DOCSLIB.ORG

Pharmacologic Therapy for Primary Restless Legs Syndrome a Systematic Review and Meta-Analysis

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Pharmacologic Therapy for Primary Restless Legs Syndrome a Systematic Review and Meta-Analysis REVIEW ARTICLE Pharmacologic Therapy for Primary Restless Legs Syndrome A Systematic Review and Meta-analysis Timothy J. Wilt, MD, MPH; Roderick MacDonald, MS; Jeannine Ouellette; Imran S. Khawaja, MD; Indulis Rutks, BA; Mary Butler, PhD, MBA; Howard A. Fink, MD, MPH Importance: Restless legs syndrome (RLS) is a neuro- proved patient-reported sleep scale scores and quality- logical disorder characterized by unpleasant sensations of-life measures. High-strength evidence demonstrated in the legs and a distressing, irresistible urge to move them. that calcium channel alpha-2-delta ligands increased the We conducted a systematic review to evaluate efficacy, proportion of IRLS responders compared with placebo safety, and comparative effectiveness of pharmacologic (61% vs 37%) (risk ratio, 1.66 [95% CI, 1.33-2.09]; 3 treatments for primary RLS. trials). Adverse events associated with dopamine ago- nists included nausea, vomiting, and somnolence. Alpha- Evidence Acquisition: We included randomized con- 2-delta ligands adverse events included somnolence and trolled trials (RCTs), published in English, reporting ef- unsteadiness or dizziness. ficacy outcomes and harms of pharmacologic treat- ments for primary RLS of at least 4 weeks’ duration. Conclusions and Relevance: On the basis of short- MEDLINE and other databases were searched through term RCTs that enrolled highly selected populations with June 2012. Reviewers extracted outcomes and adverse events and rated the strength of evidence. long-term high-moderate to very severe symptoms, dopa- mine agonists and calcium channel alpha-2-delta li- Results: We identified 29 eligible RCTs. We found high- gands reduced RLS symptoms and improved sleep out- strength evidence that the proportion of patients who had comes and disease-specific quality of life. Adverse effects a clinically important response (International Restless Legs and treatment withdrawals due to adverse effects were Syndrome [IRLS] responders), defined as a 50% or greater common. reduction from baseline in mean IRLS symptom scale scores, was greater with dopamine agonist therapy com- JAMA Intern Med. 2013;173(7):496-505. pared with placebo (61% vs 41% ) (risk ratio, 1.60 [95% Published online March 4, 2013. CI, 1.38-1.86]; 7 trials). Dopamine agonists also im- doi:10.1001/jamainternmed.2013.3733 Author Affil Chronic Dis Research (D ESTLESS LEGS SYNDROME Diagnostic criteria for RLS were estab- and Messrs M (RLS) is characterized by lished by the International Restless Legs Rutks) and D unpleasant sensations in Syndrome (IRLS) Study Group in 19953 Psychiatry ( the legs and a distressing, and revised in 2003.1 The criteria include Minneapolis irresistible urge to move the following: (1) an urge to move the legs, System, Min Minnesota; M Rthem. The etiology of primary RLS is un- usually accompanied by uncomfortable or Evidence-Ba known. The disorder also occurs second- unpleasant sensations in the legs; (2) un- Minneapolis ary to other conditions such as iron defi- pleasant sensations or urge to move that and Fink, M ciency, end-stage renal disease, and begin or worsen during periods of rest or and Rutks, a pregnancy.1 A family history of RLS is com- inactivity such as lying or sitting; (3) un- Department 1 Wilt and Fin mon, but genome-wide association stud- pleasant sensations or urge to move that (Dr Khawaja ies have produced inconsistent findings.2 are partly or totally relieved by move- Minnesota, M Restless leg syndrome can result in re- ment such as walking, bending, and University o duced quality of life (QoL) and have a stretching, at least as long as the activity of Public He negative impact on sleep, leading to day- continues; and (4) unpleasant sensations (Drs Wilt, B Ms Ouellette time fatigue. Effective treatment options or urge to move that are worse in the eve- Research Ed Author