADHD in children and adolescents using meta-analysis. Eur Child Adolesc Psychiatry 19:353-364, 2010.
34. Faraone SV, Sergeant J, Gillberg C, Biederman J: The worldwide prevalence of ADHD: Is it an American condition? World Psychiatry 2:104-113, 2003.
35. Franowicz JS, Kessler LE, Borja CM, Kobilka BK, Limbird LE, Arnsten AF: Mutation of the alpha2A-adrenoceptor impairs working memory performance and annuls cognitive enhancement by guanfacine. J Neurosci 22:8771-8777, 2002. (Pubitemid 35387619)
36. Gyires K, Zadori ZS, Torok T, Matyus P: alpha(2)-Adrenoceptor subtypes-mediated physiological, pharmacological actions. Neurochem Int 55:447-453, 2009.
37. Hazell PL, Stuart JE: A randomized controlled trial of clonidine added to psychostimulant medication for hyperactive and aggressive children. J Am Acad Child Adolesc Psychiatry 42:886-894, 2003. (Pubitemid 44515836)
38. Hoza B: Peer functioning in children with ADHD. Ambul Pediatr 7:101-106, 2007. (Pubitemid 46140753)
39. Hunt RD, Arnsten AF, Asbell MD: An open trial of guanfacine in the treatment of attention-deficit hyperactivity disorder. J Am Acad Child Adolesc Psychiatry 34:50-54, 1995.
40. Hunt RD, Capper L, O'Connell P: Clonidine in child and adolescent psychiatry. J Child Adolesc Psychopharmacol 1:87-102, 1990.
41. Hunt RD, Minderaa RB, Cohen DJ: Clonidine benefits children with attention deficit disorder and hyperactivity: report of a double-blind placebo-crossover therapeutic trial. J Am Acad Child Psychiatry 24:617-629, 1985. (Pubitemid 15249217)
42. Hunt RD, Minderaa RB, Cohen DJ: The therapeutic effect of clonidine in attention deficit disorder with hyperactivity: a comparison with placebo and methylphenidate. Psychopharmacol Bull 22:229-236, 1986. (Pubitemid 16101362)
43. Intuniv (guanfacine) extended-release tablets [package insert]. Wayne, PA: Shire Pharmaceuticals LLC; 2011.
44. Jain R, Kollins S, Bailey C, Holloway W, Horacek HJ, Khayrallah M: Developing a sustained release formulation of clonidine for the treatment of children and adolescents with attention deficit hyperactivity disorder (ADHD). Poster presented at the 47th Annual Meeting of the American College of Neuropsychopharmacology, Scottsdale, AZ, December 7-11, 2008.
45. Jain R, Segal S, Kollins SH, Khayrallah M: Clonidine extendedrelease tablets for pediatric patients with attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry 50:171-179, 2011.
46. Jensen PS: Clinical considerations for the diagnosis and treatment of ADHD in the managed care setting. Am J Manag Care 15:S129-S140, 2009.
47. Kapvay [package insert]. Atlanta GA: Shionogi Pharma Inc.; 2010.
48. Karachalios GN, Charalabopoulos A, Papalimneou V, Kiortsis D, Dimicco P, Kostoula OK, Charalabopoulos K: Withdrawal syndrome following cessation of antihypertensive drug therapy. Int J Clin Pract 59:562-570, 2005. (Pubitemid 41632462)
49. Keranen A, Nykanen S, Taskinen J: Pharmacokinetics and side-effects of clonidine. Eur J Clin Pharmacol 13:97-101, 1978. (Pubitemid 8346368)
50. Kiechel JR: Pharmacokinetics and metabolism of guanfacine in man: A review. Br J Clin Pharmacol 10 Suppl 1:25S-32S, 1980. (Pubitemid 10065106)
51. Kisicki JC, Fiske K, Lyne A: Phase I, double-blind, randomized, placebo-controlled, dose-escalation study of the effects on blood pressure of abrupt cessation versus taper down of guanfacine extended-release tablets in adults aged 19 to 24 years. Clin Ther 29: 1967-1979, 2007. (Pubitemid 350212810)
52. Kollins SH, Jain R, Brams M, Segal S, Findling RL, Wigal SB, Khayrallah M: Clonidine extended-release tablets as add-on therapy to psychostimulants in children and adolescents with ADHD. Pediatrics 127:e1406-e1413, 2011a.
