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https://www.readbyqxmd.com/read/28421383/pharmacokinetics-safety-and-tolerability-of-single-and-multiple-doses-of-guanfacine-extended-release-formulation-in-healthy-japanese-and-caucasian-male-adults
#1
Yumiko Matsuo, Masafumi Okita, James Ermer, Toshihiro Wajima
BACKGROUND AND OBJECTIVE: Guanfacine extended-release (guanfacine XR) could be a useful treatment option for children and adolescent patients with attention-deficit/hyperactivity disorder (ADHD). As an initial step in the development in Japan, the pharmacokinetics, safety and tolerability were assessed in healthy Japanese and non-Hispanic Caucasian adults. METHODS: A Phase 1, double-blind, randomized, placebo-controlled, single- and multiple-oral dose escalation study of guanfacine XR was conducted...
April 18, 2017: Clinical Drug Investigation
https://www.readbyqxmd.com/read/28393639/the-safety-of-extended-release-drug-formulations-for-the-treatment-of-adhd
#2
Ann Childress
Attention-deficit/hyperactivity disorder (ADHD) is a complex neurobehavioral disorder affecting millions of patients worldwide. Effective treatments have been available for more than 60 years in the form of immediate-release (IR) stimulants However, stimulants have a high risk for abuse and are associated with adverse effects Including elevated blood pressure and heart rate, insomnia and decreased appetite. IR formulations also require multiple daily dosing. The search for improved safety, tolerability and convenience has led to the development of multiple extended-release (ER) stimulant and non-stimulant formulations...
May 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/28391425/safety-tolerability-and-efficacy-of-drugs-for-treating-behavioural-insomnia-in-children-with-attention-deficit-hyperactivity-disorder-a-systematic-review-with-methodological-quality-assessment
#3
REVIEW
Shweta Anand, Henry Tong, Frank M C Besag, Esther W Chan, Samuele Cortese, Ian C K Wong
OBJECTIVE: A large proportion of paediatric patients with attention-deficit/hyperactivity disorder (ADHD) have associated sleep problems which not only affect the child's wellbeing but also impact family functioning. Management of sleep problems is consequently an important aspect of overall ADHD management in paediatric patients. Although some drugs are being used off-label for the management of paediatric insomnia, there is scant clinical evidence supporting their use. Our aim was to identify and assess the quality of published studies reporting the safety, tolerability and efficacy of drugs used for treating behavioural insomnia in children with ADHD...
June 2017: Paediatric Drugs
https://www.readbyqxmd.com/read/28336568/cholinergic-but-not-dopaminergic-or-noradrenergic-enhancement-sharpens-visual-spatial-perception-in-humans
#4
Caterina Gratton, Sahar Yousef, Esther Aarts, Deanna L Wallace, Mark D'Esposito, Michael A Silver
The neuromodulator acetylcholine modulates spatial integration in visual cortex by altering the balance of inputs that generate neuronal receptive fields. These cholinergic effects may provide a neurobiological mechanism underlying the modulation of visual representations by visual spatial attention. However, the consequences of cholinergic enhancement on visuospatial perception in humans are unknown. We conducted two experiments to test whether enhancing cholinergic signaling selectively alters perceptual measures of visuospatial interactions in human subjects...
April 19, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28272733/-an-update-on-the-pharmacological-treatment-of-attention-deficit-hyperactivity-disorder-lisdexamphetamine-and-extended-release-guanfacine
#5
REVIEW
D Martin Fernandez-Mayoralas, A L Fernandez-Perrone, N Munoz-Jareno, A Fernandez-Jaen
INTRODUCTION: Attention deficit hyperactivity disorder (ADHD) is one of the most frequent neurodevelopmental disorders in the child population. Its treatment is complex and must include psychoeducational, environmental and pharmacological measures. In recent years, the main novelties as regards its pharmacological treatment have been the appearance of lisdexamphetamine and extended-release guanfacine. AIMS: The increase in the number of drugs available for the treatment of ADHD makes it possible to treat and cover a very wide range of different clinical situations...
