Presentation on theme: "Future pharmacological treatments on stopping smoking"— Presentation transcript:
1 Future pharmacological treatments on stopping smoking VI Brazilian Congress on AsthmaII Brazilian Congress on COPDII Brazilian Congress on SmokingBelo Horizonte, August 22-25, 2007DURATA: 1 ORAFuture pharmacological treatments on stopping smokingGiovanni Viegi, MD. Director of Research, Italian National Research Council,Head, Pulmonary Environmental Epidemiology Unit,CNR Institute of Clinical Physiology, Pisa – Italy. Professor of “Health Effects of Pollution”, School of EnvironmentalSciences, University of Pisa - ItalyPast-President, European Respiratory Society (ERS)
3 7. Psychological and behavioural interventions 8. Pharmacological treatment for smoking cessation9. Other interventions10. Smoking reduction11. Organisational anchorage and education12. The costs of smoking and economics of smoking cessation13. Research prospects14. References
4 7. Psychological and behavioural interventions Three interventions can be included as psychological and behavioural strategies to aid smoking cessation: self-help interventions, brief advice and counselling.
5 7.1. Self-help programmesSelf-help is defined as structured programming for smokers trying to quit, without intensive contact with the therapist.tailored self-help materials can be recommended for smoking cessation (Evidence A).
6 7.2. Brief adviceBrief advice given by physicians or nurses can be defined as routinely providing smokers with brief information to help them quit smoking and increase their motivation to make quit attempts.It can be recommended that physicians give brief advice on smoking cessation to smokers, including respiratory patients who smoke. Nurses should do the same (Evidence A).However, when dealing with most pulmonary patients brief advice cannot stand alone, and much more intensive intervention is required.
7 7.3. CounsellingThere are three types of counselling - individual, group and telephone – which vary in terms of the manner of providing counselling and the time taken.Individual counselling is defined as a face-to-face encounter between a patient and a trained smoking cessation counsellor.There is a strong dose-response relation between the session length of person-to-person contact and successful treatment outcomes. Intensive interventions are more effective than less intensive interventions (Evidence A).
8 Group counsellingGroup therapy offers individuals the opportunity to learn behavioural techniques for smoking cessation and to provide each other with mutual support.Using this kind of support allows more people to be treated by one therapist and could be more cost-effective than individual counselling.Part I of II
9 There is no evidence about the efficacy of group therapy in respiratory patients. Group counselling is effective for smoking cessation (Evidence A). It is unclear whether group counselling is more or less effective than individual counselling (Evidence A).Part II of II
10 7.3.2. Telephone counselling In the proactive approach, the counsellor initiates the calls to provide the smoker with support to make an attempt at quitting (OR 1.41; 95% CI ).Reactive counselling is provided via help-lines or hotlines that take calls from smokers (OR 1.33; 95 % CI ) .The findings suggest that proactive telephone counselling is effective compared to other minimal interventions (Evidence A).
12 Aversive smokingAversion therapy pairs the pleasurable stimulus of smoking a cigarette with some unpleasant stimulus.There is insufficient evidence to support the use of aversive smoking to quit .Exercise therapyThere is insufficient evidence to support exercise for smoking cessation. .
