guanfacine and ADDH studies

Guanfacine: A centrally acting antihypertensive agent with specificity towards ADRENERGIC ALPHA-2 RECEPTORS.

Research Excerpts

Excerpt	Relevance	Reference
"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."	9.27	A randomized, placebo-controlled trial of extended-release guanfacine in children with autism spectrum disorder and ADHD symptoms: an analysis of secondary outcome measures. ( Figueroa, J; King, B; McCracken, JT; McDougle, CJ; Politte, LC; Scahill, L, 2018)
"While guanfacine appears to be an alternative to psychostimulants among children with developmental disabilities, clinicians need to remain vigilant to the possibility of side effects."	9.13	Guanfacine in children with autism and/or intellectual disabilities. ( Handen, BL; Hardan, AY; Sahl, R, 2008)
"The purpose of this study was to characterize children with Down syndrome and attention-deficit hyperactivity disorder (ADHD) with disruptive behaviors using the Aberrant Behavior Checklist (ABC), and to measure the treatment effects of guanfacine on maladaptive behaviors."	7.83	Guanfacine Use in Children With Down Syndrome and Comorbid Attention-Deficit Hyperactivity Disorder (ADHD) With Disruptive Behaviors. ( Bay, M; Brecher, L; Capone, GT, 2016)
"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."	5.27	A randomized, placebo-controlled trial of extended-release guanfacine in children with autism spectrum disorder and ADHD symptoms: an analysis of secondary outcome measures. ( Figueroa, J; King, B; McCracken, JT; McDougle, CJ; Politte, LC; Scahill, L, 2018)
"To determine whether treatment with guanfacine extended release (GXR) in subjects with attention-deficit/hyperactivity disorder (ADHD) disrupted psychomotor functioning and alertness, or impacted daytime sleepiness."	5.15	Psychomotor functioning and alertness with guanfacine extended release in subjects with attention-deficit/hyperactivity disorder. ( Farrand, K; Kollins, SH; López, FA; Lyne, A; Roth, T; Turnbow, JM; Vince, BD; Wigal, SB, 2011)
"While guanfacine appears to be an alternative to psychostimulants among children with developmental disabilities, clinicians need to remain vigilant to the possibility of side effects."	5.13	Guanfacine in children with autism and/or intellectual disabilities. ( Handen, BL; Hardan, AY; Sahl, R, 2008)
" Search terms included guanfacine, guanfacine extended release, attention deficit disorder with hyperactivity, ADHD, nonstimulant, and alpha-2 adrenergic receptor."	4.89	Guanfacine extended release: a novel treatment for attention-deficit/hyperactivity disorder in children and adolescents. ( Faraone, SV; López, FA; McBurnett, K; Sallee, FR; Steeber, J, 2013)
"In this report, we discuss the case of a 9-year-old male with Attention Deficit Hyperactivity Disorder (ADHD) on long-term methylphenidate and guanfacine who experienced acute orofacial dystonia that resolved immediately with the administration of benztropine."	4.12	Unprovoked Dystonic Reaction in a Child Taking Long-Term Methylphenidate. ( Fromm, C; Mattio, B; Pagliaro, A; Paulson, N; Vidal, J, 2022)
" (2020) present a systematic review with meta-analyses that reports the efficacy of five treatments for children with attention-deficit hyperactivity disorder symptoms in the context of autism spectrum disorder - (a) methylphenidate; (b) atomoxetine; (c) guanfacine; (d) aripiprazole; and (e) risperidone."	4.02	Commentary: Identifying individualized predictions of response in ADHD pharmacotherapy - a commentary on Rodrigues et al. (2020). ( Bloch, MH; Farhat, LC, 2021)
"The purpose of this study was to characterize children with Down syndrome and attention-deficit hyperactivity disorder (ADHD) with disruptive behaviors using the Aberrant Behavior Checklist (ABC), and to measure the treatment effects of guanfacine on maladaptive behaviors."	3.83	Guanfacine Use in Children With Down Syndrome and Comorbid Attention-Deficit Hyperactivity Disorder (ADHD) With Disruptive Behaviors. ( Bay, M; Brecher, L; Capone, GT, 2016)
"We describe a 4-year-old boy who presents to the emergency department with lethargy, bradycardia, and initial hypertension followed by hypotension due to guanfacine toxicity after ingestion of standard doses of the extended release formulation."	3.78	Treatment of guanfacine toxicity with naloxone. ( Dayan, PS; Tsze, DS, 2012)
"Guanfacine is a α2A adrenergic receptor agonist approved for treating attention deficit hyperactivity disorder (ADHD)."	3.11	Noradrenergic Add-on Therapy with Extended-Release Guanfacine in Alzheimer's Disease (NorAD): study protocol for a randomised clinical trial and COVID-19 amendments. ( Fox, C; Golemme, M; Hoang, K; Howard, R; Malhotra, PA; Perry, RJ; Pickett, J; Ritchie, C; Watt, H; Wilson, D, 2022)
" There were no major differences in the incidence/types of treatment-emergent adverse events (TEAEs) across the subgroups."	3.01	Efficacy and safety of guanfacine extended-release in Japanese adults with attention-deficit/hyperactivity disorder: Exploratory post hoc subgroup analyses of a randomized, double-blind, placebo-controlled study. ( Fujiwara, M; Iwanami, A; Kiguchi, R; Naya, N; Okutsu, D; Sakai, C; Tsuji, T, 2021)
" Other measures were ADHD-RS-IV subscales, Clinical Global Impression-Improvement scale (CGI-I) and Patient Global Impression-Improvement scale (PGI-I) (percentage of patients very much improved/much improved), treatment-emergent adverse event (TEAE) incidences, and TEAEs leading to discontinuation."	2.94	Efficacy and Safety of Guanfacine Extended-Release in the Treatment of Attention-Deficit/Hyperactivity Disorder in Adults: Results of a Randomized, Double-Blind, Placebo-Controlled Study. ( Fujiwara, M; Ichikawa, H; Iwanami, A; Okutsu, D; Saito, K, 2020)
" Primary outcome measures were the frequency and nature of treatment-emergent adverse events (TEAEs); secondary outcome measures included the change from week 0 in ADHD Rating Scale IV with Adult Prompts (ADHD-RS-IV; Japanese version) total and subscale scores, Conners' Adult ADHD Rating Scales (CAARS), Clinical Global Impression-Improvement (CGI-I) and Patient Global Impression-Improvement (PGI-I) scales, and quality of life (QoL) and executive functioning measures."	2.94	Safety and efficacy of guanfacine extended-release in adults with attention-deficit/hyperactivity disorder: an open-label, long-term, phase 3 extension study. ( Fujiwara, M; Ichikawa, H; Iwanami, A; Okutsu, D; Saito, K, 2020)
"Guanfacine XR was generally well tolerated by both ethnic groups, with most adverse events being mild in both groups."	2.84	Pharmacokinetics, Safety, and Tolerability of Single and Multiple Doses of Guanfacine Extended-Release Formulation in Healthy Japanese and Caucasian Male Adults. ( Ermer, J; Matsuo, Y; Okita, M; Wajima, T, 2017)
" Trials of amphetamines, atomoxetine, bupropion, clonidine, guanfacine, methylphenidate, and modafinil with a placebo arm and reporting data on headache as an adverse event, were included."	2.82	Headache in ADHD as comorbidity and a side effect of medications: a systematic review and meta-analysis. ( Banaschewski, T; Bölte, S; Buitelaar, JK; Coghill, D; Cortese, S; Häge, A; Hohmann, S; Jonsson, U; Nobel Norrman, H; Pan, PY; Şahpazoğlu Çakmak, SS, 2022)
"Attention Deficit Hyperactivity Disorder is a neurodevelopmental disorder with three presentations: inattentive, hyperactive/impulsive and combined."	2.82	Therapeutic Approaches for ADHD by Developmental Stage and Clinical Presentation. ( Beltran-Navarro, B; Galvez-Contreras, AY; Gonzalez-Castaneda, RE; Gonzalez-Perez, O; Vargas-de la Cruz, I, 2022)
"Two hundred seven participants aged 7-14 years enrolled in an 8-week double-blind randomized trial of GUAN-IR (1-3 milligrams (mg)/day), DMPH (5-20 mg/day), or COMB with fixed-flexible dosing and titrated to optimal behavioral response."	2.82	Acute and Long-Term Cardiovascular Effects of Stimulant, Guanfacine, and Combination Therapy for Attention-Deficit/Hyperactivity Disorder. ( Castelo, E; Cowen, J; Levitt, J; McCracken, JT; McGough, JJ; Sayer, GR; Sturm, A, 2016)
"670) h(-1) for the absorption rate constant, and 0."	2.80	Population Pharmacokinetic Modeling of Guanfacine in Pediatric Patients. ( Corcoran, M; Ermer, J; Gastonguay, MR; Knebel, W, 2015)
" Safety assessments included treatment-emergent adverse events (TEAEs), electrocardiograms and vital signs."	2.79	Efficacy and safety of extended-release guanfacine hydrochloride in children and adolescents with attention-deficit/hyperactivity disorder: a randomized, controlled, phase III trial. ( Bloomfield, R; Hervas, A; Huss, M; Johnson, M; Lyne, A; McNicholas, F; Robertson, B; Sikirica, V; Sreckovic, S; van Stralen, J, 2014)
" For many adolescents, such dosing would exceed 4 mg/day, the highest approved dose."	2.79	Pharmacokinetics and pharmacodynamics of guanfacine extended release in adolescents aged 13-17 years with attention-deficit/hyperactivity disorder. ( Corcoran, M; Ermer, J; Martin, P; Padilla, AF; Satin, L; Stevenson, A; Vince, BD; White, C, 2014)
" The levels of response and tolerability observed with GXR were similar regardless of time of dosing (morning versus evening), indicating that once-daily GXR monotherapy is effective whether administered in the morning or evening."	2.78	Randomized, double-blind trial of guanfacine extended release in children with attention-deficit/hyperactivity disorder: morning or evening administration. ( Childress, AC; Enright, G; Newcorn, JH; Rubin, J; Stein, MA; White, C; Youcha, S, 2013)
"In the presence of PTSD symptoms, children with ADHD experienced significantly improved ADHD symptom scores, suggesting that comorbidity does not attenuate an ADHD symptom response to GXR therapy."	2.78	An open-label study of guanfacine extended release for traumatic stress related symptoms in children and adolescents. ( Banga, A; Connor, DF; Grasso, DJ; Pearson, GS; Slivinsky, MD, 2013)
" change in the ADHD rating scale, fourth edition [ADHD-RS-IV] total score from baseline) was compared between each GXR dosing group and the ATX group."	2.77	Cost effectiveness of guanfacine extended-release versus atomoxetine for the treatment of attention-deficit/hyperactivity disorder: application of a matching-adjusted indirect comparison. ( Chen, KS; Erder, MH; Hodgkins, P; Lu, M; Signorovitch, JE; Sikirica, V; Wu, EQ; Xie, J, 2012)
"Treatment with guanfacine XR at optimized doses was associated with mostly mild or moderate TEAEs."	2.75	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. ( Connor, DF; Findling, RL; Kollins, SH; López, FA; Lyne, A; Sallee, F; Tremblay, G, 2010)
"Guanfacine has been shown to reduce hyperactive behaviors in children with attention-deficit/hyperactivity disorder (ADHD) and possibly in children with pervasive developmental disorder (PDD) and hyperactivity."	2.75	Possible influence of variant of the P-glycoprotein gene (MDR1/ABCB1) on clinical response to guanfacine in children with pervasive developmental disorders and hyperactivity. ( Aman, MG; Arnold, LE; McCracken, JT; McDougle, CJ; Posey, D; Ritz, L; Scahill, L; Shiraga, S; Tierney, E; Vitiello, B; Whelan, F, 2010)
"Safety assessments included adverse events (AEs), vital signs, physical examination, clinical laboratory tests, the Pediatric Daytime Sleepiness Scale, and the Pittsburgh Side Effects Rating Scale."	2.74	Safety and effectiveness of coadministration of guanfacine extended release and psychostimulants in children and adolescents with attention-deficit/hyperactivity disorder. ( Ginsberg, LD; Greenbaum, M; Murphy, WR; Spencer, TJ, 2009)
"The majority of adverse events (AEs) were mild to moderate, and few patients discontinued the study because of an AE."	2.74	Long-term safety and efficacy of guanfacine extended release in children and adolescents with attention-deficit/hyperactivity disorder. ( Lyne, A; McGough, JJ; Sallee, FR; Wigal, T, 2009)
" Somnolence, sedation, and fatigue adverse events emerged within the first 2 weeks of dosing and generally resolved by study end."	2.74	Guanfacine extended release in children and adolescents with attention-deficit/hyperactivity disorder: a placebo-controlled trial. ( Biederman, J; Donahue, J; Lyne, A; McGough, J; Sallee, FR; Wigal, T, 2009)
