VI Brazilian Congress on Asthma II Brazilian Congress on COPD II Brazilian Congress on Smoking Belo Horizonte, August 22-25, 2007 DURATA: 1 ORA Future pharmacological treatments on stopping smoking Giovanni 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 Environmental Sciences, University of Pisa - Italy . 2006-07 Past-President, European Respiratory Society (ERS)
7. Psychological and behavioural interventions 8. Pharmacological treatment for smoking cessation 9. Other interventions 10. Smoking reduction 11. Organisational anchorage and education 12. The costs of smoking and economics of smoking cessation 13. Research prospects 14. References
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.
7.1. Self-help programmes Self-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).
7.2. Brief advice Brief 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.
7.3. Counselling There 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).
7.3.1. Group counselling Group 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
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
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 1.27-1.57). Reactive counselling is provided via help-lines or hotlines that take calls from smokers (OR 1.33; 95 % CI 1.21-1.47) . The findings suggest that proactive telephone counselling is effective compared to other minimal interventions (Evidence A).
7.4.1. Aversive smoking Aversion 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 . 7.4.2. Exercise therapy There is insufficient evidence to support exercise for smoking cessation. .
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
- 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
8.1. First-line treatment Nicotine replacement therapy and/or sustained-released bupropion, in conjunction with behavioural intervention, are recommended as first-line pharmacotherapy in current guidelines for smoking cessation [10,146-149]. Except in the presence of contraindications, these drugs should be used in almost all patients attempting to quit smoking. Part I of II
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
8.1.1. Nicotine replacement therapy (NRT) This treatment aims to replace the nicotine obtained from cigarettes, thus reducing withdrawal symptoms when stopping smoking The 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
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
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 rate Higher 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
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
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
Table 4. Available nicotine replacement therapy (NRT) formulations Part I of II
Table 4. Available nicotine replacement therapy (NRT) formulations Part II of II
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  Part I of II *Data from ref 140
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  *Data from ref 140 Part II of II
Table 6. One-year success rates from smoking cessation studies in patients with respiratory diseases who smoke. Modified from reference 163. 1Low intervention and 2high intervention in same study36‑month success rate4 5 mg nicotine patch used as ‘placebo’ Part I of II
Table 6. One-year success rates from smoking cessation studies in patients with respiratory diseases who smoke. Modified from reference 163. 1Low intervention and 2high intervention in same study36‑month success rate4 5 mg nicotine patch used as ‘placebo’ Part II of II
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.
8.1.3. Bupropion SR Bupropion 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
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
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
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
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, 167-170]. Part V of V
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.”
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
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
SMOKING CESSATION New Medication Treatment Ch Gratziou Ass.Prof Pulmonary and Crit Care Medical Schools, Athens University
Addiction Blood Nicotine REWARD Blood Brain Barrier Nicotine Achetylocholine Brain receptors Dopamine release Nicotine Addiction
Addiction Nicotine in Blood Reward Blood brain Barrier Nicotine Ach Receptors Dopamine release Medication Treatment X X X
New Medications for Smoking Cessation Cannabinoid Receptor Antagonists
CB1 CB1 Glu GABA DA CB1plays an important role in Nac dopamine release by inhibition of GABA release Cannabinoid Receptors CB1 Rewarding stimulies (including palatable food) and other abuse substances produce dopamine release in the nucleus accumbens
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
Cannabinoids Receptors CB1-receptor CB2-receptor Appetite Pain Brain+++ ++ Lung+ ++ • CB1are associated with the intake of food and smoking addiction • Blocking 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
Rimonabant :a CB1-cannabinoid receptor antagonistPharmacological Characteristics • T ½ : 8-15 days • Metabolised by oxidation in the liver
Why Rimonabant has a place for Smoking Cessation Animal Studies • Endocannabinoids are released by chronic nicotine administration (Gonzalez et al, 2002) • Rimonabantblocks nicotine –induced reinforcementand nicotine self -administration(Cohen et al, 2002) • Rimonabant produces loss of weight
Rimonabant Clinical trials phase ΙΙΙ ( 7 studies) Dose 20mg /day for 10 w Weight Control Diabetics, Hyper cholesterolemia Multicentre International study (RIO Europe)
Placebo Rimonabant 5 mg Rimonabant 20 mg Rimonabant 5 or 20 mg/dayProlonged Abstinence (10 weeks) OR=2.0 - 95% CI=[1.296; 3.046] 40 P=.004 35 30 27.6 25 Abstinent (%) 20 16.1 15.6 15 10 5 USA study American College of Cardiology 2004 0 n=261 n=262 n=261 ITT