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.