Effects of Guanfacine Extended Release on Oppositional Symptoms in Children Aged 6–12 Years with Attention-Deficit Hyperactivity Disorder and Oppositional Symptoms

Connor, Daniel F.; Findling, Robert L.; Kollins, Scott H.; Sallee, Floyd R.; López, Frank A.; Lyne, A. G.; Tremblay, G

doi:10.2165/11537790-000000000-00000

Cited by 54 publications

(91 citation statements)

References 52 publications

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“…A post-hoc analysis from that study reported a positive correlation (r = 0.74) between reductions in CPRS-R:L oppositional scores and ADHD-RS-IV scores (Connor et al 2010). This is consistent with a meta-analysis of three placebo-controlled studies of atomoxetine in children and adolescents with ADHD, which showed correlations of similar magnitude between changes in oppositional and ADHD symptoms .…”

supporting

confidence: 81%

“…A more recent double-blind, placebo-controlled monotherapy study examined treatment with GXR in children with ADHD and the presence of significant oppositional symptoms (Connor et al 2010). In this study, the presence of significant oppositional symptoms was defined as a baseline Conners' Parent Rating ScaleRevised: Long Form (CPRS-R:L) oppositional subscale score ‡ 14 (for boys) or ‡ 12 (for girls).…”

mentioning

confidence: 99%

“…Statistically significant reductions in oppositional symptoms, as measured by CPRS-R:L oppositional subscale scores, were observed with GXR monotherapy compared with placebo ( p < 0.001; effect size = 0.59). Significant reductions in the core symptoms of ADHD as measured by the ADHD Rating Scale IV (ADHD-RS-IV) were also observed with GXR monotherapy compared with placebo ( p < 0.001; effect size = 0.92) (Connor et al 2010).…”

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confidence: 99%

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Guanfacine Extended Release Adjunctive to a Psychostimulant in the Treatment of Comorbid Oppositional Symptoms in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder

Findling

McBurnett

White

et al. 2014

Journal of Child and Adolescent Psychopharmacology

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Objective: The purpose of this study was to assess the effect of guanfacine extended release (GXR) adjunctive to a psychostimulant on oppositional symptoms in children and adolescents with attention-deficit/hyperactivity disorder (ADHD). Methods: A multicenter, double-blind, placebo-controlled dose-optimization study of GXR (1-4 mg/d) or placebo administered morning (a.m.) or evening (p.m.) adjunctive to psychostimulant was conducted in subjects ages 6-17 with suboptimal response to psychostimulant alone. Suboptimal response was defined as treatment with a stable dose of psychostimulant for ‡ 4 weeks with ADHD Rating Scale IV total score ‡ 24 and Clinical Global Impressions-Severity of Illness score ‡ 3, as well as investigator opinion. Primary efficacy and safety results have been reported previously. Secondary efficacy measures included the oppositional subscale of the Conners' Parent Rating Scale-Revised: Long Form (CPRS-R:L); these are reported herein. Results: Significant reductions from baseline to the final on-treatment assessment on the oppositional subscale of the CPRS-R:L were seen with GXR plus psychostimulant compared with placebo plus psychostimulant, both in the overall study population (placebo-adjusted least squares [LS] mean change from baseline to the final on-treatment assessment: GXR a.m. + psychostimulant, -2.4, p = 0.001; GXR p.m. + psychostimulant, -2.2, p = 0.003) as well as in the subgroup of subjects with significant baseline oppositional symptoms (GXR a.m. + psychostimulant, -3.6, p = 0.001; GXR p.m. + psychostimulant, -2.7, p = 0.013). Treatment-emergent adverse events were reported by 77.3%, 76.3%, and 63.4% of subjects in the GXR a.m., GXR p.m., and placebo groups, respectively, in the overall study population. Conclusions: GXR adjunctive to a psychostimulant significantly reduced oppositional symptoms compared with placebo plus a psychostimulant in subjects with ADHD and a suboptimal response to psychostimulant alone.

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confidence: 81%

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confidence: 99%

mentioning

confidence: 99%

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Guanfacine Extended Release Adjunctive to a Psychostimulant in the Treatment of Comorbid Oppositional Symptoms in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder

Findling

McBurnett

White

et al. 2014

Journal of Child and Adolescent Psychopharmacology

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“…Likewise, doses above 54,55 as well as adjunctive pharmacotherapy in combination with stimulants for those patients who failed to have an adequate response with the latter medication. 26,50 All the different studies but one relied on changes on changes from baseline in the Attention-Deficit/ Hyperactivity Disorder Rating Scale IV (ADHD-RS-IV) as the primary outcome measure, with one exception 53 that used the ADHD-RS-IV as secondary outcome measure. Other secondary measures in the different reports included the BeforeSchool Functioning Questionnaire, Conners Global IndexParent, Conners Parent Rating Scale -revised: short form (CPRS-R:SF), CPRS-R: long form (CPRS-R:LF), Conners Teacher Rating Scale -revised, Clinical Global Impressionimprovement (CGI-I), CGI -severity, Parent Global Assessment (PGA), and Child Health Questionnaire -parent form.…”