"Guanfacine is a noradrenergic agonist that is believed to improve symptoms of attention-deficit/hyperactivity disorder (ADHD) through selective actions at alpha2A-adrenoceptors in the prefrontal cortex."	2.73	Long-term, open-label extension study of guanfacine extended release in children and adolescents with ADHD. ( Biederman, J; Donahue, J; Lyne, A; McBurnett, K; Melmed, RD; Patel, A, 2008)
" All mean vital-sign measurements and mean ECG parameters remained within normal limits after dosing and no marked changes from baseline measurements were noted."	2.73	A phase I, randomized, open-label, crossover study of the single-dose pharmacokinetic properties of guanfacine extended-release 1-, 2-, and 4-mg tablets in healthy adults. ( Fiske, K; Lyne, A; Pennick, M; Shojaei, A; Swearingen, D, 2007)
"Blood samples, vital signs, and electrocardiograms (ECGs) were obtained before dosing on day 1 and at intervals over 24 hours, with repeat measurements on days 14 and 28."	2.73	Pharmacokinetics of a guanfacine extended-release formulation in children and adolescents with attention-deficit-hyperactivity disorder. ( Boellner, SW; Fiske, K; Lyne, A; Pennick, M; Shojaei, A, 2007)
"Methylphenidate was associated with a nonsignificant elevated risk of dropout due to adverse events."	2.72	Practitioner Review: Pharmacological treatment of attention-deficit/hyperactivity disorder symptoms in children and youth with autism spectrum disorder: a systematic review and meta-analysis. ( Ameis, SH; Anagnostou, E; Anderson, KK; Beswick, A; Gorman, DA; Lai, MC; Rodrigues, R; Szatmari, P, 2021)
"Guanfacine is an alpha2-adrenergic receptor agonist that has been shown to have beneficial effects on working memory and attentional functions in monkeys and in patients with attention deficit hyperactivity disorder."	2.71	Lack of effects of guanfacine on executive and memory functions in healthy male volunteers. ( Clark, L; Lam, ML; Menon, DK; Moore, RM; Müller, U; Murphy, CL; Richmond, NK; Robbins, TW; Sahakian, BJ; Sandhu, RS; Wilkins, IA, 2005)
"Subjects from a specialty tic disorders clinic were randomly assigned to receive 8 weeks of treatment with guanfacine or placebo under double-blind conditions."	2.70	A placebo-controlled study of guanfacine in the treatment of children with tic disorders and attention deficit hyperactivity disorder. ( Arnsten, AF; Chappell, PB; Cohen, DJ; Katsovich, L; Kim, YS; Leckman, JF; Scahill, L; Schultz, RT; Shepherd, E, 2001)
" The mechanism of this proposed interaction may involve drug-drug competition at the level of hepatic glucuronidation (conjugation), although shifts in protein binding cannot be ruled out."	2.69	Increased plasma valproate concentrations when coadministered with guanfacine. ( Ambrosini, PJ; Sheikh, RM, 1998)
"A 6-year-old boy referred for language delay and hyperactivity."	2.66	[ADCY5-associated dyskinesia in young children: a case report of a family and an updated review]. ( Aguilera-Nieto, L; Calvo-Medina, R; Ferrero-Turrión, J; Mora-Ramírez, MD; Ramos-Fernández, JM; Ruiz-García, C, 2020)
" In one study, tics limited further dosage increases of methylphenidate."	2.58	Pharmacological treatment for attention deficit hyperactivity disorder (ADHD) in children with comorbid tic disorders. ( Osland, ST; Pringsheim, T; Steeves, TD, 2018)
" 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."	2.55	Comparative efficacy and safety of attention-deficit/hyperactivity disorder pharmacotherapies, including guanfacine extended release: a mixed treatment comparison. ( Ayyagari, R; Cai, S; Huss, M; Joseph, A; Sikirica, V; Xie, J; Xie, M, 2017)
" Clonidine, melatonin, L-theanine, eszopiclone and guanfacine were well tolerated with mild to moderate adverse events; zolpidem was associated with neuropsychiatric adverse effects."	2.55	Safety, Tolerability and Efficacy of Drugs for Treating Behavioural Insomnia in Children with Attention-Deficit/Hyperactivity Disorder: A Systematic Review with Methodological Quality Assessment. ( Anand, S; Besag, FMC; Chan, EW; Cortese, S; Tong, H; Wong, ICK, 2017)
"Guanfacine is a selective α2A-adrenergic receptor agonist that has been shown to improve prefrontal cortical cognitive function, including working memory."	2.53	Guanfacine Extended Release: A New Pharmacological Treatment Option in Europe. ( Chen, W; Huss, M; Ludolph, AG, 2016)
"Guanfacine is an important medication option in very young children; however, there is a significant pharmacologic "information gap," and further research is needed to help establish appropriate, safe, and effective dosing of guanfacine in this population."	2.53	Clinical and Pharmacologic Considerations for Guanfacine Use in Very Young Children. ( Black, BT; Jones, BL; Kearns, GL; Soden, SE, 2016)
"Guanfacine is an α2A-adrenoreceptor agonist currently indicated for the treatment of attention deficit hyperactivity disorder (ADHD)."	2.52	Guanfacine for the treatment of attention deficit hyperactivity disorder in children and adolescents. ( Martino, D; Rizzo, R, 2015)
" While medications for ADHD are generally well-tolerated, there are common, although less severe, as well as rare but severe adverse events AEs during treatment with ADHD drugs."	2.49	Practitioner review: current best practice in the management of adverse events during treatment with ADHD medications in children and adolescents. ( Banaschewski, T; Buitelaar, J; Coghill, D; Cortese, S; Danckaerts, M; Dittmann, RW; Graham, J; Holtmann, M; Sergeant, J; Taylor, E, 2013)
"Guanfacine ER was relatively well tolerated in clinical trials in children and adolescents."	2.46	Guanfacine extended-release: in attention deficit hyperactivity disorder. ( Muir, VJ; Perry, CM, 2010)
" Side effects of stimulants are generally mild, short lived, and responsive to adjustments in dosage or timing."	2.44	Changes and challenges: managing ADHD in a fast-paced world. ( Bukstein, OG; Crismon, ML; Manos, MJ; Tom-Revzon, C, 2007)
" This review focuses on the tolerability, occurrence of adverse events, precautions required to prevent severe adverse events, and essential pharmacological interaction in the treatment of ADHD symptoms by non-stimulants."	2.43	The safety of non-stimulant agents for the treatment of attention-deficit hyperactivity disorder. ( Banaschewski, T; Heise, CA; Himpel, S; Rothenberger, A, 2005)
" Methylphenidate and amphetamine-based stimulants are now available in longer-acting, once-daily and shorter-acting divided dosing schedules."	2.42	Pharmacological management of attention-deficit hyperactivity disorder. ( Reeves, G; Schweitzer, J, 2004)
"Clonidine has not been adequately examined but seems to have small or uncertain effects."	2.40	Antidepressants in the treatment of attention-deficit/hyperactivity disorder. ( Popper, CW, 1997)
" The dosage administered as milligram per body weight to balance the potential benefits and risks of treatment."	1.72	Determination of Guanfacine in Oral Fluid and Serum of Children and Adolescents with Attention-Deficit/Hyperactivity Disorder: A Short Communication. ( Fekete, S; Gerlach, M; Högger, P; Romanos, M; Scherf-Clavel, O; Wohkittel, C, 2022)
" Human mesenchymal stem cells (hMSCs) were incubated with a therapeutic plasma dosage of modafinil, atomoxetine and guanfacine."	1.72	Psychostimulants Modafinil, Atomoxetine and Guanfacine Impair Bone Cell Differentiation and MSC Migration. ( Böker, KO; Di Fazio, P; Jäckle, K; Lehmann, W; Schilling, AF; Wagener, N; Weiser, L, 2022)
" However, its pharmacokinetic properties and tolerability make viloxazine ER a useful addition to the collection of FDA approved ADHD treatments."	1.72	Evaluating the pharmacokinetics of extended release viloxazine in the treatment of children with attention-deficit/hyperactivity disorder. ( Burton, S; Childress, A, 2022)
"Only daytime sleepiness was more common for those receiving α2-adrenergic agonists vs stimulants (38% vs 3%); several adverse effects were reported more commonly for those receiving stimulants vs α2-adrenergic agonists, including moodiness/irritability (50% vs 29%), appetite suppression (38% vs 7%), and difficulty sleeping (21% vs 11%)."	1.62	α2-Adrenergic Agonists or Stimulants for Preschool-Age Children With Attention-Deficit/Hyperactivity Disorder. ( Barbaresi, W; Bax, A; Blum, NJ; Cacia, J; Deavenport-Saman, A; Friedman, S; Harstad, E; LaRosa, A; Loe, IM; Mittal, S; Shults, J; Tulio, S; Vanderbilt, D, 2021)
" Systemically, chronic administration of therapeutically relevant doses of guanfacine for 14 days increased the basal release of norepinephrine in the OFC, VTA, RTN, and dopamine release in the OFC via the downregulation of the α2A adrenoceptor in the LC, OFC and VTA."	1.62	Chronic Administrations of Guanfacine on Mesocortical Catecholaminergic and Thalamocortical Glutamatergic Transmissions. ( Fukuyama, K; Nakano, T; Okada, M; Shiroyama, T, 2021)
" The aims of this study were to develop a population pharmacokinetic model of guanfacine after administration of GXR and to evaluate factors influencing the pharmacokinetics of guanfacine in pediatric ADHD patients."	1.51	Population pharmacokinetic and exposure-response analyses of guanfacine in Japanese pediatric ADHD patients. ( Matsumoto, S; Matsuo, Y; Tsuda, Y; Wajima, T, 2019)
"7%) experienced a treatment-emergent adverse event (TEAE)."	1.48	Long-term safety and efficacy of guanfacine extended release in children and adolescents with ADHD. ( Dirks, B; Gu, J; Huss, M; Newcorn, JH; Ramos-Quiroga, JA; Robertson, B, 2018)
" The results of clinical pharmacokinetic (PK) studies indicate that guanfacine is sensitive to drug-drug interactions (DDIs) perpetrated by strong inhibitors and inducers of CYP3A4."	1.48	Development of Guanfacine Extended-Release Dosing Strategies in Children and Adolescents with ADHD Using a Physiologically Based Pharmacokinetic Model to Predict Drug-Drug Interactions with Moderate CYP3A4 Inhibitors or Inducers. ( Li, A; Rong, H; Welty, D; Yeo, K, 2018)
" The IR forms, while themselves not FDA approved for ADHD, may, with dosage adjustment, be reasonable alternatives (with considerable cost savings)."	1.43	Treating ADHD in Prison: Focus on Alpha-2 Agonists (Clonidine and Guanfacine). ( Mattes, JA, 2016)
" Results were consistent in a variety of dosage range comparisons and within increasingly heterogeneous trial populations."	1.39	Comparative efficacy of guanfacine extended release versus atomoxetine for the treatment of attention-deficit/hyperactivity disorder in children and adolescents: applying matching-adjusted indirect comparison methodology. ( Dammerman, R; Erder, MH; Findling, RL; Hodgkins, P; Lu, M; Signorovitch, J; Sikirica, V; Wu, EQ; Xie, J, 2013)
" This report documents the time course and predictors of symptom efficacy and sedation-related adverse events (AEs) that emerge during GXR treatment throughout 3 randomized, placebo-controlled, double-blind trials of the drug."	1.36	Effects of extended-release guanfacine on ADHD symptoms and sedation-related adverse events in children with ADHD. ( Faraone, SV; Glatt, SJ, 2010)
"Guanfacine was well tolerated, and did not lead to significant changes in blood pressure or heart rate."	1.32	Guanfacine treatment of hyperactivity and inattention in pervasive developmental disorders: a retrospective analysis of 80 cases. ( Kem, DL; McDougle, CJ; Posey, DJ; Puntney, JI; Sasher, TM, 2004)
"Guanfacine exposures reported to the American Association of Poison Control Centers Toxic Exposure Surveillance System from 1993 to 1999 in children and adolescents <19 years of age were analyzed."	1.31	Epidemiology and toxicity of pediatric guanfacine exposures. ( Klein-Schwartz, W; McGrath, JC, 2002)
"Guanfacine hydrochloride is an alpha-2 adrenergic agonist, which has gained recent attention in the field of child and adolescent psychiatry."	1.30	Guanfacine and secondary mania in children. ( Barnhill, LJ; Horrigan, JP, 1999)
"Many children with Tourette's syndrome (TS) are handicapped more by difficulties with inattention, impulsivity, and hyperactivity than by their tics."	1.29	Guanfacine treatment of comorbid attention-deficit hyperactivity disorder and Tourette's syndrome: preliminary clinical experience. ( Arnsten, A; Chappell, PB; Cohen, DJ; Leckman, JF; Lynch, KA; Riddle, MA; Scahill, L; Schultz, R, 1995)

