DOCSLIB.ORG

NETSCC, HTA 20 December 2012

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
NETSCC, HTA 20 December 2012 NETSCC, HTA 20 December 2012 The Health Technology Assessment programme is managed by NETSCC, HTA as part of the NIHR Evaluation, Trials and Studies Coordinating Centre at the University of Southampton. Alpha House, University of Southampton Science Park tel: +44(0)23 8059 5586 Southampton SO16 7NS fax: +44(0)23 8059 5639 Suggest a topic for research via our online form at www.hta.ac.uk/suggest email: [email protected] www.hta.ac.uk The NIHR Evaluation, Trials and Studies Coordinating Centre (NETSCC), based at the University of Southampton, manages evaluation research programmes and activities for the NIHR Health Technology Assessment Programme tel: +44(0)23 8059 5586 email: [email protected] National Institute for Health Research Evaluation, Trials and Studies Coordinating Centre University of Southampton, Alpha House fax: +44(0)23 8059 5639 web: www.hta.ac.uk Enterprise Road, Southampton, SO16 7NS Cytisine for smoking cessation HTA 12/46 Protocol 29 October 2012 1. Title of the project: What is the clinical and cost effectiveness of cytisine compared with varenicline for smoking cessation? 2. Project lead The University of Sheffield, School of Health and Related Research (ScHARR) Dr Joanna Leaviss Research Associate ScHARR University of Sheffield Regent Court 30 Regent Street Sheffield, S1 4DA Tel: 0114 22 20895 Email: [email protected] 1 3. Background Tobacco smoking is a major cause of a number of chronic diseases, including heart disease and cancers, and is attributed as the leading cause of preventable deaths worldwide (Peto et al. 1996, Mokdad 2004). Despite these statistics, one fifth of adults in the UK are regular cigarette smokers (Allender et al 2008). In 2006-07, smoking-related ill-health cost the NHS £3.3 billion (Scarborough et al 2011). Stopping smoking is known to reduce the risk of smoking-related disease, but it is challenging. Without smoking cessation aids, only between 2% and 5% of quit attempts are successful (Hughes et al 2004, West et al 2000). Smoking cessation strategies have varied success rates. Behavioural interventions designed to encourage people to stop smoking, for example individual, group or telephone counselling, have shown modest efficacy (Motillo et al 2009). A number of pharmacological interventions exist that aid smoking cessation. These include Nicotine Replacement Therapy (NRT), typical antidepressant medications such as buproprion, and nicotine receptor partial agonists e.g. varenicline, cytisine, dianicline. Nicotine receptor partial agonists offer a pharmacological method to aid smoking cessation. varenicline (Champix or Chantix), and cytisine (Tabex), are included in this class of drug. These drugs may aid smoking cessation by the relief of the symptoms of nicotine withdrawal and cigarette craving through agonist actions, whilst blocking the reinforcing effects of nicotine through an antagonist action (Jorenby et al 20061). Cytisine is a naturally occurring product, extracted from the seeds of the plant Cytisus Laborium. It has been used as an aid to smoking cessation for over 40 years, and is manufactured by the Bulgarian pharmaceutical company Sopharma. Varenicline is a synthentic product developed by Pfizer, with a similar structure to cytisine. Varenicline is licensed for use as an aid to smoking cessation in the US and Canada and across Europe including the UK. Cytisine is considerably less expensive than varenicline, and whilst costs vary between countries, the cost of a course of cytisine is generally about 10 – 20% that of varenicline (West et al 20112). A recent Cochrane review of nicotine receptor partial agonists as aids to smoking cessation (Cahill et al 20123) showed a modest efficacy for cytisine over placebo in helping people to stop smoking, and a two-fold increase in quit rates for varenicline over placebo. No head to head trials between varenicline and cytisine were identified in the review, and no indirect comparisons of the two drugs have been conducted to date in the absence of such trials. Concerns have been raised regarding the safety profile of varenicline. The US Food and Drug Administration (FDA) has issued a series of warnings, resulting from post-marketing reports of increased risk of suicidal behaviour or depression, serious adverse cardiac events and 2 gastrointestinal complaints. A meta-analysis of adverse gastrointestinal events by Leung et al (2011) showed an increased risk after treatment with varenicline. In a review of ten trials, Tonstad (2010) found no evidence of a link between varenicline and serious neuropsychiatric events. Reviews by Singh et al (20114) and Prochaska et al (20125) report conflicting findings, with Singh et