THE DAWN REPORT: Emergency Department Visits Attributed to Overmedication That Involved the Insomnia Medication Zolpidem August 7, 2014
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Drugs Inducing Insomnia As an Adverse Effect
2 Drugs Inducing Insomnia as an Adverse Effect Ntambwe Malangu University of Limpopo, Medunsa Campus, School of Public Health, South Africa 1. Introduction Insomnia is a symptom, not a stand-alone disease. By definition, insomnia is "difficulty initiating or maintaining sleep, or both" or the perception of poor quality sleep (APA, 1994). As an adverse effect of medicines, it has been documented for several drugs. This chapter describes some drugs whose safety profile includes insomnia. In doing so, it discusses the mechanisms through which drug-induced insomnia occurs, the risk factors associated with its occurrence, and ends with some guidance on strategies to prevent and manage drug- induced insomnia. 2. How drugs induce insomnia There are several mechanisms involved in the induction of insomnia by drugs. Some drugs affects sleep negatively when being used, while others affect sleep and lead to insomnia when they are withdrawn. Drugs belonging to the first category include anticonvulsants, some antidepressants, steroids and central nervous stimulant drugs such amphetamine and caffeine. With regard to caffeine, the mechanism by which caffeine is able to promote wakefulness and insomnia has not been fully elucidated (Lieberman, 1992). However, it seems that, at the levels reached during normal consumption, caffeine exerts its action through antagonism of central adenosine receptors; thereby, it reduces physiologic sleepiness and enhances vigilance (Benington et al., 1993; Walsh et al., 1990; Rosenthal et al., 1991; Bonnet and Arand, 1994; Lorist et al., 1994). In contrast to caffeine, methamphetamine and methylphenidate produce wakefulness by increasing dopaminergic and noradrenergic neurotransmission (Gillman and Goodman, 1985). With regard to withdrawal, it may occur in 40% to 100% of patients treated chronically with benzodiazepines, and can persist for days or weeks following discontinuation. -
THE USE of MIRTAZAPINE AS a HYPNOTIC O Uso Da Mirtazapina Como Hipnótico Francisca Magalhães Scoralicka, Einstein Francisco Camargosa, Otávio Toledo Nóbregaa
ARTIGO ESPECIAL THE USE OF MIRTAZAPINE AS A HYPNOTIC O uso da mirtazapina como hipnótico Francisca Magalhães Scoralicka, Einstein Francisco Camargosa, Otávio Toledo Nóbregaa Prescription of approved hypnotics for insomnia decreased by more than 50%, whereas of antidepressive agents outstripped that of hypnotics. However, there is little data on their efficacy to treat insomnia, and many of these medications may be associated with known side effects. Antidepressants are associated with various effects on sleep patterns, depending on the intrinsic pharmacological properties of the active agent, such as degree of inhibition of serotonin or noradrenaline reuptake, effects on 5-HT1A and 5-HT2 receptors, action(s) at alpha-adrenoceptors, and/or histamine H1 sites. Mirtazapine is a noradrenergic and specific serotonergic antidepressive agent that acts by antagonizing alpha-2 adrenergic receptors and blocking 5-HT2 and 5-HT3 receptors. It has high affinity for histamine H1 receptors, low affinity for dopaminergic receptors, and lacks anticholinergic activity. In spite of these potential beneficial effects of mirtazapine on sleep, no placebo-controlled randomized clinical trials of ABSTRACT mirtazapine in primary insomniacs have been conducted. Mirtazapine was associated with improvements in sleep on normal sleepers and depressed patients. The most common side effects of mirtazapine, i.e. dry mouth, drowsiness, increased appetite and increased body weight, were mostly mild and transient. Considering its use in elderly people, this paper provides a revision about studies regarding mirtazapine for sleep disorders. KEYWORDS: sleep; antidepressive agents; sleep disorders; treatment� A prescrição de hipnóticos aprovados para insônia diminuiu em mais de 50%, enquanto de antidepressivos ultrapassou a dos primeiros. -
(Zolpidem) Stilnox UK/W/067/Pdws/001