Affiliations are listed at are not well established, and scant evi- ning or at night than during the day or only Clinical Cen the end of this article. dence exists to guide treatment selection. occur in the evening or night. Center, Min JAMA INTERN MED/ VOL 173 (NO. 7), APR 8, 2013 WWW.JAMAINTERNALMED.COM 496 ©2013 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/28/2021 Restless leg syndrome varies in INFORMATION SOURCES mates of overall risk ratios (RRs), symptom severity and frequency. weighted mean differences (WMDs), Mild RLS may cause minor annoy- We searched the bibliographic data- or standardized mean differences ance, but severe RLS can negatively bases MEDLINE, EMBASE, and Natu- (SMDs) and the corresponding 95% affect work, social activities, func- ral Standards through June 2012 for confidence intervals. Data were pooled RCTs evaluating treatment efficacy and and analyzed in Review Manager statis- tion, and emotional well-being. Sleep tical software (RevMan version 5.1; disruption induced by RLS may lead reported adverse effects (eAppendix 1; http://www.jamainternalmed.com). To The Nordic Cochrane Centre, The to poor daytime functioning, anxi- identify completed trials and to reduce Cochrane Collaboration). We assessed ety, and depression. Sleep depriva- publication bias, we searched Coch- statistical heterogeneity between trials tion and daytime fatigue are com- rane Central, the International Con- and for subgroups of drugs using the I2 mon reasons patients with RLS seek trolled Trials Registry Platform test and observation of the direction of treatment.4 Prevalence estimates for (ICTRP), Clinicaltrials.gov, FDA web- the effect of the studies. Scores of ap- bothersome RLS in the United States sites, and the National Institutes of proximately 50% and effect sizes that range from 1.5% to 7.4% in adults.1,5 Health (NIH) RePORTer. We included did not fall on the same side of “no ef- The variation reflects different ap- eligible unidentified trials referred by fect” suggested substantial heteroge- peer reviewers. neity. Number needed to treat (NNT) proaches to diagnosing RLS and de- and number needed to harm (NNH) fining its presence and severity and DATA EXTRACTION AND were calculated for dichotomous out- the fact that many RLS question- comes. For the fixed-dose trials, we naires do not account for individu- QUALITY ASSESSMENT analyzed only doses recommended for als who have other conditions with current clinical practice if possible. We similar symptoms. Data from included studies were ab- examined funnel plots and performed Pharmacologic treatment is gen- stracted into evidence tables by 1 re- Egger intercept tests9 to detect publica- viewer (R.M.) and validated by a sec- tion bias. erally reserved for patients whose ond reviewer (T.J.W.). Our primary symptoms are frequent (several outcome was IRLS responders defined times per week) and cause moder- as patients with a 50% or greater reduc- RESULTS ate to very severe discomfort and tion in IRLS scale score from baseline. bother. Three dopamine agonists We also assessed the mean change in Our literature search for RCTs of (pramipexole, ropinirole, and roti- IRLS scale score from baseline; percent- pharmacologic treatments of pri- gotine) and 1 calcium channel alpha- age of patients with complete remis- mary RLS yielded 29 references 2-delta ligand (gabapentin enacar- sion; percentage of patients reporting meeting our inclusion criteria, bil) are currently approved by the “much improved” or “very much im- shown in Figure 1. Food and Drug Administration proved” on clinician-assessed global im- pression (CGI) or patient-assessed global (FDA) for treatment of moderate to impression scales; RLS QoL; patient- DOPAMINE severe RLS. reported sleep quality; number of indi- We conducted a systematic re- viduals experiencing adverse effects; AGONIST THERAPY view to evaluate the effectiveness and dropouts; dropouts due to adverse ef- harms of pharmacologic treat- fects; treatment discontinuation be- Efficacy of dopamine agonists ments for patients with primary RLS. cause of adverse effects; specific ad- was