Transcript Document 7335951
Philip Tønnesen,2005 •Smoking cessation • Philip Tønnesen, M.D, Dr.med.sci.
Most smokers need help to quit
% Abstinent 40 30 20 10 0 30 90 Days Post-Cessation 180
11: 331-4
Basic principles Principle: quit cigarettes Use Nicotine (”NRT”) or bupropion Break the psychological addiction Adjunctive behavioural support Bupropion for 7-9 weeks NRT for 2-4 months Philip Tønnesen,2005
Intensity of intervention
Minimal (<3 minutes) is effective (A) Dose-response effect (person-to-person) (A) Four or more sessions especially effective (A) Philip Tønnesen,2005
Intensity of intervention
43 studies No contact < 3 min.
3-10 min.
> 10 min.
Odds ratio Succes rate 1.0
11 % 1.3 (1.01-1.6) 13 %* 1.6 (1.2-2.0) 2.3 (2.0-2.7) 16 %* 22 %* Philip Tønnesen,2005
Intensity of intervention
Number of sessions sessions: (n = 45) Odds ratio Succes rate 0-1 2-3 1.0
1.4
12 % 16 % * 4-8 >8 1.9
2.3
21 % * 25 % * Philip Tønnesen,2005
Nicotine Replacement Therapy from the Cochrane register. Success rates: Sustained for 1-year
NRT versus placebo
(108 studies) Nicotine GUM Nicotine PATCH
1.73
(95 % CI, 1.62-1.85) 1.66 1.76
Nicotine NASAL SPRAY Nicotine INHALER: 2.27
2.08
Nicotine SUBLINGUAL TABLET 1.73
Bupropion SR versus placebo
(16 studies) Philip Tønnesen,2005
1.97
(95% CI, 1.67-2.34)
Lung Clinic Study
Tonnesen & Mikkelsen, 2000 Eur Respir J (N = 500) 1-year point prevalence 5-mg Patch 6 % 15-mg Patch 16 % Inhaler 9 % Combination 11 % Philip Tønnesen,2005
Intensive group therapy and NRT.
12 month success. Data from Hjalmarson et al.
• Gum: : 29 % • Placebo: 16 % • Nasal Spray: 27 % • Placebo: 15 % • Inhaler: 28 % • Placebo: 18 % Philip Tønnesen,2005
Lung Health Study Continous abstinence (N=5,587)
15 10 5 0 35 30 25 20 1-year 2-year 3-year
Philip Tønnesen,2005
4-year 5-year S-I U-C
Lung Health Study: Point prevalence (N=5587)
40 35 30 25 20 15 10 5 0 1-year 2-year 3-year 4-year 5-year S-I U-C
Philip Tønnesen,2005
Guideline : NRT
•
Dose:
one piece of NRT equals one cigarette (except patch). Underdosing is common. •
Side effects:
Local irritation of skin and mouth and throat. Nicotine overdosing: nausea, palpitations. Philip Tønnesen,2005
Guideline : NRT
Duration: Up to 3 months.
Individually when needed up to 12 months, except patch which should only be used for 3 months.
Major clinical problem: Underdosing New administration forms under development Philip Tønnesen,2005
Treatment of nicotine dependency with antidepressants
Philip Tønnesen,2005
Different antidepressants
• Bupropion • Nortriptyline • SSRI • MAO-inhibitors Philip Tønnesen,2005
Bupropion
• amino-ketone agent • inhibits re-uptake of dopamine and • noradrenaline • almost no effect on serotonin • drug specific effect ?
• also effect of nortryptyline Philip Tønnesen,2005
Randomized trial with Bupropion plus Nicotine Patch, NEJM 1999.
Placebo (N=160) 4 centre 7 weeks treatment Success: 12 month-point 12 month-sustained Nicotine Patch (21 mg) Bupropion (300 mg) Bupropion plus Patch (N = 244) Philip Tønnesen,2005 (N = 244) (N = 245 )
NEJM 1999 Jorgenby
893 smokers CO = 29 ppm 44 years 27 cigarettes/ day in 25 years s-cotinine = 360 ng /ml FTQ = 7.5
1/3 tried Patch/ gum Philip Tønnesen,2005
NEJM 1999 Jorgenby
DESIGN: Treatment 9 weeks week Quit ______0__1*_2__3__4__5__6__7__8__9_ Weekly session of 15 min. with counseling 10 session (>150 min) Philip Tønnesen,2005
NEJM 1999 Jorgenby
DESIGN: Follow-up week ______10___12_______26___________52 8 telephone calls (Months 3-4-5-7-8-9-10-11) Philip Tønnesen,2005
NEJM 1999, 12 months
40 30 20 10 0 Placebo Patch 300 BUP
Philip Tønnesen,2005
BUP+P Point Sust.