Section: Dosage and Administrationmentioning

confidence: 99%

“…57 Data from 143 children with ADHD (6-12 years of age) taking GXR from the 9-week RCT evaluating the effects of GXR on comorbid oppositional symptoms 53 were compared with the data from a subset analysis of 98 children aged 7-13 years taking ATX from two identical, 9-week, multisite, doubleblind RCTs assessing the safety and efficacy of ATX in ADHD and comorbid ODD. 58 GXR was associated with a significantly greater reduction in mean CPRS-R:LF oppositional subscale scores compared with ATX (-5.0 versus -2.4, ES 0.58; P=0.01).…”

mentioning

confidence: 99%

Profile of guanfacine extended release and its potential in the treatment of attention-deficit hyperactivity disorder

Martínez-Raga¹,

Knecht²,

Alvaro³

2015

OTT

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Abstract:The α 2 -adrenergic receptor agonist guanfacine, in its extended-release formulation (GXR), is the most recent nonstimulant medication approved in several countries for the treatment of attention-deficit hyperactivity disorder (ADHD) as monotherapy and as adjunctive pharmacotherapy to stimulants in children and adolescents. The present paper aims to review comprehensively and critically the pharmacodynamic and pharmacokinetic characteristics and the published evidence on the efficacy and safety profile of GXR in the treatment of ADHD. A comprehensive search of relevant databases (PubMed, Embase, and PsycInfo) was conducted to identify studies published in peer-reviewed journals until January 15, 2015. Though the precise mechanism of action of guanfacine in the treatment of ADHD is not fully understood, it is thought to act directly by enhancing noradrenaline functioning via α 2A -adrenoceptors in the prefrontal cortex. Weight-adjusted doses should be used, with a dosing regime on a milligram per kilogram basis, starting at doses in the range 0.05-0.08 mg/kg/day, up to 0.12 mg/ kg/day. As evidenced in short-term randomized controlled trials and in long-term open-label extension studies, GXR has been shown to be effective as monotherapy in the treatment of ADHD. Furthermore, GXR has also been found to be effective as adjunctive therapy to stimulant medications in patients with suboptimal responses to stimulants. Many of the adverse reactions associated with GXR, particularly sedation-related effects, were dose-related, transient, mild to moderate in severity, and did not interfere with attention or overall efficacy. There are no reports of serious cardiovascular adverse events associated with GXR alone or in combination with psychostimulants.

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Development and validation of a simple, sensitive and accurate LC‐MS/MS method for the determination of guanfacine, a selective α_2A‐adrenergicreceptor agonist, in plasma and its application to a pharmacokinetic study

Sun

et al. 2013

Biomedical Chromatography

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A simple, practical, accurate and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and fully validated for the quantitation of guanfacine in beagle dog plasma. After protein precipitation by acetonitrile, the analytes were separated on a C18 chromatographic column by methanol and water containing 0.1% (v/v) formic acid with a gradient elution. The subsequent detection utilized a mass spectrometry under positive ion mode with multiple reaction monitoring of guanfacine and enalaprilat (internal standard) at m/z 246.2 → 159.0 and m/z 349.2 → 205.9, respectively. Good linearity was obtained over the concentration range of 0.1-20 ng/mL for guanfacine in dog plasma and the lower limit of quantification of this method was 0.1 ng/mL. The intra- and inter-day precisions were <10.8% relative standard deviation with an accuracy of 92.9-108.4%. The matrix effects ranged from 89.4 to 100.7% and extraction recoveries were >90%. Stability studies showed that both analytes were stable during sample preparation and analysis. The established method was successfully applied to an in vivo pharmacokinetic study in beagle dogs after a single oral dose of 4 mg guanfacine extended-release tablets.

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Effects of Guanfacine Extended Release on Oppositional Symptoms in Children Aged 6–12 Years with Attention-Deficit Hyperactivity Disorder and Oppositional Symptoms

Abstract: NCT00367835.

Cited by 54 publications

References 52 publications

Guanfacine Extended Release Adjunctive to a Psychostimulant in the Treatment of Comorbid Oppositional Symptoms in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder

Guanfacine Extended Release Adjunctive to a Psychostimulant in the Treatment of Comorbid Oppositional Symptoms in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder

Profile of guanfacine extended release and its potential in the treatment of attention-deficit hyperactivity disorder

Development and validation of a simple, sensitive and accurate LC‐MS/MS method for the determination of guanfacine, a selective α_2A‐adrenergicreceptor agonist, in plasma and its application to a pharmacokinetic study

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Effects of Guanfacine Extended Release on Oppositional Symptoms in Children Aged 6–12 Years with Attention-Deficit Hyperactivity Disorder and Oppositional Symptoms

Abstract: NCT00367835.

Cited by 54 publications

References 52 publications

Guanfacine Extended Release Adjunctive to a Psychostimulant in the Treatment of Comorbid Oppositional Symptoms in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder

Guanfacine Extended Release Adjunctive to a Psychostimulant in the Treatment of Comorbid Oppositional Symptoms in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder

Profile of guanfacine extended release and its potential in the treatment of attention-deficit hyperactivity disorder

Development and validation of a simple, sensitive and accurate LC‐MS/MS method for the determination of guanfacine, a selective α2A‐adrenergicreceptor agonist, in plasma and its application to a pharmacokinetic study

Contact Info

Product

Resources

About

Development and validation of a simple, sensitive and accurate LC‐MS/MS method for the determination of guanfacine, a selective α_2A‐adrenergicreceptor agonist, in plasma and its application to a pharmacokinetic study