al showing an increased risk of serious cardiovascular events after treatment with varenicline, and Prochaska finding no evidence of a link. Cahill et al (20123) found a lack of trial evidence indicating serious adverse events for varenicline. However they do not rule out the possibility of a link. It is beyond the scope of this short report to conduct a systematic review of adverse events for varenicline and cytisine, taking into account long- term observational studies. Therefore this assessment will adopt the same approach to adverse events as the Cahill review, extracting this information from RCTs retrieved through an update of their efficacy search. This assessment aims to review the efficacy of varenicline and cytisine as an aid to smoking cessation by updating the Cahill et al (2012)3 review, and conducting indirect comparisons where appropriate. A mathematical model to compare the cost-effectiveness of cytisine with varenicline in the context of NHS stopping smoking services will also be developed. 3 4. Decision problem 4.1 Purpose of the decision to be made The assessment will address the questions: What is the clinical and cost effectiveness of cytisine compared with varenicline for smoking cessation? Specifically, the assessment will: i) Review evidence on the effectiveness and safety of Cytisine in smoking cessation compared with Varenicline; ii) Develop an economic model to estimate the cost effectiveness of Cytisine in the context of NHS smoking cessation services; and iii) provide recommendations based on value of information analyses as to whether a head to head trial of cytisine and varenicline would represent effective use of resources. 4.2 Clear definition of the intervention Cytisine, a nicotine receptor partial agonist, used as an aid to smoking cessation. 4.3 Place of the intervention in the treatment pathway(s) This review will focus on the use of interventions in the treatment of smoking cessation. 4.4 Relevant comparators Varenicline, in any formulation. Varenicline is a nicotine receptor partial agonist used as an aid to smoking cessation. In the absence of data from head to head studies of Cytisine with Varenicline, any comparators (e.g. placebo, Nicotine Replacement Therapy, Buproprion, Dianicline) will be considered that would allow an indirect comparison or network meta- analysis. 4.5 Population and relevant sub-groups Adult smokers. 4.6 Key factors to be addressed 1. Update the Cochrane review of clinical effectiveness and safety for Cytisine compared with Varenicline in helping people to stop smoking. Updated searches from December 2011 to 2012 will be undertaken. 2. Model the cost-effectiveness of Cytisine in the context of NHS smoking cessation services. 3. Make recommendations for commissioning a full trial. 4 5. Report methods for synthesis of evidence of clinical effectiveness and safety An updated review of the evidence for clinical effectiveness and safety will be undertaken systematically following the general principles recommended in the PRISMA statement. English and non-English language studies will be included. The updated review will include papers from December 2011-2012. 5.1 Population Adult smokers. 5.2 Intervention Cytisine at any dose. 5.3 Comparator Varenicline at any dose. 5.4 Settings Smoking cessation programmes/trials. 5.5 Outcomes 5.5.1 Clinical outcomes. Outcomes relating to clinical effectiveness will follow the same criteria as the existing Cochrane review: 1. The primary outcome is abstinence from smoking: minimum 6 months abstinence. Sustained cessation rates will be used in preference to point prevalence. Biochemically verified cessation rates will be used in preference to self-reported cessation. 2. Adverse events: Any reported adverse events from retrieved RCTs will be recorded. It is beyond the scope of this short report to perform specific searches for adverse events. Therefore this data will be based on adverse events reported in RCTs retrieved for the efficacy search, as in the Cahill 2012 review. Studies of long-term observational data will not be included. 5. 6 Study design Randomised Controlled Trials (RCTs) only. 5 5.7 Search strategy The search strategy will update the existing Cochrane review and comprise the following main elements: . Searching of electronic databases . Contact with experts in the field . Scrutiny of bibliographies of retrieved papers The search will update the recent Cochrane Review and rerun their search strategy for trials in the period December 2011-2012, excluding ‘dianicline’ from the interventions. Although dianicline was included in the Cahill searches, development of the drug has been discontinued and will therefore not be included in the comparisons for this report. Additionally, the search will be rerun with a cost effectiveness filter with no date restriction for cost effectiveness literature. All searches