Point Prevalence
100 80 60 * 40 20 0 3 4 5
Weeks
ZYB40017 PBO 6 7 ZYB40017 Zyban *
Bupropion, 2003,Tønnesen
• N = 707 • 527 Bupropion, 180 placebo • 42 years old, 22-23 cig. per day, FTND:5 • 11 visits and 10 telephone calls • 1-year sustained abstinence: • 21 % versus 12 % Philip Tønnesen,2005
COPD, BUP
Chronic obstructive pulmonary disease 404 smokers 28 cigarettes/ day FTQ: 7.4
300 mg BUP/placebo for 12-weeks 11 centers Philip Tønnesen,2005
Continuous quit rate in COPD patients with bupropion versus placebo (N = 404).
30 25 20 15 10 5 0
*
week 6
* *
week 12
Philip Tønnesen,2005
week 52 BUP Placebo
Side effects from bupropion used in smoking cessation Side effects Insomnia Percentage Bupropion Placebo (n =399) (n =312) 39 20 Dry mouth 12 Worsening hypertension 1 Discontinuation of drug 12 Urticaria Seizure Philip Tønnesen,2005 2 0.1
1 5 <1 8 0 0
Guideline: Bupropion dosage
• 150 mg AM for 7 days • then 150 mg b.i.d. for 7-9 weeks • quit after 1 week • prescription only • at least 8 hours between each dose • if insomnia last dose in afternoon Philip Tønnesen,2005
Conclusion 1: Bupropion
• Bupropion SR is an efficacious smoking cessation treatment • Bupropion SR is a second line and also a first-line medication • Bupropion is relative safe to use Philip Tønnesen,2005
Nortriptyline
• • 2 studies + 1 • 3 placebo arms • 3 active arms odds ratio 1.0
3.2
Success 12 % 30 %(18-42) • second-line drug due to adverse events Philip Tønnesen,2005
Other drugs
• Different antidepressants: • Nortriptyline • SSRI: No effect Philip Tønnesen,2005
Philip Tønnesen,2005
•Other methods ?
Other methods
• Clonidine • Aversion therapy/ Silver acetate • Mecamylamine • Hypnosis • Acupuncture • Herbal medicine • Glucose • Varinicline • Rimonabant
Clonidine
• Alfa 2 -partiel agonist effect (central)(+anta) • Antihypertensive agent • Climacterial symptoms • Migraine • Smoking cessation Philip Tønnesen,2005
Clonidine
• Tablets or Patches 0.1-0.75 mg/day • Success rates: 5 studies • placebo • 1.0 clonidine_____ 2.1 (1.4-3.2) • 13.9 % 25.6 % (17.7-33.6) • Cochrane meta-analysis: • 1.89 (95% confidence interval 1.30 to 2.74) Philip Tønnesen,2005
<<<<<
• Rapid smoking • 12 studies • The odds ratio (OR) for abstinence following rapid smoking compared to control was 1.98 (95% confidence intervals (CI): 1.36 to 2.90). • Difficult to compare studies • Smoke holding Philip Tønnesen,2005
<<<<<
• ”US. Method”: no effect.
