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Methylphenidate Hydrochloride
Application for Inclusion to the 22nd Expert Committee on the Selection and Use of Essential Medicines: METHYLPHENIDATE HYDROCHLORIDE December 7, 2018 Submitted by: Patricia Moscibrodzki, M.P.H., and Craig L. Katz, M.D. The Icahn School of Medicine at Mount Sinai Graduate Program in Public Health New York NY, United States Contact: [email protected] TABLE OF CONTENTS Page 3 Summary Statement Page 4 Focal Point Person in WHO Page 5 Name of Organizations Consulted Page 6 International Nonproprietary Name Page 7 Formulations Proposed for Inclusion Page 8 International Availability Page 10 Listing Requested Page 11 Public Health Relevance Page 13 Treatment Details Page 19 Comparative Effectiveness Page 29 Comparative Safety Page 41 Comparative Cost and Cost-Effectiveness Page 45 Regulatory Status Page 48 Pharmacoepial Standards Page 49 Text for the WHO Model Formulary Page 52 References Page 61 Appendix – Letters of Support 2 1. Summary Statement of the Proposal for Inclusion of Methylphenidate Methylphenidate (MPH), a central nervous system (CNS) stimulant, of the phenethylamine class, is proposed for inclusion in the WHO Model List of Essential Medications (EML) & the Model List of Essential Medications for Children (EMLc) for treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) under ICD-11, 6C9Z mental, behavioral or neurodevelopmental disorder, disruptive behavior or dissocial disorders. To date, the list of essential medications does not include stimulants, which play a critical role in the treatment of psychotic disorders. Methylphenidate is proposed for inclusion on the complimentary list for both children and adults. This application provides a systematic review of the use, efficacy, safety, availability, and cost-effectiveness of methylphenidate compared with other stimulant (first-line) and non-stimulant (second-line) medications. -
Implications in the Management of Depression and Anxiety
Journal name: Neuropsychiatric Disease and Treatment Article Designation: Review Year: 2016 Volume: 12 Neuropsychiatric Disease and Treatment Dovepress Running head verso: Montoya et al Running head recto: Noradrenergic paradox in depression and anxiety open access to scientific and medical research DOI: http://dx.doi.org/10.2147/NDT.S91311 Open Access Full Text Article REVIEW The noradrenergic paradox: implications in the management of depression and anxiety Alonso Montoya1 Abstract: Both major depressive disorder and the anxiety disorders are major causes of disability Robert Bruins1 and markedly contribute to a significant global burden of the disease worldwide. In part because Martin A Katzman2 of the significant socioeconomic burden associated with these disorders, theories have been devel- Pierre Blier3 oped to specifically build clinical treatment approaches. One such theory, the monoaminergic hypothesis, has led to the development of several generations of selective and nonselective inhibi- 1Eli Lilly Canada Inc, 2START Clinic for the Mood and Anxiety Disorders, tors of transporters of serotonin and norepinephrine, with the goal of augmenting monoaminergic Toronto, 3Mood Disorders Research transmission. These efforts have led to considerable success in the development of antidepressant Unit, Institute of Mental Health therapeutics. However, there is a strong correlation between enhanced noradrenergic activity Research, University of Ottawa, Ottawa, ON, Canada and fear and anxiety. Consequently, some physicians have expressed concerns that the same enhanced noradrenergic activity that alleviates depression could also promote anxiety. The fact that the serotonergic and noradrenergic reuptake inhibitors are successfully used in the treatment For personal use only. of anxiety and panic disorders seems paradoxical. This review was undertaken to determine if any clinical evidence exists to show that serotonergic and noradrenergic reuptake inhibitors can cause anxiety. -
Identification of Small Molecule Modulators of Diguanylate Cyclase