Research

Studies (190)

Authors

Clinical Trials (29)

Trial Overview

Trial Outcomes

ADHD IV Rating Scale (Attention Deficit Hyperactivity Disorder Rating Scale)

Timeframe	Studies, this research(%)	All Research%
pre-1990	0 (0.00)	18.7374
1990's	9 (4.74)	18.2507
2000's	33 (17.37)	29.6817
2010's	108 (56.84)	24.3611
2020's	40 (21.05)	2.80

Authors	Studies
Pan, PY	1
Jonsson, U	1
Şahpazoğlu Çakmak, SS	1
Häge, A	1
Hohmann, S	1
Nobel Norrman, H	1
Buitelaar, JK	1
Banaschewski, T	3
Cortese, S	5
Coghill, D	3
Bölte, S	1
Roessner, V	1
Eichele, H	1
Stern, JS	1
Skov, L	1
Rizzo, R	2
Debes, NM	1
Nagy, P	1
Cavanna, AE	1
Termine, C	1
Ganos, C	1
Münchau, A	1
Szejko, N	1
Cath, D	1
Müller-Vahl, KR	1
Verdellen, C	1
Hartmann, A	1
Rothenberger, A	2
Hoekstra, PJ	1
Plessen, KJ	1
Holden, JM	1
Newcorn, JH	12
Krone, B	2
Dittmann, RW	2
Takahashi, Y	1
Mikami, K	1
Kimoto, K	1
Onishi, Y	1
Yamamoto, K	1
Matsumoto, H	1
Childress, A	2
Burton, S	1
Hoang, K	1
Watt, H	1
Golemme, M	1
Perry, RJ	1
Ritchie, C	1
Wilson, D	1
Pickett, J	1
Fox, C	1
Howard, R	1
Malhotra, PA	1
Michelini, G	2
Lenartowicz, A	2
Diaz-Fong, JP	1
Bilder, RM	5
McGough, JJ	7
McCracken, JT	10
Loo, SK	5
Vera, JD	1
Bruno, C	1
Havard, A	1
Gillies, MB	1
Brett, J	1
Guastella, AJ	1
Pearson, SA	1
Zoega, H	1
Wagener, N	1
Lehmann, W	1
Weiser, L	1
Jäckle, K	1
Di Fazio, P	1
Schilling, AF	1
Böker, KO	1
Galvez-Contreras, AY	1
Vargas-de la Cruz, I	1
Beltran-Navarro, B	1
Gonzalez-Castaneda, RE	1
Gonzalez-Perez, O	1
Shimozato, A	3
Ohashi, K	3
Saitoh, S	3
Yu, S	1
Shen, S	1
Tao, M	1
Radonjić, NV	1
Bellato, A	1
Khoury, NM	1
Faraone, SV	5
Ayata, R	1
Fujita, M	1
Harada, K	2
Esaki, Y	1
Koga, Y	1
Hisamoto, Y	1
Asami-Noyama, M	1
Takeda, S	1
Tsuruta, R	1
Tsuda, Y	1
Matsuo, Y	2
Matsumoto, S	1
Wajima, T	2
Kawabe, K	1
Horiuchi, F	1
Ueno, SI	1
de Groof, C	1
De La Marche, W	1
Danckaerts, M	2
Iwanami, A	3
Saito, K	3
Fujiwara, M	3
Okutsu, D	3
Ichikawa, H	2
Huss, M	8
Connor, DF	7
Hervás, A	3
Werner-Kiechle, T	1
Robertson, B	6
Anderson, J	1
Wang, C	1
Zaidi, A	1
Rice, T	2
Coffey, BJ	2
Aguilera-Nieto, L	1
Ferrero-Turrión, J	1
Mora-Ramírez, MD	1
Calvo-Medina, R	1
Ruiz-García, C	1
Ramos-Fernández, JM	1
Downs, JW	1
Wills, BK	1
Cumpston, KL	1
Wolf, CE	2
Rose, SR	1
Grimmsmann, T	1
Himmel, W	1
Rodrigues, R	1
Lai, MC	1
Beswick, A	1
Gorman, DA	1
Anagnostou, E	1
Szatmari, P	1
Anderson, KK	1
Ameis, SH	1
Jogamoto, T	1
Utsunomiya, R	1
Sato, A	1
Kihara, N	1
Choudhury, ME	1
Miyanishi, K	1
Kubo, M	1
Nagai, M	1
Nomoto, M	1
Yano, H	1
Shimizu, YI	1
Fukuda, M	1
Ishii, E	1
Eguchi, M	1
Tanaka, J	1
Arnsten, AFT	1
Elliott, J	1
Johnston, A	1
Husereau, D	1
Kelly, SE	1
Eagles, C	1
Charach, A	1
Hsieh, SC	1
Bai, Z	1
Hossain, A	1
Skidmore, B	1
Tsakonas, E	1
Chojecki, D	1
Mamdani, M	1
Wells, GA	1
Cutler, AJ	5
Mattingly, GW	2
Jain, R	2
O'Neal, W	1
Naya, N	1
Sakai, C	1
Kiguchi, R	1
Tsuji, T	1
Joshi, G	1
Wilens, T	2
Firmin, ES	1
Hoskova, B	1
Biederman, J	7
Farhat, LC	1
Bloch, MH	1
Hasan, SS	1
Bal, N	1
Baker, I	1
Kow, CS	1
Khan, MU	1
Pagliaro, A	1
Mattio, B	1
Paulson, N	1
Fromm, C	1
Vidal, J	1
Fukuyama, K	1
Nakano, T	1
Shiroyama, T	1
Okada, M	1
Harstad, E	1
Shults, J	1
Barbaresi, W	1
Bax, A	1
Cacia, J	1
Deavenport-Saman, A	1
Friedman, S	1
LaRosa, A	1
Loe, IM	1
Mittal, S	1
Tulio, S	1
Vanderbilt, D	1
Blum, NJ	1
Ota, T	1
Yamamuro, K	1
Okazaki, K	1
Kishimoto, T	1
Sasaki, Y	1
Tsujii, N	1
Sasaki, S	1
Sunakawa, H	1
Toguchi, Y	1
Tanase, S	1
Shinohara, R	1
Kurokouchi, T	1
Sugimoto, K	1
Itagaki, K	1
Yoshida, Y	1
Namekata, S	1
Takahashi, M	1
Harada, I	1
Hakosima, Y	1
Inazaki, K	1
Yoshimura, Y	1
Mizumoto, Y	1
Okada, T	1
Usami, M	1
Wohkittel, C	1
Scherf-Clavel, O	1
Fekete, S	1
Romanos, M	1
Högger, P	1
Gerlach, M	1
Anand, S	1
Tong, H	1
Besag, FMC	1
Chan, EW	1
Wong, ICK	1
Okita, M	1
Ermer, J	4
Naguy, A	1
Li, A	1
Yeo, K	1
Welty, D	1
Rong, H	1
Howes, OD	1
Rogdaki, M	1
Findon, JL	1
Wichers, RH	1
Charman, T	1
King, BH	1
Loth, E	1
McAlonan, GM	1
Parr, JR	1
Povey, C	1
Santosh, P	1
Wallace, S	1
Simonoff, E	1
Murphy, DG	1
Molife, C	1
Haynes, VS	1
Nyhuis, A	1
Faries, DE	1
Gelwicks, S	1
Kelsey, DK	1
Alatorre, CI	2
van Stralen, JPM	1
Dirks, B	2
Gu, J	1
Ramos-Quiroga, JA	2
Politte, LC	1
Scahill, L	9
Figueroa, J	1
King, B	1
McDougle, CJ	6
Weiss-Goldman, N	1
Arditi, B	1
Osland, ST	1
Steeves, TD	1
Pringsheim, T	1
Strathaus, RS	1
McBurnett, K	7
Bliss, C	1
Gao, J	1
Bastiaens, L	1
Scott, O	1
Galus, J	1
Rostain, A	1
Jensen, PS	1
Miesle, LM	1
Haynes, V	1
Faries, D	1
Upadhyaya, H	1
Kelsey, D	1
Erder, MH	5
Xie, J	6
Signorovitch, JE	2
Chen, KS	2
Hodgkins, P	4
Lu, M	4
Wu, EQ	5
Sikirica, V	14
Grasso, DJ	1
Slivinsky, MD	1
Pearson, GS	2
Banga, A	1
Sallee, F	2
Fernández-Jaén, A	2
Martín Fernández-Mayoralas, D	2
Fernández-Perrone, AL	2
Calleja-Pérez, B	1
Muñoz-Jareño, N	2
López-Arribas, S	1
Fein, DM	1
Hafeez, ZF	1
Cavagnaro, C	1
Stein, MA	2
Childress, AC	2
Youcha, S	5
White, C	5
Enright, G	1
Rubin, J	3
Findling, RL	4
Signorovitch, J	2
Dammerman, R	2
Wilens, TE	5
Turnbow, J	1
Rugino, T	3
Sallee, FR	6
Steeber, J	1
López, FA	3
Fontane, E	1
Shiber, J	1
Kawaura, K	1
Karasawa, J	1
Chaki, S	1
Hikichi, H	1
Arnsten, AF	8
Greco, GF	1
Walton, J	1
Byrum, M	1
Shumaker, A	1
Coury, DL	1
Pillidge, K	1
Porter, AJ	1
Dudley, JA	1
Tsai, YC	1
Heal, DJ	1
Stanford, SC	1
Martin, P	2
Satin, L	2
Kahn, RS	1
Robinson, A	1
Corcoran, M	3
Purkayastha, J	1
Ermer, JC	1
Ruggiero, S	1
Clavenna, A	1
Reale, L	1
Capuano, A	1
Rossi, F	1
Bonati, M	1
Brams, M	2
Bukstein, O	2
Mattingly, G	1
Young, J	1
Lyne, A	14
Knebel, W	2
Rogers, J	1
Polhamus, D	1
Gastonguay, MR	2
Rugino, TA	1
Johnson, M	2
McNicholas, F	1
van Stralen, J	2
Sreckovic, S	2
Bloomfield, R	3
Gaiser, EC	1
Matuskey, D	1
Perkins, E	1
D'Amico, C	1
Abdelghany, O	1
McKee, SA	1
Cosgrove, KP	1
Bédard, AC	1
Schulz, KP	1
Pedraza, J	1
Duhoux, S	1
Halperin, JM	2
Kim, RK	1
Chayer, R	1
Martino, D	1
Suehs, BT	1
Mudumby, P	1
Dufour, R	1
Patel, NC	1
Harper, L	1
Young, JL	2
Rynkowski, G	1
Weiss, MD	2
Chen, W	1
Ludolph, AG	1
Buoli, M	1
Serati, M	1
Cahn, W	1
Butterfield, ME	1
Saal, J	1
Young, B	1
Lachaine, J	2
Mathurin, K	1
Harpin, V	1
Dutray, B	1
Black, BT	1
Soden, SE	1
Kearns, GL	1
Jones, BL	1
Capone, GT	1
Brecher, L	1
Bay, M	1
Vince, BD	2
Padilla, AF	1
Stevenson, A	1
Sohn, M	1
Talbert, J	1
Moga, DC	1
Blumenschein, K	1
Chan, E	1
Fogler, JM	1
Hammerness, PG	1
Elbe, D	1
Perel-Panar, C	1
Wicholas, L	1
Mattes, JA	1
Alamo, C	1
López-Muñoz, F	1
Sánchez-García, J	1
Levitt, J	3
Del'Homme, M	3
Cowen, J	4
Sturm, A	4
Whelan, F	3
Hellemann, G	2
Sugar, C	2
Hanada, G	1
Cho, AL	1
Walshaw, P	1
Piacentini, J	1
Sayer, GR	1
Castelo, E	1
Shafrin, J	1
Shrestha, A	1
Chandra, A	1
Katic, A	1
Anderson, RH	1
Meyers, J	1
Gajria, K	1
Candrilli, SD	1
Fridman, M	1
Joseph, A	1
Ayyagari, R	1
Xie, M	1
Cai, S	1
Handen, BL	1
Sahl, R	1
Hardan, AY	1
McGough, J	1
Wigal, T	2
Donahue, J	2
Levy, F	1
Hollander, E	1
Melmed, RD	2
Patel, A	3
Glatt, SJ	1
Rostain, AL	1
Spencer, TJ	2
Greenbaum, M	1
Ginsberg, LD	1
Murphy, WR	1
Aman, MG	2
Tierney, E	2
Shiraga, S	1
Arnold, LE	2
Posey, D	2
Ritz, L	2
Vitiello, B	2
Glazer, WM	1
Stahl, SM	1

Trial	Phase	Enrollment	Study Type	Start Date	Status
Randomised Clinical Trial of Noradrenergic Add-on Therapy With Extended-Release Guanfacine in Alzheimer's Disease[NCT03116126]	Phase 3	160 participants (Anticipated)	Interventional	2019-01-04	Recruiting
An Eight-Week, Randomized, Double-Blind Comparison of Guanfacine, Focalin XR, and the Combination, With a Twelve Month Open-Label Extension for the Treatment of ADHD in Pediatric Subjects Aged 7 to 14 Years[NCT00429273]	Phase 4	212 participants (Actual)	Interventional	2007-01-31	Completed
Efficacy of Pharmacologic Management of ADHD in Children and Youth With Autism Spectrum Disorder[NCT05916339]	Phase 4	500 participants (Anticipated)	Interventional	2023-10-01	Not yet recruiting
An Observational Study Investigating the Experience of Patients Undergoing Active Insomnia Clinical Trials[NCT05978271]		500 participants (Anticipated)	Observational	2024-08-31	Not yet recruiting
A Phase 3, Open-label, Multicentre Study to Provide Access to Guanfacine Hydrochloride Extended-release for European Subjects With Attention-deficit/Hyperactivity Disorder (ADHD) Who Participated in Study SPD503-315 or SPD503-316[NCT01500694]	Phase 3	215 participants (Actual)	Interventional	2012-03-20	Completed
A Phase 3, Double-blind, Randomized, Multicenter, Placebo-controlled, Dose Optimization Study Evaluating the Tolerability and Efficacy of AM and PM Once Daily Dosing With Extended-release Guanfacine Hydrochloride in Children Aged 6-12 With a Diagnosis of [NCT00997984]	Phase 3	340 participants (Actual)	Interventional	2009-11-17	Completed
Guanfacine for PONV and Pain After Sinus Surgery[NCT02882854]		84 participants (Actual)	Interventional	2016-11-30	Completed
A Phase I, Randomized, Gender Stratified, Double-Blind, Placebo- and Positive-Controlled, Three Period Crossover Trial to Assess the Effect of Guanfacine Hydrochloride on QT/QTc Interval in Healthy Men and Women[NCT00672984]	Phase 1	83 participants (Actual)	Interventional	2008-04-18	Completed
A Phase III, Double-Blind, Randomized, Placebo-Controlled, Multi-Center, Dose Optimization Study Evaluating the Efficacy and Safety of SPD503 in Combination With Psychostimulants in Children and Adolescents Aged 6-17 Years With a Diagnosis of Attention-De[NCT00734578]	Phase 3	461 participants (Actual)	Interventional	2008-09-02	Completed
A Phase 3, Randomised, Double-blind, Multicentre, Parallel-group, Placebo- and Active-reference, Dose-optimisation Efficacy and Safety Study of Extended-release Guanfacine Hydrochloride in Children and Adolescents Aged 6-17 Years With Attention-Deficit/Hy[NCT01244490]	Phase 3	338 participants (Actual)	Interventional	2011-01-17	Completed
Neurobiological Basis of Response to Guanfacine Extended Release in Children and Adolescents With Attention-deficit/Hyperactivity Disorder (ADHD): an Functional Magnetic Resonance Imaging(fMRI) Study of Brain Activation Pre and Post Treatment[NCT01709695]	Phase 4	27 participants (Actual)	Interventional	2011-03-31	Completed
A Phase 3, Double-blind, Randomized, Multi-center, Placebo Controlled, Dose-optimization Study Evaluating the Safety, Efficacy, and Tolerability of Once Daily Dosing With Extended-release Guanfacine Hydrochloride in Adolescents Aged 13-17 Years Diagnosed [NCT01081132]	Phase 3	314 participants (Actual)	Interventional	2011-09-19	Completed
Double-Blind, Randomized, Placebo-Controlled, Single- Center, Dose Optimization Study Evaluating Efficacy and Safety of Guanfacine Hydrochloride in Combination With Psychostimulants in Adults Aged 18-65 Years With a Diagnosis of ADHD[NCT02141113]	Phase 4	26 participants (Actual)	Interventional	2012-11-30	Completed
A Phase 3, Double-blind, Placebo-controlled, Multicentre, Randomised Withdrawal, Long-term Maintenance of Efficacy and Safety Study of Extended-release Guanfacine Hydrochloride in Children and Adolescents Aged 6-17 With Attention Deficit/Hyperactivity Dis[NCT01081145]	Phase 3	528 participants (Actual)	Interventional	2010-05-11	Completed
Open Label Study for the Use of Transcranial Ultrasound Treatment of Attention Deficit Hyperactive Disorder[NCT04497363]		100 participants (Anticipated)	Interventional	2020-07-01	Enrolling by invitation
A Phase III, Randomized, Double-Blind, Multi-Center, Parallel-Group, Placebo-Controlled Safety and Efficacy Study of SPD503 in Children and Adolescents Aged 6-17 With Attention Deficit Hyperactivity Disorder (ADHD)[NCT00150618]	Phase 3	324 participants (Actual)	Interventional	2004-03-30	Completed
Phase 4 Study of the Effect of Extended Release Guanfacine on Working Memory in Children With ADHD[NCT01177306]	Phase 4	18 participants (Actual)	Interventional	2010-07-31	Completed
A Phase II, Open-Label Co-Administration Study of SPD503 and Psychostimulants in Children and Adolescents Aged 6-17 With Attention-Deficit/Hyperactivity Disorder (ADHD)[NCT00151996]	Phase 2	75 participants (Actual)	Interventional	2004-08-16	Completed
A Double-Blind, Randomized, Multi-Center, Flexible Dose Study Evaluating the Efficacy and Safety of SPD503 (Guanfacine Hydrochloride) in Children Aged 6-12 With Symptoms of Oppositionality and a Diagnosis of Attention Deficit/Hyperactivity Disorder[NCT00367835]	Phase 3	217 participants (Actual)	Interventional	2006-12-04	Completed
A Phase II Study to Assess the Safety, Tolerability and Efficacy of SPD503 Administered to Children and Adolescents Aged 6-17 With Attention-Deficit/Hyperactivity Disorder (ADHD)[NCT00150592]	Phase 2	182 participants (Actual)	Interventional	2005-05-12	Completed
Therapeutic Use of Repetitive Transcranial Magnetic Stimulation (rTMS) in Pediatric Autism Spectrum Disorder (ASD) and Attention Deficit Hyperactivity Cohorts (ADHD): a Randomized, Sham-controlled Study.[NCT06069323]		80 participants (Anticipated)	Interventional	2023-06-01	Recruiting
A Multi-Center, Open Label, Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With Attention Deficit Hyperactivity Disorder and Autism Spectrum Disorder[NCT03337646]	Phase 4	48 participants (Actual)	Interventional	2018-09-26	Active, not recruiting
Methylphenidate for Hyperactivity and Impulsiveness in Children and Adolescents With Pervasive Developmental Disorders[NCT00025779]		60 participants	Interventional	2001-10-31	Completed
Characterization of Endogenous Melatonin Profiles in Children With Autism Spectrum Disorder.[NCT00691080]		58 participants (Actual)	Observational	2007-09-30	Completed
Guanfacine for the Treatment of Hyperactivity in Pervasive Developmental Disorder[NCT01238575]	Phase 4	62 participants (Actual)	Interventional	2011-12-31	Completed
A Phase III, Randomized, Multi-Center, Double-Blind, Parallel-Group, Placebo-Controlled Safety and Efficacy Study of SPD503 in Children and Adolescents Aged 6-17 With Attention-Deficit/Hyperactivity Disorder (ADHD)[NCT00152009]	Phase 3	345 participants (Actual)	Interventional	2003-01-29	Completed
The Effects of Ketamine and Guanfacine on Working Memory in Healthy Subjects[NCT01600885]		16 participants (Actual)	Interventional	2008-08-31	Completed
A Single-blind, Randomised, Sham Controlled, Phase IIa Exploratory Clinical Trial, to Examine the Safety and Efficacy of BGX-3006 (tPCS) on Paediatric ADHD Participants.[NCT02323633]	Phase 2	48 participants (Anticipated)	Interventional	2015-01-31	Not yet recruiting
Transcranial Magnetic Stimulation for Individuals With Tourette's Syndrome[NCT00529308]	Phase 2	20 participants (Actual)	Interventional	2007-07-31	Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