Public Assessment Report for paediatric studies submitted in accordance with Article 45 of Regulation (EC) No1901/2006, as amended (Zolpidem) Stilnox UK/W/067/pdWS/001 Rapporteur: UK Finalisation procedure (day 120): 25 March 2014 Date of finalisation of PAR 02 June 2014 Zolpidem UK/W/067/pdWS/001 Page 1/35 TABLE OF CONTENTS I. Executive Summary ......................................................................................................... 4 II. RecommendatioN ............................................................................................................ 5 III. INTRODUCTION ............................................................................................................... 6 IV. SCIENTIFIC DISCUSSION ............................................................................................... 6 IV.1 Information on the pharmaceutical formulation used in the clinical study(ies) ........ 6 IV.2 Non-clinical aspects ........................................................................................................ 6 IV.3 Clinical aspects .............................................................................................................. 12 IV.4 Safety Review ................................................................................................................. 21 V. MEMBER STATES Overall Conclusion AND RECOMMENDATION ........................... 34 VI. List of Medicinal products and marketing authorisation holders involved ............. 35 Page 2/35 ADMINISTRATIVE INFORMATION Invented -
Comparison of Short-And Long-Acting Benzodiazepine-Receptor Agonists
J Pharmacol Sci 107, 277 – 284 (2008)3 Journal of Pharmacological Sciences ©2008 The Japanese Pharmacological Society Full Paper Comparison of Short- and Long-Acting Benzodiazepine-Receptor Agonists With Different Receptor Selectivity on Motor Coordination and Muscle Relaxation Following Thiopental-Induced Anesthesia in Mice Mamoru Tanaka1, Katsuya Suemaru1,2,*, Shinichi Watanabe1, Ranji Cui2, Bingjin Li2, and Hiroaki Araki1,2 1Division of Pharmacy, Ehime University Hospital, Shitsukawa, Toon, Ehime 791-0295, Japan 2Department of Clinical Pharmacology and Pharmacy, Neuroscience, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime 791-0295, Japan Received November 7, 2007; Accepted May 15, 2008 Abstract. In this study, we compared the effects of Type I benzodiazepine receptor–selective agonists (zolpidem, quazepam) and Type I/II non-selective agonists (zopiclone, triazolam, nitrazepam) with either an ultra-short action (zolpidem, zopiclone, triazolam) or long action (quazepam, nitrazepam) on motor coordination (rota-rod test) and muscle relaxation (traction test) following the recovery from thiopental-induced anesthesia (20 mg/kg) in ddY mice. Zolpidem (3 mg/kg), zopiclone (6 mg/kg), and triazolam (0.3 mg/kg) similarly caused an approximately 2-fold prolongation of the thiopental-induced anesthesia. Nitrazepam (1 mg/kg) and quazepam (3 mg/kg) showed a 6- or 10-fold prolongation of the anesthesia, respectively. Zolpidem and zopiclone had no effect on the rota-rod and traction test. Moreover, zolpidem did not affect motor coordination and caused no muscle relaxation following the recovery from the thiopental-induced anesthesia. However, zopiclone significantly impaired the motor coordination at the beginning of the recovery. Triazolam significantly impaired the motor coordination and muscle relaxant activity by itself, and these impairments were markedly exacerbated after the recovery from anesthesia. -
The Safety Risk Associated with Z-Medications to Treat Insomnia in Substance Use Disorder Patients
Riaz U, et al., J Addict Addictv Disord 2020, 7: 054 DOI: 10.24966/AAD-7276/100054 HSOA Journal of Addiction & Addictive Disorders Review Article Introduction The Safety Risk Associated Benzodiazepine receptor agonist is divided in two categories: with Z-Medications to Treat a) Benzodiazepine hypnotics and Insomnia in Substance Use b) Non-benzodiazepine hypnotics. The prescription of Z-medications which is non-benzodiazepine Disorder Patients hypnotic is common in daily clinical practice, particularly among primary medical providers to treat patients with insomnia. This trend Usman Riaz, MD1* and Syed Ali Riaz, MD2 is less observed among psychiatrist, but does exist. While treating substance use disorder population the prescription of Z-medications 1 Division of Substance Abuse, Department of Psychiatry, Montefiore Medical should be strongly discouraged secondary to well documented Center/Albert Einstein College of Medicine, Bronx NY, USA safety risks. There is sufficient data available suggesting against the 2Department of