evaluated in 18 randomized, This report is based on research con- verse effects; and augmentation. double-blind, placebo-controlled We used criteria developed by the studies10-27 and 2 comparative effec- ducted by the Minnesota Evidence- 7 based Practice Center under con- Cochrane Collaboration in rating in- tiveness studies.28,29 Two placebo- tract to the Agency for Healthcare dividual RCTs as good, fair, or poor controlled studies26,27 and 1 com- quality based on the adequacy of allo- Research and Quality (AHRQ) and parative effectiveness trial29 assessed 6 cation concealment, blinding, report- is available on the AHRQ web site. ing of reasons for attrition, and how cabergoline (an ergot-derived dopa- analyses accounted for incomplete mine agonist). Cabergoline is not METHODS data (eAppendices 2-4). Using meth- FDA approved for RLS treatment and ods developed by AHRQ and the Effec- is rarely used in the United States 8 STUDY SELECTION tive Health Care Program, we evalu- owing in part to FDA warnings about ated overall strength of evidence for cardiac valvular complications. For outcomes for each treatment compari- We included randomized controlled this reason, we did not include 2 cab- son based on the criteria of risk of bias, trials (RCTs) that enrolled individuals ergoline placebo–controlled stud- consistency, directness, and precision. with primary RLS as defined by the ies26,27 with the other dopaminergic We resolved discrepancies in quality and IRLS Study Group.1,3 Eligible trials strength of evidence ratings by discus- trials. We describe findings of the were published in English, evaluated sion and consensus. single comparative effectiveness trial pharmacologic interventions for RLS of cabergoline vs levodopa because vs placebo or active intervention, DATA SYNTHESIS it is one of two comparative effec- lasted at least 4 weeks, and reported tiveness studies identified29; the validated RLS symptom or QoL scale AND ANALYSIS scores, clinician and patient global other was a crossover trial compar- impact scale scores, or measures of For trials that included similar popula- ing pramipexole to dual-release le- 28 sleep quality. We limited interven- tions, interventions, and outcomes and vodopa-benserazide.
Load more

Recommended publications
  • Neuroenhancement in Healthy Adults, Part I: Pharmaceutical
    l Rese ca arc ni h li & C f B o i o l e Journal of a t h n Fond et al., J Clinic Res Bioeth 2015, 6:2 r i c u s o J DOI: 10.4172/2155-9627.1000213 ISSN: 2155-9627 Clinical Research & Bioethics Review Article Open Access Neuroenhancement in Healthy Adults, Part I: Pharmaceutical Cognitive Enhancement: A Systematic Review Fond G1,2*, Micoulaud-Franchi JA3, Macgregor A2, Richieri R3,4, Miot S5,6, Lopez R2, Abbar M7, Lancon C3 and Repantis D8 1Université Paris Est-Créteil, Psychiatry and Addiction Pole University Hospitals Henri Mondor, Inserm U955, Eq 15 Psychiatric Genetics, DHU Pe-psy, FondaMental Foundation, Scientific Cooperation Foundation Mental Health, National Network of Schizophrenia Expert Centers, F-94000, France 2Inserm 1061, University Psychiatry Service, University of Montpellier 1, CHU Montpellier F-34000, France 3POLE Academic Psychiatry, CHU Sainte-Marguerite, F-13274 Marseille, Cedex 09, France 4 Public Health Laboratory, Faculty of Medicine, EA 3279, F-13385 Marseille, Cedex 05, France 5Inserm U1061, Idiopathic Hypersomnia Narcolepsy National Reference Centre, Unit of sleep disorders, University of Montpellier 1, CHU Montpellier F-34000, Paris, France 6Inserm U952, CNRS UMR 7224, Pierre and Marie Curie University, F-75000, Paris, France 7CHU Carémeau, University of Nîmes, Nîmes, F-31000, France 8Department of Psychiatry, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Eschenallee 3, 14050 Berlin, Germany *Corresponding author: Dr. Guillaume Fond, Pole de Psychiatrie, Hôpital A. Chenevier, 40 rue de Mesly, Créteil F-94010, France, Tel: (33)178682372; Fax: (33)178682381; E-mail: [email protected] Received date: January 06, 2015, Accepted date: February 23, 2015, Published date: February 28, 2015 Copyright: © 2015 Fond G, et al.
