nieuwe behandeling van tabaksverslaving prof. dr. c.p. onno van schayck slotbijeenkomst...
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Nieuwe behandeling van tabaksverslaving
Prof. dr. C.P. Onno van Schayck
Slotbijeenkomst praktijkprojecten ZonMw20 maart 2012, Utrecht
Simple supportive organisational infrastructure – identifying andrecording all patients’ smoking status, placing smoking cessationliterature and posters in waiting areas, promoting quit supportservices such as telephone counselling.
Brief advice to quit given by a primary care doctor.
Telephone smoking cessation counselling services (‘quit lines’).
Pharmacotherapy for nicotine dependence.
Face-to-face individual counselling by a healthcare workertrained in behavioural change and not involved in the person’sroutine clinical care.
Which smoking cessation strategies are effective?
No-smoking practice: identify and record patients’ smoking status, place smoking cessation literature and posters in waiting areas, promote quit support services;
Brief intervention: discuss smoking status, assess motivation to quit and nicotine dependence, give encouragement to quit, offer advice, information and self-help materials, make a separate appointment to discuss smoking cessation, refer to quit line;
Moderate intervention: assess barriers to quitting (quitting history, high-risk situations), briefly explore motivation, ambivalence, barriers and confidence, advise on overcoming dependence, discuss solutions, prescribe pharmacotherapy, offer support and referral to quit line, arrange follow-up;
Intensive intervention: in addition to all of the above, offer more intensive exploration of person’s motivation, attitudes and confidence, make a quit plan.
SMOKING: A GLOBAL PHENOMENON
Mackay J, Eriksen M. The Tobacco Atlas. Second Ed. American Cancer Society, 2006
1.25 billion smokers worldwide1
US24%19%
Australia19%16%
Belarus53%7%
Brazil22%14%
Canada22%17%
Chile48%37%
China67%2%
Egypt45%12%
France30%21%
Iceland25%20%
Mexico13%5%
Iran22%2%
Kenya21%1%
Sweden17%18%
Philippines41%8%
Portugal33%10%
South Africa23%8%
India47%17%
Russian Federation60%16%
Italy33%17%
Spain39%25%
Germany37%28%
MenWomen
Doll R et al. BMJ 2004;328:1519–27
Quitting at age 45–54 years may increase life expactancy
Results From a Study of Male Physician Smokers in the United Kingdom
45–54 years Stopped Age
Non-smokers
Cigarette Smokers
Su
rviv
al A
t E
ach
Ag
e
Po
int
(%) 90
80
70
60
50
40
30
20
10
0
50
100
Age (Years)40 50 60 70 80 90 100
Quitting earlier (35–44 years) may have a greater impact on life expectancy
Results From a Study of Male Physician Smokers in the United Kingdom
Age (Years)
35–44 years Stopped Age
Non-smokers
Cigarette Smokers
Su
rviv
al A
t E
ach
Ag
e
Po
int
(%) 90
80
70
60
50
40
30
20
10
040 50 60 70 80 90 100
50
100
• Quitting sooner appears most beneficial
MODEL OF DEATHS PREVENTED OR POSTPONED THROUGH RISK-FACTOR REDUCTION
QuittingSmoking
CholesterolReduction
Blood PressureReduction
Unal B et al. BMJ. 2005;331:1–6.
HOW MANY PHYSICIANS ENGAGE IN SMOKING CESSATION ADVICE ACROSS EUROPE?
• Report asking patients about smoking status
28% (Belgium) to 63% (UK) of GPs
• Report always advisingpatients to quit smoking (study across 12 European countries)
36% of health professionals
Stead M et al. Br J Gen Pract 2009;59:682–90
WHAT ARE THE BARRIERS TO EFFECTIVE ENGAGEMENT BY GPs?
Common negative beliefs among GPs towards discussing smoking cessation with patients:
– ‘Too time-consuming’ (42%)– ‘Ineffective’ (38%)– Lack confidence in ability to discuss smoking cessation (22%)– ‘Unpleasant’ (18%)– Lacked knowledge (16%)– Outside their professional duty (5%)– Discussions were inappropriate (5%)
Vogt F et al. Addiction 2005;100:1423–31
WHAT ARE THE BARRIERS TO EFFECTIVE ENGAGEMENT BY GPs?