bioRxiv preprint doi: https://doi.org/10.1101/402909; this version posted August 28, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Identification of Small Molecule Modulators of Diguanylate Cyclase by FRET-based High-Throughput-Screening Matthias Christen1, , Cassandra Kamischke2, Hemantha D. Kulasekara2, Kathleen C. Olivas3, Bridget R. Kulasekara4, Beat Christen1, Toni Kline5, and Samuel I. Miller2,4,6, 1Institute of Molecular Systems Biology, Eidgenössische Technische Hochschule (ETH) Zürich, CH-8093 Zürich, Switzerland 2Department of Microbiology, University of Washington, Seattle, United States 3Seattle Genetics, Inc., 21823 30th Drive SE, Bothell, Washington 98021 4Department of Genome Sciences, University of Washington, Seattle 5Sutro Biopharma, 310 Utah Avenue, South San Francisco, CA 94080 6Department of Medicine, University of Washington, Seattle The bacterial second messenger cyclic diguanosine monophos- parent role of c-di-GMP in the cell cycle and the presence of phate (c-di-GMP) is a key regulator of cellular motility, the cell many paralogous DGC enzymes controlling diverse cellular cycle, and biofilm formation with its resultant antibiotic tol- functions indicate that there is likely tight spatial and tem- erance, which may make chronic infections difficult to treat. poral regulation of c-di-GMP (10–12). Bacterial genomes Therefore, diguanylate cyclases, which regulate the spatiotem- encode multiple GGDEF domains in proteins with signal- poral production of c-di-GMP, may be attractive drug tar- sensing domains (13). -
Lilly Announces Edivoxetine Did Not Meet Primary Endpoint of Phase III Clinical Studies As Add-On Therapy for Major Depressive Disorder
December 5, 2013 Lilly Announces Edivoxetine Did Not Meet Primary Endpoint of Phase III Clinical Studies as Add-On Therapy for Major Depressive Disorder INDIANAPOLIS, Dec. 5, 2013 /PRNewswire/ -- Eli Lilly and Company (NYSE: LLY) announced today that results from three studies of edivoxetine did not meet the primary study objective of superior efficacy in depression after eight weeks of treatment. When added to a selective serotonin reuptake inhibitor (SSRI), edivoxetine did not separate from placebo on the Montgomery- Asberg Depression Rating Scale (MADRS) in three acute randomized placebo-controlled Phase III studies (LNBM, LNBQ and LNBR). While the safety and tolerability of edivoxetine was consistent with previous studies, the efficacy results do not support a regulatory submission for adjunctive treatment in patients with Major Depressive Disorder (MDD). Data from all three studies will be disclosed in appropriate scientific forums in 2014. In 2010, Lilly launched the Phase III program for edivoxetine — a potent and highly selective norepinephrine reuptake inhibitor — to assess the benefits and risks of edivoxetine as an add-on therapy in patients with MDD. The Phase III program specifically focused on meeting the unmet needs of patients with major depression who had achieved only a partial response to treatment with an SSRI. In these three trials, patients remained on SSRI treatment and additionally received either edivoxetine or placebo. "Lilly undertook a robust Phase III program to address a significant unmet need for people suffering from depression," said David Ricks, senior vice president, and president, Lilly Bio-Medicines. "However, the lack of efficacy compared to SSRI alone in three separate clinical trials means that Lilly will not proceed with development of edivoxetine as an add-on treatment for depression." The ongoing clinical study evaluating the long-term maintenance effect of edivoxetine will continue to completion. -
Addressing 360O of Biochemical Imbalances to Restore Balance and Relieve Symptoms
Addressing 360o of biochemical imbalances to restore balance and relieve symptoms. Product Guide Effective June 2015 Product availability subject to change without notice. View the most current catalog electronically at www.neuroscienceinc.com/productcatalog Dr. Gottfried Kellermann and Mieke Kellermann Ushering in a New Age of Personalized Care As NeuroScience, Inc. enters its 15th year in business, we reflect on the driving force behind our services- providing you, the practitioner, with tools that allow you to more efficiently and effectively care for your patients. Together with our laboratory partner, Pharmasan Labs, Inc. we pioneered the Assess and Address™ approach for personalized patient care. New and Exciting Direction We recognize the evolving changes in patient care and patient expectation from their healthcare practitioners. More than ever, patients are taking control of their health and demanding care that allows them to get better faster and