Load more

Recommended publications
  • (19) United States (12) Patent Application Publication (10) Pub
    US 20130289061A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2013/0289061 A1 Bhide et al. (43) Pub. Date: Oct. 31, 2013 (54) METHODS AND COMPOSITIONS TO Publication Classi?cation PREVENT ADDICTION (51) Int. Cl. (71) Applicant: The General Hospital Corporation, A61K 31/485 (2006-01) Boston’ MA (Us) A61K 31/4458 (2006.01) (52) U.S. Cl. (72) Inventors: Pradeep G. Bhide; Peabody, MA (US); CPC """"" " A61K31/485 (201301); ‘4161223011? Jmm‘“ Zhu’ Ansm’ MA. (Us); USPC ......... .. 514/282; 514/317; 514/654; 514/618; Thomas J. Spencer; Carhsle; MA (US); 514/279 Joseph Biederman; Brookline; MA (Us) (57) ABSTRACT Disclosed herein is a method of reducing or preventing the development of aversion to a CNS stimulant in a subject (21) App1_ NO_; 13/924,815 comprising; administering a therapeutic amount of the neu rological stimulant and administering an antagonist of the kappa opioid receptor; to thereby reduce or prevent the devel - . opment of aversion to the CNS stimulant in the subject. Also (22) Flled' Jun‘ 24’ 2013 disclosed is a method of reducing or preventing the develop ment of addiction to a CNS stimulant in a subj ect; comprising; _ _ administering the CNS stimulant and administering a mu Related U‘s‘ Apphcatlon Data opioid receptor antagonist to thereby reduce or prevent the (63) Continuation of application NO 13/389,959, ?led on development of addiction to the CNS stimulant in the subject. Apt 27’ 2012’ ?led as application NO_ PCT/US2010/ Also disclosed are pharmaceutical compositions comprising 045486 on Aug' 13 2010' a central nervous system stimulant and an opioid receptor ’ antagonist.
    [Show full text]
  • Modifications to the Harmonized Tariff Schedule of the United States To
    U.S. International Trade Commission COMMISSIONERS Shara L. Aranoff, Chairman Daniel R. Pearson, Vice Chairman Deanna Tanner Okun Charlotte R. Lane Irving A. Williamson Dean A. Pinkert Address all communications to Secretary to the Commission United States International Trade Commission Washington, DC 20436 U.S. International Trade Commission Washington, DC 20436 www.usitc.gov Modifications to the Harmonized Tariff Schedule of the United States to Implement the Dominican Republic- Central America-United States Free Trade Agreement With Respect to Costa Rica Publication 4038 December 2008 (This page is intentionally blank) Pursuant to the letter of request from the United States Trade Representative of December 18, 2008, set forth in the Appendix hereto, and pursuant to section 1207(a) of the Omnibus Trade and Competitiveness Act, the Commission is publishing the following modifications to the Harmonized Tariff Schedule of the United States (HTS) to implement the Dominican Republic- Central America-United States Free Trade Agreement, as approved in the Dominican Republic-Central America- United States Free Trade Agreement Implementation Act, with respect to Costa Rica. (This page is intentionally blank) Annex I Effective with respect to goods that are entered, or withdrawn from warehouse for consumption, on or after January 1, 2009, the Harmonized Tariff Schedule of the United States (HTS) is modified as provided herein, with bracketed matter included to assist in the understanding of proclaimed modifications. The following supersedes matter now in the HTS. (1). General note 4 is modified as follows: (a). by deleting from subdivision (a) the following country from the enumeration of independent beneficiary developing countries: Costa Rica (b).
    [Show full text]
  • The Use of Stems in the Selection of International Nonproprietary Names (INN) for Pharmaceutical Substances
    WHO/PSM/QSM/2006.3 The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances 2006 Programme on International Nonproprietary Names (INN) Quality Assurance and Safety: Medicines Medicines Policy and Standards The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances FORMER DOCUMENT NUMBER: WHO/PHARM S/NOM 15 © World Health Organization 2006 All rights reserved. Publications of the World Health Organization can be obtained from WHO Press, World Health Organization, 20 Avenue Appia, 1211 Geneva 27, Switzerland (tel.: +41 22 791 3264; fax: +41 22 791 4857; e-mail: [email protected]). Requests for permission to reproduce or translate WHO publications – whether for sale or for noncommercial distribution – should be addressed to WHO Press, at the above address (fax: +41 22 791 4806; e-mail: [email protected]). The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. The mention of specific companies or of certain manufacturers’ products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters.