Common negative beliefs among GPs towards discussing smoking cessation with patients:
– ‘Too time-consuming’ (42%)– ‘Ineffective’ (38%)– Lack confidence in ability to discuss smoking cessation (22%)– ‘Unpleasant’ (18%)– Lacked knowledge (16%)– Outside their professional duty (5%)– Discussions were inappropriate (5%)
Vogt F et al. Addiction 2005;100:1423–31
EVEN BRIEF ADVICE CAN INCREASE LIKELIHOOD OF QUITTING SUCCESS
ComparisonN
TrialsN
ParticipantsPooled OR*
(95% CI)
Physician advice1
Brief vs no advice (usual care) Intensive vs minimal advice
1715
13,7249775
1.66 (1.42–1.94)1.37 (1.20–1.56)
Individual counselling2
vs minimal behaviour intervention 17 6384 1.56 (1.32–1.84)
Group counselling3
vs self-help vs no intervention
167
4395815
2.04 (1.60–2.60)2.17 (1.37–3.45)
Proactive telephone counselling4
vs less intensive interventions 8 18,468 1.41 (1.27–1.57)
Self-help5
vs no intervention 11 13,733 1.24 (1.07–1.45)
*Abstinence assessed at least 6-months following intervention1. Lancaster T, Stead LF. Cochrane Database Syst Rev 2008;(2):CD000165 2. Lancaster T, Stead LF. Cochrane Database Syst Rev 2005;(2):CD001292 3. Stead LF, Lancaster T. Cochrane Database Syst Rev 2005;(2): CD001007 4. Stead LF et al. Cochrane Database Syst Rev 2006;(3):CD002850 5. Lancaster T, Stead LF. Cochrane Database Syst Rev 2005;(3):CD001118
EVEN BRIEF ADVICE CAN INCREASE LIKELIHOOD OF QUITTING SUCCESS
ComparisonN
TrialsN
ParticipantsPooled OR*
(95% CI)
Physician advice1
Brief vs no advice (usual care) Intensive vs minimal advice
1715
13,7249775
1.66 (1.42–1.94)1.37 (1.20–1.56)
Individual counselling2
vs minimal behaviour intervention 17 6384 1.56 (1.32–1.84)
Group counselling3
vs self-help vs no intervention
167
4395815
2.04 (1.60–2.60)2.17 (1.37–3.45)
Proactive telephone counselling4
vs less intensive interventions 8 18,468 1.41 (1.27–1.57)
Self-help5
vs no intervention 11 13,733 1.24 (1.07–1.45)
*Abstinence assessed at least 6-months following intervention1. Lancaster T, Stead LF. Cochrane Database Syst Rev 2008;(2):CD000165 2. Lancaster T, Stead LF. Cochrane Database Syst Rev 2005;(2):CD001292 3. Stead LF, Lancaster T. Cochrane Database Syst Rev 2005;(2): CD001007 4. Stead LF et al. Cochrane Database Syst Rev 2006;(3):CD002850 5. Lancaster T, Stead LF. Cochrane Database Syst Rev 2005;(3):CD001118
• Only 3 -5% manage to quit on willpower alone and to stay abstinent after 6 – 12 months¹
• Patients with nicotine addiction need approximately 5–7 quit attempts, before they manage to finally quit smoking²
• With current therapies only modest efficacy
• Abstinence rate maximum 20-25% at 1 year
1. Hughes JR, et al. Shape of the relapse curve and long-term abstinence among untreated smokers. Addiction 2004; 99(1): 29-382. Hughes JR. New treatments for smoking cessation. CA Cancer J Clin 2000; 50(3): 143-151
Indication pharmacotherapy– patient smokes more than ten cigarettes per day– additional support
• Counselling
• Nicotine replacement therapies– nicotine patch– chewing gum– sublingual tablets
• Antidepressants – Bupropion– Nortriptyline
• Partial nicotine agonist– Varenicline
• NicVAX® (Nicotine conjugate vaccine)
Cochrane review NRT
All types NRT higher abstinence rate (p<0.05)
• all types vs. placebo RR=1.58111 RCTs, N=40.000 17% vs. 10%