    [Show full text]
  • Pramipexole V2.1 Last Reviewed: 22/04/2021 Review Date: 22/04/2024
    Pramipexole V2.1 Last reviewed: 22/04/2021 Review date: 22/04/2024 Pramipexole Traffic light classification- Amber 2 Information sheet for Primary Care Prescribers CLINICAL INFORMATION Key points/interactions Nausea is a common early side effect but usually responds to domperidone (10mg tds, or lowest effective dose – see MHRA advice) Ropinirole MR is first line dopamine agonist. Pramipexole MR should be reserved for patients in whom this is not suitable- see formulary. Dopamine agonists may cause compulsive/addictive behaviours such as gambling, compulsive shopping and hyper sexuality. Patients rarely recognise such changes as side effects and rarely report them unless specifically asked. Licensed Indications Treatment of idiopathic Parkinson's disease. Pramipexole may be used alone (without levodopa) or in combination with levodopa throughout the disease, through to late stages when the effect of levodopa wears off or becomes inconsistent and fluctuations of the therapeutic effect occur (end of dose or “on-off” fluctuations). Therapeutic Summary As per the licensed indication. NICE recommendations for the use of Pramipexole in Parkinson’s disease are: Consider a choice of dopamine agonists, levodopa or monoamine oxidase B (MAO-B) inhibitors for people in the early stages of Parkinson's disease whose motor symptoms do not impact their quality of life. Do not offer ergot-derived dopamine agonists as first-line treatment for Parkinson's disease. Offer a choice of dopamine agonists, MAO-B inhibitors or catechol-O-methyltransferase (COMT)
    [Show full text]
  • List Item Pramipexole Teva
    ANNEX I SUMMARY OF PRODUCT CHARACTERISTICS 1 1. NAME OF THE MEDICINAL PRODUCT Pramipexole Teva 0.088 mg tablets Pramipexole Teva 0.18 mg tablets Pramipexole Teva 0.35 mg tablets Pramipexole Teva 0.7 mg tablets 2. QUALITATIVE AND QUANTITATIVE COMPOSITION Pramipexole Teva 0.088 mg tablets Each tablet contains 0.125 mg pramipexole dihydrochloride monohydrate equivalent to 0.088 mg pramipexole. Pramipexole Teva 0.18 mg tablets Each tablet contains 0.25 mg pramipexole dihydrochloride monohydrate equivalent to 0.18 mg pramipexole. Pramipexole Teva 0.35 mg tablets Each tablet contains 0.5 mg pramipexole dihydrochloride monohydrate equivalent to 0.35 mg pramipexole. Pramipexole Teva 0.7 mg tablets Each tablet contains 1.0 mg pramipexole dihydrochloride monohydrate equivalent to 0.7 mg pramipexole. Please note: Pramipexole doses as published in the literature refer to the salt form. Therefore, doses will be expressed in terms of both pramipexole base and pramipexole salt (in brackets). For the full list of excipients, see section 6.1. 3. PHARMACEUTICAL FORM Tablet Pramipexole Teva 0.088 mg tablets White, round, flat face bevel edge tablet, 5.55 mm diameter, embossed with “93” on one side and “P1” on the other side. Pramipexole Teva 0.18 mg tablets White, round, flat face bevel edge tablet, 7.00 mm diameter, embossed with "P2" over "P2" on the scored side and "93" on the other side. The tablet can be divided into equal halves. Pramipexole Teva 0.35 mg tablets White to off-white, oval, biconvex tablets, engraved with 9 vertical scoreline 3 on the scored side, and 8023 on the other side.