53. Kollins SH, Lopez FA, Vince BD, Turnbow JM, Farrand K, Lyne A, Wigal SB, Roth T: Psychomotor functioning and alertness with guanfacine extended release in subjects with attention-deficit/hyperactivity disorder. J Child Adolesc Psychopharmacol 21:111-120, 2011b.
54. Larsson P, Nordlinder A, Bergendahl HT, Lonnqvist PA, Eksborg S, Almenrader N, Anderson BJ: Oral bioavailability of clonidine in children. Paediatr Anaesth 21:335-340, 2011.
55. Levy F: Pharmacological and therapeutic directions in ADHD: Specificity in the PFC. Behav Brain Funct 4:12, 2008.
56. Li BM, Mei ZT: Delayed-response deficit induced by local injection of the alpha 2-adrenergic antagonist yohimbine into the dorsolateral prefrontal cortex in young adult monkeys. Behav Neural Biol 62:134-139, 1994.
57. Lopez FA, White C, Rubin J: Effects of guanfacine extended release on parent-reported behaviors in a randomized double-blind study of subjects with attention-deficit/hyperactivity disorder. Poster presented at the American Professional Society of ADHD and Related Disorders, Washington, DC, November 5-6, 2010.
58. MacDonald E, Kobilka BK, Scheinin M. Gene targeting-homing in on alpha 2-adrenoceptor-subtype function. Trends Pharmacol Sci 18:211-219, 1997. (Pubitemid 27283651)
59. MacMillan LB, Hein L, Smith MS, Piascik MT, Limbird LE: Central hypotensive effects of the alpha2a-adrenergic receptor subtype. Science 273:801-803, 1996. (Pubitemid 26271526)
60. Manos MJ, Tom-Revzon C, Bukstein OG, Crismon ML: Changes and challenges: Managing ADHD in a fast-paced world. J Manag Care Pharm 13:S2-S13, 2007.
61. Muller U, Clark L, Lam ML, Moore RM, Murphy CL, Richmond NK, Sandhu RS, Wilkins IA, Menon DK, Sahakian BJ, Robbins TW: Lack of effects of guanfacine on executive and memory functions in healthy male volunteers. Psychopharmacology (Berl) 182:205-213, 2005. (Pubitemid 41464613)
62. Nair V, Mahadevan S: Randomised controlled study-efficacy of clonidine versus carbamazepine in children with ADHD. J Trop Pediatr 55:116-121, 2009.
63. Newcorn JH, Clerkin S, Schulz KP, Halperin JM: Adrenergic agonists: Clomidine amd guanfacine. In: Textbook of Child and Adolescent Psychopharmacology, edited by A Martin, L Scahill, D Charney, J Leckman. New York: Oxford University Press, 2003, pp. 264-273.
64. Newcorn JH, Clerkin S, Schulz KP, Halperin JM: Adrenergic agonists: Clonidine and guanfacine. In: Textbook of Child and Adolescent Psychopharmacology, 2nd ed, edited by A. Martin, L. Scahill, D. Charney, J. Leckman. New York: Oxford University Press; 2011, pp 263-274.
65. Olfson M: New options in the pharmacological management of attention-deficit/hyperactivity disorder. Am J Manag Care 10:S117-S124, 2004. (Pubitemid 38970247)
66. Palumbo DR, Sallee FR, Pelham WE, Jr., Bukstein OG, Daviss WB, McDermott MP: Clonidine for attention-deficit/hyperactivity disorder: I. Efficacy and tolerability outcomes. J Am Acad Child Adolesc Psychiatry 47:180-188, 2008. (Pubitemid 351158786)
67. PDR Network LLC, Staff PDR: Physicians' Desk Reference 2012. Mantriale, NJ: Physicians Desk Reference Incorporated, 2011.
68. Pliszka S: Practice parameter for the assessment and treatment of children and adolescents with attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry 46:894-921, 2007.