13 7.5. Procedures for psychological and behavioural interventions in smoking cessation The following visit schedule can be recommended: Weeks 1, 2, 4, 8, and 12 and 6 and 12 months after quit day.Some considerations should be taken into account in order to provide the smoker with the best help during the follow-up period:- At times, ex-smokers feel that they need to smoke again even more than during the first days after quitting.Part I of II
14 - Sometimes abstinent smokers can suffer from withdrawal symptoms for long periods. - Coinciding with special situations (social occasions, eating and drinking, meeting friends, etc.), smokers can feel confident enough to try smoking just one cigarette.- Smokers who continue smoking daily 2-3 weeks after receiving adequate treatment for their addiction should be considered unsuccessful.Part II of II
15 8. Pharmacological treatment for smoking cessation
16 8.1. First-line treatmentNicotine replacement therapy and/or sustained-released bupropion, in conjunction with behavioural intervention, are recommended as first-line pharmacotherapy in current guidelines for smoking cessation [10, ].Except in the presence of contraindications, these drugs should be used in almost all patients attempting to quit smoking.Part I of II
17 Smokers of 10 or more cigarettes a day who are ready to stop should be encouraged to use NRT or bupropion to aid cessation.Health professionals who deliver smoking cessation interventions should give smokers accurate information and advice on these products.Part II of II
18 8.1.1. Nicotine replacement therapy (NRT) This treatment aims to replace the nicotine obtained from cigarettes, thus reducing withdrawal symptoms when stopping smokingThe recommended dosages of NRT vary depending on the degree of dependence.Use should normally be restricted to the licensed duration, but may continue for up to and beyond 3 months in instances of continuing nicotine dependency.Part I of V
19 Nicotine replacement therapy should be discontinued if the user restarts smoking [150,151,153]. There is little direct evidence that one NRT product is more effective than another, so the decision about which product to use should be guided by individual preferences.Combination NRT has been reported to improve outcome but long-term results are conflicting.Part II of V
20 No differences have been found between 16‑hour and 24‑hour nicotine patches and prolongation of treatment for more than 3 months did not increase quit rateHigher doses of nicotine patches have resulted in modest increases in success rates.Tapering of patch dosage is not more effective than abruptly ceasing use.Part III of V
21 Relative contraindications given for NRT are cardiovascular disease, hyperthyroidism, diabetes mellitus, severe renal or hepatic impairment and peptic ulcer.NRT has been shown to be safe in patients with coronary heart disease and it should be used in these patients for whom quitting smoking is one of the most important factors influencing prognosis.Part IV of V
22 A risk-benefit assessment should be made as to using NRT in breastfeeding or pregnant women taking into account the fact that continuing smoking will deliver more nicotine than NRT.Nicotine replacement is generally well tolerated. The most common adverse effects are localised irritation from nicotine, such as local skin irritation with the patch, or with oral preparations mucous menbrane irritation in the mouth and throat, that generally lessen or disappear due to development of local tolerance after a few days.Part V of V
23 Table 4. Available nicotine replacement therapy (NRT) formulations Marketed productNicotine transdermal patches5 mg, 10 mg, 15 mg/16 h (Nicorette, Pfizer) 7 mg, 14 mg, 21 mg/24 h (Nicotnell TTS 10, TTS 20, TTS 30, Novartis) 7 mg, 14 mg. 21 mg/24 h (NiQuitin CQ, GlaxoSmithKline (GSK)Part I of II
24 Table 4. Available nicotine replacement therapy (NRT) formulations Nicotine chewing gum2 mg, 4 mg (Nicorette, Pfizer; Nicotinell, Novartis)Nicotine oral tablets2 mg sublingual tablet (Nicorette Microtab, Pfizer) 1 mg lozenge (Nicotinell, Novartis) 2 mg and 4 mg lozenge (NiQuitin CQ, GSK)Nicotine “oral” inhaler10 mg inhalation cartridge, plus mouthpiece (Nicorette Inhalator, Pfizer)Nicotine nasal spray0.5 mg per spray into each nostril (Nicorette Nasal Spray, Pfizer)Part II of II
25 NRT vs. placebo Odds ratio (95% CI) Abstinence rate Control Table 5. Cochrane meta-analysis of effect of NRT formulations as odds ratio of abstinence with NRT versus controls. A total of 39,503 subjects were included in the analysis Smoking cessation therapyNRT vs. placebo Odds ratio (95% CI)Abstinence rate NRTAbstinence rate ControlAll NRT formulations1.77 ( )17%10%Nicotine gum1.66 ( )Nicotine patch1.81 ( )14%Nicotine inhaler2.14 ( )Nicotine nasal spray2.35 ( )24%*Data from ref 140Part I of II
