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Long-Term, Open-Label Extension Study of Guanfacine Extended Release in Children and Adolescents with ADHD

Published online by Cambridge University Press:  07 November 2014

Joseph Biederman ,
Raun D. Melmed ,
Anil Patel ,
Keith McBurnett ,
Jessica Donahue  and
Andrew Lyne
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Abstract

Introduction:

Guanfacine is a noradrenergic agonist that is believed to improve symptoms of attention-deficit/hyperactivity disorder (ADHD) through selective actions at α2A-adrenoceptors in the prefrontal cortex. A recent double-blind, multicenter trial supports the efficacy and safety of guanfacine extended release (GXR) for pediatric ADHD. This long-term, open-label extension was conducted to study the safety profile and effectiveness of GXR for up to 2 years.

Methods:

Subjects were 240 children 6–17 years of age with a diagnosis of ADHD who participated in the preceding randomized trial. GXR was initiated at 2 mg/day and titrated as needed in 1-mg increments to a maximum of 4 mg/day to achieve optimal clinical response.

Results:

The most common adverse events were somnolence (30.4%), headache (26.3%), fatigue (14.2%), and sedation (13.3%). Somnolence, sedation, and fatigue were usually transient. Cardiovascular-related adverse events were uncommon, although small reductions in mean blood pressure and pulse rate were evident at monthly visits. ADHD Rating Scale, Version IV, total and subscale scores improved significantly from baseline to endpoint for all dose groups (P<.001 for all comparisons, intent-to-treat population).

Conclusion:

Long-term treatment with GXR was generally safe for up to 24 months of treatment, and effectiveness was maintained over this treatment period.

Type
Original Research
Information
CNS Spectrums , Volume 13 , Issue 12 , December 2008 , pp. 1047 - 1055
Copyright
Copyright © Cambridge University Press 2008