69. Pliszka SR, Crismon ML, Hughes CW, Corners CK, Emslie GJ, Jensen PS, McCracken JT, Swanson JM, Lopez M: The Texas Children's Medication Algorithm Project: Revision of the algorithm for pharmacotherapy of attention-deficit/ hyperactivity disorder. J Am Acad Child Adolesc Psychiatry 45:642-657, 2006. (Pubitemid 43833097)
70. Pohl GM, Van Brunt DL, Ye W, Stoops WW, Johnston JA: A retrospective claims analysis of combination therapy in the treatment of adult attention-deficit/hyperactivity disorder (ADHD). BMC Health Serv Res 9:95, 2009.
71. Popper CW: Combining methylphenidate and clonidine: Pharmacologic questions and news reports about sudden death. J Child Adolesc Psychopharmacol 5:157-166, 1995.
72. Potts AL, Larsson P, Eksborg S, Warman G, Lonnqvist PA, Anderson BJ: Clonidine disposition in children; a population analysis. Paediatr Anaesth 17:924-933, 2007. (Pubitemid 47339712)
73. Puolivali J, Bjorklund M, Holmberg M, Ihalainen JA, Scheinin M, Tanila H: Alpha 2C-adrenoceptor mediated regulation of cortical EEG arousal. Neuropharmacology 43:1305-1312, 2002. (Pubitemid 36084441)
74. Reiff MI, Stein MT: Attention-deficit/hyperactivity disorder evaluation and diagnosis: A practical approach in office practice. Pediatr Clin North Am 50:1019-1048, 2003. (Pubitemid 37204483)
75. Robbins TW, Arnsten AF: The neuropsychopharmacology of frontoexecutive function: Monoaminergic modulation. Annu Rev Neurosci 32:267-287, 2009.
76. Rubin J, Lopez FA, Youcha S: Impact of guanfacine extended release on cognitive problems and inattention. Poster presented at the 2010 Annual Meeting of the Society for Developmental and Behavioral Pediatrics, Boston, MA, September 11-14, 2010.
77. Sallee FR: The role of alpha2-adrenergic agonists in attention-deficit/ hyperactivity disorder. Postgrad Med 122:78-87, 2010.
78. Sallee FR, Lyne A, Wigal T, McGough JJ: 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, 2009a.
79. Sallee FR, McGough J, Wigal T, Donahue J, Lyne A, Biederman J: Guanfacine extended release in children and adolescents with attention-deficit/ hyperactivity disorder: A placebo-controlled trial. J Am Acad Child Adolesc Psychiatry 48:155-165, 2009b.
80. Sara SJ: The locus coeruleus and noradrenergic modulation of cognition. Nat Rev Neurosci 10:211-223, 2009.
81. Scahill L, Aman MG, McDougle CJ, McCracken JT, Tierney E, Dziura J, Arnold LE, Posey D, Young C, Shah B, Ghuman J, Ritz L, Vitiello B: A prospective open trial of guanfacine in children with pervasive developmental disorders. J Child Adolesc Psychopharmacol 16:589-598, 2006. (Pubitemid 44737213)
82. Scahill L, Barloon L, Farkas L: Alpha-2 agonists in the treatment of attention deficit hyperactivity disorder. J Child Adolesc Psychiatr Nurs 12:168-173, 1999.
83. Scahill L, Chappell PB, Kim YS, Schultz RT, Katsovich L, Shepherd E, Arnsten AF, Cohen DJ, Leckman JF: 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, 2001. (Pubitemid 32623110)
84. Schulz KP, Clerkin SM, Fan J, Halperin JM, Newcorn JH: Guanfacine modulates the influence of emotional cues on prefrontal cortex activation for cognitive control. Psychopharmacology (Berl) 226:261-271, 2013.
85. Shojaei AH, Chang R-K, Pennick M: Guanfacine extended release tablets as treatment for attention-deficit/hyperactivity disorder: Formulation characteristics. Poster presented at the U.S. Psychiatric & Mental Health Congress, New Orleans, Louisiana, November 16-19, 2006.
86. Signorovitch J, Erder MH, Xie J, Sikirica V, Lu M, Hodgkins PS, Wu EQ: Comparative effectiveness research using matching-adjusted indirect comparison: An application to treatment with guanfacine extended release or atomoxetine in children with attention-deficit/hyperactivity disorder and comorbid oppositional defiant disorder. Pharmacoepidemiol Drug Saf 21:130-137, 2012.