    [Show full text]
  • Pharmaceutical Appendix to the Tariff Schedule 2
    Harmonized Tariff Schedule of the United States (2007) (Rev. 2) Annotated for Statistical Reporting Purposes PHARMACEUTICAL APPENDIX TO THE HARMONIZED TARIFF SCHEDULE Harmonized Tariff Schedule of the United States (2007) (Rev. 2) Annotated for Statistical Reporting Purposes PHARMACEUTICAL APPENDIX TO THE TARIFF SCHEDULE 2 Table 1. This table enumerates products described by International Non-proprietary Names (INN) which shall be entered free of duty under general note 13 to the tariff schedule. The Chemical Abstracts Service (CAS) registry numbers also set forth in this table are included to assist in the identification of the products concerned. For purposes of the tariff schedule, any references to a product enumerated in this table includes such product by whatever name known. ABACAVIR 136470-78-5 ACIDUM LIDADRONICUM 63132-38-7 ABAFUNGIN 129639-79-8 ACIDUM SALCAPROZICUM 183990-46-7 ABAMECTIN 65195-55-3 ACIDUM SALCLOBUZICUM 387825-03-8 ABANOQUIL 90402-40-7 ACIFRAN 72420-38-3 ABAPERIDONUM 183849-43-6 ACIPIMOX 51037-30-0 ABARELIX 183552-38-7 ACITAZANOLAST 114607-46-4 ABATACEPTUM 332348-12-6 ACITEMATE 101197-99-3 ABCIXIMAB 143653-53-6 ACITRETIN 55079-83-9 ABECARNIL 111841-85-1 ACIVICIN 42228-92-2 ABETIMUSUM 167362-48-3 ACLANTATE 39633-62-0 ABIRATERONE 154229-19-3 ACLARUBICIN 57576-44-0 ABITESARTAN 137882-98-5 ACLATONIUM NAPADISILATE 55077-30-0 ABLUKAST 96566-25-5 ACODAZOLE 79152-85-5 ABRINEURINUM 178535-93-8 ACOLBIFENUM 182167-02-8 ABUNIDAZOLE 91017-58-2 ACONIAZIDE 13410-86-1 ACADESINE 2627-69-2 ACOTIAMIDUM 185106-16-5 ACAMPROSATE 77337-76-9
    [Show full text]
  • Rationale, Pharmacology and Clinical Efficacy of Partial Agonists of A4b2
    Opinion TRENDS in Pharmacological Sciences Vol.28 No.7 Rationale, pharmacology and clinical efficacy of partial agonists of a4b2 nACh receptors for smoking cessation Hans Rollema1, Jotham W. Coe2, Leslie K. Chambers1, Raymond S. Hurst1, Stephen M. Stahl4 and Kathryn E. Williams3 1 Department of Neuroscience Biology, Pfizer Global Research and Development, Groton, CT 06340, USA 2 Department of Chemistry, Pfizer Global Research and Development, Groton, CT 06340, USA 3 Department of Clinical Development, Pfizer Global Research and Development, Groton, CT 06340, USA 4 Department of Psychiatry, University of California at San Diego, 1930 Palomar Point Way, Suite 103 Carlsbad, CA 92008, USA Most smokers repeatedly fail in their attempts to stop [7–9]. Cigarettes are particularly addictive because they smoking because of the addictive nature of the nicotine are readily available and are extremely efficient at deliver- in tobacco products. Nicotine dependence is probably ing the neuroactive components of tobacco to the brain. In mediated through the activation of multiple subtypes essence, cigarettes provide, with each inhalation, indivi- of neuronal nicotinic acetylcholine receptor (nAChR), dualized control over the amount and frequency of nicotine among which the mesolimbic a4b2 subtype has a pivotal that is delivered to the brain and, thus, over mesolimbic role. Here, we discuss the rationale for and the design of dopamine (DA) neurotransmission – a crucial element of a4b2 nAChR partial agonists as novel treatments for the response to addictive substances. The rapid and tran- tobacco addiction. Such agents are expected to exhibit sient increases in DA release in the nucleus accumbens a dual action by sufficiently stimulating a4b2-nAChR- that inhaled nicotine produces will initiate and sustain mediated dopamine release to reduce craving when compulsive substance-seeking behavior and drug depen- quitting and by inhibiting nicotine reinforcement when dence in humans, as described for other drugs of abuse.