Stead, Cochrane Dat Sys Rev (2008)
Cochrane review Antidepressants
• bupropion vs. placebo OR=1.94 31 RCTs, N=10.000 19% vs. 10%
• nortriptyline vs. placebo OR=2.34 4 RCTs, N=1.000 20% vs. 10%
Hughes, Cochrane Dat Sys Rev (2007)
Varenicline Bupropion Placebo
OR=2.66OR=2.66 (95% CI 1.72, 4.11) p<0.0001
OR=1.72OR=1.72 (95% CI 1.16, 2.55) p<0.0062
23.0
15.010.3
0
20
40
Res
po
nse
Rat
e (%
)
100
N=343 N=340 N=340
Jorenby, Jama (2006)
Nicotine addictionCNS effect
• Nicotine binds to the nicotine acetylcholine (nACh) receptors in the central nervous system; the Ventral Tegmental Area (VTA)
• After binding to the 42 nicotinic receptor in the VTA, dopamine is released in the Nucleus Accumbens (nAcc)
• This dopamine release is causing the feeling of reward
4 222 4
42Nicotine Receptor
1. Picciotto MR, Zoli M, Changeux J. Nicotine Tob Res. 1999; Suppl 2:S121-125. 2. Dani JA, Harris RA. Nature Neuroscience 2005; 8:1465-1470.
Nicotine vaccination
… The magic bullet?
Relevance
The influential German news site Spiegel Online mentions NicVAX in a recent article as one of the 15 revolutionary inventions that could change our life:
www.spiegel.de/wissenschaft/technik/0,1518,694845-6,00.html
Nicotine addiction
NicVAX – the vaccine
Overcome the addiction
Working mechanism
• Antibodies to nicotine
• Prevents nicotine entering the brain
• No satisfaction as a result
NicVAX studies thusfar in the Netherlands
• 4503 Phase I/II, Maastricht 2003– 30 subjects (24 NicVAX, 6 Placebo)
• Double-Blind, Placebo-Controlled, safety and immunogenicity • 100 ug NicVAX, 4 vaccinations, Weeks 0, 2, 4, 26
• 4505 Phase II Dose ranging, Maastricht 2004– 50 subjects (50 NicVAX)
• Open label, Single center, dose escalation study • 100-400 ug NicVAX, 5 vaccinations, Weeks 0, 3, 6, 9, 26
• 4508 Phase II/III, Maastricht 2008– 600 subjects (300 NicVAX, 300 Placebo)
• Double-Blind, Placebo-Controlled, safety and immunogenicity • RCT NicVAX placebo-controlled
In the Netherlands 27% of the general population still smokes.
The good news is that adolescents do not seem to start smoking as much as before.
Smoking cessation in adolescents
Study among 20 000 – 27 500 adolescents from 1996 - 2005.
Reduction of smoking in Dutch adolescents over the past decade and its health gains: a repeated cross-sectional study
Cindy M. Gielkens-Sijstermans, Monique A. Mommers, Rudolf T. Hoogenveen, Talitha L. Feenstra, Jacqueline de Vreede, Fons M. Bovens, Onno C. van Schayck
Eur J Public Health 2009; doi:10.1093/eurpub/ckp115
• In 1996, 2001 and 2005, a survey was conducted in the south-eastern region of the Netherlands.
• All students in second and fourth year of secondary education (1996: n=20 000; 2001: n=27 500; 2005: n=24 000) completed a questionnaire.
Methods
Results (1)
Results (2)
• Time trends were not influenced by gender or educational level.
• Model projections show that if these students not take up smoking later in life, 11 500 new cases of COPD, 3400 new cases of lung cancer and 1800 new cases of myocardial infarction could be prevented for the Dutch 13-year-olds.
Results (3)
So the good news is that in the past decade smoking prevalence among adolescents has declined by almost 50%, potentially resulting in a considerable reduction in new cases of COPD, lung cancer or cardiovascular diseases.