Randomized, Double-Blind Trial of Guanfacine Extended Release in Children With Attention-Deficit/Hyperactivity Disorder: Morning or Evening Administration

Newcorn, Jeffrey H.; Stein, Mark A.; Childress, Ann; Youcha, Sharon; White, Carla; Enright, Gail; Rubin, Jonathan

doi:10.1016/j.jaac.2013.06.006

Cited by 47 publications

(44 citation statements)

References 15 publications

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“…24,25,49,50 However, weightadjusted doses are preferable, by using a dosing regime on a milligram-per-kilogram basis, considering the results from randomized controlled trials (RCTs), starting at doses in the range of 0.05-0.08 mg/kg/day, up to 0.12 mg/kg/day. 33,49,51,52 Indeed, as reported in an open-label dose-escalation pharmacokinetic evaluation, 40 with equal doses of GXR, observed guanfacine plasma concentrations were higher in children than in adolescents and adults, presumably due to the lower body weight of children. 42 Doses above 4 mg/day in children (aged 6-12 years) and above 7 mg/day in adolescents (aged 13-17 years) have not been studied.…”

Section: Dosage and Administrationmentioning

confidence: 91%

“…24,25,49,[51][52][53] The most common TEAEs in these studies associated with GXR compared with placebo were somnolence (27.0%-50.7% versus 3.5%-22.8%), headache (16.7%-26.3% versus 10.6%-24.3%), upper abdominal pain (6.1%-14.3% versus 2.6%-9.1%), fatigue (10.9%-25.4% versus 2.0%-18.0%), and sedation (5.9%-14.5% versus 2.7%-4.5%). Similar rates of TEAEs were detected in long-term extension studies of GXR for ADHD, with somnolence, headache, fatigue, and upper abdominal pain the most common TEAEs.…”

Section: Safety and Tolerability Of Guanfacinementioning

confidence: 99%

“…Indeed, 3.3%-16.2% of patients in the active GXR groups compared to 0%-7.6% in the placebo groups discontinued the study because of TEAEs in short-term RCTs. 24,25,49,[51][52][53] Likewise, the incidence of discontinuation as a result of TEAEs in studies evaluating the safety and efficacy of GXR as an adjunctive treatment to stimulant medications was 6.6%-6.7% for individuals taking GXR and stimulants 26,50 and 0.7% for placebo and stimulants. 26 In the two long-term extension Cardiovascular safety of GXR Dose-dependent, small-to-modest reductions in systolic BP (SBP), diastolic BP (DBP), and HR have been observed in GXR-treated patients, as monotherapy or as an addon to psychostimulants, compared to placebo, approximately -5 mmHg (SBP), -3 mmHg (DBP), and -6 bpm (HR) for all dose groups combined.…”

Section: Safety and Tolerability Of Guanfacinementioning

confidence: 99%

mentioning

confidence: 93%

“…52 GXR-AM or -PM was associated with significant and clinically meaningful improvements in ADHD symptoms, as evidenced by reductions in ADHD-RS-IV scores compared to placebo, with ESs of 0.75 for GXR-AM and 0.78 for GXR-PM, and onset of efficacy starting at first postbaseline visit. 52 A post hoc analysis of the data from this dose-optimization study assessed the consistency of the effects on oppositional and ADHD symptoms throughout the day of once-daily GXR-AM or -PM monotherapy using the CPRS-R:SF. 56 At end point, children taking GXR showed significantly greater improvement from baseline in mean CPRS-R:SF total score, and in each of the morning, afternoon, and evening CPRS-R:SF assessments compared with placebo, regardless of the time of GXR administration (P,0.001).…”

mentioning

confidence: 93%

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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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Section: Dosage and Administrationmentioning

confidence: 91%

Section: Safety and Tolerability Of Guanfacinementioning

confidence: 99%

Section: Safety and Tolerability Of Guanfacinementioning

confidence: 99%

mentioning

confidence: 93%

mentioning

confidence: 93%

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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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Effects of norepinephrine transporter gene variants on NET binding in ADHD and healthy controls investigated by PET

