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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. -
Methadone Information Your Safety and the Safety of Everyone
Methadone Information Your Safety and the Safety of Everyone Methadone, when taken as prescribed is safe. Methadone taken by any individual it is NOT prescribed to, can be deadly; and when mixed with other drugs, can be deadly; and in the hands of a child, is most certainly deadly. Why? Because it is often difficult to know what other drugs including prescription medications others are being prescribed including herbal/ natural medications; and because unless you are a pharmacist or an experienced physician who is knowledgeable about METHADONE you truly don’t know what will happen when medications are mixed. Treatment Rules and Regulations clearly state: “It is extremely important that medication (this means METHADONE!) be stored in a VERY secure place away from children once the patient takes it to their home. It is not advisable to store the medication in the refrigerator unless it is in a locked, childproof container.” “Patients are not to give away… (Take) home medications (methadone).”It is clearly stated in Rules and Regulations that “Children cannot be held while dosing.” “…The mixing of chemicals may be harmful or fatal.” This is why Locked boxes must meet stringent criteria; to protect you, and those around you. Methadone is a Central Nervous System (CNS) Depressant. This means that Methadone slows down all your central nervous systems including breathing, heart rate, Some medications should NEVER be taken with methadone because they too are CNS depressants. These include alcohol, Benzodiazepines, Naltrexone, Soma, other Opiates and Barbiturates. These drugs taken together potentiate or add to each other: 1+1 no longer = 2; it equals 5 or more If you are a child or anyone the drug is NOT prescribed for you may not know you are in danger as your heart slows, and your breathing becomes shallower and then you die. -
Neonatal Drug Withdrawal Abstract
Guidance for the Clinician in Rendering Pediatric Care CLINICAL REPORT Neonatal Drug Withdrawal Mark L. Hudak, MD, Rosemarie C. Tan, MD,, PhD, THE abstract COMMITTEE ON DRUGS, and THE COMMITTEE ON FETUS AND Maternal use of certain drugs during pregnancy can result in transient NEWBORN neonatal signs consistent with withdrawal or acute toxicity or cause KEY WORDS opioid, methadone, heroin, fentanyl, benzodiazepine, cocaine, sustained signs consistent with a lasting drug effect. In addition, hos- methamphetamine, SSRI, drug withdrawal, neonate, abstinence pitalized infants who are treated with opioids or benzodiazepines to syndrome provide analgesia or sedation may be at risk for manifesting signs ABBREVIATIONS of withdrawal. This statement updates information about the clinical CNS—central nervous system — presentation of infants exposed to intrauterine drugs and the thera- DTO diluted tincture of opium ECMO—extracorporeal membrane oxygenation peutic options for treatment of withdrawal and is expanded to include FDA—Food and Drug Administration evidence-based approaches to the management of the hospitalized in- 5-HIAA—5-hydroxyindoleacetic acid fant who requires weaning from analgesics or sedatives. Pediatrics ICD-9—International Classification of Diseases, Ninth Revision — – NAS neonatal abstinence syndrome 2012;129:e540 e560 SSRI—selective serotonin reuptake inhibitor INTRODUCTION This document is copyrighted and is property of the American fi Academy of Pediatrics and its Board of Directors. All authors Use and abuse of drugs, alcohol, and tobacco contribute signi cantly have filed conflict of interest statements with the American to the health burden of society. The 2009 National Survey on Drug Use Academy of Pediatrics. Any conflicts have been resolved through and Health reported that recent (within the past month) use of illicit a process approved by the Board of Directors. -
Drug and Alcohol Withdrawal Clinical Practice Guidelines - NSW