enjoy the healthy lifestyle they deserve. NeuroScience, along with Pharmasan Labs, has taken the lead in focusing on a model that not only identifies the imbalances behind many symptoms but how the network of those imbalances indicates deeper issues. This network approach points you in the direction of the root cause of patient symptoms, which when resolved can lead to improved, long-term health outcomes. Never satisfied with the status quo, we will continue to innovate to provide you with unparalleled support toward this end. A Provider of Personalized, Clinical Solutions…this is WHO WE ARE. Together, NeuroScience and Pharmasan are committed to providing you with the clinical assessments and tools you need to thrive in this rapidly changing healthcare market while better serving your patients. -
Treatment of Attention Deficit Hyperactivity Disorder: New Agents and Assessment Tools Marcia L
PEDIATRIC PHARMACOTHERAPY Volume 20 Number 8 August 2014 Treatment of Attention Deficit Hyperactivity Disorder: New Agents and Assessment Tools Marcia L. Buck, PharmD, FCCP, FPPAG he currently available treatments for seen in ADHD Rating Scale–IV (ADHD-RS-IV) T attention deficit hyperactivity disorder total scores, with a mean change at endpoint of - (ADHD), stimulants, alpha-2 adrenergic 17.6 + 12.4. Both hyperactivity/impulsivity and agonists, and atomoxetine, are highly effective in inattentive subscores improved, with a mean increasing attention and reducing impulsivity in reduction of -8.8 for each. Global Impressions- most patients. Research continues to expand the ADHD Severity (CGI-ADHD-S) scores also range of treatment options, with new drugs and demonstrated significant improvement from dosage formulations, as well as new methods to baseline. Adverse effects were typically mild, predict or assess treatment response. with the most commonly reported including nausea, decreased appetite, somnolence, and Potential Treatment Options upper respiratory tract infections. The mean Two novel ADHD medications are currently increase in systolic blood pressure was 1.9 mm being studied in children and adults with ADHD. Hg in children and 0.22 mm Hg in adolescents, Edivoxetine, a selective norepinephrine reuptake with a mean change in heart rate of 3.5 bpm in inhibitor similar to atomoxetine, is in phase 3 children and 3 bpm in adolescents. Three trials. Both atomoxetine and edivoxetine are Eli patients discontinued treatment because of Lilly products. Tipepidine, 3-[di-2- adverse effects. One patient experienced thienylmethylene]-1-methylpiperidine, is being treatment-emergent mania, another developed studied in Japan. It has been available there as an signs of depression, and the third had over-the-counter cough suppressant since 1959. -
Current Phase III Clinical Trials
Toolbox: Current phase III clinical trials Tiffany-Jade Kreys, PharmD1 1Assistant Professor of Pharmacy Practice University of the Incarnate Word Feik School of Pharmacy, San Antonio, Texas KEYWORDS clinical trials, depression, bipolar, schizophrenia, medications Table 1. Novel Agents for Major Depression, Bipolar Disorder, and/or Schizophrenia Product Name Sponsor Indication Mechanism of Action (previous name) Downloaded from http://meridian.allenpress.com/mhc/article-pdf/2/6/138/2094102/mhc_n129046.pdf by guest on 26 September 2021 Amitifadine Euthymics MDD Triple Reuptake Inhibitor (EB-1010) Bioscience (1:2:8 ratio of serotonin: norepinephrine: dopamine inhibition) Bitopertin Roche Schizophrenia Glycine reuptake inhibitor (RG1678) Enhances NMDA receptor activity Brexpiprazole Lundbeck MDD, Claimed to have "broad activity across multiple monoamine (OPC-34712) Otsuka America Schizophrenia systems and exhibits reduced partial agonist activity at D2 Pharmaceuticals receptors and enhanced affinity for specific serotonin receptors" Cariprazine Forest Laboratories BPAD, MDD adjunct D3-preferring/D2 receptor partial agonist (RGH-188) therapy, Schizophrenia Citalopram/ PharmaNeuro- MDD 5HT2A/D4 antagonist Pipamperone Boost (PNB01) Edivoxetine Eli Lilly MDD adjunct therapy Norepinephrine reuptake inhibitor (LY2216684) Vortioxetine Lundbeck MDD In vitro studies: 5HT3 and 7 receptor antagonist, 5HT1B partial (LUAA21004) Takeda agonist, 5HT1A agonist, serotonin transporter inhibitor Pharmaceuticals In vivo: Increases serotonin, norepinephrine, dopamine, -