Pulmonology/Critical Care and Sleep Medicine, Virtua Health, prescription of Z-medications to treat insomnia in substance abuse New Jersey, USA patients. Though treating insomnia is essential in substance use disorder patients to prevent relapse on alcohol/drugs, be mindful of risk associated with hypnotics particularly with BZRA (Benzodiazepines Abstract and Non benzodiazepines hypnotics). Z-medications are commonly prescribed in clinical practices Classification of Z-medications despite the safety concerns. Although these medications are Name of medication Half-life (hr) Adult dose (mg). considered safer than benzodiazepines, both act on GABA-A receptors as an allosteric modulator. In clinical practice, the risk Zaleplon 1 5-20 profile for both medications is not any different, particularly in Zolpidem 1.5-4.5 5-10 substance use disorder population. -
Herbal Remedies and Sleep
HERBAL REMEDIES AND SLEEP • Some people use herbal remedies to treat sleep problems. They may choose this in preference to sleeping pills. • There have been studies on some of these herbs. However, not all of them have been conducted properly. For some herbs, there is virtually no evidence to show whether they are effective or not. • The most frequently studied herbs are Valerian, Kava, Hops, Chamomile, and Passionflower. However, there is little convincing evidence to suggest that they work well for improving sleep. • Some herbal remedies have been associated with adverse health effects. Note: All words that are underlined relate to topics in the Sleep Health Foundation Information Library at www.sleephealthfoundation.org.au 1. Why try herbs to help your sold by a specific manufacturer for a certain time-period. Trials testing effectiveness are expensive, and without a patent, companies may not sleep? be able to recover their costs through guaranteed sales, even if the herb has potential. However, there have been studies of some herbs About 40% of people use alternative or complementary medicines at used for insomnia and anxiety. Here we focus on herbs where least occasionally, and 4.5% use them to treat sleep problem. Some reasonable information exists from clinical research trials. people who are concerned about using sleeping pills will turn to herbal remedies to help them sleep (see our page on Sleeping Tablets). Melatonin is not a herbal remedy (for more information see Melatonin). 3. What does the evidence say about herbs helping sleep? 2. Has the effectiveness of herbs In the table below, we look at the effectiveness of eight herbal remedies in treating sleep problems as treatments of insomnia. -
Evaluation of Zolpidem, Triazolam, and Placebo As Hypnotic Drugs the Night Before Surgery
ELSEVIER Evaluation of Zolpidem, Triazolam, and Placebo as Hypnotic Drugs the Night Before Surgery Pamela J. Morgan, MD, CCFP, FRCPC, Roger Chapados, MD,? Frances F. Chung, MD,x Marlene Gauthier, MD,5 John W.D. Knox, MD,” Jacques Le Lorier, MD# . Departments of Xnaesthesia, University of Toronto, Toronto, Ontario; Maisonneuve Kosemont Hospital, Montreal, Quebec; Royal Victoria Hospital, Montreal, Quebec; Queen Elizabeth II Health Sciences Center. Halifax, Nova Scotia; Hospital Sainte .Justine, Montreal. Quebec, Canada Study Objectke: To wmpare the hypnotic effects of a bedtime dose ofzolpidem, triazolam, and placebo. Design: Double-blind, randomized, plucebo- and active-controlled, parallel-group trial. Setting: Six Canadiun hospitals. Patients: 357 patients (aged 19 to 71 years) hospitalized the night before a surgical p,octdnre. Interventions: At bedtime, each patient received either zolpidem 10 mg, triazolam 0.25 mg, or placebo, and 71~1s allowed to sleep for a maximum of 8 hourr. Measurements: Outcovtw rmmure.s wo-e subjjrctive in nntuw and included a morning qrr&ionnairp, 7Gsual analog scales, and obsPl‘c!ation ji)rms b study personnel. All con- tinuou,s variables wyre analyzed ty analysis of variance. All rategotical data were com- pared using the C:ochra,l-lL~an tel-Hams-e1 (CAfH) test, and the percentage of patients arle+ 71~7s compared using a CMH chi-syuarr analysis. When .signijcant overall treat- ment effects were obsprourl, pai,wisr compnrirons u&e undertaken. Compared with the placebo‘ group, the ,/oilort~1ng paramrter~ were c@~ficantl~ (p < 0.001) dz;ffent in the zolpidpm and tm’cc~olam groups: sleep IatancT roar shorter, total &ep time was longer, p&n ts fell asleep morp rnsity, and the n umbm of patients awake 2 hours Ffter drug trdminictration 7uas 1071~1. -