"The primary clinical efficacy variable for treatment was the ADHD-RS-IV (Attention-Deficit/Hyperactivity Disorder Rating Scale) Total Score and two sub-scales (Inattentive and Hyperactive-Impulsive ).~The rating scale has 18 questions with answer options: None (0), Mild (1), Moderate (2) and Severe (3). Min 0; max 3.~Scores are obtained by summing each item; The higher the score, the worse the outcome.~Total score range: 0-54 Total Inattentive score range: 0-27 Total Hyperactive/Impulsive score range: 0-27" (NCT00429273)
Timeframe: Measured at baseline Week 4 and Week 8

"Number of Participants With Suicidal Behavior and / or Ideation (Yes Response) on the Columbia Suicide Severity Rating Scale (C-SSRS)"

Intervention	units on a scale (Least Squares Mean)
	Total ADHD-RS Score	Inattentive Subscale	Hyperactive Impulsive Subscale
Estimated Difference Between DMPH and Placebo	-7.99	-4.10	-4.0
Estimated Difference Between Guan and Placebo	-7.77	-4.14	-3.73
Estimated Difference Between Placebo and Combo	-10.66	-5.89	-5.10

"C-SSRS is a clinician rated assessment of suicidal behavior and / or intent categorized as: Suicidal behavior=a yes response to any of 5 suicidal behavior questions (preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide); Suicidal ideation=a yes response to any one of 5 suicidal ideation questions which includes wish to be dead, and 4 different categories of active suicidal ideation (thought, thought with method, thought with intent, thought with plan and intent)." (NCT01500694)
Timeframe: Final Assessment (last non missing data/up to Day 714)

Change From Baseline in Attention-deficit and Hyperactivity Disorder Rating Scale-IV (ADHD-RS-IV) - Total Score at Final Assessment

Intervention	participants (Number)
	Suicidal Ideation: Wish to be Dead	Suicidal Ideation: Non-specific Suicidal Thoughts	Suicidal Behaviour: Actual Attempt	Suicidal Behaviour: Non-Suicidal Self-Injurious	Suicidal Behaviour: Interrupted Attempt	Suicidal Behaviour: Aborted Attempt
SPD503 (13-18 Years)	1	0	0	1	0	0
SPD503 (6-12 Years)	0	0	0	0	0	0

ADHD-RS-IV was developed to measure the behaviours of children with ADHD with 18 items. Each item is scored from a range of 0 (reflecting no symptoms) to 3 (reflecting severe symptoms) with total scores ranging from 0-54. The 18 items may be grouped into 2 subscales: hyperactivity/impulsivity (even numbered items 2-18) and inattentiveness (odd numbered items 1-17) with possible score range from 0 (no symptoms) to 27 (most severe symptoms). The ADHD-RS-IV possible total scores range from 0 (no symptoms) to 54 (most severe symptoms). Final Assessment is the last valid assessment obtained after Baseline (Visit 2/Day 0) whilst on investigational product and before first dose taper medication (Visit 19/ET/Day 714). (NCT01500694)
Timeframe: Baseline (Day 0) and Final Assessment (last non missing data/up to Day 714)

Change From Baseline in Electrocardiogram Result (QRS Interval) at Final Assessment

Intervention	units on a scale (Mean)
	Baseline (n = 127, 81)	Change at Final Assessment (n = 126, 80)
SPD503 (13-18 Years)	31.2	-19.3
SPD503 (6-12 Years)	40.0	-20.2

Final Assessment is the last valid assessment obtained after Baseline (Visit 2/Day 0) whilst on investigational product and before first dose taper medication (Visit 19/ET/Day 714). (NCT01500694)
Timeframe: Baseline (Day 0) and Final Assessment (last non missing data/up to Day 714)

Change From Baseline in Electrocardiogram Result (QT Interval) at Final Assessment

Intervention	millisecond (ms) (Mean)
	Baseline (n=131, 83)	Change at Final Assessment (n=127, 77)
SPD503 (13-18 Years)	89.7	1.8
SPD503 (6-12 Years)	84.9	1.8

Change From Baseline in Mean Diastolic Blood Pressure at Final Assessment

Intervention	millisecond (ms) (Mean)
	Baseline (n = 131, 83)	Change at Final Assessment (n = 127, 77)
SPD503 (13-18 Years)	375.9	9.5
SPD503 (6-12 Years)	361.4	16.9

Diastolic Blood pressure was measured at supine and standing position and mean supine diastolic blood pressure was reported here. Final Assessment is the last valid assessment obtained after Baseline (Visit 2/Day 0) whilst on investigational product and before first dose taper medication (Visit 19/ET/Day 714). (NCT01500694)
Timeframe: Baseline (Day 0) and Final Assessment (last non missing data/up to Day 714)

Change From Baseline in Mean Height at Final Assessment

Intervention	millimeter of mercury (mmHg) (Mean)
	Baseline (n=131, 83)	Change at Final Assessment (n = 130, 82)
SPD503 (13-18 Years)	66.8	0.1
SPD503 (6-12 Years)	64.3	0.2

Change From Baseline in Mean Supine Pulse at Final Assessment

Intervention	centimeter (cm) (Mean)
	Baseline (n = 131, 83)	Change at Final Assessment (n = 128, 79)
SPD503 (13-18 Years)	166.32	5.54
SPD503 (6-12 Years)	142.03	8.80

Pulse was measured at supine and standing position and mean supine pulse was reported here. Final Assessment is the last valid assessment obtained after Baseline (Visit 2/Day 0) whilst on investigational product and before first dose taper medication (Visit 19/ET/Day 714). (NCT01500694)
Timeframe: Baseline (Day 0) and Final Assessment (last non missing data/up to Day 714)

Change From Baseline in Mean Systolic Blood Pressure at Final Assessment

Intervention	beats per minute (bpm) (Mean)
	Baseline (n = 131, 83)	Change at Final Assessment (n = 130, 82)
SPD503 (13-18 Years)	72.1	-2.9
SPD503 (6-12 Years)	79.3	-7.1

Systolic Blood pressure was measured at supine and standing position and mean supine systolic blood pressure was reported here. Final Assessment is the last valid assessment obtained after Baseline (Visit 2/Day 0) whilst on investigational product and before first dose taper medication [Visit 19/Early Termination (ET)/Day 714]. (NCT01500694)
Timeframe: Baseline (Day 0) and Final Assessment (last non missing data/up to Day 714)

Change From Baseline in Mean Weight at Final Assessment

Intervention	millimeter of mercury (mmHg) (Mean)
	Baseline (n = 131, 83)	Change at Final Assessment (n = 130, 82)
SPD503 (13-18 Years)	113.5	0.3
SPD503 (6-12 Years)	107.5	0.9

Number of Participants Assessed With Clinical Global Impression Severity of Illness (CGI-S) Scale

Intervention	kilogram (kg) (Mean)
	Baseline (n = 131, 83)	Change at Final Assessment (n = 128, 79)
SPD503 (13-18 Years)	58.53	6.74
SPD503 (6-12 Years)	37.29	8.96

The CGI-S evaluate each participant's severity and improvement over time. The severity of a participant's condition is rated on a 7-point scale ranging from 1 to 7. The scale measures 0 = Not assessed, 1 = Normal, not at all ill, 2 = Borderline mentally ill (BL-MI), 3 = Mildly ill, 4 = Moderately ill, 5 = Markedly ill, 6 = Severely ill, 7 = Among the most extremely ill participant. Final Assessment is the last valid assessment obtained after Baseline (Visit 2/Day 0) whilst on investigational product and before first dose taper medication (Visit 19/ET/Day 714). (NCT01500694)
Timeframe: Baseline (Day 0) and Final Assessment (last non missing data/up to Day 714)

Change From Baseline in Attention-Deficit/Hyperactivity Disorder-Rating Scale-IV (ADHD-RS-IV) Total Score at Week 8 - Last Observation Carried Forward (LOCF)

Intervention	participants (Number)
	Baseline: Normal/BL-MI (n=127,81)	Baseline: Mildly ill or greater (n=127, 81)	Final assessment: Normal/BL-MI (n=127,80)	Final Assessment:Mildly ill or greater(n=127,80)
SPD503 (13-18 Years)	2	79	51	29
SPD503 (6-12 Years)	0	127	45	82

The ADHD-RS-IV consists of 18 items scored on a 4-point scale ranging from 0 (no symptoms) to 3 (severe symptoms) with total score ranging from 0 to 54. (NCT00997984)
Timeframe: Baseline and up to 8 weeks

Change From Baseline in Conner's Parent Rating Scale - Revised Short Version (CPRS-R:S) Score at Week 8 - LOCF

Intervention	Units on a scale (Least Squares Mean)
Placebo	-10.6
SPD503 AM	-20.0
SPD503 PM	-20.4
All-Active	-20.2

The Conner's Parent rating Scale-revised short version (CPRS-R) consists of 27 questions graded on a scale from 0 (not true at all) to 3 (very much true) with a total score ranging from 0 to 81. Higher scores are indicative of increased ADHD. This scale allows parents to respond on the basis of the child's behavior and help assess ADHD and evaluate problem behavior. (NCT00997984)
Timeframe: Baseline and up to 8 weeks

Change From Baseline in Health Utilities Index-2/3 (HUI 2/3) Scores at Week 8 - LOCF

Intervention	Units on a scale (Least Squares Mean)
Placebo	-10.4
SPD503 AM	-22.9
SPD503 PM	-21.2
All-Active	-22.0

Change From Baseline in Height at Week 8 - LOCF

Change From Baseline in Mean Weiss Functional Impairment Rating Scale - Parent Report (WFIRS-P) Global Score at Week 8 - LOCF

Intervention	Units on a scale (Mean)
Placebo	0.043
SPD503 AM	0.056
SPD503 PM	0.063
All-Active	0.060

Intervention	inches (Mean)
Placebo	0.28
SPD503 AM	0.39
SPD503 PM	0.43
All-Active	0.41

The WFIRS-P is a 50-item scale with each item scored from 0 (never/not at all) to 3 (very often/very much). Higher scores indicate greater functional impairment. Mean scores range from 0 to 3. (NCT00997984)
Timeframe: Baseline and up to 8 weeks

Change From Baseline in Oral Temperature at Week 8 - LOCF

Change From Baseline in Pediatric Daytime Sleepiness Scale (PDSS) Total Score at Week 8 - LOCF

Intervention	Units on a scale (Least Squares Mean)
Placebo	-0.20
SPD503 AM	-0.35
SPD503 PM	-0.37
All-Active	-0.36

Intervention	º F (Mean)
Placebo	0.06
SPD503 AM	-0.12
SPD503 PM	-0.09
All-Active	-0.10

The Pediatric Daytime Sleepiness Scale (PDSS) is an 8 question questionnaire scored on a scale from 0 (never) to 4 (always). Total scores range from 0 to 32, with increasing score reflecting greater sleepiness. (NCT00997984)
Timeframe: Baseline and up to 8 weeks

Change From Baseline in the Bedtime Resistance Subscale of Child's Sleep Habits Questionnaire (CSHQ) at Week 8 - LOCF

Intervention	Units on a scale (Least Squares Mean)
Placebo	-3.1
SPD503 AM	-2.7
SPD503 PM	-1.4
All-Active	-2.0

The bedtime resistance subscale of CSHQ consists of 6 items scored on a scale from 1 (never/rarely) to 3 (Usually). A higher score reflects more disturbed sleep behavior. (NCT00997984)
Timeframe: Baseline and up to 8 weeks

Change From Baseline in Weight at Week 8 - LOCF

Improvement on Clinical Global Impression-Improvement (CGI-I) Scale at Week 8 - LOCF

Intervention	Units on a scale (Least Squares Mean)
Placebo	-0.7
SPD503 AM	-0.5
SPD503 PM	-1.0
All-Active	-0.8

Intervention	pounds (Mean)
Placebo	2.15
SPD503 AM	2.37
SPD503 PM	2.64
All-Active	2.50

Clinical Global Impression-Improvement (CGI-I) consists of a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). Improvement includes a score of 1 (very much improved) or 2 (much improved) on the scale. (NCT00997984)
Timeframe: up to 8 weeks

Assessment of Clinical Global Impression-Severity of Illness (CGI-S) at Week 8 - LOCF

Intervention	Percent of Participants (Number)
Placebo	31.8
SPD503 AM	66.3
SPD503 PM	67.0
All-Active	66.7

CGI-S assesses the severity of the subject's condition on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill) (NCT00997984)
Timeframe: Baseline and up to 8 weeks