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References

REFERENCES

1.Clinical practice guideline: diagnosis and evaluation of the child with attention-deficit/hyperactivity disorder. American Academy of Pediatrics. Pediatrics. 2000;105:1158–1170.Google Scholar
2.Barkley, RA, Fischer, M, Smallish, L, Fletcher, K. The persistence of attention-deficit/hyperactivity disorder into young adulthood as a function of reporting source and definition of disorder. J Abnorm Psychol. 2002;111:279–289.Google Scholar
3.American Academy of Pediatrics Subcommittee on Attention-Deficit/Hyperactivity Disorder Committee on Quality Improvement. Clinical practice guideline: treatment of the school-aged child with attention-deficit/hyperactivity disorder. Pediatrics. 2001;108:1033–1044.CrossRefGoogle Scholar
4.Stein, MA, Sarampote, CS, Waldman, ID, et al.A dose-response study of OROS methylphenidate in children with attention-deficit/hyperactivity disorder. Pediatrics. 2003;112:e404.Google Scholar
5.McGough, JJ, Biederman, J, Wigal, SB, et al.Long-term tolerability and effectiveness of once-daily mixed amphetamine salts (Adderall XR) in children with ADHD. J Am Acad Child Adolesc Psychiatry. 2005;44:530–538.CrossRefGoogle ScholarPubMed
6.Biederman, J, Spencer, TJ, Wilens, TE, Weisler, RH, Read, SC, Tulloch, SJ. Long-term safety and effectiveness of mixed amphetamine salts extended release in adults with ADHD. CNS Spectr. 2005;10:16–25.CrossRefGoogle ScholarPubMed
7.Wilens, T, McBurnett, K, Stein, M, Lerner, M, Spencer, T, Wolraich, M. ADHD treatment with once-daily OROS methylphenidate: final results from a long-term open-label study. J Am Acad Child Adolesc Psychiatry. 2005;44:1015–1023.Google Scholar
8.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. 1988;8:4287–4298.Google Scholar
9.Uhlén, S, Wikberg, JE. Delineation of rat kidney alpha 2A- and alpha 2B-adrenoceptors with [3H]RX821002 radioligand binding: computer modelling reveals that guan-facine is an alpha 2A-selective compound. Eur J Pharmacol. 1991;202:235–243.Google Scholar
10.Arnsten, AF, Steere, JC, Hunt, RD. The contribution of α2-noradrenergic mechanisms to prefrontal cortical cognitive function. Potential significance for attention-deficit hyperactivity disorder. Arch Gen Psychiatry. 1996;53:448–455.Google Scholar
11.Hunt, RD, Arnsten, AFT, Asbell, MD. An open trial of guanfacine in the treatment of attention-deficit hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 1995;34:50–54.Google Scholar
12.Horrigan, JP, Barnhill, LJ. Guanfacine for treatment of attention-deficit hyperactivity disorder in boys. J Child Adolesc Psychopharmacol. 1995;5:215–223.Google Scholar
13.Scahill, L, Chappell, PB, Kim, YS, et al.A placebo-controlled study of guanfacine in the treatment of children with tic disorders and attention deficit hyperactivity disorder. Am J Psychiatry. 2001;158:1067–1074.Google Scholar
14.Taylor, FB, Russo, J. Comparing guanfacine and dextroamphetamine for the treatment of adult attention-deficit/hyperactivity disorder. J Clin Psychopharmacol. 2001;21:223–228.CrossRefGoogle ScholarPubMed
15.Sallee, FR, McGough, J, Wigal, T, Donahue, J, Lyne, A, Biederman, J, for the SPD503 Study Group. Guanfacine extended release in children and adolescents with attention-deficit/hyperactivity disorder: a placebo-controlled trial. J Am Acad Child Adolesc Psychiatry. In press.Google Scholar
16.Biederman, J, Melmed, RD, Patel, A, et al, for the SPD503 Study Group. A randomized, double-blind, placebo-controlled study of guanfacine extended release in children and adolescents with attention-deficit/hyperactivity disorder. Pediatrics. 2008;121:e73–e84.Google Scholar
17.DuPaul, GJ, Power, TJ, Anastopoulos, AD, Reid, R. ADHD Rating Scale-IV: Checklists, Norms, and Clinical Interpretation. New York, NY: Guilford Press; 1998.Google Scholar
18.Spencer, TJ, Faraone, SV, Biederman, J, Lerner, M, Cooper, KM, Zimmerman, B. Does prolonged therapy with a long-acting stimulant suppress growth in children with ADHD? J Am Acad Child Adolesc Psychiatry. 2006;45:527–537.Google Scholar
19.Faraone, SV, Biederman, J, Monuteaux, M, Spencer, T. Long-term effects of extended-release mixed amphetamine salts treatment of attention-deficit/hyperactivity disorder on growth. J Child Adolesc Psychopharmacol. 2005;15:191–202.Google Scholar
20.Adler, LA, Spencer, TJ, Milton, DR, Moore, RJ, Michelson, D. 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;66:294–299.CrossRefGoogle ScholarPubMed
21.Hoare, P, Remschmidt, H, Medori, R, et al.12-month efficacy and safety of OROS MPH in children and adolescents with attention-deficit/hyperactivity disorder switched from MPH. Eur Child Adolesc Psychiatry. 2005;14:305–309.Google Scholar
22.Chappell, PB, Riddle, MA, Scahill, L, et al.Guanfacine treatment of comorbid attention-deficit hyperactivity disorder and Tourette's syndrome: preliminary clinical experience. J Am Acad Child Adolesc Psychiatry. 1995;34:1140–1146.Google Scholar
23.Charach, A, Figueroa, M, Chen, S, Ickowicz, A, Schachar, R. Stimulant treatment over 5 years: effects on growth. J Am Acad Child Adolesc Psychiatry. 2006;45:415–421.Google Scholar
24.Poulton, A, Cowell, CT. Slowing of growth in height and weight on stimulants: a characteristic pattern. J Paediatr Child Health. 2003;39:180–185.Google Scholar
25.Gillberg, C, Melander, H, von Knorring, AL, et al.Long-term stimulant treatment of children with attention-deficit hyperactivity disorder symptoms. A randomized, double-blind, placebo-controlled trial. Arch Gen Psychiatry. 1997;54:857–864.Google Scholar