Guideline Drug and Alcohol Withdrawal Clinical Practice Guidelines - NSW Summary To provide the most up-to-date knowledge and current level of best practice for the treatment of withdrawal from alcohol and other drugs such as heroin, and other opioids, benzodiazepines, cannabis and psychostimulants. Document type Guideline Document number GL2008_011 Publication date 04 July 2008 Author branch Centre for Alcohol and Other Drugs Branch contact (02) 9424 5938 Review date 18 April 2018 Policy manual Not applicable File number 04/2766 Previous reference N/A Status Active Functional group Clinical/Patient Services - Pharmaceutical, Medical Treatment Population Health - Pharmaceutical Applies to Area Health Services/Chief Executive Governed Statutory Health Corporation, Board Governed Statutory Health Corporations, Affiliated Health Organisations, Affiliated Health Organisations - Declared Distributed to Public Health System, Ministry of Health, Public Hospitals Audience All groups of health care workers;particularly prescribers of opioid treatments Secretary, NSW Health Guideline Ministry of Health, NSW 73 Miller Street North Sydney NSW 2060 Locked Mail Bag 961 North Sydney NSW 2059 Telephone (02) 9391 9000 Fax (02) 9391 9101 http://www.health.nsw.gov.au/policies/ space space Drug and Alcohol Withdrawal Clinical Practice Guidelines - NSW space Document Number GL2008_011 Publication date 04-Jul-2008 Functional Sub group Clinical/ Patient Services - Pharmaceutical Clinical/ Patient Services - Medical Treatment Population Health - Pharmaceutical -
GABA Systems, Benzodiazepines, and Substance Dependence
Robert J. Malcolm GABA Systems, Benzodiazepines, and Substance Dependence Robert J. Malcolm, M.D. Alterations in the γ-aminobutyric acid (GABA) receptor complex and GABA neurotransmission influence the reinforcing and intoxicating effects of alcohol and benzodiazepines. Chronic modulation of the GABAA-benzodiazepine receptor complex plays a major role in central nervous system dysregulation during alcohol abstinence. Withdrawal symptoms stem in part from a decreased GABAergic inhibitory function and an increase in glutamatergic excitatory function. GABAA recep- tors play a role in both reward and withdrawal phenomena from alcohol and sedative-hypnotics. Although less well understood, GABAB receptor complexes appear to play a role in inhibition of moti- vation and diminish relapse potential to reinforcing drugs. Evidence suggests that long-term alcohol use and concomitant serial withdrawals permanently alter GABAergic function, down-regulate ben- zodiazepine binding sites, and in preclinical models lead to cell death. Benzodiazepines have substan- tial drawbacks in the treatment of substance use–related disorders that include interactions with alco- hol, rebound effects, alcohol priming, and the risk of supplanting alcohol dependency with addiction to both alcohol and benzodiazepines. Polysubstance-dependent individuals frequently self-medicate with benzodiazepines. Selective GABA agents with novel mechanisms of action have anxiolytic, anticonvulsant, and reward inhibition profiles that have potential in treating substance use and with- drawal and enhancing relapse prevention with less liability than benzodiazepines. The GABAB receptor agonist baclofen has promise in relapse prevention in a number of substance dependence dis- orders. The GABAA and GABAB pump reuptake inhibitor tiagabine has potential for managing alcohol and sedative-hypnotic withdrawal and also possibly a role in relapse prevention. -
International Standards for the Treatment of Drug Use Disorders