Change From Baseline in Diastolic Blood Pressure at Week 8 - LOCF

Change From Baseline in Pulse Rate at Week 8 - LOCF

Change From Baseline in Systolic Blood Pressure at Week 8 - LOCF

Post Sleep Questionnaire (PSQ) Quality of Sleep at Week 8 - LOCF

Intervention	Percent of Participants (Number)
	Normal, not at all ill	Borderline mentally ill	Mildly ill	Moderately ill	Markedly ill	Severely ill	Among the most extremely ill
All-Active	13.9	20.4	30.1	22.2	11.1	1.9	0.5
Placebo	4.5	8.2	15.5	34.5	30.0	7.3	0.0
SPD503 AM	11.5	20.2	32.7	22.1	11.5	1.0	1.0
SPD503 PM	16.1	20.5	27.7	22.3	10.7	2.7	0.0

Intervention	mmHg (Mean)
	Supine	Standing	Orthostatic
All-Active	-1.5	-2.4	-0.9
Placebo	-0.3	0.2	0.4
SPD503 AM	-0.8	-2.2	-1.4
SPD503 PM	-2.1	-2.5	-0.4

Intervention	beats per minute (Mean)
	Supine	Standing
All-Active	-3.8	-2.1
Placebo	1.0	0.9
SPD503 AM	-3.7	-1.9
SPD503 PM	-3.8	-2.3

Intervention	mmHg (Mean)
	Supine	Standing	Orthostatic
All-Active	-1.9	-3.0	-1.1
Placebo	-0.5	-1.4	-0.9
SPD503 AM	-1.6	-3.3	-1.7
SPD503 PM	-2.1	-2.7	-0.6

Post Sleep Questionnaire (PSQ) overall rating of quality of sleep. There are 5 rating responses ranging from very poor to very good. No numbers are associated with the rating responses. (NCT00997984)
Timeframe: up to 8 weeks

PACU Length of Stay in Minutes

Intervention	Percent of Participants (Number)
	Very poor	Poor	Average	Good	Very good
All-Active	0.5	6.5	26.9	46.8	19.4
Placebo	2.7	6.4	29.1	35.5	26.4
SPD503 AM	1.0	5.8	26.0	42.3	25.0
SPD503 PM	0.0	7.1	27.7	50.9	14.3

(NCT02882854)
Timeframe: Time frame between arrival and discharge in PACU, approximately 90 minutes

Postoperative Nausea Assessment Using 11-point Nausea Scale (nVRS)

Intervention	minutes (Median)
Guanfacine	128
Placebo	110

PONV assessed using nVRS at 24 hours postop when 0 is no nausea and 10 is worst nausea. (NCT02882854)
Timeframe: 24 hours post op

Postoperative Pain Assessment Using 11-point Visual/Verbal Analog (VAS)

Intervention	score on a scale (Median)
Guanfacine	0.00
Placebo	0.00

Postoperative pain assessment using VAS at 24 hours postop when 0 is no pain and 10 is worst pain (NCT02882854)
Timeframe: 24 hours postop

Total Narcotic Requirement in PACU

Intervention	score on a scale (Median)
Guanfacine	3
Placebo	2

Total narcotic requirement in PACU tallied in morphine equivalents during PACU stay (NCT02882854)
Timeframe: Time frame between arrival and discharge in PACU, approximately 90 minutes

Maximum Postoperative Pain Assessment Using 11-point Visual/Verbal Analog (VAS)

Intervention	morphine equivalents (Median)
Guanfacine	8.75
Placebo	7.50

Maximum postoperative pain assessment assessed in PACU at 15, 30 and 60 minutes after PACU arrival using VAS when 0 is no pain and 10 is worst pain (NCT02882854)
Timeframe: 15, 30, 60 minutes after arriving in PACU

Area Under the Steady-state Plasma Concentration-time Curve (AUC) for Guanfacine and Moxifloxacin on Day 1

Intervention	Participants (Count of Participants)
	15 minutes after PACU admission72482977	15 minutes after PACU admission72482978	30 minutes after PACU admission72482977	30 minutes after PACU admission72482978	60 minutes after PACU admission72482977	60 minutes after PACU admission72482978
	Mild (Pain nVRS 1-5)	Moderate/Severe (Pain nVRS 6-10)	None (Pain nVRS 0)
Guanfacine	31
Placebo	24
Guanfacine	0
Placebo	5
Guanfacine	8
Placebo	10
Guanfacine	18
Placebo	20
Guanfacine	7
Placebo	6
Guanfacine	14
Placebo	14
Guanfacine	12
Placebo	16
Guanfacine	6
Placebo	13
Guanfacine	21
Placebo	12

(NCT00672984)
Timeframe: pre-dose and 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose

Area Under the Steady-state Plasma Concentration-time Curve (AUC) for Guanfacine and Moxifloxacin on Day 6

Intervention	ng.h/ml (Mean)
Guanfacine 4 mg	110.8
Moxifloxacin	19892

(NCT00672984)
Timeframe: pre-dose and 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose

Change From Baseline in Electrocardiogram Results (QT) Interval at Tmax on Day 1

Intervention	ng.h/ml (Mean)
Guanfacine 8 mg	370.3
Moxifloxacin	20767

QT interval is a measure of time between the start of the Q wave and the end of the T wave and is dependent on the heart rate (e.g., the faster the heart rate, the shorter the QT interval). (NCT00672984)
Timeframe: Baseline and Tmax (time of subject-specific maximum plasma concentration)

Change From Baseline in Electrocardiogram Results (QT) Interval at Tmax on Day 6

Intervention	msec (Least Squares Mean)
Guanfacine 4 mg	15.88
Moxifloxacin	-1.27
Placebo (Guanfacine)	0.56
Placebo (Moxifloxacin)	-2.20

Change From Baseline in Electrocardiogram Results (QTcF) at Tmax on Day 1

Intervention	msec (Least Squares Mean)
Guanfacine 8 mg	46.21
Moxifloxacin	-3.09
Placebo (Guanfacine)	-3.63
Placebo (Moxifloxacin)	-6.71

QTcF is the QT interval using Fridericia's correction formula. QT interval is a measure of time between the start of the Q wave and the end of the T wave and is dependent on the heart rate (e.g., the faster the heart rate, the shorter the QT interval). The QT interval has to be corrected in order to aid interpretation. (NCT00672984)
Timeframe: Baseline and Tmax (time of subject-specific maximum plasma concentration)

Change From Baseline in Electrocardiogram Results (QTcF) at Tmax on Day 6

Intervention	msec (Least Squares Mean)
Guanfacine 4 mg	0.15
Moxifloxacin	9.96
Placebo (Guanfacine)	-0.83
Placebo (Moxifloxacin)	-1.14

Change From Baseline in Electrocardiogram Results (QTcNi) at Time of Maximum Plasma Concentration (Tmax) on Day 1

Intervention	msec (Least Squares Mean)
Guanfacine 8 mg	-2.67
Moxifloxacin	6.44
Placebo (Guanfacine)	-4.31
Placebo (Moxifloxacin)	-4.35

QTcNi is the QT interval using a subject-specific correction formula. QT interval is a measure of time between the start of the Q wave and the end of the T wave and is dependent on the heart rate (e.g., the faster the heart rate, the shorter the QT interval). The QT interval has to be corrected in order to aid interpretation. (NCT00672984)
Timeframe: Baseline, Tmax (time of subject-specific maximum plasma concentration)

Change From Baseline in Electrocardiogram Results (QTcNi) at Tmax on Day 6

Intervention	msec (Least Squares Mean)
Guanfacine 4 mg	-3.37
Moxifloxacin	12.96
Placebo (Guanfacine)	-0.94
Placebo (Moxifloxacin)	-0.91

QTcNi is the QT interval using a subject-specific correction formula. QT interval is a measure of time between the start of the Q wave and the end of the T wave and is dependent on the heart rate (e.g., the faster the heart rate, the shorter the QT interval). The QT interval has to be corrected in order to aid interpretation. (NCT00672984)
Timeframe: Baseline and Tmax (time of subject-specific maximum plasma concentration)

Change From Baseline in Heart Rate (HR) at Tmax on Day 1

Intervention	msec (Least Squares Mean)
Guanfacine 8 mg	-12.45
Moxifloxacin	8.99
Placebo (Guanfacine)	-4.37
Placebo (Moxifloxacin)	-4.13

(NCT00672984)
Timeframe: Baseline and Tmax (time of subject-specific maximum plasma concentration)

Change From Baseline in Heart Rate (HR) at Tmax on Day 6

Intervention	bpm (Least Squares Mean)
Guanfacine 4 mg	-7.18
Moxifloxacin	5.46
Placebo (Guanfacine)	-0.42
Placebo (Moxifloxacin)	0.73

(NCT00672984)
Timeframe: Baseline and Tmax (time of subject-specific maximum plasma concentration)

Maximum Plasma Concentration (Cmax) of Guanfacine and Moxifloxacin on Day 1

Intervention	bpm (Least Squares Mean)
Guanfacine 8 mg	-19.74
Moxifloxacin	4.66
Placebo (Guanfacine)	0.11
Placebo (Moxifloxacin)	1.22

(NCT00672984)
Timeframe: pre-dose and 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose

Maximum Plasma Concentration (Cmax) of Guanfacine and Moxifloxacin on Day 6

Intervention	ng/ml (Mean)
Guanfacine 4 mg	8.51
Moxifloxacin	1943.1

(NCT00672984)
Timeframe: pre-dose and 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose

Time of Maximum Plasma Concentration (Tmax) of Guanfacine and Moxifloxacin on Day 1

Intervention	ng/ml (Mean)
Guanfacine 8 mg	24.70
Moxifloxacin	2003.4

(NCT00672984)
Timeframe: pre-dose and 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose

Time of Maximum Plasma Concentration (Tmax) of Guanfacine and Moxifloxacin on Day 6

Intervention	hours (Mean)
Guanfacine 4 mg	3.9
Moxifloxacin	2.13

(NCT00672984)
Timeframe: pre-dose and 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose

Change From Baseline in Attention Deficit Hyperactivity Disorder Rating Scale-fourth Edition (ADHD-RS-IV) Total Score at Week 8 - Last Observation Carried Forward (LOCF)

Intervention	hours (Mean)
Guanfacine 8 mg	5.2
Moxifloxacin	1.78

The ADHD-RS-IV consists of 18 items scored on a 4-point scale ranging from 0 (no symptoms) to 3 (severe symptoms) with total score ranging from 0 to 54. (NCT00734578)
Timeframe: Baseline and weekly up to 8 weeks

Change From Baseline in Before School Functioning Questionnaire (BSFQ) at Week 8 - LOCF

Intervention	Units on a scale (Mean)
SPD503-AM + Psychostimulant	-20.4
SPD503-PM + Psychostimulant	-21.0
Placebo + Psychostimulant	-16.0

This scale was designed to assess symptoms of ADHD that typically occur in the morning. The BSFQ consists of two components. The first, a 20-item scale with ratings from 0 (none) to 3 (severe) with a range of 0-60 followed by two questions answered with duration of time (in minutes). The second, a 14-item scale with ratings from 0 (no) to 2 (a lot) with a range of 0-28. The results reported here are from the 20-item scale. Lower scores are better. (NCT00734578)
Timeframe: Baseline and weekly up to 8 weeks

Change From Baseline in Conners' Global Index - Parent (CGI-P) Total Score at Week 8 - LOCF: Evening Assessment (Before Bedtime)

The index contains 10 items. Each item on the scale is scored from a range of 0 (reflecting never, seldom) to 3 (reflecting very often, very frequent) with total scores ranging from 0 30. (NCT00734578)
Timeframe: Baseline and weekly up to 8 weeks

Change From Baseline in Conners' Global Index - Parent (CGI-P) Total Score at Week 8 - LOCF: Morning Assessment (Before School)

The index contains 10 items. Each item on the scale is scored from a range of 0 (reflecting never, seldom) to 3 (reflecting very often, very frequent) with total scores ranging from 0 to 30. (NCT00734578)
Timeframe: Baseline and weekly up to 8 weeks

Change From Baseline in the Oppositional Subscale of the Conners' Parent Rating Scale-Revised Long Form (CPRS-R:L) Score at Week 8 - LOCF

The oppositional subscale of the CPRS-R:L contains 10 items designed to reflect criteria for oppositional defiance disorder (ODD). Each item is scored on a range from 0 (not true at all) to 3 (very much true) with total scores ranging from 0 to 30. Higher scores are reflective of more severe symptoms. (NCT00734578)
Timeframe: Baseline and weekly up to 8 weeks

Percentage of Participants With Improvement on Clinical Global Impression-Improvement (CGI-I) at Week 8 - LOCF

Percentage of Participants With Improvement on Parent Global Assessment (PGA) at Week 8 - LOCF

Parent Global Assessment (PGA) consists of a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved) or 2 (much improved) on the scale. (NCT00734578)
Timeframe: Baseline and week 8

Assessment of Clinical Global Impression-Severity of Illness (CGI-S) at Week 8 - LOCF

CGI-S assesses the severity of the subject's condition on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill) (NCT00734578)
Timeframe: Baseline and weekly up to 8 weeks

Post Sleep Questionnaire (PSQ) Quality of Sleep at Week 8 - LOCF

Change From Baseline in Attention Deficit Hyperactivity Disorder Rating Scale-fourth Edition (ADHD-RS-IV) Total Score at Week 10/13 - Last Observation Carried Forward (LOCF)

The ADHD-RS-IV consists of 18 items scored on a 4-point scale ranging from 0 (no symptoms) to 3 (severe symptoms) with total score ranging from 0 to 54. Outcome measure is at 10 weeks for ages 6-12 years and at 13 weeks for ages 13-17 years. (NCT01244490)
Timeframe: Baseline and Up to 10 weeks for children aged 6-12 years and up to 13 weeks for adolescents aged 13-17 years

Change From Baseline in Brief Psychiatric Rating Scale for Children (BPRS-C) Total Score at Weeks 10/13 - LOCF

The BPRS-C characterizes childhood behavioral and emotional symptomatology. A total of 21 items are rated on a scale from 0 (not present) to 6 (extremely severe) with a total score ranging from 0 to 126. A decrease in score indicates a reduction in psychopathology. Outcome measure is at 10 weeks for ages 6-12 years and at 13 weeks for ages 13-17 years. (NCT01244490)
Timeframe: Baseline and up to 10 weeks for children aged 6-12 years and up to 13 weeks for adolescents aged 13-17 years

Change From Baseline in the Weiss Functional Impairment Rating Scale - Parent Report (WFIRS-P) Learning and School Domain Scores at Week 10/13 - LOCF

The WFIRS-P Learning in School Domain is the mean of 10 items, ranging from 0 (never/not at all) to 3 (very often/very much). Higher scores indicate greater functional impairment. Outcome measure is at 10 weeks for ages 6-12 years and at 13 weeks for ages 13-17 years. (NCT01244490)
Timeframe: Baseline and Up to 10 weeks for children aged 6-12 years and up to 13 weeks for adolescents aged 13-17 years

Change From Baseline in the WFIRS-P Academic Performance Domain Score at Week 10/13 - LOCF

