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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, 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
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
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
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...
2016: Toxins
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
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
Gregory R Sayer, James J McGough, Jennifer Levitt, Jennifer Cowen, Alexandra Sturm, Edward Castelo, James T McCracken
OBJECTIVES: This study examines cardiovascular (CV) effects of guanfacine immediate-release (GUAN-IR), dexmethylphenidate extended-release (DMPH), and their combination (COMB) during acute and long-term treatment of youth with attention-deficit/hyperactivity disorder. METHODS: 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...
August 2, 2016: Journal of Child and Adolescent Psychopharmacology
Sandra K Loo, Robert M Bilder, Alexander L Cho, Alexandra Sturm, Jennifer Cowen, Patricia Walshaw, Jennifer Levitt, Melissa Del'Homme, John Piacentini, James J McGough, James T McCracken
OBJECTIVE: Psychostimulant medications are the gold standard of treatment for attention-deficit/hyperactivity disorder (ADHD); however, a significant minority (∼30%) of individuals with ADHD fail to respond favorably. Noradrenergic agents are increasingly used as ADHD monotherapies or adjuncts for suboptimal stimulant response, yet knowledge of their cortical effects is limited. This study is the first to examine comparative effects of guanfacine (an α adrenergic 2A agonist), psychostimulant, and their combination on resting state cortical activity in ADHD...
August 2016: Journal of the American Academy of Child and Adolescent Psychiatry
Robert M Bilder, Sandra K Loo, James J McGough, Fiona Whelan, Gerhard Hellemann, Catherine Sugar, Melissa Del'Homme, Alexandra Sturm, Jennifer Cowen, Grant Hanada, James T McCracken
OBJECTIVE: Psychostimulants are partially effective in reducing cognitive dysfunction associated with attention-deficit/hyperactivity disorder (ADHD). Cognitive effects of guanfacine, an alternative treatment, are poorly understood. Given its distinct action on α2A receptors, guanfacine may have different or complementary effects relative to stimulants. This study tested stimulant and guanfacine monotherapies relative to combined treatment on cognitive functions important in ADHD. METHOD: Children with ADHD (n = 182; aged 7-14 years) completed an 8-week, double blind, randomized, controlled trial with 3 arms: d-methylphenidate (DMPH), guanfacine (GUAN), or combination treatment with DMPH and GUAN (COMB)...
August 2016: Journal of the American Academy of Child and Adolescent Psychiatry
James T McCracken, James J McGough, Sandra K Loo, Jennifer Levitt, Melissa Del'Homme, Jennifer Cowen, Alexandra Sturm, Fiona Whelan, Gerhard Hellemann, Catherine Sugar, Robert M Bilder
OBJECTIVE: Because models of attention-deficit/hyperactivity disorder (ADHD) therapeutics emphasize benefits of both enhanced dopaminergic and noradrenergic signaling, strategies to enhance D1 and α2A agonism may yield enhanced clinical and cognitive responses. This study tested the hypothesis that combined effects of a dopamine and noradrenergic agonist, d-methylphenidate extended-release (DMPH) with guanfacine (GUAN), an α2A receptor agonist, would be clinically superior to either monotherapy and would have equal tolerability...
August 2016: Journal of the American Academy of Child and Adolescent Psychiatry
Giovanni Sansoè, Manuela Aragno, Raffaella Mastrocola, Giulio Mengozzi, Maurizio Parola
BACKGROUND: In human cirrhosis, adrenergic hyperfunction causes proximal tubular fluid retention and contributes to diuretic-resistant ascites, and clonidine, a sympatholytic drug, improves natriuresis in difficult-to-treat ascites. AIM: To compare clonidine (aspecific α2-adrenoceptor agonist) to SSP-002021R (prodrug of guanfacine, specific α2A-receptor agonist), both associated with diuretics, in experimental cirrhotic ascites. METHODS AND RESULTS: Six groups of 12 rats were studied: controls (G1); controls receiving furosemide and potassium canrenoate (G2); rats with ascitic cirrhosis due to 14-week CCl4 treatment (G3); cirrhotic rats treated (over the 11th-14th CCl4 weeks) with furosemide and canrenoate (G4), furosemide, canrenoate and clonidine (G5), or diuretics and SSP002021R (G6)...
2016: PloS One
Ming-Horng Tsai, Jen-Fu Hsu, Yu-Shu Huang
Attention deficit hyperactivity disorder (ADHD) affects approximately 5 % of children and adolescents, and sleep problems are common in these patients. There is growing evidence informing the significant importance of sleep problems in youth with ADHD. The sleep problems in children with ADHD include specific sleep disorders and sleep disturbances due to comorbid psychiatric disorders or ADHD medications. The specific sleep disorders of ADHD children include behaviorally based insomnia, sleep-disordered breathing, and restless legs syndrome/periodic limb movement disorder...
