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

Findling, Robert L.; McBurnett, Keith; White, Carla; Youcha, Sharon

doi:10.1089/cap.2013.0103

Cited by 29 publications

(22 citation statements)

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“…As in ADHD, high levels of hyperactivity and impulsiveness can contribute to oppositional behavior in children with ASD. In a placebo-controlled trial of 461 children aged 6-17-year-old with ADHD, the use of GEXR as an adjunct to stimulant treatment resulted in significantly greater improvement in oppositional behavior, as measured by the oppositional subscale of the Conners' Parent Rating Scale-Revised: Long Form (CPRS-R:L), compared with stimulant treatment alone [14]. Compared to placebo, atomoxetine also showed significant improvement in oppositional behavior, as measured by the HSQ, in a sample of children with ASD and moderate or greater ADHD symptoms [5].…”

Section: Discussionmentioning

confidence: 99%

“…Collectively, these results suggest that GEXR may be an alternative to methylphenidate for monotherapy in children with ASD complicated by hyperactivity and oppositional behavior, particularly for those who do not show a positive response or cannot tolerate methylphenidate. It may also be useful in combined treatment with methylphenidate [14].…”

Section: Discussionmentioning

confidence: 99%

“…Studies in non-ASD pediatric samples suggest that GEXR may be beneficial for oppositional behavior in ADHD and for treatment of anxiety disorders [14][15][16]. A pilot study by Murphy and colleagues showed no difference between GEXR and placebo for the treatment of tics [17].…”

Section: Introductionmentioning

confidence: 99%

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A randomized, placebo-controlled trial of extended-release guanfacine in children with autism spectrum disorder and ADHD symptoms: an analysis of secondary outcome measures

Politte¹,

Scahill

Figueroa

et al. 2018

Neuropsychopharmacol

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In a prior report, we showed that extended-release guanfacine (GEXR) is safe and effective for children with autism spectrum disorder (ASD) accompanied by ADHD symptoms. Here, we examine the impact of GEXR on oppositional behavior, anxiety, repetitive behavior, and sleep disturbance. Sixty-two subjects with ASD (53 boys, 9 girls; ages 5-14 years) were randomly assigned to GEXR (n = 30) or placebo (n = 32) for 8 weeks. Outcomes include the Home Situation Questionnaire-Modified for ASD (HSQ-ASD), Anxiety scale of the Child and Adolescent Symptom Inventory (CASI), Children's Yale-Brown Obsessive-Compulsive Scale-Modified for ASD (CYBOCS-ASD), and Children's Sleep Habits Questionnaire (CSHQ). A repeated measures linear mixed model was used to determine the effects of treatment group and time on HSQ scores. For other measures, change from baseline was evaluated with Analysis of Covariance (ANCOVA).After 8 weeks of treatment, parent ratings of oppositional behavior on the HSQ declined by 44% (per item mean from 3.4 to 1.9) in the GEXR group compared to 12% (from 3.3 to 2.9) for placebo (p = 0.004). Repetitive behavior on the CYBOCS-ASD showed a significantly greater decline in GEXR-treated participants compared to placebo (24% vs. <1%, p = 0.01). No group differences were observed on CASI Anxiety or CSHQ (p = 0.64 and 0.75, respectively). GEXR was effective in reducing oppositional behavior and, more modestly, repetitive behavior. GEXR was not superior to placebo for anxiety, though baseline anxiety ratings were low. GEXR did not significantly improve sleep habits. Future studies could focus on repetitive behavior or anxiety, symptoms with limited treatment options.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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A randomized, placebo-controlled trial of extended-release guanfacine in children with autism spectrum disorder and ADHD symptoms: an analysis of secondary outcome measures

Politte¹,

Scahill

Figueroa

et al. 2018

Neuropsychopharmacol

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“…These results verify the feasibility and acceptability of treating ADHD by stimulating α 2A -adrenoceptors in the PFC or up-regulating the NE concentration in synapses and extrasynaptic space in the PFC. Actually, the α 2A -adrenergic agonists guanfacine and clonidine have been used experimentally and clinically to treat ADHD [92][93][94][95][96][97] . The selective inhibitor of the NE transporter atomoxetine (tomoxetine or LY139603) has also been reported to alleviate ADHD symptoms [98] .…”

Section: N Ew Insights To Develop a Primate Model Of Adhdmentioning

confidence: 99%

Prefrontal cortical α2A-adrenoceptors and a possible primate model of attention deficit and hyperactivity disorder

Sun

Luo

et al. 2015

Neurosci. Bull.

