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Smoking Cessation Treatments and Clinical Practice

Smoking Cessation Treatments and Clinical Practice. Dr Alex Bobak GP and GPSI in Smoking Cessation Wandsworth. More than 50% of long term smokers die prematurely of smoking related diseases. Why do people keep smoking?. NICOTINE ADDICTION. HABIT. SOCIAL. Mechanics of nicotine addiction.

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Smoking Cessation Treatments and Clinical Practice

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  1. Smoking Cessation Treatments and Clinical Practice Dr Alex Bobak GP and GPSI in Smoking Cessation Wandsworth

  2. More than 50% of long term smokers die prematurely of smoking related diseases

  3. Why do people keep smoking? NICOTINE ADDICTION HABIT SOCIAL

  4. Mechanics of nicotine addiction

  5. β2 β2 α4 α4 β2 α4β2 Nicotinic Receptor Nicotine Dopamine NIC NucleusAccumbens(NAcc) NIC VentralTegmentalArea(VTA)

  6. The dopamine triggered by inhaled nicotine rapidly gets reabsorbed which leads to….. low mood and craving which leads to…..

  7. Regular smoking leads to a 300% increase in brain nicotine receptors

  8. On stopping smoking: • It takes 24-48 hours for nicotine to leave the body • It takes 8-12 weeks for the nicotine receptors to down-regulate

  9. Smokers want to stop All smokers ~70% want to stop1 ~2–3% succeed in stopping each year3 ~30% try each year2 1.Bridgwood et al, General Household Survey 1998. 2.West,Getting serious about stopping smoking 1997. 3.Arnsten,Prim Psychiatry 1996.

  10. Stopping smoking:What works, what doesn’t

  11. Long term cessation rates

  12. Nicotine replacement therapy

  13. Nicotine replacement therapy • Based on nicotine weaning1 • Well tolerated • Significantly reduced withdrawal symptoms and cravings • Treatment lasts 8–12 weeks with gradual withdrawal 1. Thompson et al., 1998. 2. Henningfield, 1995.

  14. NRT-Dosage and use • Gum upto 15 or 25/day 2mg or 4mg • Patch 16 or 24 hours 3 strengths • S/L tabs upto 40/day 2mg • Lozenges min 9 max 15/day 2mg or 4mg • Inhalator 6-12 cartridges/day • Spray upto 64 sprays/day

  15. Plasma nicotine levels – contrast between cigarettes and NRT 25 20 15 10 5 0 Cigarette Spray Plasma nicotine (ng/ml) Gum/Inhalator/Tablet/lozenge Patch 0 10 20 30 40 50 60 Time (minutes) Adapted from: Tobacco Advisory Group of the Royal College of Physicians 2000.

  16. Considerationsfor patients using NRT • USE ENOUGH! Avoid under-dosing and irregular use. • LONG ENOUGH! Don’t stop early, continue 8-12 weeks. • NOT A PUFF! Slower and less efficient source of nicotine than cigarettes so can not compete.

  17. Bupropion

  18. Background to Bupropion (Zyban) • Non-nicotine prescription tablet • Modifies dopamine levels and noradrenergic activity • Used by approx. 15 million people worldwide for smoking cessation (incl. > 700,000 smokers in UK) • Well established safety profile

  19. 150 mg b.d. for remainder of 120 tablet treatment course 150 mg o.d. for 6 days Bupropion treatment regime • Patients should choose a quit date in the second week, for example day 11, or earlier if the patient feels ready to stop

  20. Adverse events on bupropion in smokers with CVD. McRobbie 2001 Bupropion Placebo 25 24 20 18 15 13 12 11 11 10 10 6 5 0 Insomnia Headache Dry mouth Nausea

  21. Varenicline

  22. Varenicline (Champix) • Specifically designed • Oral prescription medicine • Targets the 42 nicotinic acetylcholine receptor 1. Coe JW. J Med Chem 2005; 48:3474-3477. 2. Dani JA, Harris RA. Nature Neuroscience 2005; 8:1465-1470.