August 2016: Current Psychiatry Reports
Cecilio Alamo, Francisco López-Muñoz, Javier Sánchez-García
The treatment of ADHD has focused on the use of psychostimulants drugs such as methylphenidate or amphetamine and derivatives, or not stimulants agents, such as atomoxetine. These agents act mainly on catecholaminergic presynaptic mechanisms. Recently the European Medicines Agency (EMA) has approved another not psychostimulant drug, guanfacine extended release (ER), as a new option to the treatment of ADHD, which acts at postsynaptic level. Guanfacine stimulates postsynaptic alfa-2A adrenergic receptors so it inhibits the production of cAMP and closes HCN channels enhancing the effectiveness of the signal of the pyramidal neurons of the prefrontal cortex (PFC), thus improving working memory and attention...
May 2016: Actas Españolas de Psiquiatría
Jeffrey A Mattes
Attention deficit/hyperactivity disorder (ADHD) is prevalent in prison populations, but optimal treatment recommendations in prison are uncertain. Stimulants are problematic because of the potential for abuse. This article is a review of medication options for ADHD, focusing on the α2 agonists clonidine and guanfacine, which, in their extended-release (ER) forms, are U.S. Food and Drug Administration (FDA) approved for the treatment of ADHD, although they are probably less efficacious, overall, than stimulants...
June 2016: Journal of the American Academy of Psychiatry and the Law
Dean Elbe, Carina Perel-Panar, Leslie Wicholas
No abstract text is available yet for this article.
August 2016: Journal of Child and Adolescent Psychopharmacology
Michael Huss, Vanja Sikirica, Amaia Hervas, Jeffrey H Newcorn, Valerie Harpin, Brigitte Robertson
Guanfacine extended release (GXR) and atomoxetine (ATX) are nonstimulant treatments for attention-deficit/hyperactivity disorder (ADHD). As nonstimulant treatments are often used after stimulants in ADHD, GXR was assessed relative to prior stimulant treatment in a randomized controlled trial (RCT), in which ATX was included as a reference arm, and in the open-label phase of a randomized-withdrawal study (RWS). Participants were 6-17 years old with ADHD Rating Scale version IV (ADHD-RS-IV) scores ≥32 and Clinical Global Impressions - Severity scores ≥4...
2016: Neuropsychiatric Disease and Treatment
(no author information available yet)
Prolonged-action ▼guanfacine (Intuniv-Shire Pharmaceuticals Ltd) is a non-stimulant drug that has recently been licensed in Europe for the management of attention deficit hyperactivity disorder (ADHD) in children and adolescents aged 6-17 years for whom stimulants are unsuitable.(1) The company suggests that it has a unique mechanism of action in ADHD, providing improvement in core symptoms within 3 weeks with once-daily flexible dosing.(2) Here we review the evidence on the efficacy and safety of guanfacine in ADHD and consider whether it offers any advantages over other therapeutic options...
May 2016: Drug and Therapeutics Bulletin
Eugenia Chan, Jason M Fogler, Paul G Hammerness
IMPORTANCE: Although attention-deficit/hyperactivity disorder (ADHD) is highly prevalent in adolescents and often persists into adulthood, most studies about treatment were performed in children. Less is known about ADHD treatment in adolescents. OBJECTIVE: To review the evidence for pharmacological and psychosocial treatment of ADHD in adolescents. EVIDENCE REVIEW: The databases of CINAHL Plus, MEDLINE, PsycINFO, ERIC, and the Cochrane Database of Systematic Reviews were searched for articles published between January 1, 1999, and January 31, 2016, on ADHD treatment in adolescents...
May 10, 2016: JAMA: the Journal of the American Medical Association
Minji Sohn, Jeffery Talbert, Daniela C Moga, Karen Blumenschein
The objectives of this study are: (1) to estimate the expected health outcomes of atypical antipsychotics (AAPs) and other non-stimulant attention-deficit/hyperactivity disorder (ADHD) medications and (2) to evaluate the cost-effectiveness of AAPs compared to other non-stimulant ADHD medications. We used decision analysis to compare three alternatives for treating children and adolescents with ADHD who failed initial stimulant treatment: (1) AAPs, (2) a selective norepinephrine reuptake inhibitor (atomoxetine), and (3) selective α2-adrenergic agonists (clonidine and guanfacine)...
September 2016: Attention Deficit and Hyperactivity Disorders
Linda Gowing, Michael Farrell, Robert Ali, Jason M White
BACKGROUND: Withdrawal is a necessary step prior to drug-free treatment or as the endpoint of long-term substitution treatment. OBJECTIVES: To assess the effectiveness of interventions involving the use of alpha2-adrenergic agonists compared with placebo, reducing doses of methadone, symptomatic medications, or an alpha2-adrenergic agonist regimen different to the experimental intervention, for the management of the acute phase of opioid withdrawal. Outcomes included the withdrawal syndrome experienced, duration of treatment, occurrence of adverse effects, and completion of treatment...
2016: Cochrane Database of Systematic Reviews
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