    [Show full text]
  • Latest Reviews from Cochrane
    EVIDENCE-BASED MEDICINE n Latest reviews from Cochrane In this section we present an abstract of a review relevant to prescribing in general practice from the latest issue of The Cochrane Database of Systematic Reviews. To view the article in full or for further information, visit www.thecochranelibrary.com Main results detected no significant excess of The authors identified 12 treatment-spe - neuropsychiatric events (RR 0.53; cific reviews. The analyses covered 267 0.17 –1.67) or of cardiac events (RR 1.26; studies, involving 101 804 participants. 0.62 –2.56). Pharmacological interventions Both NRT and bupropion were superior to Nortriptyline increased the chances for smoking cessation: an placebo (odds ratio – OR 1.84; 95% CI of quitting (RR 2.03; 1.48 –2.78). Neither overview and network meta- 1.71 –1.99, and 1.82; 1.60 –2.06 respec - nortriptyline nor bupropion were shown analysis tively). Varenicline also increased the to enhance the effect of NRT compared odds of quitting compared with placebo with NRT alone. Clonidine increased the Objectives (OR 2.88; 2.40 –3.47). chances of quitting (RR 1.63; 1.22 –2.18), Smoking is the leading preventable cause Head-to-head comparisons between but this was offset by a dose-dependent of illness and premature death worldwide. bupropion and NRT showed equal effi - rise in adverse events. Other treatments Some medications have been proven to cacy (OR 0.99; 0.86 –1.13). Varenicline failed to demonstrate a benefit compared help people to quit, with three licensed for was superior to single forms of NRT (OR with placebo.
    [Show full text]
  • Involvement of Nicotinic Receptor Subtypes in the Behavioral Effects of Nicotinic Drugs in Squirrel Monkeys
    1521-0103/366/2/397–409$35.00 https://doi.org/10.1124/jpet.118.248070 THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS J Pharmacol Exp Ther 366:397–409, August 2018 Copyright ª 2018 by The American Society for Pharmacology and Experimental Therapeutics Involvement of Nicotinic Receptor Subtypes in the Behavioral Effects of Nicotinic Drugs in Squirrel Monkeys Sarah L. Withey,1 Michelle R. Doyle,1,2 Jack Bergman, and Rajeev I. Desai Preclinical Pharmacology Laboratory, McLean Hospital/Harvard Medical School, Belmont, Massachusetts Received January 27, 2018; accepted May 17, 2018 ABSTRACT Evidence suggests that the a4b2, but not the a7, subtype of the except for lobeline, the nicotinic agonists produced either full nicotinic acetylcholine receptor (nAChR) plays a key role in [(1)-epibatidine, (2)-epibatidine, and nicotine] or partial (vare- Downloaded from mediating the behavioral effects of nicotine and related drugs. nicline, cytisine, anabaseine, and isoarecolone) substitution for However, the importance of other nAChR subtypes remains (1)-epibatidine. In interaction studies with antagonists differing unclear. The present studies were conducted to examine the in selectivity, (1)-epibatidine discrimination was substan- involvement of nAChR subtypes by determining the effects of tively antagonized by mecamylamine, slightly attenuated selected nicotinic agonists and antagonists in squirrel monkeys by hexamethonium (peripherally restricted) or dihydro- b a either 1) responding for food reinforcement or 2) discriminating the -erythroidine, and not altered by methyllycaconitine ( 7 jpet.aspetjournals.org nicotinic agonist (1)-epibatidine (0.001 mg/kg) from vehicle. In selective). Varenicline and cytisine enhanced (1)-epibati- food-reinforcement studies, nicotine, (1)-epibatidine, varenicline dine’s discriminative-stimulus effects.