2018-2019 Florida Best Practice Psychotherapeutic Medication Guidelines for Children and Adolescents
2018-2019 Florida Best Practice Psychotherapeutic Medication Guidelines for Children and Adolescents medicaidmentalhealth.org For more information, visit us at medicaidmentalhealth.org. These guidelines are available in the public domain and do not require permission from the authors for use. However, we request when using any of its content that the publication is cited as follows: 2018-2019 Florida Best Practice Psychotherapeutic Medication Guidelines for Children and Adolescents (2019). The University of South Florida, Florida Medicaid Drug Therapy Management Program sponsored by the Florida Agency for Health Care Administration (AHCA). © January 2019 medicaidmentalhealth.org TABLE OF CONTENTS Introduction ................................................................................................................................................................................... 3 Principles of Practice Regarding the Use of Psychotherapeutic Medications in Children under Age 6 ........................................................................................................................................................... 5 Principles of Practice Regarding the Use of Psychotherapeutic Medications in Children and Adolescents 6 to 17 Years Old .............................................................................................................. 8 General Procedures for Monitoring Side Effects of Antipsychotic Medication in Children and Adolescents................................................................................................................................................................................. -
ADHD Across the Lifecycle Diagnostic Issues DSM-5 ADHD Changes from DSM-IV
Managing ADHD Across the Lifecycle Diagnostic Issues DSM-5 ADHD Changes from DSM-IV • Impairing symptoms by 12 not 7 years old • “Neurodevelopmental”- not “Disruptive” • “Presentations” not subtypes – Inattentive/hyperactive-impulsive/combined • Over 17: ≥5 inattentive + or ≥5 impulsive/ hyperactive symptoms; Under 17: 6 or more of either • Adult symptom-examples included • Autism/PDD non-exclusionary DSM-5 ADHD: Criteria Unchanged from DSM-IV • Symptoms present in 2 or more settings – (school, work, home) • Not explained by another disorder DSM-5 Inattention Symptoms Include Memory and Organization Deficits 5/6 of the following often apply: • Easily distracted • Careless mistakes • Difficulty sustaining attention • Poor listening • Leaves tasks unfinished • Avoids tasks requiring sustained attention • Loses things • Forgetful • Difficulty organizing DSM-5 Hyperactivity/Impulsivity Traits Emphasize Internal Drive and Activity 5/6 of the following often apply: •Fidgeting •Inability to stay seated •Moving excessively (restlessness) •Difficulty doing quiet activities •“On the go” •Talks excessively •Blurts out answers •Difficulty awaiting turn •Interrupting/intruding Collateral Information Gathering clinical information to make diagnosis varies based on developmental level; most adult patients rely on self-report; efforts must be made to gather collateral info as much as possible AGE: 7 12 18 25 32 Child Adolescent Adult Teacher Self Self Parent Teacher Spouse/Partner Self Parent Sibling Grandparent Grandparent Friend Other adult Other Adult -
Integrated Approach for Identifying the Molecular, Cellular, and Host Responses to Chemical Insults
Integrated Approach for Identifying the Molecular, Cellular, and Host Responses to Chemical Insults Audrey E. Fischer, Emily P. English, Julia B. Patrone, Kathlyn Santos, Jody B. G. Proescher, Rachel S. Quizon, Kelly A. Van Houten, Robert S. Pilato, Eric J. Van Gieson, and Lucy M. Carruth e performed a pilot study to characterize the molecular, cellular, and whole-organism response to nonlethal chemical agent exposure in the central nervous system. Multiple methodologies were applied to measure in vitro enzyme inhibition, neuronal cell pathway signaling, and in vivo zebrafish neural development in response to challenge with two different classes of chemical compounds. While all compounds tested exhibited expected enzyme inhibitory activity against acetylcholinesterase (AChE), a well-characterized target of chemical agents, distinct differences between chemical exposures were detected in cellular toxicity and pathway