March 13, 2017: Revista de Neurologia
https://www.readbyqxmd.com/read/28258319/comparative-efficacy-and-safety-of-attention-deficit-hyperactivity-disorder-pharmacotherapies-including-guanfacine-extended-release-a-mixed-treatment-comparison
#6
REVIEW
Alain Joseph, Rajeev Ayyagari, Meng Xie, Sean Cai, Jipan Xie, Michael Huss, Vanja Sikirica
This study compared the clinical efficacy and safety of attention-deficit/hyperactivity disorder (ADHD) pharmacotherapy in children and adolescents 6-17 years of age. A systematic literature review was conducted to identify randomized controlled trials (RCTs) of pharmacologic monotherapies among children and adolescents with ADHD. A Bayesian network meta-analysis was conducted to compare change in symptoms using the ADHD Rating Scale Version IV (ADHD-RS-IV), Clinical Global Impression-Improvement (CGI-I) response, all-cause discontinuation, and adverse event-related discontinuation...
March 3, 2017: European Child & Adolescent Psychiatry
https://www.readbyqxmd.com/read/28165762/extended-release-guanfacine-in-pediatric-anxiety-disorders-a-pilot-randomized-placebo-controlled-trial
#7
Jeffrey R Strawn, Scott N Compton, Brigitte Robertson, Anne Marie Albano, Mohamed Hamdani, Moira A Rynn
OBJECTIVE: This is a feasibility study evaluating the safety, tolerability, and potential anxiolytic efficacy of the α2 agonist guanfacine extended-release (GXR) in children and adolescents with generalized anxiety disorder (GAD), separation anxiety disorder (SAD), or social phobia/social anxiety disorder. METHODS: Youth aged 6-17 years with a primary diagnosis of GAD, SAD, and/or social anxiety disorder were treated with flexibly dosed GXR (1-6 mg daily, n = 62) or placebo (n = 21) for 12 weeks...
February 2017: Journal of Child and Adolescent Psychopharmacology
https://www.readbyqxmd.com/read/28118752/the-impact-of-adjunctive-guanfacine-extended-release-on-stimulant-adherence-in-children-adolescents-with-attention-deficit-hyperactivity-disorder
#8
Juliana Meyers, Kavita Gajria, Sean D Candrilli, Moshe Fridman, Vanja Sikirica
AIM: To assess stimulant adherence among children/adolescents with attention-deficit/hyperactivity disorder (ADHD) augmenting stimulants with guanfacine extended-release (GXR). PATIENTS & METHODS: Inclusion criteria: 6-17 years, ≥1 ADHD diagnosis, ≥1 long-acting and/or short-acting stimulant with GXR augmentation. Modified medication possession ratio (mMPR; days medication available/days in period, excluding medication holidays) was assessed; mMPR <0.80 nonadherent...
March 2017: Journal of Comparative Effectiveness Research
https://www.readbyqxmd.com/read/28091572/a-computational-psychiatry-approach-identifies-how-alpha-2a-noradrenergic-agonist-guanfacine-affects-feature-based-reinforcement-learning-in-the-macaque
#9
S A Hassani, M Oemisch, M Balcarras, S Westendorff, S Ardid, M A van der Meer, P Tiesinga, T Womelsdorf
Noradrenaline is believed to support cognitive flexibility through the alpha 2A noradrenergic receptor (a2A-NAR) acting in prefrontal cortex. Enhanced flexibility has been inferred from improved working memory with the a2A-NA agonist Guanfacine. But it has been unclear whether Guanfacine improves specific attention and learning mechanisms beyond working memory, and whether the drug effects can be formalized computationally to allow single subject predictions. We tested and confirmed these suggestions in a case study with a healthy nonhuman primate performing a feature-based reversal learning task evaluating performance using Bayesian and Reinforcement learning models...
January 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28073796/comparative-efficacy-and-tolerability-of-pharmacological-interventions-for-attention-deficit-hyperactivity-disorder-in-children-adolescents-and-adults-protocol-for-a-systematic-review-and-network-meta-analysis
#10
Samuele Cortese, Nicoletta Adamo, Christina Mohr-Jensen, Adrian J Hayes, Sahar Bhatti, Sara Carucci, Cinzia Del Giovane, Lauren Z Atkinson, Tobias Banaschewski, Emily Simonoff, Alessandro Zuddas, Corrado Barbui, Marianna Purgato, Hans-Christoph Steinhausen, Farhad Shokraneh, Jun Xia, Andrea Cipriani, David Coghill
INTRODUCTION: Attention-deficit/hyperactivity disorder (ADHD) is a major public health issue. Pharmacological treatments play an important role in the multimodal treatment of ADHD. Currently, there is a lack of up-to-date and comprehensive evidence on how available ADHD drugs compare and rank in terms of efficacy and tolerability, in children or adolescents as well as in adults. We will conduct a network meta-analysis (NMA), integrating direct and indirect comparisons from randomised controlled trials (RCTs), to rank pharmacological treatments for ADHD according to their efficacy and tolerability profiles...