• Rapid smoking • Smoke holding • Silver acetate: 2 studies • 1.05 (95% confidence interval 0.63 to 1.73) • Unplesant taste when smoking Philip Tønnesen,2005
<<<<<<<
• 9 studies • Not more effective than no intervention • Ohter studies did not show effect after 3 months Philip Tønnesen,2005
<<<<<
• 22 studies • 1-year success: • 1.08 (95% confidence interval 0.77) • No evidence that acupuncture should be used Philip Tønnesen,2005
New: Varinicline
• Rationale: • Direct nicotine receptor antagonist/partiel agonist • On-going phase 2 studies Philip Tønnesen,2005
New: Rimonabant
• Rationale: • A Cannabinoid-receptor antagonist • CB-1 CB-2 • Appetitte pain • Short term smoking cessation • Prevent weight gain Philip Tønnesen,2005
New: Nicotine vaccination
• Rationale: • Antibodies against nicotine • Nicotine bound in blood by antibody • Lesser nicotine reach the brain • Phase 1 and 2: human produce antibodies • Vaccine tolerated Philip Tønnesen,2005
Conclusion
Clonidine second line drug Rapid smoking, mecamylamine and glucose should be tested In the pipeline under research: • Varinicline • Rimonabant • Nicotine vaccination Philip Tønnesen,2005
Overall conclusion
Principle: quit cigarettes Use NRT or bupropion Break the psychological addiction Adjunctive behavioural support Bupropion for 7-9 weeks NRT for 2-4 months Doubles 1-year quit rate Philip Tønnesen,2005
Smoking Reduction • Tools: • Cigarettes • Cigarettes • Cigarettes + NRT long-term use + Bupropion long-term use + Snuff • Less toxic cigarettes = product modification Philip Tønnesen,2005
Smoking reduction
Wennike, Tønnesen et al. Addiction 2003 • 411 smokers • 24 cigarettes/day • Motivation to reduce on 10-cm VAS: 9 • Motivation to quit on 10-cm VAS: 5 • Nicotine gum for up to 12 months Philip Tønnesen,2005
Smoking reduction
Wennike, Tønnesen et al. Addiction 2003
Reduction (sustained):
4-months 1-year 2-years Active 14 % 8.8 % 6.3 % Placebo 5 % (p<0.002) 1.5 % (p<0.001) 0.5 % (p<0.001) Philip Tønnesen,2005
Smoking reduction
Wennike, Tønnesen et al, Addiction 2003
Cessation (point):
4 months Active 6.3 % 1-year 2-years 11.2 % 9.3 % Placebo 0.5 % (p<0.001) 3.9 % (p<0.005) 3.4% (p<0.01) (2-year sust.) 2.9 % 0.0 % (p<0.015) Philip Tønnesen,2005
Conclusion
• Smoking reduction promotes smoking cessation • Smokeless tobacco (snus, chewing tobacco)?
Philip Tønnesen,2005
Cigarettes!
Tobacco: It is the only product that kills the consumer, when used after the instructions of the producer!
Philip Tønnesen,2005
Philip Tønnesen,2005
• Rapid smoking • 12 studies • The odds ratio (OR) for abstinence following rapid smoking compared to control was 1.98 (95% confidence intervals (CI): 1.36 to 2.90). • Difficult to compare studies • Smoke holding Philip Tønnesen,2005
<<<<<
• ”US. Method”: no effect.
• Rapid smoking • Smoke holding • Silver acetate: 2 studies • 1.05 (95% confidence interval 0.63 to 1.73) • Unplesant taste when smoking Philip Tønnesen,2005
<<<<<<<
• 9 studies • Not more effective than no intervention • Ohter studies did not show effect after 3 months Philip Tønnesen,2005
<<<<<
• 22 studies • 1-year success: • 1.08 (95% confidence interval 0.77) • No evidence that acupuncture should be used Philip Tønnesen,2005
New: Varinicline
• Rationale: • Direct nicotine receptor antagonist/partiel agonist • On-going phase 2 studies Philip Tønnesen,2005
New: Rimonabant
• Rationale: • A Cannabinoid-receptor antagonist • CB-1 CB-2 • Appetitte pain • Short term smoking cessation • Prevent weight gain Philip Tønnesen,2005
New: Nicotine vaccination
• Rationale: • Antibodies against nicotine • Nicotine bound in blood by antibody • Lesser nicotine reach the brain • Phase 1 and 2: human produce antibodies • Vaccine tolerated Philip Tønnesen,2005
Conclusion
Clonidine second line drug Rapid smoking, mecamylamine and glucose should be tested In the pipeline under research: • Varinicline • Rimonabant • Nicotine vaccination Philip Tønnesen,2005
Overall conclusion
Principle: quit cigarettes Use NRT or bupropion Break the psychological addiction Adjunctive behavioural support Bupropion for 7-9 weeks NRT for 2-4 months Doubles 1-year quit rate Philip Tønnesen,2005
Smoking Reduction • Tools: • Cigarettes • Cigarettes • Cigarettes + NRT long-term use + Bupropion long-term use + Snuff • Less toxic cigarettes = product modification Philip Tønnesen,2005
Smoking reduction
Wennike, Tønnesen et al. Addiction 2003 • 411 smokers • 24 cigarettes/day • Motivation to reduce on 10-cm VAS: 9 • Motivation to quit on 10-cm VAS: 5 • Nicotine gum for up to 12 months Philip Tønnesen,2005
Smoking reduction
Wennike, Tønnesen et al. Addiction 2003
Reduction (sustained):
4-months 1-year 2-years Active 14 % 8.8 % 6.3 % Placebo 5 % (p<0.002) 1.5 % (p<0.001) 0.5 % (p<0.001) Philip Tønnesen,2005
Smoking reduction
Wennike, Tønnesen et al, Addiction 2003
Cessation (point):
4 months Active 6.3 % 1-year 2-years 11.2 % 9.3 % Placebo 0.5 % (p<0.001) 3.9 % (p<0.005) 3.4% (p<0.01) (2-year sust.) 2.9 % 0.0 % (p<0.015) Philip Tønnesen,2005
Conclusion
• Smoking reduction promotes smoking cessation • Smokeless tobacco (snus, chewing tobacco)?