26 NRT vs. placebo Odds ratio (95% CI) Abstinence rate Control Table 5. Cochrane meta-analysis of effect of NRT formulations as odds ratio of abstinence with NRT versus controls. A total of 39,503 subjects were included in the analysis Smoking cessation therapyNRT vs. placebo Odds ratio (95% CI)Abstinence rate NRTAbstinence rate ControlNicotine sublingual tablet/lozenge2.05 ( )17%4 mg gum vs. 2 mg gum2.20 ( )Fixed gum vs. ad libitum gum1.29 ( )Combination of two NRT vs. single NRT1.42 ( )Bupropion SR*2.06 ( )*Data from ref 140Part II of II
27 8.1.2. Efficacy of NRT in smokers with respiratory diseases
28 Hospitalised patients Campbell (1990) 111 20 (+NRT/placebo) 20 NS Table 6. One-year success rates from smoking cessation studies in patients with respiratory diseases who smoke. Modified from reference 163.ReferenceNo of patientsSustained success (%)P valueInterventionControl / Usual careHospitalised patientsCampbell (1990)11120 (+NRT/placebo)20NSCampbell (1996)23421 (+NRT/placebo)14Miller (1997)1,402114 (+NRT)131,482219 (+NRT)<0.01Lewis (1998)18536.5 (+Placebo)4.99.7 (+NRT)1Low intervention and 2high intervention in same study 36‑month success rate 4 5 mg nicotine patch used as ‘placebo’Part I of II
29 Reference No of patients Sustained success (%) P value Intervention Table 6. One-year success rates from smoking cessation studies in patients with respiratory diseases who smoke. Modified from reference 163.ReferenceNo of patientsSustained success (%)P valueInterventionControl / Usual careAmbulatory patientsBTS I (1983)1,5509.8 (+NRT/placebo)8.9NSLung Health Study (1994)5,88728 (+NRT)7<0.001Tønnesen I (1996)4465.6 (+NRT/placebo4)1.8<0.01Taskin (2001)404323 (bupropion/placebo)16Hand (2002)24515 (+NRT)14Tønnesen II (2006)37017 (+NRT/placebo)101Low intervention and 2high intervention in same study 36‑month success rate 4 5 mg nicotine patch used as ‘placebo’Part II of II
30 Indication for smoking reduction Smoking reduction indication is approved in:Europe: Austria, Belgium, Czech Rep., Denmark, France, Iceland, Italy, Netherlands, Russia, Switzerland, Sweden, UK.Rest of the world: Brazil, Malaysia, New-Zealand, Philippines.
31 Bupropion SRBupropion hydrochloride is an antidepressive drug (an aminoketone) which has been shown to be an effective aid to cessation in smokers who smoke more than 10 cigarettes/day and who are motivated to stop.Bupropion inhibits neuronal reuptake of noradrenaline and dopamine, with minimal effect on the re-uptake of serotonin and no inhibitory effect on monoamine oxidase.Part I of V
32 It has been shown to reduce the activity of these dopamine-releasing neurones and thereby may deactivate the reward circuit and reduce craving.Sustained-release (SR) bupropion is considered a useful option for smokers attempting to stop smoking for the first time, especially those who cannot tolerate NRT, who prefer non-nicotine treatment or who have failed to quit with NRT [2-6,16-19].For smoking cessation the recommended dose of bupropion SR is 150 mg/day for the first week, thereafter increasing to 300 mg/day (150 mg twice daily).Part II of V
33 Smokers using bupropion SR are advised to continue to smoke until the target quit day which usually is set after 1 week of treatment.A reduced maintenance dose—that is, 150 mg daily—is recommended in elderly smokers, or those with liver or renal impairment or below 45 kg in body-weight.The recommended duration of treatment for smoking cessation is 7–12 weeks.Part III of V
34 Bupropion SR is a prescription-only medicine. The most common side effects are sleep disturbances and dry mouth.A serious but rare side effect is seizures (<1:1000).. The drug is contraindicated in patients with current or past epilepsy, and should be used with extreme caution in smokers with conditions predisposing to a low threshold for seizure, such as history of head trauma, or alcohol abuse.Part IV of V
35 Caution is needed regarding the dose in patients with diabetes treated with hypoglycaemic agents or insulin, and in patients taking drugs that lower the seizure threshold (e.g, antipsychotics, antidepressants, theophylline and systemic corticosteroids).Bupropion is also contraindicated in patients with a history of anorexia nervosa and bulimia, severe hepatic necrosis, or bipolar disorder.Bupropion should not be used with a monoamine oxidase inhibitor, and at least 14 days should elapse between stopping such treatment and starting bupropion [9,139, ].Part V of V
36 8.1.4. Efficacy of bupropion in patients with COPD who smoke Very few studies have used bupropion SR for smoking cessation in patients with chronic diseases such as COPD.These abstinence rates are much lower than those observed in similar studies with bupropion SR in healthy subjects, suggesting that COPD patients may be relatively “hard core.”