"*+,-.*--- -!"#$%&-'",()0"ÿ23 45 "6789!"7(@&A($!7,0B"67$!C#+D"%"*+,9779C&B"!7%EE F33"*+,-.*--- -!"#$%&-'",()0" International standards for the treatment of drug use disorders REVISED EDITION INCORPORATING RESULTS OF FIELD-TESTING International standards for the treatment of drug use disorders: revised edition incorporating results of field-testing ISBN 978-92-4-000219-7 (electronic version) ISBN 978-92-4-000220-3 (print version) © World Health Organization and United Nations Office on Drugs and Crime, 2020 Some rights reserved. This work is available under the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 IGO licence (CC BY-NC-SA 3.0 IGO; https://creativecommons. org/licenses/by-nc-sa/3.0/igo). Under the terms of this license, you may copy, redistribute and adapt the work for non-commercial purposes, provided the work is appropriately cited, as indicated below. In any use of this work, there should be no suggestion that WHO or UNODC endorses any specific organization, products or services. The unauthorized use of the WHO or UNODC names or logos is not permitted. If you adapt the work, then you must license your work under the same or equivalent Creative Commons license. If you create a translation of this work, you should add the following disclaimer along with the suggested citation: “This translation was not created by the World Health Organization (WHO) or the United Nations Office on Drugs and Crime (UNODC). Neither WHO nor UNODC are responsible for the content or accuracy of this translation. The original English edition shall be the binding and authentic edition”. Any mediation relating to disputes arising under the license shall be conducted in accordance with the mediation rules of the World Intellectual Property Organization (http://www. -
Barriers and Solutions to Addressing Tobacco Dependence in Addiction Treatment Programs
Barriers and Solutions to Addressing Tobacco Dependence in Addiction Treatment Programs Douglas M. Ziedonis, M.D., M.P.H.; Joseph Guydish, Ph.D., M.P.H.; Jill Williams, M.D.; Marc Steinberg, Ph.D.; and Jonathan Foulds, Ph.D. Despite the high prevalence of tobacco use among people with substance use disorders, tobacco dependence is often overlooked in addiction treatment programs. Several studies and a meta-analytic review have concluded that patients who receive tobacco dependence treatment during addiction treatment have better overall substance abuse treatment outcomes compared with those who do not. Barriers that contribute to the lack of attention given to this important problem include staff attitudes about and use of tobacco, lack of adequate staff training to address tobacco use, unfounded fears among treatment staff and administration regarding tobacco policies, and limited tobacco dependence treatment resources. Specific clinical-, program-, and system-level changes are recommended to fully address the problem of tobacco use among alcohol and other drug abuse patients. KEY WORDS: Alcohol and tobacco; alcohol, tobacco, and other drug (ATOD) use, abuse, dependence; addiction care; tobacco dependence; smoking; secondhand smoke; nicotine; nicotine replacement; tobacco dependence screening; tobacco dependence treatment; treatment facility-based prevention; co-treatment; treatment issues; treatment barriers; treatment provider characteristics; treatment staff; staff training; AODD counselor; client counselor interaction; smoking cessation; Tobacco Dependence Program at the University of Medicine and Dentistry of New Jersey obacco dependence is one of to the other. The common genetic vul stance use was considered a potential the most common substance use nerability may be located on chromo trigger for the primary addiction. -
Adverse Reactions to Hallucinogenic Drugs. 1Rnstttutton National Test
DOCUMENT RESUME ED 034 696 SE 007 743 AUTROP Meyer, Roger E. , Fd. TITLE Adverse Reactions to Hallucinogenic Drugs. 1rNSTTTUTTON National Test. of Mental Health (DHEW), Bethesda, Md. PUB DATP Sep 67 NOTE 118p.; Conference held at the National Institute of Mental Health, Chevy Chase, Maryland, September 29, 1967 AVATLABLE FROM Superintendent of Documents, Government Printing Office, Washington, D. C. 20402 ($1.25). FDPS PRICE FDPS Price MFc0.50 HC Not Available from EDRS. DESCPTPTOPS Conference Reports, *Drug Abuse, Health Education, *Lysergic Acid Diethylamide, *Medical Research, *Mental Health IDENTIFIEPS Hallucinogenic Drugs ABSTPACT This reports a conference of psychologists, psychiatrists, geneticists and others concerned with the biological and psychological effects of lysergic acid diethylamide and other hallucinogenic drugs. Clinical data are presented on adverse drug reactions. The difficulty of determining the causes of adverse