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
Abstract
Objective To evaluate the efficacy and safety of guanfacine extended release (XR, Intuniv; Shire Development Inc., Wayne, PA, USA) in the treatment of oppositional symptoms in children aged 6-12 years with a diagnosis of attention-deficit hyperactivity disorder (ADHD) and the presence of oppositional symptoms. Subjects and methods In this randomized, double-blind, placebo-controlled, multicentre, flexible-dose, dose-optimization study, children aged 6-12 years were randomized to receive guanfacine XR (1-4 mg/day) or placebo for 9 weeks. Screening and washout periods were followed by a 5-week dose-optimization period, a 3-week dose-maintenance period and a 1-week tapering period. The primary efficacy measure was change from baseline to endpoint in the oppositional subscale of the Conners' Parent Rating Scale-Revised: Long Form (CPRS-R:L) score. Change in ADHD Rating Scale IV (ADHD-RS-IV) total score was a secondary efficacy measure. Safety assessments included adverse events (AEs), vital signs, ECG readings and laboratory studies. Results A total of 217 children were enrolled: 138 were randomized to receive guanfacine XR and 79 to receive placebo. Least-squares mean reductions from baseline to endpoint in CPRS-R:L oppositional subscale scores were 10.9 in the guanfacine XR group compared with 6.8 in the placebo group (p Conclusions In this population of children aged 6-12 years with ADHD and the presence of oppositional symptoms, significant reductions in CPRS-R:L oppositional…
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Postsynaptic alpha-2 adrenoceptor agonists such as guanfacine treat core symptoms of ADHD and oppositionality.
“Postsynaptic alpha-2 adrenoceptor agonists such as guanfacine treat core symptoms of ADHD and oppositionality (129).”
From Emotion Dysregulation in Attention Deficit Hyperactivity Disorder (2014) · cites this paper as [129]
In clinical trials for children with ADHD with oppositional symptoms, guanfacine decreased oppositional scores compared with placebo.
“In clinical trials for children with ADHD with oppositional symptoms (displays of anger, irritability, and hostility towards others), guanfacine decreased oppositional scores compared with placebo (Connor et al. 2010).”
From Decoding the bidirectional links between alcohol misuse and aggression: toward a unified translational framework (2026) · cites this paper as Connor et al. 2010
Guanfacine is helpful in treating oppositional symptoms.
“Guanfacine is helpful in treating oppositional symptoms (Connor et al., 2010, Findling et al., 2014)”
From Guanfacine’s mechanism of action in treating prefrontal cortical disorders: Successful translation across species (2020) · cites this paper as Connor et al., 2010
Cites
Willcutt, E. G., Doyle, A. E., Nigg, J. T., Faraone, S. V., & Pennington, B. F. (2005) · Biological Psychiatry · doi:10.1016/j.biopsych.2005.02.006 · Cited by 3,568 · see citing works
Neurobiology of Executive Functions: Catecholamine Influences on Prefrontal Cortical Functions
Arnsten, A. F. T., & Li, B.-M. (2005) · Biological Psychiatry · doi:10.1016/j.biopsych.2004.08.019 · Cited by 948 · see citing works
Berridge, C. W., Devilbiss, D. M., Andrzejewski, M. E., Arnsten, A. F. T., Kelley, A. E., Schmeichel, B., Hamilton, C., & Spencer, R. C. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.04.022 · Cited by 617 · see citing works
Barkley, R. A. (1997) · Psychological Bulletin · doi:10.1037//0033-2909.121.1.65 · Cited by 580 · see citing works
Kelsey, D. K., Sumner, C. R., Casat, C. D., Coury, D. L., Quintana, H., Saylor, K. E., Sutton, V. K., Gonzales, J., Malcolm, S. K., Schuh, K. J., et al. (2004) · Pediatrics · doi:10.1542/peds.114.1.e1 · Cited by 464 · see citing works
Arnsten, A. F., & Dudley, A. G. (2005) · Behavioral and Brain Functions · doi:10.1186/1744-9081-1-2 · Cited by 363 · see citing works
Spencer, T., Heiligenstein, J. H., Biederman, J., Faries, D. E., Kratochvil, C. J., Conners, C. K., & Potter, W. Z. (2002) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.v63n1209 · Cited by 333 · see citing works
Bangs, M. E., Hazell, P., Danckaerts, M., Hoare, P., Coghill, D. R., Wehmeier, P. M., Williams, D. W., Moore, R. J., Levine, L., & for the Atomoxetine ADHD/ODD Study Group (2008) · Pediatrics · doi:10.1542/peds.2006-1880 · Cited by 79 · see citing works