    [Show full text]
  • Effects of Ketamine and Ketamine Metabolites on Evoked Striatal Dopamine Release, Dopamine Receptors, and Monoamine Transporters
    1521-0103/359/1/159–170$25.00 http://dx.doi.org/10.1124/jpet.116.235838 THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS J Pharmacol Exp Ther 359:159–170, October 2016 U.S. Government work not protected by U.S. copyright Effects of Ketamine and Ketamine Metabolites on Evoked Striatal Dopamine Release, Dopamine Receptors, and Monoamine Transporters Adem Can,1 Panos Zanos,1 Ruin Moaddel, Hye Jin Kang, Katinia S. S. Dossou, Irving W. Wainer, Joseph F. Cheer, Douglas O. Frost, Xi-Ping Huang, and Todd D. Gould Department of Psychiatry (A.C., P.Z., J.F.C., D.O.F., T.D.G.), Department of Pharmacology (D.O.F, T.D.G), and Department of Anatomy and Neurobiology (J.F.C, T.D.G), University of Maryland School of Medicine, Baltimore, Maryland; Department of Psychology, Notre Dame of Maryland University, Baltimore, Maryland (A.C.); Biomedical Research Center, National Institute on Aging, National Institutes of Health, Baltimore, Maryland (R.M., K.S.S.D., I.W.W.); National Institute of Mental Health Psychoactive Drug Screening Program, Department of Pharmacology, University of North Carolina Chapel Hill Medical School, Chapel Hill, North Carolina (H.J.K., X.-P.H.); and Mitchell Woods Pharmaceuticals, Shelton, Connecticut (I.W.W.) Received June 14, 2016; accepted July 27, 2016 ABSTRACT Following administration at subanesthetic doses, (R,S)-ketamine mesolimbic DA release and decay using fast-scan cyclic (ketamine) induces rapid and robust relief from symptoms of voltammetry following acute administration of subanesthetic depression in treatment-refractory depressed patients. Previous doses of ketamine (2, 10, and 50 mg/kg, i.p.).
    [Show full text]
  • Sustained Administration of Pramipexole Modifies the Spontaneous Firing of Dopamine, Norepinephrine, and Serotonin Neurons in the Rat Brain
    Neuropsychopharmacology (2009) 34, 651–661 & 2009 Nature Publishing Group All rights reserved 0893-133X/09 $32.00 www.neuropsychopharmacology.org Sustained Administration of Pramipexole Modifies the Spontaneous Firing of Dopamine, Norepinephrine, and Serotonin Neurons in the Rat Brain ,1 1 1,2 O Chernoloz* , M El Mansari and P Blier 1 2 Institute of Mental Health Research, University of Ottawa, Ottawa, Ontario, Canada; Department of Cellular and Molecular Medicine, University of Ottawa, Ontario, Canada Pramipexole (PPX) is a D2/D3 receptor agonist that has been shown to be effective in the treatment of depression. Serotonin (5-HT), norepinephrine (NE) and dopamine (DA) systems are known to be involved in the pathophysiology and treatment of depression. Due to reciprocal interactions between these neuronal systems, drugs selectively targeting one system-specific receptor can indirectly modify the firing activity of neurons that contribute to firing patterns in systems that operate via different neurotransmitters. It was thus hypothesized that PPX would alter the firing rate of DA, NE and 5-HT neurons. To test this hypothesis, electrophysiological experiments were carried out in anesthetized rats. Subcutaneously implanted osmotic minipumps delivered PPX at a dose of 1 mg/kg per day for 2 or 14 days. After a 2-day treatment with PPX the spontaneous neuronal firing of DA neurons was decreased by 40%, NE neuronal firing by 33% and the firing rate of 5-HT neurons remained unaltered. After 14 days of PPX treatment, the firing rate of DA had recovered as well as that of NE, whereas the firing rate of 5-HT neurons was increased by 38%.