target responses and were tested in a zebrafish model. Some of these differences have not been detected using conventional chemical toxicity screening methods. Taken together, the data demonstrate the potential value of an integrated, multimethodological approach for improved target and pathway identification for subsequent diagnostic and therapeutic biomarker development. INTRODUCTION To build capability and leverage new and growing cell models to complete living organisms. Regardless of biology and chemistry expertise at APL, a collabora- the model selected, challenges exist in sample collection, tive, cross-departmental effort was established through a dose determination, and biases inherent in each assay/ series of related independent research and development technology. Therefore, multiple experimental methodol- (IR&D) projects. The focus of this effort was on mitiga- ogies brought to bear on a particular biological question tion of chemical and biological threat agents. -
United States Patent (19) 11 4,134,792 Boguslaski Et Al
United States Patent (19) 11 4,134,792 Boguslaski et al. 45) Jan. 16, 1979 54 SPECIFIC BINDING ASSAY WITH AN Immunoassays', Conference on Non-isotopic Immuno ENZYMEMODULATOR ASALABELNG assays, (1976). SUBSTANCE Primary Examiner-Alvin E. Tanenholtz 75) Inventors: Robert C. Boguslaski; Robert J. Assistant Examiner-C. A. Fan Carrico, both of Elkhart, Ind; James Attorney, Agent, or Firm-Andrew L. Klawitter E. Christner, Ann Arbor, Mich. 57 ABSTRACT A specific binding assay method employing, as a label 73) Assignee: Miles Laboratories, Inc., Elkhart, ing substance, a reversibly binding enzyme modulator Ind. for the detection of a ligand in a liquid medium. The 21 Appl. No.: 748,005 method follows conventional specific binding assay techniques of either the homogeneous or heterogeneous (22 Filed: Dec. 6, 1976 type wherein the liquid medium to be assayed is com bined with reagent means that includes a labeled conju 51) int. C.?...................... G01N 33/00; G01N 31/14 gate to form a binding reaction system having a bound 52 U.S. C. .............................. 195/99; 195/103.5A; species and a free-species of the conjugate. The amount 424/12 of conjugate resulting in the bound-species or the free 58) Field of Search .......................... 195/103.5 A, 99; species is a function of the amount of ligand present in 424/12 the liquid medium assayed. In the present invention, the labeled conjugate comprises a reversibly binding en 56 References Cited zyme modulator covalently linked to a binding compo U.S. PATENT DOCUMENTS nent of the binding reaction system. The distribution of 3,817,837 6/1974 Rubenstein et al. -
315869674-Oa
Cochrane Library Cochrane Database of Systematic Reviews New generation antidepressants for depression in children and adolescents: a network meta-analysis (Protocol) Hetrick SE, Meader N, Bailey AP, Badcock PB, Moller CI, Cox GR, Merry SN, McKenzie JE Hetrick SE, Meader N, Bailey AP, Badcock PB, Moller CI, Cox GR, Merry SN, McKenzie JE. New generation antidepressants for depression in children and adolescents: a network meta-analysis (Protocol). Cochrane Database of Systematic Reviews 2020, Issue 7. Art. No.: CD013674. DOI: 10.1002/14651858.CD013674. www.cochranelibrary.com New generation antidepressants for depression in children and adolescents: a network meta-analysis (Protocol) Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. Cochrane Trusted evidence. Informed decisions. Library Better health. Cochrane Database of Systematic Reviews T A B L E O F C O N T E N T S HEADER......................................................................................................................................................................................................... 1 ABSTRACT..................................................................................................................................................................................................... 1 BACKGROUND.............................................................................................................................................................................................. 2 OBJECTIVES.................................................................................................................................................................................................