    [Show full text]
  • I Regulations
    23.2.2007 EN Official Journal of the European Union L 56/1 I (Acts adopted under the EC Treaty/Euratom Treaty whose publication is obligatory) REGULATIONS COUNCIL REGULATION (EC) No 129/2007 of 12 February 2007 providing for duty-free treatment for specified pharmaceutical active ingredients bearing an ‘international non-proprietary name’ (INN) from the World Health Organisation and specified products used for the manufacture of finished pharmaceuticals and amending Annex I to Regulation (EEC) No 2658/87 THE COUNCIL OF THE EUROPEAN UNION, (4) In the course of three such reviews it was concluded that a certain number of additional INNs and intermediates used for production and manufacture of finished pharmaceu- ticals should be granted duty-free treatment, that certain of Having regard to the Treaty establishing the European Commu- these intermediates should be transferred to the list of INNs, nity, and in particular Article 133 thereof, and that the list of specified prefixes and suffixes for salts, esters or hydrates of INNs should be expanded. Having regard to the proposal from the Commission, (5) Council Regulation (EEC) No 2658/87 of 23 July 1987 on the tariff and statistical nomenclature and on the Common Customs Tariff (1) established the Combined Nomenclature Whereas: (CN) and set out the conventional duty rates of the Common Customs Tariff. (1) In the course of the Uruguay Round negotiations, the Community and a number of countries agreed that duty- (6) Regulation (EEC) No 2658/87 should therefore be amended free treatment should be granted to pharmaceutical accordingly, products falling within the Harmonised System (HS) Chapter 30 and HS headings 2936, 2937, 2939 and 2941 as well as to designated pharmaceutical active HAS ADOPTED THIS REGULATION: ingredients bearing an ‘international non-proprietary name’ (INN) from the World Health Organisation, specified salts, esters or hydrates of such INNs, and designated inter- Article 1 mediates used for the production and manufacture of finished products.
    [Show full text]
  • Orthosteric and Allosteric Ligands of Nicotinic Acetylcholine Receptors for Smoking Cessation
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Frontiers - Publisher Connector MINI REVIEW published: 25 November 2015 doi: 10.3389/fnmol.2015.00071 Orthosteric and Allosteric Ligands of Nicotinic Acetylcholine Receptors for Smoking Cessation Tasnim S. Mohamed 1, Selwyn S. Jayakar 2 and Ayman K. Hamouda 1,3* 1 Department of Pharmaceutical Sciences, College of Pharmacy, Texas A&M Health Sciences Center, Kingsville, TX, USA, 2 Department of Neurobiology, Harvard Medical School, Boston, MA, USA, 3 Department of Neuroscience and Experimental Therapeutics, College of Medicine, Texas A&M Health Sciences Center, Bryan, TX, USA Nicotine addiction, the result of tobacco use, leads to over six million premature deaths world-wide per year, a number that is expected to increase by a third within the next two decades. While more than half of smokers want and attempt to quit, only a small percentage of smokers are able to quit without pharmacological interventions. Therefore, over the past decades, researchers in academia and the pharmaceutical industry have focused their attention on the development of more effective smoking cessation therapies, which is now a growing 1.9 billion dollar market. Because the role of neuronal nicotinic acetylcholine receptors (nAChR) in nicotine addiction is well established, nAChR based therapeutics remain the leading strategy for smoking cessation. However, the development of neuronal nAChR drugs that are selective for a nAChR subpopulation is challenging, and only few neuronal nAChR drugs are clinically available. Among the many neuronal nAChR subtypes that have been identified in the brain, the a4b2 subtype is the most abundant and plays a critical role in nicotine addiction.
    [Show full text]
  • Effects of Varenicline on Sympatho
    Haarmann et al. Tobacco Induced Diseases (2016) 14:26 DOI 10.1186/s12971-016-0091-x RESEARCH Open Access Effects of varenicline on sympatho-vagal balance and cue reactivity during smoking withdrawal: a randomised placebo-controlled trial Helge Haarmann1†, Alexandra Gossler1†, Peter Herrmann2, Slavtcho Bonev3, Xuan Phuc Nguyen3, Gerd Hasenfuß1, Stefan Andreas1,4 and Tobias Raupach1,5* Abstract Background: Varenicline is an effective smoking cessation medication. Some concern has been raised that its use may precipitate adverse cardiovascular events although no patho-physiological mechanism potentially underlying such an effect has been reported. The aim of this study was to test the hypothesis that varenicline impacts on sympatho-vagal balance during smoking withdrawal. Methods: In this randomised, placebo-controlled trial, muscle sympathetic nerve activity (MSNA), baroreflex sensitivity (BRS), heart rate, and blood pressure were assessed in 17 smokers four weeks before a quit attempt (baseline) and again on the third day of that quit attempt (acute smoking withdrawal). Results: Regarding the primary endpoint of our study, we did not find a significant effect of varenicline compared to placebo on changes in MSNA burst incidence between baseline and acute smoking withdrawal (−3.0 ± 3.3 vs.−3.9 ± 5.0 bursts/100 heart beats; p = 0.308). However, heart rate and systolic blood pressure significantly decreased in the placebo group only, while no significant changes in these parameters were observed in the varenicline group. Exposure to smoking cues during acute withdrawal lead to a significant increase of heart rate in the placebo group, while heart rate decreased in the varenicline group, and the difference in these changes was significant between groups (+2.7 ± 1.0 vs.−1.8 ± 0.5 1/min; p = 0.002).