January 10, 2017: BMJ Open
https://www.readbyqxmd.com/read/28063948/cytokine-il-10-activators-of-pi3-kinase-agonists-of-%C3%AE-2-adrenoreceptor-and-antioxidants-prevent-ischemia-induced-cell-death-in-rat-hippocampal-cultures
#11
Egor A Turovsky, Maria V Turovskaya, Sergei G Gaidin, Valery P Zinchenko
In the present work we compared the protective effect of anti-inflammatory cytokine IL-10 with the action of a PI3-kinase selective activator 740 Y-P, selective agonists of alpha-2 adrenoreceptor, guanfacine and UK-14,304, and compounds having antioxidant effect: recombinant human peroxiredoxin 6 and B27, in hippocampal cell culture during OGD (ischemia-like conditions). It has been shown that the response of cells to OGD in the control includes two phases. The first phase was accompanied by an increase in the frequency of spontaneous synchronous Ca(2+)-oscillations (SSCO) in neurons and Ca(2+)-pulse in astrocytes...
February 1, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28028603/guanfacine-alters-the-effect-of-stress-and-smoking-on-heart-rate-variability-in-regular-daily-smokers
#12
Terril L Verplaetse, Philip H Smith, Kathryn M Z Smith, Lindsay M Oberleitner, Sherry A McKee
BACKGROUND: We had previously demonstrated that guanfacine, an α2a-adrenergic agonist, attenuated the effect of stress on smoking-lapse behavior in regular daily smokers. Heart rate variability (HRV), a measure of vagal activity, may be a potential mechanism underlying the relationship between stress, smoking, and relapse. METHODS: We examined whether guanfacine (0 mg/day vs. 3 mg/day; n = 26) altered changes in high-frequency heart rate variability (HF-HRV) following stress and ad-lib smoking using a validated laboratory analogue of smoking-lapse behavior...
March 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28001002/the-effects-of-guanfacine-and-phenylephrine-on-a-spiking-neuron-model-of-working-memory
#13
Peter Duggins, Terrence C Stewart, Xuan Choo, Chris Eliasmith
We use a spiking neural network model of working memory (WM) capable of performing the spatial delayed response task (DRT) to investigate two drugs that affect WM: guanfacine (GFC) and phenylephrine (PHE). In this model, the loss of information over time results from changes in the spiking neural activity through recurrent connections. We reproduce the standard forgetting curve and then show that this curve changes in the presence of GFC and PHE, whose application is simulated by manipulating functional, neural, and biophysical properties of the model...
December 21, 2016: Topics in Cognitive Science
https://www.readbyqxmd.com/read/27972888/a-cost-effectiveness-analysis-of-guanfacine-extended-release-treatment-in-pediatric-attention-deficit-hyperactivity-disorder
#14
S Maeda, K Shimozuma, Y Takeda
No abstract text is available yet for this article.
November 2016: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
https://www.readbyqxmd.com/read/27828696/current-and-investigational-medication-delivery-systems-for-treating-attention-deficit-hyperactivity-disorder
#15
REVIEW
Rakesh Jain, Alain Katic
OBJECTIVE: To review currently available formulations and emphasize unmet needs in the pharmacologic management of attention-deficit/hyperactivity disorder (ADHD). DATA SOURCES: Publications and clinical trials were identified through PubMed and ClinicalTrials.gov, respectively. A Web-based search identified prescribing information for approved agents for treating ADHD, along with relevant guidelines and diagnostic criteria. STUDY SELECTION: The following search terms were used: (1) ADHD or attention-deficit/hyperactivity disorder or ADD or attention deficit hyperactivity disorder and/or (2) amphetamine or methylphenidate or atomoxetine or guanfacine or clonidine...