reactions is discussed, as are different methods of therapy. Data are also presented on the psychological and physiolcgical effects of L.S.D. given as a treatment under controlled medical conditions. Possible genetic effects of L.S.D. and other drugs are discussed on the basis of data from laboratory animals and humans. Also discussed are needs for futher research. The necessity to aviod scare techniques in disseminating information about drugs is emphasized. An aprentlix includes seven background papers reprinted from professional journals, and a bibliography of current articles on the possible genetic effects of drugs. (EB) National Clearinghouse for Mental Health Information VA-w. Alb alb !bAm I.S. MOMS Of NAM MON tMAN IONE Of NMI 105 NUNN NU IN WINES UAWAS RCM NIN 01 NUN N ONMININI 01011110 0. -
XANAX® Alprazolam Tablets, USP
XANAX® alprazolam tablets, USP CIV WARNING: RISKS FROM CONCOMITANT USE WITH OPIOIDS Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death [see Warnings, Drug Interactions]. Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required. Follow patients for signs and symptoms of respiratory depression and sedation. DESCRIPTION XANAX Tablets contain alprazolam which is a triazolo analog of the 1,4 benzodiazepine class of central nervous system-active compounds. The chemical name of alprazolam is 8-Chloro-1-methyl-6-phenyl-4H-s-triazolo [4,3-α] [1,4] benzodiazepine. The structural formula is represented to the right: Alprazolam is a white crystalline powder, which is soluble in methanol or ethanol but which has no appreciable solubility in water at physiological pH. Each XANAX Tablet, for oral administration, contains 0.25, 0.5, 1 or 2 mg of alprazolam. XANAX Tablets, 2 mg, are multi-scored and may be divided as shown below: 1 Reference ID: 4029640 Inactive ingredients: Cellulose, corn starch, docusate sodium, lactose, magnesium stearate, silicon dioxide and sodium benzoate. In addition, the 0.5 mg tablet contains FD&C Yellow No. 6 and the 1 mg tablet contains FD&C Blue No. 2. CLINICAL PHARMACOLOGY Pharmacodynamics CNS agents of the 1,4 benzodiazepine class presumably exert their effects by binding at stereo specific receptors at several sites within the central nervous system. Their exact mechanism of action is unknown. Clinically, all benzodiazepines cause a dose-related central nervous system depressant activity varying from mild impairment of task performance to hypnosis. -
PSYCHEDELIC DRUGS (P.L) 1. Terminology “Hallucinogens
PSYCHEDELIC DRUGS (p.l) 1. Terminology “hallucinogens” – induce hallucinations, although sensory distortions are more common “psychotomimetics” – to minic psychotic states, although truly most drugs in this class do not do so “phantasticums”or “psychedelics” – alter sensory perception (Julien uses “psychedelics”) alterations in perception, cognition, and mood, in presence of otherwise clear ability to sense” may increase sensory awareness, increase clarity, decrease control over what is sensed/experienced “self-A” may feel a passive observer of what “self-B” is experiencing often accompanied by a sense of profound meaningfulness, of divine or cosmic importance (limbic system?) these drugs can be classified by what NT they mimic: anti-ACh, agonists for NE, 5HT, or glutamate (See p. 332, Table 12.l in Julien, 9th Ed.) 2. The Anti-ACh Psychedelics e.g. scopolamine (classified as an ACh blocker) high affinity, no efficacy plant product: Belladonna or “deadly nightshade” (Atropa belladonna) Datura stramonium (jimson weed, stinkweed) Mandragora officinarum (mandrake plant) pupillary dilation (2nd to atropine) PSYCHEDELIC DRUGS (p.2) 2. Anti-ACh Psychedelics (cont.) pharmacological effects: e.g. scopolamine (Donnatal) clinically used to tx motion sickness, relax smooth muscles (gastric cramping), mild sedation/anesthetic effect PNS effects --- dry mouth relaxation of smooth muscles decreased sweating increased body temperature blurred vision dry skin pupillary dilation tachycardia, increased BP CNS effects --- drowsiness, mild euphoria profound amnesia fatigue decreased attention, focus delirium, mental confusion decreased REM sleep no increase in sensory awareness as dose increases --- restlessness, excitement, hallucinations, euphoria, disorientation at toxic dose levels --- “psychotic delirium”, confusion, stupor, coma, respiratory depression so drug is really an intoxicant, amnestic, and deliriant 3. -
