A Placebo-Controlled Study of Guanfacine in the Treatment of Children With Tic Disorders and Attention Deficit Hyperactivity Disorder

Scahill, Lawrence; Chappell, Phillip B.; Kim, Young S.; Schultz, Robert T.; Katsovich, Lily; Shepherd, Elizabeth; Arnsten, Amy F.T.; Cohen, Donald J.; Leckman, James F.

doi:10.1176/appi.ajp.158.7.1067

Cited by 507 publications

(312 citation statements)

References 54 publications

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“…Another alpha-2 agonist, guanfacine, was studied in a randomized clinical trial with 34 children with ADHD and chronic tic disorder. At doses ranging from 1.5 to 3 mg per day given in three divided doses, guanfacine was superior to placebo for ADHD symptoms and tics [41].…”

Section: Medications For Tsmentioning

confidence: 92%

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Tourette syndrome and obsessive–compulsive disorder

Lombroso

Scahill

2008

Brain and Development

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Tourette syndrome and obsessive-compulsive disorder are neuropsychiatric disorders that have sparked considerable interest over the decades. They are the focus of research for a remarkable diversity of disciplines, ranging from neuroimagers and prenatal epidemiologists to experts in the neural circuits that connect the cortex with the basal ganglia, as well as neuroimmunologists focusing on brain-based autoimmune phenomena. Several hypotheses have been put forward to explain the onset and exacerbation of these illnesses. Here we discuss the clinical phenomenology and treatment options that are currently available. New psychopharmacological agents are being used that are based on a greater understanding of the neurobiology and are being used in combination with behavioral interventions. Longitudinal clinical investigations into clinical symptoms and the natural course are providing additional clues on the underlying pathophysiology. Recent advances in research models are also reviewed in an attempt to clarify some of the molecular etiologies that lead to these disorders. KeywordsTorrette syndrome; obsessive-compulsive disorder; basal ganglia; autoimmune disorders; streptococcal infections; neuroleptic treatment Tourette syndrome (TS) and obsessive-compulsive disorder (OCD) are model neuropsychiatric disorders that have been the subject of medical interest for centuries [1]. Many explanations have been suggested for the etiology of tics and OCD symptoms and have included genetic factors, the influence of toxins, psychological, and infectious processes. There have been significant advances of our understanding of the neurobiological mechanisms at work in these disorders, as well as improvements in the treatments available. Several reviews on more specialized aspect of TS, OCD and related disorders have appeared over the last several years [2][3][4]. Here we concentrate on the clinical features of tic disorders and OCD and discuss evidence-based interventions for these disorders. Tourette syndromeTourette syndrome is one of several tic disorders that are classified either by their type (motor or phonic tic) or their duration (transient or chronic). The diagnosis of a transient tic is made if the tics are present for less than 12 months. If the tics persist for more than 12 months, they

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Section: Medications For Tsmentioning

confidence: 92%

“…In addition, a conservative approach to dosing of the stimulant as well as combined use of an alpha-2 agonist may reduce the likelihood of tic worsening. Nonstimulant medications such as guanfacine or atomoxetine should be considered for children with ADHD who cannot tolerate stimulant medications [41] [42].…”

Section: Medications For Tsmentioning

confidence: 99%

Tourette syndrome and obsessive–compulsive disorder

Lombroso

Scahill

2008

Brain and Development

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“…It has been reported that clonidine and guanfacine are effective for treatment of human psychiatric disorders that involve PFC dysfunctions, such as attention-deficit/hyperactivity disorder (ADHD) (Arnsten et al, 1996;Arnsten and Li, 2005;Chappell et al, 1995;Hunt et al, 1995;Scahill et al, 2001;Taylor and Russo, 2001), schizophrenia (Friedman et al, 2001(Friedman et al, , 2004 and post-traumatic stress disorder (Horrigan, 1996;Porter and Bell, 1999). Atomoxetine is a reuptake inhibitor of norepinephrine (NE) and has also been used for treatment of ADHD (Gilbert et al, 2007;Perwien et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Stimulation of α2-Adrenoceptors Suppresses Excitatory Synaptic Transmission in the Medial Prefrontal Cortex of Rat

Zhang

et al. 2007

Neuropsychopharmacol

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Stimulation of a 2 -, especially a 2A -adrenoceptor (AR), in the prefrontal cortex (PFC) produces a beneficial effect on cognitive functions such as working memory. a 2 -Adrenergic agonists like clonidine and guanfacine have been used experimentally and clinically for treatment of psychiatric disorders such as attention-deficit/hyperactivity disorder (ADHD) and schizophrenia. However, the neurophysiological actions of a 2 -ARs in the PFC are poorly understood. In the present study, we recorded field excitatory post-synaptic potential (fEPSP) and evoked excitatory post-synaptic current (eEPSC) in the medial prefrontal cortex (mPFC) of rats, using in vivo field-potential recording and in vitro whole-cell patch-clamp recording techniques, and examined the effects of the a 2 -AR agonist clonidine and the selective a 2A -AR agonist guanfacine on fEPSP and eEPSC. Systemic or intra-mPFC application of clonidine or guanfacine significantly reduced fEPSP in the mPFC, either in anesthetized or freely moving rats. Consistently, bath-application of guanfacine suppressed eEPSC in layer V/VI pyramidal neurons, and this effect was blocked by the a 2 -AR antagonist yohimbine or the G i inhibitor NF023. Moreover, treatment with guanfacine had no effect on paired-pulse facilitation (PPF) of fEPSP and eEPSC. The present study provides the first electrophysiological evidence that stimulation of a 2A -AR inhibits excitatory synaptic transmission in the mPFC through a post-synaptic mechanism.

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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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A Placebo-Controlled Study of Guanfacine in the Treatment of Children With Tic Disorders and Attention Deficit Hyperactivity Disorder

Abstract: Guanfacine appears to be a safe and effective treatment for children with tic disorders and ADHD.

Cited by 507 publications

References 54 publications

Tourette syndrome and obsessive–compulsive disorder

Tourette syndrome and obsessive–compulsive disorder

Stimulation of α2-Adrenoceptors Suppresses Excitatory Synaptic Transmission in the Medial Prefrontal Cortex of Rat

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

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