  23. Varenicline- partial nicotine agonist Part blocking • Reduces the pleasurable effects of smoking and potentially the risk of full relapse after a temporary lapse1-4 Part Stimulating • Relieves craving and withdrawal symptoms1-3 1. Coe JW. J Med Chem 2005; 48:3474-3477. 2. Gonzales D et al. JAMA 2006; 296:47-55. 3. Jorenby DE et al. JAMA 2006; 296:56-63. 4. Foulds J. Int J Clin Pract 2006; 60:571-576.

  24. “Recruitment” to Abstinence: Gonzaleset al. JAMA. 2006;296:47-55.

  25. 52 week quit rates Continuous abstinence rate weeks 9 - 52 (%) n=692 n=669 n=684 varenicline vs. bupropion OR = 1.56 (95% CI 1.19, 2.06) †p<0.0013 varenicline vs. placebo OR = 2.82 (95% CI e.06, 3.86), †p<0.0001 Secondary endpoint – Pooled Analysis Comparator Studies 1 & 2 (n=2,045) 1. Gonzales DH et al. Presented at 12th SRNT, 15-18th Feb, 2006, Orlando, Florida. Abstract PA9-2.

  26. The real world! Early UK Data

  27. Leeds Stop Smoking Service 4 week Quit rates (%): NRT Zyban Varenicline Specialist advisers: 68.6 68.6 77.1 Registered advisers: 61.4 61.5 66.3

  28. East Lancashire Stop Smoking Service 1/1/07-30/9/07: NRT Varenicline Set a quit date: 2121 789 Quit at 4 weeks: 1283 703 % Quit at 4 weeks: 60%89%

  29. Maudsley (London) study of varenicline v NRT in routine treatment of tobacco dependence (Stapleton et al Addiction Oct 2007) NRT Varenicline Set a quit date: 204 208 Quit at 4 weeks: 125 150 % Quit at 4 weeks: 61.3%72.1%

  30. Adverse events on varenicline compared with placebo

  31. What about nausea? • Warn before prescribing • Usually self limiting • Take with food or water • Adjust dose • Can use anti-emetics ?prochlorperazine (Stemetil)

  32. Extended therapy study 1927 smokers Initial phase 12 weeks varenicline treatment Inclusion criteria: participants adherent to drug and with CO confirmed abstinence during week 12 n=1236 Randomised double-blind phase n=1,210 12 weeks placebo n=607 Additional 12 weeks varenicline treatment n=603 Primary endpoint 24 week continuous quit rate Follow-up phase Secondary endpoint 52 week continuous quit rate 1. Tonstad S et al. JAMA 2006; 296:64-71.

  33. 12 vs 24 Weeks Use: Results Varenicline 24 wksVarenicline 12 wks P=0.02 OR = 1.34 70.5% % of Patients 43.6% 49.6% 36.9% Week Tonstad S, et al. JAMA. 2006;296:64-71.

  34. Contraindicated: Hypersensitivity to Varenicline Not Recommended: Pregnancy Under 18 yrs End stage renal disease Who Can Use It?

  35. Severe renal disease as primarily excreted via kidneys (unchanged) Epilepsy (not tested) Psychiatric illness (not tested) Quitting smoking may exacerbate underlying condition Breast feeding Cautions for Use

  36. Pharmacological Properties: • Steady-state reached within 4 days • Elimination half-life of ~24 hours • No significant hepatic effects • No clinically meaningful drug interactions

  37. Dose of varenicline Quit date

  38. Comparative NNTs 1. Bandolier 2. Gates, Am Fam Phys 2001.

  39. Numbers Needed to Treat (NNT) to Obtain 1 Long-Term Quitter? • Brief advice (<5 mins) = 40(1) • Adding medication to behavioural support….. • NRT = 20(2) • Bupropion = 15(2) • Varenicline = 8(2) 1. West (2006) 2. Cochrane Review. (2007)

  40. Numbers Needed to Treat (NNT) to Prevent a Premature Death? • Brief advice (<5 mins) = 80 • Adding medication to behavioural support….. • NRT = 40 • Bupropion = 30 • Varenicline = 16

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