The WFIRS-P Academic Performance Domain is the mean of 4 items, ranging from 0 (never/not at all) to 3 (very often/very much). Higher scores indicate greater functional impairment. Outcome measure is at 10 weeks for ages 6-12 years and at 13 weeks for ages 13-17 years. (NCT01244490)
Timeframe: Up to 10 weeks for children aged 6-12 years and up to 13 weeks for adolescents aged 13-17 years

Change From Baseline in the WFIRS-P Behavior in School Domain Score at Week 10/13 - LOCF

The WFIRS-P Behavior in School Domain is the mean of 6 items, ranging from 0 (never/not at all) to 3 (very often/very much). Higher scores indicate greater functional impairment. Outcome measure is at 10 weeks for ages 6-12 years and at 13 weeks for ages 13-17 years. (NCT01244490)
Timeframe: Up to 10 weeks for children aged 6-12 years and up to 13 weeks for adolescents aged 13-17 years

Change From Baseline in the WFIRS-P Child Self-Concept Domain Score at Week 10/13 - LOCF

The WFIRS-P Child Self-Concept Domain is the mean of 3 items, ranging from 0 (never/not at all) to 3 (very often/very much). Higher scores indicate greater functional impairment. Outcome measure is at 10 weeks for ages 6-12 years and at 13 weeks for ages 13-17 years. (NCT01244490)
Timeframe: Up to 10 weeks for children aged 6-12 years and up to 13 weeks for adolescents aged 13-17 years

Change From Baseline in the WFIRS-P Family Domain Score at Week 10/13 - LOCF

The WFIRS-P Family Domain is the mean of 10 items, ranging from 0 (never/not at all) to 3 (very often/very much). Higher scores indicate greater functional impairment. Outcome measure is at 10 weeks for ages 6-12 years and at 13 weeks for ages 13-17 years. (NCT01244490)
Timeframe: Baseline and Up to 10 weeks for children aged 6-12 years and up to 13 weeks for adolescents aged 13-17 years

Change From Baseline in the WFIRS-P Global Score at Week 10/13 - LOCF

The WFIRS-P Global Score is the mean of 50 items, ranging from 0 (never/not at all) to 3 (very often/very much). Higher scores indicate greater functional impairment. Outcome measure is at 10 weeks for ages 6-12 years and at 13 weeks for ages 13-17 years. (NCT01244490)
Timeframe: Baseline and Up to 10 weeks for children aged 6-12 years and up to 13 weeks for adolescents aged 13-17 years

Change From Baseline in the WFIRS-P Life Skills Domain Score at Week 10/13 - LOCF

The WFIRS-P Life Skills Domain is the mean of 10 items, ranging from 0 (never/not at all) to 3 (very often/very much). Higher scores indicate greater functional impairment. Outcome measure is at 10 weeks for ages 6-12 years and at 13 weeks for ages 13-17 years. (NCT01244490)
Timeframe: Up to 10 weeks for children aged 6-12 years and up to 13 weeks for adolescents aged 13-17 years

Change From Baseline in the WFIRS-P Risk Domain Score at Week 10/13 - LOCF

The WFIRS-P Risk Domain is the mean of 10 items, ranging from 0 (never/not at all) to 3 (very often/very much). Higher scores indicate greater functional impairment. Outcome measure is at 10 weeks for ages 6-12 years and at 13 weeks for ages 13-17 years. (NCT01244490)
Timeframe: Up to 10 weeks for children aged 6-12 years and up to 13 weeks for adolescents aged 13-17 years

Change From Baseline in the WFIRS-P Social Domain Score at Week 10/13 - LOCF

The WFIRS-P Social Domain is the mean of 7 items, ranging from 0 (never/not at all) to 3 (very often/very much). Higher scores indicate greater functional impairment. Outcome measure is at 10 weeks for ages 6-12 years and at 13 weeks for ages 13-17 years. (NCT01244490)
Timeframe: Up to 10 weeks for children aged 6-12 years and up to 13 weeks for adolescents aged 13-17 years

Health Utilities Index-2/3 (HUI 2/3) Scores - LOCF

HUI is used to describe health status and to obtain utility scores by collecting data using one or more questionnaires in formats selected to match the specific study design criteria. Scoring ranges from 0.00 (dead) to 1.00 (perfect health). Higher scores represent better health status. Outcome measure is at 10 weeks for ages 6-12 years and at 13 weeks for ages 13-17 years. (NCT01244490)
Timeframe: Up to 10 weeks for children aged 6-12 years and up to 13 weeks for adolescents aged 13-17 years

Percentage of Participants With Improvement on Clinical Global Impression-Improvement (CGI-I) Scores

Clinical Global Impression-Improvement (CGI-I) consists of a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved) or 2 (much improved) on the scale. Outcome measure is at 10 weeks for ages 6-12 years and at 13 weeks for ages 13-17 years. (NCT01244490)
Timeframe: Up to 10 weeks for children aged 6-12 years and up to 13 weeks for adolescents aged 13-17 years

Clinical Global Impression-Severity of Illness (CGI-S) - LOCF

CGI-S assesses the severity of the subject's condition on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill). Outcome measure is at 10 weeks for ages 6-12 years and at 13 weeks for ages 13-17 years. (NCT01244490)
Timeframe: Up to 10 weeks for children aged 6-12 years and up to 13 weeks for adolescents aged 13-17 years

Columbia-Suicide Severity Rating Scale (C-SSRS)

C-SSRS is a semi-structured interview that captures the occurence, severity, and frequency of suicide-related thoughts and behaviors during the assessment period. The interview includes definitions and suggested questions to solicit the type of information needed to determine if a suicide-related thought or behaviour occurred. The assessment is done by the nature of the responses, not by a numbered scale. Outcome measure is at 12 weeks for ages 6-12 years and at 15 weeks for ages 13-17 years. (NCT01244490)
Timeframe: Up to 12 weeks for children aged 6-12 years and up to 15 weeks for adolescents aged 13-17 years

Structure Side-Effect Questionnaire

The Structured Side-effect Questionnaire is a simple checklist of 17 side effects. The subject indicates whether a side effect has occurred since the last visit by marking 'yes' on the checklist for each of the events listed. Outcome measure is at 12 weeks for ages 6-12 years and at 15 weeks for ages 13-17 years. (NCT01244490)
Timeframe: Up to 12 weeks for children aged 6-12 years and up to 15 weeks for adolescents aged 13-17 years

Clinical Global Impressions (CGI-I)

Clinical response was the Clinical Global Impression-Improvement scale (CGI-I). Lower CGI-I scores indicate greater improvement (1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6= much worse; 7=very much worse.) (NCT01709695)
Timeframe: up to 8 weeks

Continuous Performance Test - Commissions

Neuropsychological assessment - Continuous Performance Test - Commissions. CPT is a task-oriented computerized assessment of attention-related problems. Scores are compared with the normative scores for the age, group and gender of the person being tested. A t-score of 50 is equal to the mean, with higher values indicating more problematic behaviors and lower scores indicating less problematic behaviors. (NCT01709695)
Timeframe: Baseline

Percentage Change in Atomoxetine Stimulant Side Effects Rating Scale (ASSERS)

Side effects rating scale. Assesses side effects known to occur in prior research using stimulant and non stimulant medications for treatment of ADHD. Scores range from 0 (not present) to 9 (severe side effects) and have been reported in aggregate as sum of severity responses on highest dose. This number is the sum of ASSERS, meaning it is the number and severity of side effects experienced. The percentage change in score from baseline. (NCT01709695)
Timeframe: up to 8 weeks

Attention Deficit Hyperactivity Disorder Rating Scale IV (ADHDRS IV)

Norm referenced parent interview to assess severity and frequency of ADHD symptoms. Scores are reported as sums 0 (no symptoms) to 54 (severe). (NCT01709695)
Timeframe: baseline and 8 weeks

Digit Span

Neuropsychological assessment - Digit Span. The Digit Span test is either conducted verbally or using a computer program. A sequence of numbers is shown or read out to the participant. The participant is then told to repeat the numbers that were shown or read to them. This process continues until the participant can no longer remember either the full sequence of numbers or the correct order. This sequence is also continued until the participant makes an error. The Digit Span test is scored by the amount of numbers the participant was able to remember in each test. The scorer must add the total number of correct sequences, backwards and forwards. This test is also scored differently for a range of ages. (NCT01709695)
Timeframe: Baseline

Finger Windows

Neuropsychological assessment: Finger Windows - a measure of spatial working memory. The participant shows memory of a demonstrated visual pattern. The examiner models a given sequence of windows and ask the participant to imitate the sequence by placing their finger through the same windows in the correct order. The total number of correct sequences achieved determines the level of performance. (NCT01709695)
Timeframe: Baseline

Go/No-go Task Performance Correct Inhibitions

Measures of go/no-go task performance during functional magnetic resonance imaging. Performance on a go-nogo task inside the scanner. (NCT01709695)
Timeframe: Baseline and 8 weeks

Go/No-go Task Performance Correct Responses

Measures of go/no-go task performance during functional magnetic resonance imaging. Performance on a go-nogo task inside the scanner. (NCT01709695)
Timeframe: Baseline and 8 weeks

Go/No-go Task Reaction Time

Measures of go/no-go task performance during functional magnetic resonance imaging. Performance on a go-nogo task inside the scanner. (NCT01709695)
Timeframe: Baseline and 8 weeks

Change From Baseline in Attention Deficit Hyperactivity Disorder Rating Scale-fourth Edition (ADHD-RS-IV) Total Score at Week 13

The ADHD-RS-IV consists of 18 items scored on a 4-point scale ranging from 0 (no symptoms) to 3 (severe symptoms) with total score ranging from 0 to 54. (NCT01081132)
Timeframe: Baseline through week 13

Change From Baseline in Brief Psychiatric Rating Scale for Children (BPRS-C) Total Score at Last On-Treatment Assessment

Change From Baseline in Pediatric Daytime Sleepiness Scale (PDSS) Total Score at Week 13

The Pediatric Daytime Sleepiness Scale (PDSS) is an 8 item questionnaire scored on a scale from 0 (never) to 4 (always/very often). Total scores range from 0 to 32, with increasing score reflecting greater sleepiness. (NCT01081132)
Timeframe: Baseline through week 13

Change From Baseline in the Weiss Functional Impairment Rating Scale - Parent Report (WFIRS-P) Learning and School Domain Scores at Week 13

The WFIRS-P is a 50-item scale with each item scored from 0 (never/not at all) to 3 (very often/very much). The Learning and School Domain consists of 10-items. Mean scores range from 0 to 3. Higher scores indicate greater functional impairment. (NCT01081132)
Timeframe: Baseline and week 13

Change From Baseline in the WFIRS-P Academic Performance Domain Score at Week 13

The WFIRS-P is a 50-item scale with each item scored from 0 (never/not at all) to 3 (very often/very much). Mean scores range from 0 to 3. Higher scores indicate greater functional impairment. (NCT01081132)
Timeframe: Baseline and week 13

Change From Baseline in the WFIRS-P Behavior in School Domain Score at Week 13

Change From Baseline in the WFIRS-P Child Self-Concept Domain Score at Week 13

The WFIRS-P is a 50-item scale with each item scored from 0 (never/not at all) to 3 (very often/very much). The Child Self-Concept Domain consists of 3-items. Mean scores range from 0 to 3. Higher scores indicate greater functional impairment. (NCT01081132)
Timeframe: Baseline and week 13

Change From Baseline in the WFIRS-P Family Domain Score at Week 13

The WFIRS-P is a 50-item scale with each item scored from 0 (never/not at all) to 3 (very often/very much). The Family Domain consists of 10-items. Mean scores range from 0 to 3. Higher scores indicate greater functional impairment. (NCT01081132)
Timeframe: Baseline and week 13

Change From Baseline in the WFIRS-P Global Domain Score at Week 13

Change From Baseline in the WFIRS-P Life Skills Domain Score at Week 13

The WFIRS-P is a 50-item scale with each item scored from 0 (never/not at all) to 3 (very often/very much). The Life Skills Domain consists of 10-items. Mean scores range from 0 to 3. Higher scores indicate greater functional impairment. (NCT01081132)
Timeframe: Baseline and week 13

Change From Baseline in the WFIRS-P Risk Domain Score at Week 13

The WFIRS-P is a 50-item scale with each item scored from 0 (never/not at all) to 3 (very often/very much). The Risk Domain consists of 10-items. Mean scores range from 0 to 3. Higher scores indicate greater functional impairment. (NCT01081132)
Timeframe: Baseline and week 13

Change From Baseline in the WFIRS-P Social Domain Score at Week 13

The WFIRS-P is a 50-item scale with each item scored from 0 (never/not at all) to 3 (very often/very much). The Social Domain consists of 7-items. Mean scores range from 0 to 3. Higher scores indicate greater functional impairment. (NCT01081132)
Timeframe: Baseline and week 13

Percent of Subjects With an Assessment of Normal/Borderline Mentally Ill on Clinical Global Impression-Severity of Illness (CGI-S) Scale at the Last On-Treatment Assessment

CGI-S assesses the severity of the subject's condition on a 7-point scale: 1 (normal, not at all ill), 2 (borderline mentally ill), 3 (mildly ill), 4 (moderately ill), 5 (markedly ill), 6 (severely ill), 7 (among the most extremely ill) (NCT01081132)
Timeframe: Baseline through week 13

Percent of Subjects With Improvement on Clinical Global Impression-Improvement (CGI-I) Scores at the Last On-Treatment Assessment

Changes From Baseline in Behavior Rating Inventory of Executive Function (BRIEF) Scores at Week 13

Behavior Rating Inventory of Executive Function (BRIEF) is a questionnaire composed of three indices: Global Executive Composite, Behavioral Regulation Index, and Metacognition Index. Items are rated 1 (never), 2 (sometimes), and 3 (often). The Global Executive Composite consists of 72 items with scoring ranging from 72 to 216. The Behavioral Regulation Index score is the total of 28 items and ranges from 28 to 84. The Metacognition Index score is the total of 44 items and ranges from 44 to 132. Lower scores reflect better functioning. (NCT01081132)
Timeframe: Baseline and week 13

Columbia-Suicide Severity Rating Scale (C-SSRS)

Structure Side-Effect Questionnaire (SSEQ)

Change From Double-Blind Randomized-Withdrawal Baseline in Attention Deficit Hyperactivity Disorder Rating Scale-fourth Edition (ADHD-RS-IV) Total Score at Week 26 of the Double-Blind Randomized-Withdrawal Phase - Last Observation Carried Forward (LOCF)

The ADHD-RS-IV consists of 18 items scored on a 4-point scale ranging from 0 (no symptoms) to 3 (severe symptoms) with total score ranging from 0 to 54. (NCT01081145)
Timeframe: Baseline and week 26

Change From Double-Blind Randomized-Withdrawal Baseline in the Weiss Functional Impairment Rating Scale - Parent Report (WFIRS-P) Global Score at Week 26 of the Double-Blind Randomized-Withdrawal Phase - LOCF