Current and Experimental Therapeutics of Insomnia
133 CURRENT AND EXPERIMENTAL THERAPEUTICS OF INSOMNIA DANIEL J. BUYSSE CYNTHIA M. DORSEY 15% (4,5). Epidemiologic studies point to a consistent set of risk factors for insomnia. These include a previous history INSOMNIA: DEFINITIONS, IMPACT, AND of insomnia, increasing age, female gender, psychiatric DIAGNOSIS symptoms and disorders, medical symptoms and disorders, impaired activities of daily living, anxiolytic and hypnotic Definition of Insomnia Symptoms and medication use, and low socioeconomic status. The increas- Disorders ing prevalence of insomnia with age may be explained in large part by increasing comorbidity with medical and psy- Insomnia can refer to either a symptom or clinical disorder. chiatric disorders and medication use. The incidence of in- The symptom of insomnia is the subjective complaint of somnia also increases with age and is greater in women than difficulty falling or staying asleep, poor quality sleep, or men. On the other hand, remission of insomnia decreases inadequate sleep duration, despite having an adequate op- with age and is less common in women. Together, preva- portunity for sleep. Two points in this definition deserve lence, incidence, and remission data indicate that insomnia specific attention. First, insomnia is a subjective complaint is often a chronic condition. Between 50% and 80% of not currently defined by laboratory test results or a specific individuals with insomnia at baseline have a persistent com- duration of sleep or wakefulness. Second, the insomnia plaint after follow-up intervals of 1 to 3.5 years (1,6–8). symptom occurs despite the individual having adequate op- portunity to sleep. This distinguishes insomnia from sleep deprivation, which has different causes, consequences, and Impact of Insomnia clinical presentations. -
Insomnia in Adults
New Guideline February 2017 The AASM has published a new clinical practice guideline for the pharmacologic treatment of chronic insomnia in adults. These new recommendations are based on a systematic review of the literature on individual drugs commonly used to treat insomnia, and were developed using the GRADE methodology. The recommendations in this guideline define principles of practice that should meet the needs of most adult patients, when pharmacologic treatment of chronic insomnia is indicated. The clinical practice guideline is an essential update to the clinical guideline document: Sateia MJ, Buysse DJ, Krystal AD, Neubauer DN, Heald JL. Clinical practice guideline for the pharmacologic treatment of chronic insomnia in adults: an American Academy of Sleep Medicine clinical practice guideline. J Clin Sleep Med. 2017;13(2):307–349. SPECIAL ARTICLE Clinical Guideline for the Evaluation and Management of Chronic Insomnia in Adults Sharon Schutte-Rodin, M.D.1; Lauren Broch, Ph.D.2; Daniel Buysse, M.D.3; Cynthia Dorsey, Ph.D.4; Michael Sateia, M.D.5 1Penn Sleep Centers, Philadelphia, PA; 2Good Samaritan Hospital, Suffern, NY; 3UPMC Sleep Medicine Center, Pittsburgh, PA; 4SleepHealth Centers, Bedford, MA; 5Dartmouth-Hitchcock Medical Center, Lebanon, NH Insomnia is the most prevalent sleep disorder in the general popula- and disease management of chronic adult insomnia, using existing tion, and is commonly encountered in medical practices. Insomnia is evidence-based insomnia practice parameters where available, and defined as the subjective perception of difficulty with sleep initiation, consensus-based recommendations to bridge areas where such pa- duration, consolidation, or quality that occurs despite adequate oppor- rameters do not exist. -
Herbs a T a Glance: Valerian
Valerian This fact sheet provides basic information about the herb valerian—common names, uses, potential side effects, and resources for more information. Valerian is a plant native to Europe and Asia; it is also found in North America. Valerian has been used as a medicinal herb since at least the time of ancient Greece and Rome. Its therapeutic uses were described by Hippocrates, and in the 2nd century, Galen prescribed valerian for insomnia. Common Names—valerian, all-heal, garden heliotrope Latin Name—Valeriana officinalis What It Is Used For • Valerian has long been used for sleep disorders and anxiety. • Valerian has also been used for other conditions, such as headaches, depression, irregular