87. Sikirica V, Haim EM, Xie J, Macaulay D, Diener M, Hodgkins P, Wu EQ: Cost effectiveness of guanfacine extended release as an adjunctive therapy to a stimulant compared with stimulant monotherapy for the treatment of attention-deficit hyperactivity disorder in children and adolescents. Pharmacoeconomics 30:e1-15, 2012.
88. Singer HS, Brown J, Quaskey S, Rosenberg LA, Mellits ED, Denckla MB: The treatment of attention-deficit hyperactivity disorder in Tourette's syndrome: A double-blind placebocontrolled study with clonidine and desipramine. Pediatrics 95: 74-81, 1995.
89. Sorkin EM, Heel RC: Guanfacine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in the treatment of hypertension. Drugs 31:301-336, 1986. (Pubitemid 16167001)
90. Spencer TJ, Biederman J, Harding M, O'Donnell D, Faraone SV, Wilens TE: Growth deficits in ADHD children revisited: Evidence for disorder-associated growth delays? J Am Acad Child Adolesc Psychiatry 35:1460-1469, 1996. (Pubitemid 26360931)
91. Spencer TJ, Greenbaum M, Ginsberg LD, Murphy WR: Safety and effectiveness of coadministration of guanfacine extended release and psychostimulants in children and adolescents with attentiondeficit/hyperactivity disorder. J Child Adolesc Psychopharmacol 19:501-510, 2009.
92. Swanson JM, Flockhart D, Udrea D, Cantwell DP, Connor P, Williams L: Clonidine in the treatment of ADHD: Questions about safety and efficacy. J Child Adolesc Psychopharmacol 5:301-304, 1995. (Pubitemid 26065026)
93. Swearingen D, Pennick M, Shojaei A, Lyne A, Fiske K: A phase I, randomized, open-label, crossover study of the single-dose pharmacokinetic properties of guanfacine extended-release 1-, 2-, and 4-mg tablets in healthy adults. Clin Ther 29:617-625, 2007.
94. Taylor FB, Russo J: Comparing guanfacine and dextroamphetamine for the treatment of adult attention-deficit/hyperactivity disorder. J Clin Psychopharmacol 21:223-228, 2001. (Pubitemid 32221061)
95. Tenex (guanfacine hydrochloride) tablet prescribing information. Bridgewater, NJ: Promius Pharma LLC; 2008.
96. Tourette's Syndrome StudyGroup: Treatment ofADHDin children with tics: A randomized controlled trial. Neurology 58:527-536, 2002.
97. Uhlen S, Wikberg JE: Delineation of rat kidney alpha 2A-and alpha 2B-adrenoceptors with [3H]RX821002 radioligand binding: Computer modelling reveals that guanfacine is an alpha 2A-selective compound. Eur J Pharmacol 202:235-243, 1991.
98. van der Meere J, Gunning B, Stemerdink N: The effect of methylphenidate and clonidine on response inhibition and state regulation in children with ADHD. J Child Psychol Psychiatry 40:291-298, 1999. (Pubitemid 29078374)
99. Wang M, Ramos BP, Paspalas CD, Shu Y, Simen A, Duque A, Vijayraghavan S, Brennan A, Dudley A, Nou E, Mazer JA, McCormick DA, Arnsten AF: Alpha2A-adrenoceptors strengthen working memory networks by inhibiting cAMP-HCN channel signaling in prefrontal cortex. Cell 129:397-410, 2007. (Pubitemid 46574970)
100. Weiss YA, Lavene DL, Safar ME, Simon AC, Loria Y, Georges DR, Milliez PL: Guanfacine kinetics in patients with hypertension. Clin Pharmacol Ther 25:283-293, 1979. (Pubitemid 9164947)
101. Wilens TE, Bukstein O, Brams M, Cutler AJ, Childress A, Rugino T, Lyne A, Grannis K, Youcha S: A controlled trial of extendedrelease guanfacine and psychostimulants for attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry 51:74-85, 2012.
102. Wilens TE, Spencer TJ: The stimulants revisited. Child Adolesc Psychiatr Clin N Am 9:573-603, viii, 2000. (Pubitemid 30620545)
103. Wood JG, Crager JL, Delap CM, Heiskell KD: Beyond methylphenidate: Nonstimulant medications for youth with ADHD. J Atten Disord 11:341-350, 2007.