    [Show full text]
  • DRUG TREATMENTS for Parkinson's
    DRUG TREATMENTS FOR Parkinson’s 1 There is no cure yet for Parkinson’s but there are The content in this booklet is designed to be dipped in and out many different drugs that can of – don’t feel like you need to help manage the symptoms. read everything in one go. This is particularly true because what This booklet is for people works for you when starting with Parkinson’s and their treatment for Parkinson’s may family, friends and carers. change later on. It provides information Reading the bits of this about the drugs most information that you need will commonly used to help also make this booklet more manage the condition. manageable and relevant for you. This booklet starts with some key practical points about the drugs used for treating Parkinson’s, then gives further details about categories of drugs and individual drugs. There is also a summary that gives an overview list of Parkinson’s drugs. Choosing the right medication is always a decision you should make with your specialist or Parkinson’s nurse. You can show this booklet to your specialist or Parkinson’s nurse and ask them questions about the information here. You may also find it a useful starting point when you are talking about the next steps in your treatment. Contents Section 1 This gives an overview of Parkinson’s medication and is recommended for anyone with the condition. Parkinson’s drugs: an introduction .........................................................6 This includes how drugs work, their names and what treatment to take. Other ways to manage your Parkinson’s .............................................9 This includes exercise and therapies.
    [Show full text]
  • Pramipexole Dihydrochloride) Tablets, for Oral Use None (4) Initial U.S
    HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use ---------------------DOSAGE FORMS AND STRENGTHS---------------------­ MIRAPEX safely and effectively. See full prescribing information for Tablets: 0.125 mg, 0.25 mg, 0.5 mg, 0.75 mg, 1 mg, and 1.5 mg (3) MIRAPEX. -------------------------------CONTRAINDICATIONS-------------------------­ MIRAPEX® (pramipexole dihydrochloride) tablets, for oral use None (4) Initial U.S. Approval: 1997 ---------------------------RECENT MAJOR CHANGES--------------------------­ -----------------------WARNINGS AND PRECAUTIONS-----------------------­ Warnings and Precautions , Postural Deformity (5.6) 5/2018 Falling asleep during activities of daily living: Sudden onset of sleep may Warnings and Precautions, Rhabdomyolysis (5.8) 5/2018 occur without warning; advisepatients to report symptoms (5.1) Warnings and Precautions, Symptomatic orthostatic hypotension: Monitor during doseescalation Events Reported with Dopaminergic Therapy (5.10); (5.2) Melanoma Removed 5/2018 Impulse control/Compulsive behaviors: Patients may experience compulsive behaviors and otherintenseurges (5.3) ----------------------------INDICATIONS AND USAGE--------------------------­ Hallucinations and Psychotic-like Behavior: May occur; risk increases MIRAPEX is a non-ergot dopamine agonist indicated for thetrea tment of: with age (5.4) Parkinson’s disease (PD) (1.1) Dyskinesia: May be caused or exacerbated by MIRAPEX (5.5) Moderate-to-severe primary Restless Legs Syndrome (RLS)
    [Show full text]
  • Drug Information Quarterly
    Whiskey & Taylor Pramipexole in treatment of depression drug information quarterly Psychiatric Bulletin (2004), 28,438^440 EROMONA WHISKEY AND DAVID TAYLOR Pramipexole in unipolar and bipolar depression AIMS AND METHOD RESULTS CLINICAL IMPLICATIONS To review the evidence for this use of There are limited data on the clinical use In view of the fact that the evidence pramipexole in the treatment of of pramipexole in affective disorders. for the use of pramipexole is still unipolar and bipolar depression, a Only two double-blind trials in bipolar limited at the time of writing, its literature search on Embase and depressionandoneinunipolardepression routine clinical use cannot be Medline was conducted in December were retrieved. Most information is in the recommended.The data appear 2003.The search was updated in July form of case reports and open studies. No promising, but further research is 2004.The reference sections of dose-response relationships have been required to determine its role in retrieved papers were searched for established and a wide range of doses has affective disorders. further relevant references. been employed in the reports. The monoamine hypothesis of depression has been the agonists (Maj & Rogoz, 1999; Renard et al,2001).In driving force behind antidepressant drug development for humans, the dopamine agonist bromocriptine has been several decades. The theory holds that lower levels of shown to be as effective as imipramine in the treatment serotonin, noradrenaline and dopamine may be involved of depression (Willner, 1983). For a review of dopamine in in the pathophysiology of depression. The place of sero- depression, see Willner (1995) and Rampello et al (2000).