Change From Open-Label Baseline in ADHD-RS-IV Total Score at Week 13 of the Open-Label Phase - LOCF

The ADHD-RS-IV consists of 18 items scored on a 4-point scale ranging from 0 (no symptoms) to 3 (severe symptoms) with total score ranging from 0 to 54. (NCT01081145)
Timeframe: Baseline and 13 weeks

Change From Open-Label Baseline in WFIRS-P Global Score at Week 13 of the Open-Label Phase - LOCF

Health Utilities Index-2/3 (HUI 2/3) Scores During the Double-Blind Randomized-Withdrawal Phase - LOCF

HUI 2/3 Scores During the Open-Label Phase - LOCF

Percent of Subjects With an Assessment of Normal/Borderline Mentally Ill on CGI-S Scale During the Open-Label Phase - LOCF

Percent of Subjects With an Assessment of Normal/Borderline Mentally Ill on Clinical Global Impression-Severity of Illness (CGI-S) Scale During the Double-Blind Randomized-Withdrawal Phase - LOCF

Percent of Subjects With Improvement on Clinical Global Impression-Improvement (CGI-I) Scores During Open-Label Phase - LOCF

Percentage of Participants With Treatment Failures During the Double-Blind Randomized-Withdrawal Phase

Treatment failure was defined as >= 50% increase (worsening) in ADHD-RS-IV total score and a >= 2 point increase (worsening) in CGI-S score compared with the respective scores at the Double-blind Randomized-withdrawal Baseline Visit at 2 consecutive Double-blind Randomized-withdrawal Phase visits. Subjects meeting these criteria were regarded as treatment failures regardless of whether or not they were withdrawn. All subjects who discontinued the study for any reason were regarded as treatment failures for the primary analysis. (NCT01081145)
Timeframe: 26 weeks

Percentage of Responders in the Open-Label Phase - LOCF

Response is defined as a percentage decrease (improvement) from Baseline in the ADHD-RS-IV total score of >=30% and a CGI-S score of 1 or 2. (NCT01081145)
Timeframe: 13 weeks

Time to Treatment Failure During the Double-Blind Randomized-Withdrawal Phase

Columbia-Suicide Severity Rating Scale During Double-Blind Randomized-Withdrawal Phase

Columbia-Suicide Severity Rating Scale During Open-Label Phase

Change From Baseline in Attention Deficit Hyperactivity Disorder Rating Scale (ADHD-RS-IV) Score at 6 Weeks

Change in the Attention Deficit Hyperactivity Disorder Rating Scale-fourth edition (ADHD-RS-IV) total score from baseline. The ADHD-RS-IV consists of 18 items scored on a 4-point scale ranging from 0 (no symptoms) to 3 (severe symptoms) with total score ranging from 0 to 54. (NCT00150618)
Timeframe: Baseline and 6 weeks

Change From Baseline in Conner's Parent Rating Scale-revised Short Version (CPRS-R) Score at 6 Weeks

Number of Participants With Improvement in Clinical Global Impression-Improvement (CGI-I)

Number of Participants With Improvement in Parent Global Assessment (PGA)

Change From Baseline in Child Health Questionnaire-Parent Form (CHQ-PF50) Score at 6 Weeks

The Child Health Questionnaire-Parent Form (CHQ-PF50) was developed to measure the physical and psychosocial well-being of children aged 5 years of age and older. Total scoring ranges from 0-100. Increases in scores represent improved well-being in subjects as assessed by their parents. (NCT00150618)
Timeframe: Baseline and 6 weeks

Change From Baseline in Conner's Parent Rating Scale-revised Short Version (CPRS-R) Total Score at 6 Weeks

The Conner's Parent Rating Scale-revised short version (CPRS-R) consists of 27 questions graded on a scale from 0 (not true at all) to 3 (very much true) with a total score ranging from 0 to 81. Higher scores are indicative of increased ADHD. This scale allows parents to respond on the basis of the child's behavior and help assess ADHD and evaluate problem behavior. (NCT00151996)
Timeframe: Baseline and 6 weeks

Change From Baseline in the Attention Deficit Hyperactivity Disorder Rating Scale (ADHD-RS-IV) Total Score at 6 Weeks

Number of Participants With Improvement on Clinical Global Impression-Improvement (CGI-I) Scores

Number of Participants With Improvement on Parent Global Assessment (PGA) Scores

Parent Global Assessment (PGA) consists of a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). The PGA is designed to capture parent's opinions of their child's disease (ADHD) severity and improvement. Improvement is defined as a score of 1 (very much improved) or 2 (much improved) on the scale. (NCT00151996)
Timeframe: 6 weeks

Change From Baseline in Child Health Questionnaire-Parent Form (CHQ-PF50) Scores at 6 Weeks

The Child Health Questionnaire-Parent Form (CHQ-PF50) was developed to measure the physical and psychosocial well-being of children aged 5 years of age and older. Total scoring ranges from 0-100 for each. Increases in scores represent improved well-being in subjects as assessed by their parents. (NCT00151996)
Timeframe: Baseline and 6 weeks

Change From Baseline in Attention Deficit Hyperactivity Disorder Rating Scale (ADHD-RS-IV) Total Score at Up to 8 Weeks

The ADHD-RS-IV consists of 18 items scored on a 4-point scale ranging from 0 (no symptoms) to 3 (severe symptoms) with total score ranging from 0 to 54. (NCT00367835)
Timeframe: Baseline and up to 8 weeks

Change From Baseline in Diastolic Blood Pressure at Up to 8 Weeks

Change From Baseline in Electrocardiogram Results (QTcF Interval) at Up to 8 Weeks

Change From Baseline in Pulse Rate at Up to 8 Weeks

Change From Baseline in Systolic Blood Pressure at Up to 8 Weeks

Change From Baseline in the 40-Item Conduct Problem Scale of the New York Parent's Rating Scale-School-aged (NYPRS-S) Score at Up to 8 Weeks

Each item on the NYPRS-S is scored from a range of 0 (not at all) to 3 (very much) with total scores ranging from 0 to 120. Higher scores are reflective of increased disease severity. (NCT00367835)
Timeframe: Baseline and up to 8 weeks

Change From Baseline in the Oppositional Subscale of the Conners' Parent Rating Scale-Revised Long Form (CPRS-R:L) Score at Up to 8 Weeks

Change From Baseline in the Parent Stress Index-Short Form (PSI/SF) Score at Up to 8 Weeks

The response to each of the 36 items on the PSI/SF is converted to a five-point scale from 1 (strongly agree) to 5 (strongly disagree) with total scores ranging from 36 to 180. A higher score is reflective of less stress for the parents. (NCT00367835)
Timeframe: Baseline and up to 8 weeks

Number of Participants With Improvement on Clinical Global Impression-Improvement (CGI-I)

CGI-I consists of a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved) or 2 (much improved) on the scale. (NCT00367835)
Timeframe: up to 8 weeks

Number of Participants With Overall Satisfaction on the Medication Satisfaction Survey (MSS)

"The Medication Satisfaction Survey (MSS) consists of 11 questions each being answered with one of six responses (strongly agree, agree, somewhat agree, somewhat disagree, disagree, strongly disagree). Overall satisfaction with their child taking the study medication, Question #11, with a response of strongly agree or agree." (NCT00367835)
Timeframe: up to 8 weeks

Assessment of Clinical Global Impression-Severity of Illness (CGI-S)

CGI-S assesses the severity of the subject's condition on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill) (NCT00367835)
Timeframe: up to 8 weeks

Change From Baseline in Attention Deficit Hyperactivity Disorder Rating Scale (ADHD-RS-IV) Total Score at 6 Weeks

Change From Baseline in Choice Reaction Time (CRT) at 6 Weeks

Choice reaction time (CRT) is a computerized assessment that trains the subject in holding down a press-pad and releasing the press-pad in response to stimuli presented on the screen. The task requires the subject to react as soon as a yellow dot appears in one of five locations, and the subject must respond by lifting their hand from the press-pad. This is the reaction time (RT) and ranges from 100 to 5000 msec. Lower scores indicate better performance. (NCT00150592)
Timeframe: Baseline and 6 weeks

Change From Baseline in Digital Symbol Substitution Task/Coding Test (DSST/Coding) Scores at 6 Weeks in Age Category 8-17 Years

The Digital Symbol Substitution Task/Coding Test (DSST/Coding) assesses relative contributions of speed, memory, and visual scanning. Subjects are required to copy symbols that are paired with simple geometric shapes or numbers within a specific time. Scores range from 0-65 in age category 6-7 years and 0-199 in age category 8-17 years. Higher scores indicate better performance. (NCT00150592)
Timeframe: Baseline and 6 weeks

Change From Baseline in DSST/Coding Scores at 6 Weeks in Age Category 6-7 Years

Change From Baseline in Pediatric Daytime Sleepiness Scale (PDSS) Scores at 6 Weeks

Change From Baseline in Pictorial Sleepiness Scale (PSS) Scores at 6 Weeks

The Pictorial Sleepiness Scale (PSS) scores range from 1 (far left wide awake face) to 5 (far right very sleepy face). Increasing score reflects greater sleepiness. (NCT00150592)
Timeframe: Baseline and 6 weeks

Number of Participants With Improvement in Clinical Global Impression-Improvement (CGI-I) at 6 Weeks

Change From Baseline in Spatial Working Memory (SWM) Scores at 6 Weeks

"The Spatial Working Memory (SWM) Test is a computerized assessment of working memory and strategy performance. The subject is required to find blue tokens in various displayed boxes and use the tokens to fill a column on the right side of the screen. Subjects can only find tokens in new boxes, therefore they must remember where previous tokens were found. SWM scores including number of between errors, number of within errors, and number of double errors range 0-800 and SWM strategy scores range 8-56. Lower scores indicate better performance." (NCT00150592)
Timeframe: Baseline and 6 weeks

Aberrant Behavior Checklist Hyperactivity Subscale

"The Aberrant Behavior Checklist (ABC) is a symptom checklist for assessing problem behaviors in individuals ages 6 to 54 with mental retardation. The full ABC is a 58-item parent-rating with five factors: Irritability, Social Withdrawal, Stereotypy, Hyperactivity and Inappropriate Speech.~The 16-item Hyperactivity subscale covers over-activity (7 items), impulsiveness (2 items), inattention (3 items) and noncompliance (4 items). It has been used as a primary outcome measure in several trials of children with developmental disabilities. The interpretation of the tool and its sub-scales is that a greater number of items, indicates greater severity. The range of scores is 0 to 48." (NCT01238575)
Timeframe: Baseline

Aberrant Behavior Checklist Hyperactivity Subscale

The Aberrant Behavior Checklist (ABC) is a symptom checklist for assessing problem behaviors in individuals ages 6 to 54 with mental retardation. The full ABC is a 58-item parent-rating with five factors: Irritability, Social Withdrawal, Stereotypy, Hyperactivity and Inappropriate Speech. The 16-item Hyperactivity subscale covers over-activity (7 items), impulsiveness (2 items), inattention (3 items) and noncompliance (4 items). It has been used as a primary outcome measure in several trials of children with developmental disabilities. The interpretation of the tool and its sub-scales is that a greater number of items, indicates greater severity. The range of scores is 0 to 48. (NCT01238575)
Timeframe: Week 8

Aberrant Behavior Checklist Inappropriate Speech Subscale

The Aberrant Behavior Checklist (ABC) is a symptom checklist for assessing problem behaviors in individuals ages 6 to 54 with mental retardation. The full ABC is a 58-item parent-rating with five factors: Irritability, Social Withdrawal, Stereotypy, Hyperactivity and Inappropriate Speech. It has been used as a primary outcome measure in several trials of children with developmental disabilities. The interpretation of the tool and its sub-scales is that a greater number of items, indicates greater severity. This subscale's scores can range from 0 to 12. (NCT01238575)
Timeframe: 8 weeks

Aberrant Behavior Checklist Inappropriate Speech Subscale

The Aberrant Behavior Checklist (ABC) is a symptom checklist for assessing problem behaviors in individuals ages 6 to 54 with mental retardation. The full ABC is a 58-item parent-rating with five factors: Irritability, Social Withdrawal, Stereotypy, Hyperactivity and Inappropriate Speech. It has been used as a primary outcome measure in several trials of children with developmental disabilities. The interpretation of the tool and its sub-scales is that a greater number of items, indicates greater severity. This subscale's scores can range from 0 to 12. (NCT01238575)
Timeframe: Baseline

Aberrant Behavior Checklist Irritability Subscale

The Aberrant Behavior Checklist (ABC) is a symptom checklist for assessing problem behaviors in individuals ages 6 to 54 with mental retardation. It is a 58 item checklist which takes about 10 - 15 minutes to complete. There are five subscales: a) Irritability and Agitation b) Lethargy and Social Withdrawal c) Stereotypic Behavior d) Hyperactivity and Noncompliance and e) Inappropriate Speech. The higher the number of items (score), the greater the amount of symptoms. Scores can range from 0 to 45. (NCT01238575)
Timeframe: 8 weeks

Aberrant Behavior Checklist Irritability Subscale

The Aberrant Behavior Checklist (ABC) is a symptom checklist for assessing problem behaviors in individuals ages 6 to 54 with mental retardation. The full ABC is a 58-item parent-rating with five factors: Irritability, Social Withdrawal, Stereotypy, Hyperactivity and Inappropriate Speech. It has been used as a primary outcome measure in several trials of children with developmental disabilities. The interpretation of the tool and its sub-scales is that a greater number of items, indicates greater severity. Scores for this subscale can range from 0 to 45. (NCT01238575)
Timeframe: Baseline

Aberrant Behavior Checklist Social Withdrawal Subscale

The Aberrant Behavior Checklist (ABC) is a symptom checklist for assessing problem behaviors in individuals ages 6 to 54 with mental retardation. The full ABC is a 58-item parent-rating with five factors: Irritability, Social Withdrawal, Stereotypy, Hyperactivity and Inappropriate Speech. It has been used as a primary outcome measure in several trials of children with developmental disabilities. The interpretation of the tool and its sub-scales is that a greater number of items, indicates greater severity. This subscale's scores can range from 0 to 48. (NCT01238575)
Timeframe: 8 weeks

Aberrant Behavior Checklist Social Withdrawal Subscale

The Aberrant Behavior Checklist (ABC) is a symptom checklist for assessing problem behaviors in individuals ages 6 to 54 with mental retardation. The full ABC is a 58-item parent-rating with five factors: Irritability, Social Withdrawal, Stereotypy, Hyperactivity and Inappropriate Speech. It has been used as a primary outcome measure in several trials of children with developmental disabilities. The interpretation of the tool and its sub-scales is that a greater number of items, indicates greater severity. This subscale's scores can range from 0 to 48. (NCT01238575)
Timeframe: Baseline