August 18, 2016: Primary Care Companion to CNS Disorders
https://www.readbyqxmd.com/read/27738872/an-evaluation-on-the-efficacy-and-safety-of-treatments-for-attention-deficit-hyperactivity-disorder-in-children-and-adolescents-a-comparison-of-multiple-treatments
#16
Ying Li, Jie Gao, Shu He, Yan Zhang, Qiwei Wang
Attention deficit hyperactivity disorder (ADHD) is one of the most common neurobehavioral disorders. We carried out this comparison of multiple treatments based on sufficient data in attempt to evaluate the efficacy and safety of ADHD medication for children and adolescents. PubMed, Embase and the Cochrane Database were used to search for relevant articles. Changes in the ADHD Rating Scale (ADHD-RS) scores and the Conners' Parent Rating Scale-Revised (CPRS) scores were used as outcomes for efficacy. Withdrawals due to all-cause, adverse effects and lack of efficacy were defined as primary outcomes evaluating the safety of such medications...
October 13, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27677308/ahr-cyp1a1-interplay-triggers-lymphatic-barrier-breaching-in-breast-cancer-spheroids-by-inducing-12-s-hete-synthesis
#17
Chi Huu Nguyen, Stefan Brenner, Nicole Huttary, Atanas Georgiev Atanasov, Verena Maria Dirsch, Waranya Chatuphonprasert, Sivio Holzner, Serena Stadler, Juliane Riha, Sigurd Krieger, Rainer de Martin, Zsuzsanna Bago-Horvath, Georg Krupitza, Walter Jäger
A causal link between overexpression of aryl hydrocarbon receptor (AHR) and its target cytochrome P450 1A1 (CYP1A1) and metastatic outgrowth of various cancer entities has been established. Nevertheless, the mechanism how AHR/CYP1A1 support metastasis formation is still little understood. In vitro we discovered a potential mechanism facilitating tumour dissemination based on the production of 12(S)-hydroxyeicosatetraenoic acid (12(S)-HETE). Utilising a three-dimensional lymph endothelial cell (LEC) monolayer & MDA-MB231 breast cancer cell spheroid co-culture model in combination with knock-down approach allowed elucidation of the molecular/biochemical basis of AHR/CYP1A1-induced tumour breaching through the LEC barrier...
September 27, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/27669299/vasoactivity-and-vasoconstriction-changes-in-cattle-related-to-time-off-toxic-endophyte-infected-tall-fescue
#18
James L Klotz, Glen E Aiken, Jessica R Bussard, Andrew P Foote, David L Harmon, Ben M Goff, F Neal Schrick, James R Strickland
Previous research has indicated that serotonergic and α-adrenergic receptors in peripheral vasculature are affected by exposure of cattle grazing toxic endophyte-infected (E+; Epichlöe coenophialia) tall fescue (Lolium arundinaceum). The objective of this experiment was to determine the period of time necessary for the vascular effects of ergot alkaloids to subside. Two experiments were conducted to investigate changes in vascular contractile response and vasoconstriction over time relative to removal from an ergot alkaloid-containing E+ tall fescue pasture...
September 22, 2016: Toxins
https://www.readbyqxmd.com/read/27620206/evaluating-matching-adjusted-indirect-comparisons-in-practice-a-case-study-of-patients-with-attention-deficit-hyperactivity-disorder
#19
Jason Shafrin, Anshu Shrestha, Amitabh Chandra, M Haim Erder, Vanja Sikirica
Differences in patient characteristics across trials may bias efficacy estimates from indirect treatment comparisons. To address this issue, matching-adjusted indirect comparison (MAIC) measures treatment efficacy after weighting individual patient data to match patient characteristics across trials. To date, however, there is no consensus on how best to implement MAIC. To address this issue, we applied MAIC to measure how two attention-deficit/hyperactivity disorder (ADHD) treatments (guanfacine extended release and atomoxetine hydrochloride) affect patients' ADHD symptoms, as measured by the ADHD Rating Scale IV score...
September 13, 2016: Health Economics
https://www.readbyqxmd.com/read/27509312/pharmacological-investigations-of-a-yohimbine-impulsivity-interaction-in-rats
#20
Megan K Mahoney, John H Barnes, David Wiercigroch, Mary C Olmstead
Both impulsivity and stress are risk factors for substance abuse, but it is not clear how these two processes interact to alter susceptibility for the disorder. The aim of this project was to examine the pharmacology of a stress-impulsivity interaction in rats. To do so, we tested the effects of yohimbine on impulsive action and then assessed whether behavioural changes could be reduced by antagonists at different receptor subtypes. Male Long-Evans rats were injected with various doses of yohimbine (0-5.0 mg/kg) before testing in the response-inhibition task...
October 2016: Behavioural Pharmacology
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