Philip Tønnesen,2005
Cigarettes!
Tobacco: It is the only product that kills the consumer, when used after the instructions of the producer!
Philip Tønnesen,2005
Philip Tønnesen,2005
• ”US. Method”: no effect.
• Rapid smoking • Smoke holding • Silver acetate: 2 studies • 1.05 (95% confidence interval 0.63 to 1.73) • Unplesant taste when smoking Philip Tønnesen,2005
<<<<<<<
• 9 studies • Not more effective than no intervention • Ohter studies did not show effect after 3 months Philip Tønnesen,2005
<<<<<
• 22 studies • 1-year success: • 1.08 (95% confidence interval 0.77) • No evidence that acupuncture should be used Philip Tønnesen,2005
New: Varinicline
• Rationale: • Direct nicotine receptor antagonist/partiel agonist • On-going phase 2 studies Philip Tønnesen,2005
New: Rimonabant
• Rationale: • A Cannabinoid-receptor antagonist • CB-1 CB-2 • Appetitte pain • Short term smoking cessation • Prevent weight gain Philip Tønnesen,2005
New: Nicotine vaccination
• Rationale: • Antibodies against nicotine • Nicotine bound in blood by antibody • Lesser nicotine reach the brain • Phase 1 and 2: human produce antibodies • Vaccine tolerated Philip Tønnesen,2005
Conclusion
Clonidine second line drug Rapid smoking, mecamylamine and glucose should be tested In the pipeline under research: • Varinicline • Rimonabant • Nicotine vaccination Philip Tønnesen,2005
Overall conclusion
Principle: quit cigarettes Use NRT or bupropion Break the psychological addiction Adjunctive behavioural support Bupropion for 7-9 weeks NRT for 2-4 months Doubles 1-year quit rate Philip Tønnesen,2005
Smoking Reduction • Tools: • Cigarettes • Cigarettes • Cigarettes + NRT long-term use + Bupropion long-term use + Snuff • Less toxic cigarettes = product modification Philip Tønnesen,2005
Smoking reduction
Wennike, Tønnesen et al. Addiction 2003 • 411 smokers • 24 cigarettes/day • Motivation to reduce on 10-cm VAS: 9 • Motivation to quit on 10-cm VAS: 5 • Nicotine gum for up to 12 months Philip Tønnesen,2005
Smoking reduction
Wennike, Tønnesen et al. Addiction 2003
Reduction (sustained):
4-months 1-year 2-years Active 14 % 8.8 % 6.3 % Placebo 5 % (p<0.002) 1.5 % (p<0.001) 0.5 % (p<0.001) Philip Tønnesen,2005
Smoking reduction
Wennike, Tønnesen et al, Addiction 2003
Cessation (point):
4 months Active 6.3 % 1-year 2-years 11.2 % 9.3 % Placebo 0.5 % (p<0.001) 3.9 % (p<0.005) 3.4% (p<0.01) (2-year sust.) 2.9 % 0.0 % (p<0.015) Philip Tønnesen,2005
Conclusion
• Smoking reduction promotes smoking cessation • Smokeless tobacco (snus, chewing tobacco)?
Philip Tønnesen,2005
Cigarettes!
Tobacco: It is the only product that kills the consumer, when used after the instructions of the producer!