Aberrant Behavior Checklist Sterotypy Subscale

The Aberrant Behavior Checklist (ABC) is a symptom checklist for assessing problem behaviors in individuals ages 6 to 54 with mental retardation. The full ABC is a 58-item parent-rating with five factors: Irritability, Social Withdrawal, Stereotypy, Hyperactivity and Inappropriate Speech. It has been used as a primary outcome measure in several trials of children with developmental disabilities. The interpretation of the tool and its sub-scales is that a greater number of items, indicates greater severity. This subscale's scores can range from 0 to 21. (NCT01238575)
Timeframe: 8 weeks

Aberrant Behavior Checklist Sterotypy Subscale

The Aberrant Behavior Checklist (ABC) is a symptom checklist for assessing problem behaviors in individuals ages 6 to 54 with mental retardation. The full ABC is a 58-item parent-rating with five factors: Irritability, Social Withdrawal, Stereotypy, Hyperactivity and Inappropriate Speech. It has been used as a primary outcome measure in several trials of children with developmental disabilities. The interpretation of the tool and its sub-scales is that a greater number of items, indicates greater severity. This subscale's scores can range from 0 to 21. (NCT01238575)
Timeframe: Baseline

ADHD Rating Scale - Hyperactivity Subscale

The ADHD Rating Scale (ADHD-RS) is an 18-item scale directly derived from DSM-IV criteria for Attention Deficit Hyperactivity Disorder with established reliability, validity and sensitivity to change. The ADHD Rating Scale-IV is completed independently by the parent and scored by a clinician. The scale consists of 2 subscales: inattention (9 items) and hyperactivity-impulsivity (9 items). If 3 or more items are skipped, the clinician should use extreme caution in interpreting the scale. Results from this rating scale alone should not be used to make a diagnosis. This subscale can range from 0 to 27 for scoring, with a higher score indicating greater severity. (NCT01238575)
Timeframe: Baseline

ADHD Rating Scale - Hyperactivity Subscale

The ADHD Rating Scale (ADHD-RS) is an 18-item scale directly derived from DSM-IV criteria for Attention Deficit Hyperactivity Disorder with established reliability, validity and sensitivity to change. The ADHD Rating Scale-IV is completed independently by the parent and scored by a clinician. The scale consists of 2 subscales: inattention (9 items) and hyperactivity-impulsivity (9 items). If 3 or more items are skipped, the clinician should use extreme caution in interpreting the scale. Results from this rating scale alone should not be used to make a diagnosis. This subscale can range from 0 to 27 for scoring,with a higher score indicating greater severity. (NCT01238575)
Timeframe: 8 weeks

ADHD Rating Scale - Inattention Subscale

ADHD Rating Scale - Total

The ADHD Rating Scale (ADHD-RS) is an 18-item scale directly derived from DSM-IV criteria for Attention Deficit Hyperactivity Disorder with established reliability, validity and sensitivity to change. The ADHD Rating Scale-IV is completed independently by the parent and scored by a clinician. The scale consists of 2 subscales: inattention (9 items) and hyperactivity-impulsivity (9 items). If 3 or more items are skipped, the clinician should use extreme caution in interpreting the scale. Results from this rating scale alone should not be used to make a diagnosis. The total score can range from 0 to 54, with a higher score indicating greater severity. (NCT01238575)
Timeframe: Baseline

ADHD Rating Scale - Total

The ADHD Rating Scale (ADHD-RS) is an 18-item scale directly derived from DSM-IV criteria for Attention Deficit Hyperactivity Disorder with established reliability, validity and sensitivity to change. The ADHD Rating Scale-IV is completed independently by the parent and scored by a clinician. The scale consists of 2 subscales: inattention (9 items) and hyperactivity-impulsivity (9 items). If 3 or more items are skipped, the clinician should use extreme caution in interpreting the scale. Results from this rating scale alone should not be used to make a diagnosis. The total score can range from 0 to 54, with a higher score indicating greater severity. (NCT01238575)
Timeframe: Week 8

Change From Baseline in Attention Deficit Hyperactivity Disorder Rating Scale (ADHD-RS-IV) Score at Up to 5 Weeks

Change From Baseline in Conner's Parent Rating Scale-revised Short Version (CPRS-R) Score at Up to 5 Weeks

The Conner's Parent rating Scale-revised short version (CPRS-R) consists of 27 questions graded on a scale from 0 (not true at all) reflecting no symptoms to 3 (very much true) reflecting severe symptoms with a total score ranging from 0 to 81. Higher scores are indicative of increased ADHD. This scale allows parents to respond on the basis of the child's behavior and help assess ADHD and evaluate problem behavior. (NCT00152009)
Timeframe: Baseline and up to 5 weeks

Change From Baseline in Conner's Teacher Rating Scale-revised Short Version (CTRS-R) Score at Up to 5 Weeks

The Conner's Teacher Rating Scale-revised short version (CTRS-R) consists of 28 questions graded on a scale from 0 (not true at all) reflecting no symptoms to 3 (very much true) reflecting severe symptoms with a total score ranging from 0 to 84. Higher scores are indicative of increased ADHD. This scale allows teachers to respond on the basis of the child's behavior and help assess ADHD and evaluate problem behavior. (NCT00152009)
Timeframe: Baseline and up to 5 weeks

Number of Participants With Improvement in Clinical Global Impression-Improvement (CGI-I)

Number of Participants With Improvement in Parent Global Assessment (PGA)

Change From Baseline in Child Health Questionnaire-Parent Form (CHQ-PF50) Score at 5 Weeks

The Child Health Questionnaire-Parent Form (CHQ-PF50) was developed to measure the physical and psychosocial well-being of children aged 5 years of age and older. Total score ranges from 0-100. Increases in scores represent improved well-being in subjects as assessed by their parents. (NCT00152009)
Timeframe: Baseline and 5 weeks

Percent Change in Amelioration of Ketamine-related Task Activation as Measured by Functional Magnetic Resonance Imaging in Inferior Parietal Lobule

"Scans will be analyzed for task-related prefrontal activation~Difference Score: Percent Signal Change in Regions of Interest (ketamine - saline)" (NCT01600885)
Timeframe: Within 4 hours of dose administration, after up to 1.25 hours of ketamine infusion

Percent Change in Amelioration of Ketamine-related Task Activation as Measured by Functional Magnetic Resonance Imaging in Middle Frontal Gyrus

Difference Score: Percent Signal Change in Regions of Interest (ketamine - saline) (NCT01600885)
Timeframe: Within 4 hours of dose administration, after up to 1.25 hours of ketamine infusion

Percent Change in Amelioration of Ketamine-related Task Activation as Measured by Functional Magnetic Resonance Imaging in Superior Frontal Gyrus

Difference Score: Percent Signal Change in Regions of Interest (ketamine - saline) (NCT01600885)
Timeframe: Within 4 hours of dose administration, after up to 1.25 hours of ketamine infusion

"Number of Patients With Improved or Minimally Improved in Clinical Global Impression-Improvement (CGI) Scale"

"The CGI-I is a clinician-rated scales that have been used in clinical trials for over 25 years. Clinicians rate patient improvement compared to baseline. By convention, 4 = No Change; scores of 5, 6, and 7 move in the direction of worsening; scores of 3, 2, and 1 correspond to Minimal Improvement, Much Improved or Very Much Improved, respectively. CGI-I ratings of Much or Very Much Improved at post-treatment are used to identify treatment responders." (NCT00529308)
Timeframe: 3 weeks

"Number of Patients With Much Improved or Very Much Improved on Clinical Global Impression-Improvement (CGI) Scale"

Motor Cortex Excitability Normalization-Left Motor Threshold

Motor Threshold (MT) is thought to be a measure of membrane excitability in pyramidal neurons. MT is defined as the minimum magnetic flux needed to elicit a threshold EMG response (50 µV in peak to peak amplitude) in a resting target muscle in 5 out of 10 trials using single pulse TMS administered to the contralateral primary motor cortex. MT for both right and left hand are determined, and the lowest is used to select the intensity for rTMS. (NCT00529308)
Timeframe: 3 weeks

Motor Cortex Excitability Normalization-Right Motor Threshold

Yale Global Tic Severity Scale (Y-GTSS)

Y-GTSS is a clinician-rated scale used to assess tic severity. Motor and phonic tics are rated separately from 0 to 5 on several scales including number, frequency, intensity, complexity, and interference. Thus Motor and Phonic Tic scores can range from 0 to 25; the combined Total Tic Score ranges from 0 to 50. There is also an Impairment score that rates the overall burden due to tics. The Impairment scale yields a single score from 0 to 50 with higher scores indicating higher levels of overall impairment associated with tics. (NCT00529308)
Timeframe: 3 weeks

Intervention	Units on a scale (Mean)
SPD503-AM + Psychostimulant	-16.7
SPD503-PM + Psychostimulant	-16.7
Placebo + Psychostimulant	-11.5

Intervention	Units on a scale (Mean)
SPD503-AM + Psychostimulant	-8.2
SPD503-PM + Psychostimulant	-8.8
Placebo + Psychostimulant	-6.0

Intervention	Units on a scale (Mean)
SPD503-AM + Psychostimulant	-8.4
SPD503-PM + Psychostimulant	-9.6
Placebo + Psychostimulant	-6.9

Intervention	Units on a scale (Mean)
SPD503-AM + Psychostimulant	-6.6
SPD503-PM + Psychostimulant	-6.3
Placebo + Psychostimulant	-4.2

Intervention	Percent of participants (Number)
SPD503-AM + Psychostimulant	70.5
SPD503-PM + Psychostimulant	74.3
Placebo + Psychostimulant	57.9

Intervention	Percent of participants (Number)
SPD503-AM + Psychostimulant	69.8
SPD503-PM + Psychostimulant	67.7
Placebo + Psychostimulant	47.5

Intervention	units on a scale (Least Squares Mean)
Placebo	-15.0
Guanfacine Hydrochloride	-23.9
Atomoxetine Hydrochloride	-18.8

Intervention	units on a scale (Mean)
Placebo	-5.6
Guanfacine Hydrochloride	-8.3
Atomoxetine Hydrochloride	-6.5

Intervention	units on a scale (Least Squares Mean)
Placebo	-0.419
Guanfacine Hydrochloride	-0.636
Atomoxetine Hydrochloride	-0.581

Intervention	units on a scale (Least Squares Mean)
Placebo	-0.555
Guanfacine Hydrochloride	-0.766
Atomoxetine Hydrochloride	-0.681

Intervention	units on a scale (Least Squares Mean)
Placebo	-0.363
Guanfacine Hydrochloride	-0.592
Atomoxetine Hydrochloride	-0.544

Intervention	units on a scale (Least Squares Mean)
Placebo	-0.312
Guanfacine Hydrochloride	-0.361
Atomoxetine Hydrochloride	-0.390

Intervention	units on a scale (Least Squares Mean)
Placebo	-0.409
Guanfacine Hydrochloride	-0.617
Atomoxetine Hydrochloride	-0.499

Intervention	units on a scale (Least Squares Mean)
Placebo	-0.321
Guanfacine Hydrochloride	-0.487
Atomoxetine Hydrochloride	-0.425

Intervention	units on a scale (Least Squares Mean)
Placebo	-0.383
Guanfacine Hydrochloride	-0.477
Atomoxetine Hydrochloride	-0.450

Intervention	units on a scale (Least Squares Mean)
Placebo	-0.134
Guanfacine Hydrochloride	-0.190
Atomoxetine Hydrochloride	-0.173

Intervention	units on a scale (Least Squares Mean)
Placebo	-0.322
Guanfacine Hydrochloride	-0.555
Atomoxetine Hydrochloride	-0.434

Intervention	units on a scale (Mean)
Placebo	0.927
Guanfacine Hydrochloride	0.922
Atomoxetine Hydrochloride	0.913

Intervention	percentage of participants (Number)
Placebo	44.1
Guanfacine Hydrochloride	67.9
Atomoxetine Hydrochloride	56.3

Intervention	percentage of participants (Number)
	1 (Normal, not at all ill)	2 (Borderline mentally ill)	3 (Mildly ill)	4 (Moderately ill)	5 (Markedly ill)	6 (Severely ill)	7 (Amongst the most extremely ill)
Atomoxetine Hydrochloride	6.3	19.6	32.1	19.6	13.4	7.1	1.8
Guanfacine Hydrochloride	14.3	23.2	31.3	22.3	5.4	3.6	0
Placebo	9.9	15.3	20.7	20.7	25.2	6.3	1.8

Intervention	participants (Number)
	Suicidal Ideation	Suicidal Behaviour
Atomoxetine Hydrochloride	5	0
Guanfacine Hydrochloride	3	0
Placebo	2	0

Intervention	participants (Number)
	Nausea	Vomiting	Diarrhea	Abdominal Pain	Decreased Appetite	Increased Appetite	Headache	Dizziness	Fatigue	Nervousnes/Anxiety	Insomnia	Somnolence	Depression	Itching	Rash	Missed Menses
Atomoxetine Hydrochloride	39	25	8	42	48	25	34	23	35	34	24	38	9	10	8	0
Guanfacine Hydrochloride	30	7	18	45	31	40	52	28	55	37	32	57	7	13	9	1
Placebo	19	11	15	26	25	30	35	16	30	25	19	26	7	7	4	0

Intervention	units on a scale (Mean)
	Baseline	End of treatment at 8 weeks
Guanfacine Hydrochloride XR	36.67	9.42
Placebo Group	39.15	22.69

Intervention	correct sequences (Mean)
	Digit Span - F	Digit Span - B
Guanfacine Hydrochloride XR	6.92	48.62
Placebo Group	7.54	48.62

Intervention	correct sequences (Mean)
	Finger Windows - F	Finger Windows -B
Guanfacine Hydrochloride XR	12.5	11.35
Placebo Group	10.75	8.00

Intervention	percentage correct inhibitions (Mean)
	Baseline Correct inhibitions	8 Weeks Correct inhibitions
Guanfacine Hydrochloride XR	91	94
Placebo Group	89	92

Intervention	percentage correct responses (Mean)
	Baseline Correct responses	8 Weeks Correct responses
Guanfacine Hydrochloride XR	76	79
Placebo Group	75	74

Intervention	ms (Mean)
	Baseline Reaction time (RT)	Baseline Reaction time standard deviation (RTSD)	8 weeks Reaction time (RT)	8 weeks Reaction time standard deviation (RTSD)
Guanfacine Hydrochloride XR	572	187	562	184
Placebo Group	543	165	550	166

Intervention	units on a scale (Least Squares Mean)
	Global Executive Composite	Behavioral Regulation Index	Metacognition Index
PLACEBO	-10.6	-11.5	-8.9
SPD503	-12.9	-12.4	-11.6

Intervention	participants (Number)
	Suicidal ideation	Suicidal behavior
Guanfacine Hydrochloride	2	0
Placebo	2	0