    [Show full text]
  • A Phase 2A Study to Evaluate the Kappa Opioid Receptor As a Target
    Study Title: A Phase 2a Study to Evaluate the Kappa Opioid Receptor As a Target for the Treatment of Mood and Anxiety Spectrum Disorders by Evaluation of Whether CERC-501 Engages Key Neural Circuitry Related to the Hedonic Response Version Date: October 06, 2016 NCT02218736 FAST-MAS KOR Phase 2a Study Protocol Version 6.0 Task Order #: HHSN27100004 Version Date 10/06/16 Contract #: HHSN271201200006I CLINICAL STUDY PROTOCOL Study Title: A Phase 2a Study to Evaluate the Kappa Opioid Receptor As a Target for the Treatment of Mood and Anxiety Spectrum Disorders by Evaluation of Whether CERC-501 Engages Key Neural Circuitry Related to the Hedonic Response Abbreviated Title: FAST-MAS KOR Phase 2a Protocol Version: 6.0 Version Date: October 06, 2016 Contract Title: New Experimental Medicine Studies: Fast-Fail Trials in Mood and Anxiety Spectrum Disorders (FAST-MAS) Contract #: HHSN271201200006I Contractor: Duke University Contract PI: Andrew D. Krystal, M.D., M.S. Professor, Department of Psychiatry and Behavioral Sciences Duke University Medical Center Box 3309 Durham, NC 27710 Task Order #: HHSN27100004 Overall Study PI: Andrew D. Krystal, M.D., M.S. Supported by: National Institute of Mental Health (NIMH) Confidential: This document and its contents are the property of the Duke Clinical Research Institute. The information contained herein is confidential and is to be used only in connection with matters authorized by Duke Clinical Research Institute. No portion of this document is to be disclosed to others without prior written permission of Duke Clinical Research Institute. Page 1 of 75 FAST-MAS KOR Phase 2a Study Protocol Version 6.0 Task Order #: HHSN27100004 Version Date 10/06/16 Contract #: HHSN271201200006I Abbreviated Study Title: FAST-MAS KOR Phase 2a Contract #: HHSN271201200006I Task Order #: HHSN27100004 Coordinating Center [CC]: Duke Clinical Research Institute (DCRI) Data center [DCC]: Duke Clinical Research Institute (DCRI) Phase of Study: Phase 2a Target enrollment: 90 Patients FDA Approval(s) IND No Yes Drug: CERC-501 IND #: 121225 held by Dr.
    [Show full text]
  • Acute Management of In-Patient Parkinson's Disease Patients
    NHS Fife Acute Management of Patient’s with Parkinson’s Disease Acute management of in-patient Parkinson’s Disease patients Contents Pages Introduction and Admission advice 2 Nil by Mouth Guidance 3 – 5 Complex therapy advice (Apomorphine, DBS, Duodopa) 6 Surgical peri-operative advice 7 Contacts/Directory 7 Author:- Ewan Tevendale, Nicola Chapman, Lynda Kearney Approved by the Managed Services Drug and Therapeutics Committee August 2017. (Review date August 2019) Page 1 NHS Fife Acute Management of Patient’s with Parkinson’s Disease Introduction Medication is crucial in optimal management of Parkinson’s. If medication is not given this can result in compromised swallow (increasing risk of aspiration), delirium, speech difficulties, immobility and hence more dependence. It can also lead to increased falls in a population at high risk of fractures. At worst they may develop a Neuroleptic Malignant Type Syndrome which can be fatal. People with Parkinson’s are admitted to hospital for numerous reasons. Often these are unrelated to their Parkinson’s but if not managed appropriately on admission this can lead to delayed recovery, delayed discharge and poor outcomes for patients and their families. This document has been devised to provide guidance to staff who are involved in the care of someone with Parkinson’s admitted to hospital for whatever reason should the Parkinson’s Specialist Team be unavailable. (e.g. weekend or out of hours) It should be highlighted that these guidelines provide advice to medical and nursing staff to ensure people with Parkinson’s are managed appropriately on admission i.e. receive some anti- parkinsonian medication until they can be seen by a member of the Parkinson’s Team to provide specialist advice on complex medicines management.