    [Show full text]
  • Molecular Actions of Smoking Cessation Drugs at Α4β2 Nicotinic Receptors Defined in Crystal Structures of a Homologous Binding Protein
    Molecular actions of smoking cessation drugs at α4β2 nicotinic receptors defined in crystal structures of a homologous binding protein Bert Billena, Radovan Spurnya, Marijke Bramsa, René van Elkb, Soledad Valera-Kummerc, Jerrel L. Yakeld, Thomas Voetse, Daniel Bertrandc, August B. Smitb, and Chris Ulensa,1 aLaboratory of Structural Neurobiology, KU Leuven, 3000 Leuven, Belgium; bDepartment of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, 1081 HV, Amsterdam, The Netherlands; cHiQScreen, 1211 Geneva, Switzerland; dLaboratory of Neurobiology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 22709; and eLaboratory of Ion Channel Research, KU Leuven, 3000 Leuven, Belgium Edited by Palmer Taylor, University of California at San Diego, La Jolla, CA, and accepted by the Editorial Board April 26, 2012 (received for review October 5, 2011) Partial agonists of the α4β2 nicotinic acetylcholine receptor domain in complex with α-bungarotoxin (16). However, signifi- (nAChR), such as varenicline, are therapeutically used in smoking cant progress has been made since the discovery of water-soluble cessation treatment. These drugs derive their therapeutic effect pentameric acetylcholine binding proteins (AChBPs) from snails from fundamental molecular actions, which are to desensitize and the subsequent elucidation of their high-resolution ligand- α4β2 nAChRs and induce channel opening with higher affinity, bound crystal structures. AChBPs are homologs of the extracel- but lower efficacy than a full agonist at equal receptor occupancy. lular domain of nAChRs and are the best-studied structural Here, we report X-ray crystal structures of a unique acetylcholine models of ligand recognition by the extracellular domain of binding protein (AChBP) from the annelid Capitella teleta, Ct- nAChRs (17–19).
    [Show full text]
  • New Horizons for Therapeutics in Drug and Alcohol Abuse
    Pharmacology & Therapeutics 125 (2010) 138–168 Contents lists available at ScienceDirect Pharmacology & Therapeutics journal homepage: www.elsevier.com/locate/pharmthera Associate editor: G. Dusting New horizons for therapeutics in drug and alcohol abuse Bianca Jupp a, Andrew J. Lawrence a,b,⁎ a Florey Neuroscience Institutes, The University of Melbourne, Parkville VIC 3010, Australia b The Centre for Neuroscience, The University of Melbourne, Parkville VIC 3010, Australia article info abstract Keywords: Alcohol, tobacco and illicit drug dependence represents a serious health and social issue within the Addiction community. As drug dependence has become more widely recognized as a clinical disorder and the severity Amphetamine of the problem been fully realized, options available for treatment have grown along with our understanding Cannabis of the neurobiological mechanisms underlying the development and persistence of addiction. Treatment has Cocaine progressed from purely social and behavioral approaches to now encompass pharmacotherapy to attempt to Inhalants Nicotine disrupt the mechanisms underlying these disorders. Despite these advances, many forms of addiction lack effective therapeutics and the prevalence of this disorder remains unacceptably high. As a result, a significant effort within the research community has been dedicated to the identification of novel targets for the development of therapeutics based upon our understanding of the pathological processes underlying addiction. The current review aims to provide an overview of existing and clinically trialed pharmacothera- pies for alcohol, opiate, psychostimulant, nicotine, cannabis and inhalant addictions. Further, we discuss some of the potential targets that have been recently indentified from basic studies that may hold promise for the development of novel treatments. © 2009 Elsevier Inc.
    [Show full text]