37 8.2. Second-line smoking cessation treatments Nortriptyline, a tricyclic antidepressant, is the only other antidepressant that has demonstrated evidence of efficacy for smoking cessation.The dose of nortriptyline for smoking cessation is 75–150 mg daily.There are many contraindications with nortriptyline, including common anticholinergic side effects and particularly cardiac conduction disturbances and orthostatic blood pressure drop.Part I of II
38 Clonidine, has been recommended as a second-line therapy in US smoking cessation guidelines . Adverse effects associated with clonidine, such as drowsiness, fatigue and dry mouth, may limit its use , and we consider it to be obsolete today.Part II of II
39 SMOKING CESSATION New Medication Treatment Ch Gratziou Ass.Prof Pulmonary and Crit CareMedical Schools,Athens University
41 X X X Medication Treatment Addiction Dopamine release Nicotine in BloodXRewardBlood brain BarrierXXNicotine Ach ReceptorsDopaminerelease
42 New Medications for Smoking Cessation Cannabinoid ReceptorAntagonists
43 Cannabinoid Receptors CB1 Rewarding stimulies (including palatable food ) and other abuse substances produce dopamine releasein the nucleus accumbensCB1GluGABADACB1CB1 plays an important role in Nac dopamine releaseby inhibition of GABA release
44 Cannabinoid Receptors The primary psychoactive constituent of marijuana, is related to the action on two cannabinoid receptors :CB(1) and CB(2)THE NECTAR OF DELIGHT
45 Cannabinoids Receptors CB1-receptor CB2-receptorAppetitePainBrainLungCB1 are associated with the intake of food and smoking addictionBlocking the CB1 may reduce food craving .Blocking the CB1 may reduce tobacco depedence by less motivation to take nicotine possibly due to impairment of dopamine release by the nucleus accumbens
46 Rimonabant : a CB1- cannabinoid receptor antagonist Pharmacological Characteristics T ½ : 8-15 daysMetabolised by oxidation in the liver
47 Why Rimonabant has a place for Smoking Cessation Animal StudiesEndocannabinoids are released by chronic nicotine administration (Gonzalez et al, 2002)Rimonabant blocks nicotine –induced reinforcement and nicotine self - administration(Cohen et al, 2002)Rimonabant produces loss of weight
52 Side effects with Rimonabant Placebo mg rimonbant mg rimonabant2.3 % % %Dropouts due to Adverse Events3.8 % % %Cardiovascular Safety ProfileNo safety issue has been detected through laboratory, vital signs, or ECG dataThe most frequent side effects reported with rimonabant were nausea, diarrhoea, vomiting, urinary tract infections, anxiety and upper respiratory tract infections.
53 Rimonabant Not APPROVED for Smoking Cessation Treatment Drug for a specific target group ?Hypertension , cardiovascular diseasesDiabetes,Hypercholesterolemia,Overweight
54 Rimonabant Prevention of weight gain . Relative low abstinence rate Long term results?Prevention of weight gain .Modification to the molecule might give better efficacy
55 New Medications for Smoking Cessation Nicotine Acetylcholine Receptorsn-ACh antagonists
56 Nicotine Addiction and n ACh Receptors Endogenous nACh Rs are found throughout the central and peripheral nervous system.The most abundant form of nACh receptors is a pentameric made of a4b2 unitsLeonard & BertrandNicotine Tob Res 2001;3Cholinergic actionnACh –ReceptorPre-synapticSynapsisMeta-synapsic membraneCellular Body ofDopaminergic neuronThe a4b2 receptor is critical for self administration of nicotine Picciotto et al 1998, Tanner et al 2004
57 Varenicline: New Molecule Developed specifically for targeting the main nicotinic receptor responsible for nicotine addiction : a4b2 n ACh receptorsNot a substitute for nicotineNot an antidepressantHNNHVareniclineNS-(-)-NicotineNN
58 Varenicline New mechanism of Action Varenicline was developed as Partial agonist of 42 nicotinic acetylcholine recptors combining agonist and antagonist properties in one compound
59 Varenicline : New Mechanism of Action A selective nicotinic receptor partial agonist evokes a reduced level of response, while antagonizing the response of a full agonist50100Response level (%)abThe nicotinic AcHR is a ligand-gated pentameric ion channel; downstream effects include DATOFull agonist (nicotine)Antagonist (meca- mylamine)Full agonist + antagonistPartial agonistPartial agonist+ nicotineDopamine turnover(DATO)