Gadow, K. D., Nolan, E. E., Sverd, J., Sprafkin, J., & Schneider, J. (2008) · Journal of Child Neurology · doi:10.1177/0883073808315412 · Cited by 49 · see citing works
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Attention-deficit/hyperactivity disorder
Faraone, S. V., Asherson, P., Banaschewski, T., Biederman, J., Buitelaar, J. K., Ramos-Quiroga, J. A., Rohde, L. A., Sonuga-Barke, E. J. S., Tannock, R., & Franke, B. (2015) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2015.20 · Cited by 1,479 · see citing works
Emotion Dysregulation in Attention Deficit Hyperactivity Disorder
Shaw, P., Stringaris, A., Nigg, J., & Leibenluft, E. (2014) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2013.13070966 · Cited by 1,232 · see citing works
Catecholamine Influences on Dorsolateral Prefrontal Cortical Networks
Arnsten, A. F. T. (2011) · Biological Psychiatry · doi:10.1016/j.biopsych.2011.01.027 · Cited by 493 · see citing works
Pringsheim, T., Hirsch, L., Gardner, D., & Gorman, D. A. (2015) · The Canadian Journal of Psychiatry · doi:10.1177/070674371506000202 · Cited by 163 · see citing works
Hirota, T., Schwartz, S., & Correll, C. U. (2014) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1016/j.jaac.2013.11.009 · Cited by 161 · see citing works
Datta, D., & Arnsten, A. (2019) · Brain Sciences · doi:10.3390/brainsci9050113 · Cited by 78 · see citing works
Arnsten, A. F. T. (2020) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2020.107327 · Cited by 75 · see citing works
Strawn, J. R., Compton, S. N., Robertson, B., Albano, A. M., Hamdani, M., & Rynn, M. A. (2017) · Journal of Child and Adolescent Psychopharmacology · doi:10.1089/cap.2016.0132 · Cited by 55 · see citing works
Faraone, S. V., McBurnett, K., Sallee, F. R., Steeber, J., & López, F. A. (2013) · Clinical Therapeutics · doi:10.1016/j.clinthera.2013.09.005 · Cited by 44 · see citing works
Self-citationFindling, R. L., McBurnett, K., White, C., & Youcha, S. (2014) · Journal of Child and Adolescent Psychopharmacology · doi:10.1089/cap.2013.0103 · Cited by 32 · see citing works
Self-citationSayer, G. R., McGough, J. J., Levitt, J., Cowen, J., Sturm, A., Castelo, E., & McCracken, J. T. (2016) · Journal of Child and Adolescent Psychopharmacology · doi:10.1089/cap.2015.0264 · Cited by 28 · see citing works
Managing disruptive behaviour in autism-spectrum disorder with guanfacine
Propper, L. (2018) · Journal of Psychiatry and Neuroscience · doi:10.1503/jpn.180039 · Cited by 12 · see citing works
Luan, R., Mu, Z., Yue, F., & He, S. (2017) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2017.00229 · Cited by 11 · see citing works
Russell, N. M., Frier, M. D., Bortolato, M., & Mangieri, R. A. (2026) · Psychopharmacology · doi:10.1007/s00213-025-06938-0 · Cited by 3 · see citing works
- Authors
- Connor, D. F., Findling, R. L., Kollins, S. H., Sallee, F., López, F. A., Lyne, A., & Tremblay, G.
- Affiliations
- University of Connecticut (US)
- University Hospitals Cleveland Medical Center (US)
- Duke Medical Center (US)
- University of Cincinnati (US)
- Corresponding author
- Connor, Daniel F.
- Venue
- CNS Drugs
- Published
- 2010-07
- Volume
- 24
- Issue
- 9
- Pages
- 1
- ISSN
- 1172-7047 (ISSN-L)
- OpenAlex
- W107618943
- Cited by
- 101
- References
- 9
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 3 · 2023: 5 · 2022: 5 · 2021: 6 · 2020: 4 · 2019: 3 · 2018: 5 · 2017: 5 · 2016: 7 · 2015: 11 · 2014: 14 · 2013: 10 · 2012: 8
- FWCI
- 5.67
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- CNS Drugs (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Bristol-Myers Squibb
- Shire
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmaceutical studies and practices
- Social Sciences › Psychology › Clinical Psychology › Child and Adolescent Psychosocial and Emotional Development
- Keywords
- guanfacine extended release, attention deficit hyperactivity disorder, oppositional behavior, children, ADHD medication, dose optimization, ADHD Rating Scale-IV, sleepiness, adverse events, treatment efficacy and safety
- MeSH terms
- Attention Deficit Disorder with Hyperactivity, Child, Delayed-Action Preparations, Dose-Response Relationship, Drug, Double-Blind Method, Drug Administration Schedule, Humans, Guanfacine, Attention Deficit and Disruptive Behavior Disorders, Adrenergic alpha-2 Receptor Agonists
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