Philip Tønnesen,2005
Philip Tønnesen,2005
• 9 studies • Not more effective than no intervention • Ohter studies did not show effect after 3 months Philip Tønnesen,2005
<<<<<
• 22 studies • 1-year success: • 1.08 (95% confidence interval 0.77) • No evidence that acupuncture should be used Philip Tønnesen,2005
New: Varinicline
• Rationale: • Direct nicotine receptor antagonist/partiel agonist • On-going phase 2 studies Philip Tønnesen,2005
New: Rimonabant
• Rationale: • A Cannabinoid-receptor antagonist • CB-1 CB-2 • Appetitte pain • Short term smoking cessation • Prevent weight gain Philip Tønnesen,2005
New: Nicotine vaccination
• Rationale: • Antibodies against nicotine • Nicotine bound in blood by antibody • Lesser nicotine reach the brain • Phase 1 and 2: human produce antibodies • Vaccine tolerated Philip Tønnesen,2005
Conclusion
Clonidine second line drug Rapid smoking, mecamylamine and glucose should be tested In the pipeline under research: • Varinicline • Rimonabant • Nicotine vaccination Philip Tønnesen,2005
Overall conclusion
Principle: quit cigarettes Use NRT or bupropion Break the psychological addiction Adjunctive behavioural support Bupropion for 7-9 weeks NRT for 2-4 months Doubles 1-year quit rate Philip Tønnesen,2005
Smoking Reduction • Tools: • Cigarettes • Cigarettes • Cigarettes + NRT long-term use + Bupropion long-term use + Snuff • Less toxic cigarettes = product modification Philip Tønnesen,2005
Smoking reduction
Wennike, Tønnesen et al. Addiction 2003 • 411 smokers • 24 cigarettes/day • Motivation to reduce on 10-cm VAS: 9 • Motivation to quit on 10-cm VAS: 5 • Nicotine gum for up to 12 months Philip Tønnesen,2005
Smoking reduction
Wennike, Tønnesen et al. Addiction 2003
Reduction (sustained):
4-months 1-year 2-years Active 14 % 8.8 % 6.3 % Placebo 5 % (p<0.002) 1.5 % (p<0.001) 0.5 % (p<0.001) Philip Tønnesen,2005
Smoking reduction
Wennike, Tønnesen et al, Addiction 2003
Cessation (point):
4 months Active 6.3 % 1-year 2-years 11.2 % 9.3 % Placebo 0.5 % (p<0.001) 3.9 % (p<0.005) 3.4% (p<0.01) (2-year sust.) 2.9 % 0.0 % (p<0.015) Philip Tønnesen,2005
Conclusion
• Smoking reduction promotes smoking cessation • Smokeless tobacco (snus, chewing tobacco)?
Philip Tønnesen,2005
Cigarettes!
Tobacco: It is the only product that kills the consumer, when used after the instructions of the producer!
Philip Tønnesen,2005
Philip Tønnesen,2005
• 22 studies • 1-year success: • 1.08 (95% confidence interval 0.77) • No evidence that acupuncture should be used Philip Tønnesen,2005
New: Varinicline
• Rationale: • Direct nicotine receptor antagonist/partiel agonist • On-going phase 2 studies Philip Tønnesen,2005
New: Rimonabant
• Rationale: • A Cannabinoid-receptor antagonist • CB-1 CB-2 • Appetitte pain • Short term smoking cessation • Prevent weight gain Philip Tønnesen,2005
New: Nicotine vaccination
• Rationale: • Antibodies against nicotine • Nicotine bound in blood by antibody • Lesser nicotine reach the brain • Phase 1 and 2: human produce antibodies • Vaccine tolerated Philip Tønnesen,2005
Conclusion
Clonidine second line drug Rapid smoking, mecamylamine and glucose should be tested In the pipeline under research: • Varinicline • Rimonabant • Nicotine vaccination Philip Tønnesen,2005
Overall conclusion
Principle: quit cigarettes Use NRT or bupropion Break the psychological addiction Adjunctive behavioural support Bupropion for 7-9 weeks NRT for 2-4 months Doubles 1-year quit rate Philip Tønnesen,2005
Smoking Reduction • Tools: • Cigarettes • Cigarettes • Cigarettes + NRT long-term use + Bupropion long-term use + Snuff • Less toxic cigarettes = product modification Philip Tønnesen,2005
Smoking reduction
Wennike, Tønnesen et al. Addiction 2003 • 411 smokers • 24 cigarettes/day • Motivation to reduce on 10-cm VAS: 9 • Motivation to quit on 10-cm VAS: 5 • Nicotine gum for up to 12 months Philip Tønnesen,2005
Smoking reduction
Wennike, Tønnesen et al. Addiction 2003
Reduction (sustained):
4-months 1-year 2-years Active 14 % 8.8 % 6.3 % Placebo 5 % (p<0.002) 1.5 % (p<0.001) 0.5 % (p<0.001) Philip Tønnesen,2005
Smoking reduction
Wennike, Tønnesen et al, Addiction 2003
Cessation (point):
4 months Active 6.3 % 1-year 2-years 11.2 % 9.3 % Placebo 0.5 % (p<0.001) 3.9 % (p<0.005) 3.4% (p<0.01) (2-year sust.) 2.9 % 0.0 % (p<0.015) Philip Tønnesen,2005
Conclusion
• Smoking reduction promotes smoking cessation • Smokeless tobacco (snus, chewing tobacco)?
Philip Tønnesen,2005
Cigarettes!
Tobacco: It is the only product that kills the consumer, when used after the instructions of the producer!
Philip Tønnesen,2005
Philip Tønnesen,2005