    [Show full text]
  • Dopminergic Treatment of Treatment Refractory Mood Disorders
    8/12/2014 Jan Fawcett, M.D. Professor of Psychiatry University of New Mexico School of Medicine Conflicts: More enjoyment than facts … …on Amazon! 1 8/12/2014 ABBREVIATIONS BPD Borderline Personality Disorder DSM-V Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition ECT Electroconvulsive therapy MAOI Monoamine oxidase inhibitors MDD Major depressive disorder NGA New generation antidepressants NNT Number needed to treat OCD Obsessive-Compulsive Disorder PPX Pramipexole SNRI Serotonin–norepinephrine reuptake inhibitors SSRI Selective serotonin reuptake inhibitors SUD Substance use disorder TCA Tricyclic antidepressants TRD Treatment-resistant depression VNS Vagus nerve stimulation Failed Remission and High Relapse Rates Are Common in Mood Disorders MAJOR DEPRESSION: STAR*D OUTCOMES: Sequenced Treatment Alternatives to Relieve Depression (STAR*D) was a collaborative study on the treatment of depression, funded by the National Institute of Mental Health Treatment step 1 – citalopram 36.8 % remission Overall Remission Rates steps 1-4 67% Treatment Resistant 33% after four steps of treatment BUT Four Month Recurrence rates step 1-4 40.2%- 71% Recovery rates 67% x 60% = 40.2% “Recovered” at 4 months Recovery: no episode of depression for 6 months; recovery is a more reliable outcome than remission Recurrence: an episode of MDD after six months – assumed to be a “new” episode. 2 8/12/2014 What about Bipolar Depression? Sienaert P., Bipolar Disorder 2013 Response: Best Data Quetiapine- Bipolar Depression 60% response- no follow up recovery data Lithium, lamotrigine, olanzepine, olanzepine + flouxetine combination – less favorable Antidepressants – 25% six week response Zarate et al: Ketamine 79% response same as placebo at 7 days Frye et al: Modafinil remission 44% vs 23%, ES = .47 Goldberg et al (2004): pramipexole (1.7 mg) 67% response vs.
    [Show full text]
  • Behavioral Pharmacology of Dopamine D2 and D3 Receptor Agonists and Antagonists in Rats
    Behavioral Pharmacology of Dopamine D2 and D3 Receptor Agonists and Antagonists in Rats. by Gregory T. Collins A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy (Pharmacology) in The University of Michigan 2008 Doctoral Committee: Professor James H. Woods, Chair Professor Margaret E. Gnegy Professor Shaomeng Wang Assistant Professor Roger K. Sunahara © Gregory T. Collins 2008 DEDICATION This thesis is dedicated to my parents, Thomas and Shirley Collins, without whom none of this would have been possible. Your continual support and encouragement throughout all of my endeavors has meant more than you will ever know. Thank you. ii ACKNOWLEDGMENTS First and foremost, I would like to thank my mentor, James Woods. You have been an exceptional mentor to me; I have learned more than I could have ever hoped. It has been a pleasure to work with someone who is so passionate and knowledgable, someone who has not only continued to challenge me, but has also provided an outstanding environment in which to study behavioral pharmacolgy. I truly feel lucky to have been able to learn from you. Of course, I also have to thank Gail Winger who has been a second mentor to me throughout the years. The support, encouragement, guidance, and patience that the two of you have provided has made for an exceptional experience. Thank you. I would also like to thank my committee, James Woods, Roger Sunahara, Peggy Gnegy and Shaomeng Wang. I am grateful to have been able to work with and learn from all of you over the years.
    [Show full text]