60 Varenicline: A Partial Agonist Maximum effect0%100%50%Full agonistBlocks rewardEffectPartial agonistCraving; withdrawal reliefDose, exposure
61 Varenicline a Partial Agonist How Varenicline helps to overcome nicotine addictionAs Partial agonistminimises the withdrawal symptoms ( agonist effect)blocks the pathway that is associated with reward system after nicotine intake ( antagonist effect )
62 Varenicline Pharmacological Characteristics Highly absorbed 99 %Half life 17hAbsorptionLow Protein bindingDistributionNon metabolisedNo drug interaction with c Ρ450MetabolismExcreted as unchanged in the urine Renally cleared >90 %ExcretionNo interaction with FoodNo interaction with other Medications
63 Varenicline: Clinical Studies JAMA July 2006 : 3 randomised trialsGonzales D, Rennard SI, Nides M, et al. Varenicline, an a4b2 nicotinic acetylcholine receptor partial agonist, vs sustained-release bupropion and placebo for smoking cessation: a randomized controlled trial JAMA. 2006;296:47-55.2. Jorenby DE, Hays JT, Rigotti NA, et al. Efficacy of varenicline, an a4b2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation: a randomized controlled trial JAMA. 2006;296:
65 Continuous abstinence rates (confirmed by CO ) 44%P.001Randomised double blind19 centresin USA1025 smokers(P=.007),29.5%29.5%(P=.057),21.9%20.7%17.7%P.00116.1%10.5%(P=.001)8.4%Treatment 12wFollow-up 40 wGonzales et al. JAMA. 2006;296:47-55.
66 Continuous abstinence rates (confirmed by CO ) P.00143.9%29.8%29.7%Randomised double blind14 centres1413 smokers23%20.2%17.6%14.6%13.2%10.3%Jorenby et al. JAMA. 2006;296:56-63.Treatment 12wFollow-up to 52 w
67 Side effectsJorenby et al. JAMA. 2006;296:56-63.
68 Maintenance treatment with varenicline Tonstad S, Tønnesen P, Hajek P, et al. Effect of maintenance therapy with varenicline on smoking cessation: a randomized controlled trial JAMA. 2006;296:64-71.To determine whether smokers who quit after 12 weeks of treatment with varenicline, maintain greater continuous abstinence rates than placebo controls during an additional 12 weeks of treatment and until 52 weeks after treatment initiation.
70 Maintenance treatment : 7 day point prevalence abstinence 1st phase Open study 12w2nd phase Randomised double blind additional 12w14 centres smokers63 % participate in 2nd phaseTonstad et al . JAMA. 2006;296:64-71
71 Maintenance of Abstinence Study: CO-confirmed Continuous Abstinence Rates Wks 13–24Wks 13–52Wks 24-52OR=2.47(95% CI 1.95, 3.15) p<0.0001OR=1.35(95% CI 1.07, 1.70) p=0.0126N=602VareniclineN=604PlaceboN=602VareniclineN=604PlaceboOR = odds ratio
72 Continuous abstinence rates From baseline therapy plus additional 12 w maintenance therapy and during follow-up period to 52 weeksTonstad et al . JAMA. 2006;296:64-71
73 Side effectsTonstad et al . JAMA. 2006;296:64-71
74 Varenicline: Published Studies Varenicline is an efficacious, safe, and well-tolerated smoking cessation pharmacotherapy.Varenicline’s short-term and long-term efficacy exceeded that of both placebo and bupropion SR.Gonzales et al. JAMA. 2006;296:47-55.Jorenby et al. JAMA. 2006;296:56-63.Extended use of varenicline helps recent ex-smokers tomaintain their abstinence and prevent relapseTonstad et al . JAMA. 2006;296:64-71
76 Part I of IICahill et al, Cochrane Database of SR, 2007
77 Part I of IICahill et al, Cochrane Database of SR, 2007
78 New Medications for Smoking Cessation Modifiers ofnicotine metabolism
79 Modifiers of nicotine metabolism Inhibitors of CYP2A6NicotineCYP2A6CotinineCYP2A63-hydroxycotinine
80 Cytochrome CYP2A6 CYP2A6 Polymorfism (26 alleles) is Related with Nicotine metabolismLower smoking initiation rate and lower smoking dependenceLower smoking habitReduced risk for lung cancer
81 CYP2A6 Inhibitors Enhance the action and effectiveness of NRTs. Reduce the number of cigarettes consumptionControl the desire for smokingReduce the activation of pre-carcinogens to carcinogensReduce the risk for Lung Cancer
82 CYP2A6 Inhibitors Μethoxsalen 10mg , 30 mg Tranylcypromine (MAO inhibitor)2.5mg, 10mgIncrease plasma level of nicotineReduce smoking desire and cigarette consumptionSellers et al.Research focus2003Zhang et al. Drug Metab. Dispos.2001