References to Argentina
References to Argentina Part 1 RECENT STATISTICS AND TREND ANALYSIS OF ILLICIT DRUG MARKETS A. EXTENT OF ILLICIT DRUG USE AND HEALTH CONSEQUENCES The Americas (pages 12 to 14 WDR 13) In the Americas, a high prevalence of most illicit drugs, essentially driven by estimates in North America, was observed, with the prevalence of cannabis (7.9 per cent) and cocaine (1.3 per cent) being particularly high in the region. South America, Central America and the Caribbean The annual prevalence of cocaine use in South America (1.3 per cent of the adult population) is comparable to levels in North America, while it remains much higher than the global average in Central America (0.6 per cent) and the Caribbean (0.7 per cent). Cocaine use has increased significantly in Brazil, Costa Rica and, to lesser extent, Peru while no change in its use was reported in Argentina. The use of cannabis in South America is higher (5.7 per cent) than the global average, but lower in Central America and Caribbean (2.6 and 2.8 per cent respectively). In South America and Central America the use of opioids (0.3 and 0.2 per cent, respectively) and Ecstasy (0.1 per cent each) also remain well below the global average. While opiates use remains low, countries such as Colombia report that heroin use is becoming increasingly common among certain age groups and socio-economic classes.30 Part 2 NEW PSYCHOACTIVE SUBSTANCES C. THE RECENT EMERGENCE AND SPREAD OF NEW PSYCHOACTIVE SUBSTANCES (page 67 WDR 13) Spread at the global level Number of countries reporting the emergence of new psychoactive substances Pursuant to Commission on Narcotic Drugs resolution 55/1, entitled “Promoting international cooperation in responding to the challenges posed by new psychoactive substances”, in 2012 UNODC sent a questionnaire on NPS to all Member States, to which 80 countries and territories replied. -
Substance Use Disorders (SUD) Begin in Childhood Or Adolescence (Kandel, 1992)
PSYCHIATRY TELEHEALTH, LIAISON & CONSULTS (PSYCH TLC) Substance Related Disorders in Children and Adolescents Written and initially reviewed, 11/2011: Zaid Malik, M.D. Deepmala Deepmala, M.D Jody Brown, M.D. Laurence Miller, M.D. Reviewed and updated, 03/04/2014: Deepmala Deepmala, M.D. Work submitted by Contract # 4600016732 from the Division of Medical Services, Arkansas Department of Human Services 1 | P a g e Department of Human Services Psych TLC Phone Numbers: 501-526-7425 or 1-866-273-3835 The free Child Psychiatry Telemedicine, Liaison & Consult (Psych TLC) service is available for: Consultation on psychiatric medication related issues including: . Advice on initial management for your patient . Titration of psychiatric medications . Side effects of psychiatric medications . Combination of psychiatric medications with other medications Consultation regarding children with mental health related issues Psychiatric evaluations in special cases via tele-video Educational opportunities This service is free to all Arkansas physicians caring for children. Telephone consults are made within 15 minutes of placing the call and can be accomplished while the child and/or parent are still in the office. Arkansas Division of Behavioral Health Services (DBHS): (501) 686-9465 http://humanservices.arkansas.gov/dbhs/Pages/default.aspx 2 | P a g e Substance Related Disorders in Children and Adolescents ______________________________________________________ Table of Contents 1. Epidemiology 2. Symptomatology 3. Diagnostic Criteria -- Highlights of Changes from DSM IV to DSM 5 3.1 Substance Use Disorder 3.2 Substance Induced Disorder 3.2.1 Substance Withdrawal 3.2.2 Substance Intoxication 3.2.3 Substance/Medication-Induced Mental Disorders 4. Etiology, Risk Factors and Protective Factors 4.1 Etiology 4.2 Risk Factors and Protective Factors 5.