heartbeat, and trembling. How It Is Used The roots and rhizomes (underground stems) of valerian are typically used to make supplements, including capsules, tablets, and liquid extracts, as well as teas. What the Science Says • Research suggests that valerian may be helpful for insomnia, but there is not enough evidence from well-designed studies to confirm this. • There is not enough scientific evidence to determine whether valerian works for anxiety or for other conditions, such as depression and headaches. • Recent NCCAM-funded research on valerian includes studies on the herb’s effects on sleep in healthy older adults and in people with Parkinson’s disease. Side Effects and Cautions • Studies suggest that valerian is generally safe to use for short periods of time (for example, 4 to 6 weeks). • No information is available about the long-term safety of valerian. • Valerian can cause mild side effects, such as headaches, dizziness, upset stomach, and tiredness the morning after its use. -
Insomnia-1111 30/11/11 4:37 PM Page 1
SHF-Insomnia-1111 30/11/11 4:37 PM Page 1 Insomnia Important Things to Know About Insomnia • Around 1 in 3 people have at least mild insomnia. • Many poor sleepers have developed poor sleep habits. • For specialist help, cognitive behavioural therapy for insomnia is best • In the long run, taking sleeping pills isn’t effective. • There are sleep specialists, clinics and on-line programs that can help. What is insomnia? How common is insomnia? Insomnia is said to be present when you regularly find it Most people have experience insomnia symptoms at hard to fall asleep or stay asleep. It has several patterns. some time of their lives. At any given time around 10% You may have trouble getting to sleep initially. Or even if of people have at least mild insomnia. you can fall asleep, you might not be able to stay asleep for as long as you would like. Also you may wake up Who is at risk? during the night and not be able to go back to sleep for a long time. Many people have two of the above problems, Older people with poor health have a higher risk. Also or even all three. Because of these, you might feel tired women have twice the rates compared to men. This may during the day. be related to higher rates of anxiety and depression, which can be associated with insomnia. Shift workers What causes insomnia? have a higher risk too. Insomnia has many causes which can include: How does it affect people? • Some medicines and drugs, e.g. -
Zolpidem Tartrate
DETERMINING IF A PRESCRIPTION DRUG ABUSE PROBLEM EXISTS OPIOIDS: Answering “yes” to any of the following questions may indicate a problem with the use of pain medication: What You Need Are you using someone’s else’s prescription? to Know Are you obtaining drugs from an illicit source or by illegal means? Are you no longer using the drugs for the symptoms POSSIBLE CONSEQUENCES OF for which it was originally prescribed? OPIOID MISUSE OR ABUSE Are you lying about or hiding your use? Chronic use of opioids can result in tolerance for the drugs, which means that users must take higher doses Are you obtaining medications from multiple to achieve the same initial effects. Long-term use, if physicians. not taken as prescribed, can lead to physical dependence and addiction — the body adapts to the Have your friends, family members, or co-workers presence of the drug, and withdrawal symptoms occur expressed concern? if use is reduced WARNINGSor stopped. & PRECAUTIONS Before taking zolpidem tartrate: Are you preoccupied about your medication, Symptoms of withdrawal include restlessness,Zolpidem Tartrate muscle focused on the next dose, and concerned about how • Zolpidem tartrate will make you fall asleep. (Ambien, Ambien CR, Edluar Never take this medication during your normal Growing Threat of and bone pain, insomnia, diarrhea, vomiting,Zolpimist) cold you will obtain more drugs? waking hours, unless you have a full 7 to 8 flashes with goosehours bumps to dedicate to sleeping. ("cold turkey"), and involuntary leg movements. Finally, taking a large Do you fill your prescription sooner than would be • Some people using this medicine have engaged Prescription Drug COMMONsingle SIDE EFFECTSdose OF of an opioidin activity such as driving, could eating, or making cause severe respiratory expected and make excuses for why? ZOLPIDEM TARTRATE: phone calls and later having no memory of depression that canthe activity.