83 Other New Approaches for Smoking Cessation Vaccination ????
84 Vaccine : Mechanism of Action AddictionNicotine in BloodXRewardBlood brain BarrierNicotine Ach ReceptorsDopaminerelease
85 Vaccine : Mechanism of Action AddictionNicotine in BloodXRewardBlood brain BarrierXNicotine Ach ReceptorsDopaminerelease
86 Possible place for Vaccine Relapse preventionAdvantagesNo daily useNo action in CNSCombination with other therapiesPreparation of heavy smokers for smoking abstinenceEarly prevention of Smoking Dependence ??
87 Vaccines against Smoking ΤΑ-ΝΙC (Xenova research Ltd, UK)NicVAX ( Nabi , USA)Nicotine –Qbeta ( Cytos, Switzerland)Successful clinical trials phase Ι and IIFew Side EffectsMore ongoing studies
88 1: Curr Opin Investig Drugs. 2007 Jan;8(1):71-7. Drug evaluation: CYT-002-NicQb, a therapeutic vaccine for the treatment of nicotine addiction.Heading CE.The Open University in the North, Faculty of Science, Eldon House, Regent Centre, Gosforth, Newcastleupon Tyne NE3 3PW, UK.Cytos Biotechnology AG is developing an intramuscular therapeutic vaccine, CYT-002-NicQb (also known as nicotine-Qbeta), based on its Immunodrug (formerly known as alpha vaccine) nicotine-specific antibody-generating technology, for the potential treatment of nicotine addiction. A phase II trial was initiated in Switzerland in January 2005 and in February 2006, Cytos Biotechnology announced that it planned to begin a phase IIb/III trial in 2007.
89 Vaccines against Smoking Questions !! More clinical studies in smokersSafety ( long term use)Cost of TherapyDuration of action and effectivenessUse FrequencyEthical issuesPrevention of tobacco use in adolescents ,Use in pregnancy ??
90 Further Questions on New Treatments More clinical trials and real phase studies to assess :EffectivenessLong term useRelapse PreventionWeight gainCombined use
92 VareniclineVarenicline is a partial agonist at the subtype of neuronal nicotinic receptors composed of α4 and β2 subunits.Varenicline initially stimulates the α4β2 receptors that mediate the effects of the nicotinic agonist on dopamine release in the nucleus accumbens (the agonist function).If nicotine is added to varenicline treatment no increase in dopamine response is seen (the antagonist function).Part I of II
93 As varenicline combines both agonist and antagonist function it can reduce nicotine dependence and can also attenuate the effects of nicotine withdrawal [179,180].Smokers are asked to up-titrate their dose to varenicline 1 mg twice daily during the first 7 days of treatment, the stop smoking on day 8, and continue treatment for 12 weeks.We expect that with more documentation and experience varenicline will be a first-line drug in smoking cessation.Part II of II
94 Table 7. Continuous quit rates, in percent, from week 9 to 52 in two phase III trials of varenicline for smoking cessationStudyPlaceboVarenicline 2 mg/dayBupropion SR 300 mg/dayP valueGonzalez Study 18.422.116.4varenicline vs placebo p<0.001varenicline vs bupropion p<0.07 bupropion vs varenicline p<0.001Jorenby  Study 210.323.015.0varenicline vs bupropion p<0.001bupropion vs placebo p<0.001
95 RimonabantThe stimulation of CB1 receptors by endocannabinoids within the brain plays an integral role in the development and maintenance of nicotine and tobacco dependence, and rimonabant exerts its effects in addicted individuals by inhibiting this role of the endocannabinoid system .The most frequent side effects reported with rimonabant were nausea, diarrhoea, vomiting, urinary tract infections, anxiety and upper respiratory tract infections.Part I of II
