Nieuwe behandeling van tabaksverslaving
Prof. dr. C.P. Onno van Schayck
Slotbijeenkomst praktijkprojecten ZonMw
20 maart 2012, Utrecht
Which smoking cessation strategies are effective?
Simple supportive organisational infrastructure – identifying and
recording all patients’ smoking status, placing smoking cessation
literature and posters in waiting areas, promoting quit support
services 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 worker
trained in behavioural change and not involved in the person’s
routine clinical care.
Intensive intervention: in addition to all
of the above, offer more intensive
exploration of person’s motivation, attitudes
and confidence, make a quit plan.
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;
Brief intervention: discuss smoking
status, assess motivation to quit and
nicotine dependence, give encouragement
to quit, offer advice, information and selfhelp materials, make a separate
appointment to discuss smoking cessation,
refer to quit line;
No-smoking practice: identify and record
patients’ smoking status, place smoking
cessation literature and posters in waiting
areas, promote quit support services;
SMOKING: A GLOBAL PHENOMENON
1.25 billion smokers worldwide1
Men
Women
Sweden
Iceland
17%
25%
18%
20%France
Russian Federation
Canada
30% Germany Belarus
60%
22%
37%
21%
53%
16%
17%
Portugal
28%
7%
US
33% Spain Italy
China
24%
10% 39% 33%
Egypt Iran
67%
17%
19%
India
45%
22%
25%
2%
47%
Mexico
12%
2%
Philippines
17%
13%
Kenya
41%
Brazil
5%
21%
8%
22%
1%
Australia
14%
South Africa
19%
23%
16%
Chile
8%
48%
37%
Mackay J, Eriksen M. The Tobacco Atlas. Second Ed. American Cancer Society, 2006
Quitting at age 45–54 years may increase
life expactancy
Results From a Study of Male Physician Smokers in the United Kingdom
100
Non-smokers
Stopped Age 45–54 years
80
Cigarette Smokers
70
60
50
Survival At Each Age Point (%)
90
50
40
30
20
10
0
40
Doll R et al. BMJ 2004;328:1519–27
50
60
70
80
Age (Years)
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
100
Non-smokers
Stopped Age 35–44 years
80
Cigarette Smokers
70
60
50
Survival At Each Age Point (%)
90
50
40
30
20
10
0
40
•
50
Quitting sooner appears most beneficial
60
70
80
Age (Years)
90
100
MODEL OF DEATHS PREVENTED OR POSTPONED
THROUGH RISK-FACTOR REDUCTION
Quitting
Smoking
Unal B et al. BMJ. 2005;331:1–6.
Cholesterol
Reduction
Blood Pressure
Reduction
HOW MANY PHYSICIANS ENGAGE IN SMOKING
CESSATION ADVICE ACROSS EUROPE?
28% (Belgium)
to 63% (UK) of
GPs
36% of health
professionals
Stead M et al. Br J Gen Pract 2009;59:682–90
• Report asking patients
about smoking status
• Report always advising
patients to quit smoking
(study across 12
European countries)
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
N
Trials
N
Participants
Pooled OR*
(95% CI)
Physician advice1
Brief vs no advice (usual care)
Intensive vs minimal advice
17
15
13,724
9775
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
16
7
4395
815
2.04 (1.60–2.60)
2.17 (1.37–3.45)
8
18,468
1.41 (1.27–1.57)
11
13,733
1.24 (1.07–1.45)
Comparison
Proactive telephone counselling4
vs less intensive interventions
Self-help5
vs no intervention
*Abstinence assessed at least 6-months following intervention
1. 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
N
Trials
N
Participants
Pooled OR*
(95% CI)
Physician advice1
Brief vs no advice (usual care)
Intensive vs minimal advice
17
15
13,724
9775
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
16
7
4395
815
2.04 (1.60–2.60)
2.17 (1.37–3.45)
8
18,468
1.41 (1.27–1.57)
11
13,733
1.24 (1.07–1.45)
Comparison
Proactive telephone counselling4
vs less intensive interventions
Self-help5
vs no intervention
*Abstinence assessed at least 6-months following intervention
1. 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): 29-38
2. 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
111 RCTs, N=40.000
Stead, Cochrane Dat Sys Rev (2008)
RR=1.58
17% vs. 10%
Cochrane review Antidepressants
• bupropion vs. placebo
31 RCTs, N=10.000 19%
• nortriptyline vs. placebo
4 RCTs, N=1.000
20%
Hughes, Cochrane Dat Sys Rev (2007)
OR=1.94
vs. 10%
OR=2.34
vs. 10%
100
Response Rate (%)
OR=2.66
40
(95% CI 1.72, 4.11) p<0.0001
OR=1.72
(95% CI 1.16, 2.55) p<0.0062
20
23.0
15.0
0
N=343
Varenicline
N=340
Bupropion
10.3
N=340
Placebo
Jorenby, Jama (2006)
Nicotine addiction
CNS effect
•
Nicotine binds to the nicotine
acetylcholine (nACh) receptors
in the central nervous system;
the Ventral Tegmental Area
(VTA)
•
After binding to the 42
nicotinic receptor in the VTA,
dopamine is released in the
Nucleus Accumbens (nAcc)
•
This dopamine release is
causing the feeling of reward
2 2
4 2 4
42
Nicotine
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 crosssectional 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
Methods
• 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.
Results (1)
Results (2)
Results (3)
• 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.
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.