Sigurdardottir

Kranz

Rami‐Mark

et al. 2015

Human Brain Mapping

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Attention deficit hyperactivity disorder (ADHD) is a heterogeneous disorder with a strong genetic component. The norepinephrine transporter (NET) is a key target for ADHD treatment and the NET gene has been of high interest as a possible modulator of ADHD pathophysiology. Therefore, we conducted an imaging genetics study to examine possible effects of single nucleotide polymorphisms (SNPs) within the NET gene on NET nondisplaceable binding potential (BPND) in patients with ADHD and healthy controls (HCs). Twenty adult patients with ADHD and 20 HCs underwent (S,S)‐[18F]FMeNER‐D2 positron emission tomography (PET) and were genotyped on a MassARRAY MALDI‐TOF platform using the Sequenom iPLEX assay. Linear mixed models analyses revealed a genotype‐dependent difference in NET BPND between groups in the thalamus and cerebellum. In the thalamus, a functional promoter SNP (−3081 A/T) and a 5′‐untranslated region (5′UTR) SNP (−182 T/C), showed higher binding in ADHD patients compared to HCs depending on the major allele. Furthermore, we detected an effect of genotype in HCs, with major allele carriers having lower binding. In contrast, for two 3′UTR SNPs (*269 T/C, *417 A/T), ADHD subjects had lower binding in the cerebellum compared to HCs depending on the major allele. Additionally, symptoms of hyperactivity and impulsivity correlated with NET BPND in the cerebellum depending on genotype. Symptoms correlated positively with cerebellar NET BPND for the major allele, while symptoms correlated negatively to NET BPND in minor allele carriers. Our findings support the role of genetic influence of the NE system on NET binding to be pertubated in ADHD. Hum Brain Mapp 37:884–895, 2016. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

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Comparative efficacy and safety of attention-deficit/hyperactivity disorder pharmacotherapies, including guanfacine extended release: a mixed treatment comparison

Joseph¹,

Ayyagari

Xie

et al. 2017

Eur Child Adolesc Psychiatry

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This study compared the clinical efficacy and safety of attention-deficit/hyperactivity disorder (ADHD) pharmacotherapy in children and adolescents 6–17 years of age. A systematic literature review was conducted to identify randomized controlled trials (RCTs) of pharmacologic monotherapies among children and adolescents with ADHD. A Bayesian network meta-analysis was conducted to compare change in symptoms using the ADHD Rating Scale Version IV (ADHD-RS-IV), Clinical Global Impression–Improvement (CGI-I) response, all-cause discontinuation, and adverse event-related discontinuation. Thirty-six RCTs were included in the analysis. The mean (95% credible interval [CrI]) ADHD-RS-IV total score change from baseline (active minus placebo) was −14.98 (−17.14, −12.80) for lisdexamfetamine dimesylate (LDX), −9.33 (−11.63, −7.04) for methylphenidate (MPH) extended release, −8.68 (−10.63, −6.72) for guanfacine extended release (GXR), and −6.88 (−8.22, −5.49) for atomoxetine (ATX); data were unavailable for MPH immediate release. The relative risk (95% CrI) for CGI-I response (active versus placebo) was 2.56 (2.21, 2.91) for LDX, 2.13 (1.70, 2.54) for MPH extended release, 1.94 (1.59, 2.29) for GXR, 1.77 (1.31, 2.26) for ATX, and 1.62 (1.05, 2.17) for MPH immediate release. Among non-stimulant pharmacotherapies, GXR was more effective than ATX when comparing ADHD-RS-IV total score change (with a posterior probability of 93.91%) and CGI-I response (posterior probability 76.13%). This study found that LDX had greater efficacy than GXR, ATX, and MPH in the treatment of children and adolescents with ADHD. GXR had a high posterior probability of being more efficacious than ATX, although their CrIs overlapped.Electronic supplementary materialThe online version of this article (doi:10.1007/s00787-017-0962-6) contains supplementary material, which is available to authorized users.

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Randomized, Double-Blind Trial of Guanfacine Extended Release in Children With Attention-Deficit/Hyperactivity Disorder: Morning or Evening Administration

Cited by 47 publications

References 15 publications

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

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

Effects of norepinephrine transporter gene variants on NET binding in ADHD and healthy controls investigated by PET

Comparative efficacy and safety of attention-deficit/hyperactivity disorder pharmacotherapies, including guanfacine extended release: a mixed treatment comparison

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