96 Rimonabant’s effects do not seem to be significantly better than currently available cessation treatments.With its better-documented efficacy on obesity treatment , one might speculate that rimonabant could be useful in overweight smokers for whom weight gain is a major barrier to quitting.Part II of II
97 8.4. Key points: Pharmacotherapy and smoking cessation - NRT and bupropion SR are first-line treatments for smoking cessation (Evidence A)- Smokers attempting to quit should be encouraged to use these drugs to aid cessation, except in the presence of contra-indications (Evidence A).- NRT (gum, patch, inhaler, nasal spray, lozenge and sublingual tablets) are equally effective as smoking cessation treatments (Evidence A).Part I of II
98 Combining the nicotine patch with a self-administered form of NRT can be more effective than a single form of NRT (Evidence B).- NRT should be used to aid cessation in all smokers with COPD, regardless of disease severity and number of cigarettes smoked (Evidence B).- Combined treatment with bupropion SR and NRT might be more effective in heavy smokers (Evidence C)Part II of IV
99 - Both NRT and bupropion SR are effective and well tolerated in smokers with stable cardiovascular disease and in COPD patients.(Evidence A)- Nortriptyline may be used as second-line medication to treat tobacco dependence (Evidence B).- There is no evidence that selective serotonin reuptake inhibitors (SSRIs) have any effect in smoking cessation.Part II of IV
100 - Varenicline might have additional therapeutic effect as smoking cessation treatment and are considered a second-line agent until more documentation and experience occur (Evidence B)- Regular follow-up visits are important and are linked with longer-term successful outcome (Evidence B).Part IV of IV
101 first-line interventions Figure 2. An illustration of the recommended smoking cessation steps and approvedfirst-line interventionsFigure 2. An illustration of the recommended smoking cessation steps and approvedfirst-line interventionsYesNoNoYesPart I of II
102 NRT= nicotine replacement therapy Successful quitterRelapseNRT= nicotine replacement therapyPart II of II
103 9. Other interventions9.1. Acupuncture and laser therapy9.2. HypnotherapyThere is no evidence that hypnosis, acupuncture or laser therapy has any effect in smoking cessation
104 11. Organisational anchorage and education Smoking cessation services should be an integral part of a chest unit, offering advice and help to all smokers with respiratory diseases independently of the smoker’s motivation, but focusing primarily on those who want to try to quit.As a minimum, chest departments should offer smoking cessation support, NRT and/or bupropion SR and at least four follow-up visits to all smokers.The precise details of each service are likely to depend on local factors and national differences, taking into account the fact that individual clinicians fail to intervene with more than one-third of smokers .
105 11.1. Systematic identification of smokers Focusing on hospitals - either inpatients or outpatients – there should be an organisational plan for identifying smokers, documenting smoking data in patients’ records, and delivering brief advice with an offer of referral to the smoking cessation service [9,198].
106 11.2. Equipment and staffing Certain requirement and expertise should be available in each clinic unit to perform the assessments described previously. It should be possible to assess CO level, nicotine dependence and motivation to quit [80,199,200].If the clinic cannot offer smoking cessation there should be written flow-charts stating where to refer the patients.It is also important to engage GPs in smoking cessation, as many COPD patients consult their GP frequently.