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Attention deficit and hyperactivity disorder (ADHD), a prevalent syndrome in children worldwide, is characterized by impulsivity, inappropriate inattention, and/or hyperactivity. It seriously afflicts cognitive development in childhood, and may lead to chronic under-achievement, academic failure, problematic peer relationships, and low self-esteem. There are at least three challenges for the treatment of ADHD. First, the neurobiological bases of its symptoms are still not clear. Second, the commonly prescribed medications, most showing short-term therapeutic efficacy but with a high risk of serious side-effects, are mainly based on a dopamine mechanism. Third, more novel and effi cient animal models, especially in nonhuman primates, are required to accelerate the development of new medications. In this article, we review research progress in the related fi elds, focusing on our previous studies showing that blockade of prefrontal cortical α 2A -adrenoceptors in monkeys produces almost all the typical behavioral symptoms of ADHD.Keywords: prefrontal cortex; α 2A -adrenoceptors; cognitive functions; attention defi cit and hyperactivity disorder; animal models ·Review· IntroductionAttention deficit and hyperactivity disorder (ADHD) is one of the most prevalent childhood neurodevelopmental conditions, affecting 3-5% of grade-school children worldwide [1] . It is characterized by i nappropriate levels of inattention, i mpulsivity, and/or hyperactivity [2][3][4] . These symptoms develop in childhood, and can persist into adolescence and adulthood [5] . ADHD seriously affects cognitive development [6][7][8] , and, without appropriate treatment, has consequences for the risk of anxiety, substance abuse, and depression in adulthood [ 2, 5, 9] .T he neurobiological bases o f ADHD symptoms are still not clear [10] . Clarifying them can help better understand the biological vulnerabilities that may underlie ADHD in a specifi c patient and how to modulate the responses to treatment, thereby contributing to better and more effective therapy.It has been suggested that the symptoms involve a dopaminergic mechanism in the prefrontal cortex (PFC) and striatum [11, 12] . Experimentally decreased dopamine (DA) release in the PFC results in ADHD-like symptoms [13, 14] .To date, DA dysregulation is thought to be central to the neurobiology of ADHD, and its pharmacological treatment, such as m ethylphenidate (MPH, i.e. Ritalin) [15][16][17] , levels the DA c oncentration in the synapse and extrasynaptic space in the PFC as a blocker of the DA transporter. MPH ameliorates inappropriate inattention [18][19][20] , decreases impulsivity [21] , and enhances inhibitory control [22] . However, as MPH is a prescription psychostimulant, there are strong concerns over drug dependence, paranoia, schizophrenia, and behavioral sensitization that might be caused by longterm therapy, similar to other stimulants [23][24][25].Converging evidence indicates that the pathophysiology of ADHD has multiple origins [26][27][28][29][30][31][32] ; for i...

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“…60 Finally, patients receiving GXR plus psychostimulant demonstrated significant reductions on the oppositional subscale of the CPRS-R:LF compared to those taking placebo plus psychostimulant, both in the overall study population, as well as in the subgroup of subjects with significant baseline oppositional symptoms. 61 Cost-effectiveness of guanfacine for ADHD ADHD is a costly disease associated with a large economic burden to society and the health care system. 62,63 However, a growing body of research has shown that pharmacotherapy is cost-effective compared with no treatment or behavioral therapy alone among children and adolescents with ADHD.…”

Section: 55mentioning

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

Cited by 29 publications

References 29 publications

A randomized, placebo-controlled trial of extended-release guanfacine in children with autism spectrum disorder and ADHD symptoms: an analysis of secondary outcome measures

A randomized, placebo-controlled trial of extended-release guanfacine in children with autism spectrum disorder and ADHD symptoms: an analysis of secondary outcome measures

Prefrontal cortical α2A-adrenoceptors and a possible primate model of attention deficit and hyperactivity disorder

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

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