107 - Education by physician “opinion leaders” The following tools have been shown to alter physicians’ behaviour :- Education by physician “opinion leaders”- Computerised concurrent feedback on clinical decisions,- Academic detailing i.e. one-on-one education, often by a pharmacist,- Physician incentives, but also patient education or information and patient incentives.Part I of III
108 Guidelines should be simple, pragmatic, usable and flexible with an increasing focus on implementation [201,203].Smoking cessation should be part of the core curriculum of the undergraduate and postgraduate education and training of physicians.Part II of III
109 As smoking plays so large an aetiological role for a majority of pulmonary disorders, the pulmonary clinician must know about smoking cessation at a level similar to the knowledge about other respiratory therapies e.g. bronchodilators and inhaled steroids.Formal training courses are needed to educate smoking cessation counsellors, and courses must be repeated to take account of turn-over among staff members. It would be optimal if all pulmonary clinicians participated in the above education.There should also be postgraduate smoking cessation courses at the annual ERS conference.Part III of III
110 11.4. Smoke-free health care Smoking should be banned in hospitals, both for hospitalised and ambulatory patients and for staff.The European Smoke-Free Hospital Network consists of 16 membership countries and this organisation has created implementation guidelines for turning a hospital smoke-free, as well as training guidelines and material for health care workers .
111 12. The costs of smoking and economics of smoking cessation
112 13. Research prospectsExamine the efficacy of NRT and bupropion SR and combinations for smoking cessation in patients with respiratory diseases, particularly COPD and asthma. Smoking cessation studies are also needed for smokers with several other respiratory disorders such as tuberculosis, alpha 1 antitrypsin deficiency, histiocytosis X, and candidates for lung transplantation.2) Examine the efficacy of different re-treatment interventions as well as long-term treatment for smoking cessation in patients with respiratory diseases.Part I of IV
113 3) Examine the efficacy of smokeless tobacco as a smoking cessation tool in recalcitrant smokers. 4) Examine the efficacy of lung function screening in asymptomatic and symptomatic smokers, combined with different smoking cessation approaches.5) Explore the characteristics of tobacco dependence/nicotine addiction and barriers and motivation to quit in patients with respiratory diseases.Part II of IV
114 6) Examine whether reduced smoking in patients not motivated to give up can increase self- confidence and motivation to quit.7) Examine the relationship between COPD and depression and evaluate whether treatment for depression can help dependent respiratory patients to quit.Part III of IV
115 8) Evaluate the efficacy of new drugs for smoking cessation in respiratory patients. 9) Evaluate the efficacy of smoking cessation programs in rehabilitation courses.10) Evaluate the efficacy of web-based programmes, quit-lines and other “mass-media” methods for smoking cessation.Part IV of IV
116 2. Key points of recommendations 1. Patients with respiratory disease have a greater and more urgent need to stop smoking than the average smoker. They should be encouraged to stop but many often find it more difficult to do so (B).Respiratory physicians must take a proactive and continuing role with each smoker in motivating him or her stop, and provide treatment to achieve smoking cessation, however long this might take, and deal with relapses when these occur. Smoking cessation treatment must be considered integral to the management of the patient’s respiratory condition.Part I of IV
117 The role includes:• regularly assessing smoking status using methods that can objectively detect smoking, such as expired-air carbon monoxide (CO) tests. (C)• pharmacological treatment for nicotine dependence including bupropion and/or where necessary using high-dose and/or prolonged nicotine replacement therapy (NRT); it could also include giving combinations of different forms of NRT (A). Varenicline is a promising second-line agent (B).• behavioural support, which should be intensive and multi-sessional, and provided by someone who has been appropriately trained (B).Part II of IV
118 3. To carry out this role effectively, respiratory physicians must have adequate knowledge and appropriate attitudes and skills; this requires training and continuing medical education which should be provided according to professional standards, and be accredited (C).4. The cost of this strategy will partly be offset by a reduction in attendance for exacerbations etc., but a budget must be established to enable implementation of treatment protocols and provide medication and behavioural support (A).Part III of IV
119 5. It is important to check lung function regularly in order to chart disease evolution and use this as a motivational tool (C).6. Smokers not motivated to stop should be offered NRT to reduce smoking as a gateway to cessation (B).7. Smokers who are not interested in stopping or reducing should be advised that the physician will return to the question at a later visit (C).Part IV of IV
120 Treatments for Smoking Cessation Smokers will never be able to “take just a pill” that will make them in a magic way to stop smoking !!!
121 Smoking Cessation Treatment Smokers must want to stop smoking and must be willing to work hard toachieve the goal of smoking abstinence.Brief Clinical Advice&Intensive Smoking cessation Programs