Fa?

1
Fa?µa?e?t??? a?t?µet?p?s? t?? ??s?? t??
?ap??sµat??
?. ??t???s?a ??e?µ????????? ??????? ?a?ep?st?µ??
???t??
2
The future of tobacco treatment in the health
care system

• Most smokers know they should quit
• 70 say they want to quit
• 40 report having tried to do soin the past year
• Yet the large majority of these quit attempts
  failed to produce long-term tobacco abstinence,
  despite the availability of effective treatments

The Reason Most smokers trying to quit do not
use these treatments
N. Rifotti Annals of Internal Medicine 2009
3
History
1604 King James referred to smoking as
smoking is a branch of the sin of
drunkenness, which is the root of all
sins Russel MA. Br J Med Phychol 1971
44(1) 1964 Smoking and Health Report was
chosen as one of the 10 most important
scientific works published in the last 100
years Surgeons General Report
1996 the first Smoking cessation clinical
practice guideline Agency for Healthcare Policy
and Research, US Dept. of Health and Human
Services. Since then revealed several updated
guidelines in the US, Europe and other countries
in the world
4
S?µa?t??? s?µe?a st?? ??se?? ?µ?f???a? 2008

• S?µß???e?t???
• 3 ?ept? t??????st??
• ?e?a??te?? d????e?a (gt10 ?ept?) ? ?a??te?a
  ap?te??sµata
• ?sfa??st??? ?????? ??a ?ap??st?? ?a? ?e?ape?a
  ?ap??sµat??
• ?? ?ap??st?? p?? ??t??? ß???e?a
• ? ?e?ape?a e??a? ap?te?esµat??? se s??s? µe t?
  ??st??
• ?? ???????? ?at??? p??pe? ?a p??sf????? ? ?a
  ?ate??????? t??? ?ap??st?? p??s t? ?e?ape?a t??
  ?ap??sµat??
• ?p??tas? fa?µa?e?t???? d??at?t?t??
• ?a?e??????? (3? p??t?? ??aµµ?? fa?µa?e?t???
  ??s?a)

Treating Tobacco Use and Dependence 2008 Update
5
WHO t? ??p??sµa e??a? µ?a ?????a ??s??

• ? ?e?ape?t??? pa??µßas? st????eta? se
• Motivation of patients and their willingness to
  quit
• Reinforce the motivation of the patient to
  initiate smoking cessation
• Ease the withdrawal period and
• Prevent relapse
• ?p?t?????eta? µe????? f???? µet? ap?
  epa?e???µµ??e? p??sp??e?e?
• ? ??at??? ?a p??pe? ?a ????et?s??? t?? ?d?a
  s?µpe??f??? µe ???a ?????a ??s?µata
  (hypertension, diabetes etc)

6
G?at? ??e???eta? fa?µa???e?ape?a
7
?p?te?esµat???? µ???d?? d?a??p?? ?ap??sµat??

• ??? t?p?? p??s????s?? e??a? ap?dede??µ??a
  ap?te?esµat????
• S?µß???e?t???
• Fa?µa???e?ape?a
• ?a ?a??te?a ap?te??sµata ep?t???????ta? µe
  s??d?asµ? t?? d?? p??se???se??

Fiore MC. Treating tobacco use and dependence.
Resp Care 2000451200 West R. Smoking cessation
guidelines for health professionals an update.
Thorax 200055987 Simon JA. Smoking cessation
counseling (intensive vs minimal). Am J Med
2003114(7)555
8
Aveyard P. West R BMJ 2007335-37
9
???e???µ??? Fa?µa???e?ape?a st?
d?a??p? t?? ?ap??sµat??

• ?p??at?stata ????t????
• S???st?µe?? ?e?ape?a p??t?? ??aµµ??
• ?a???? d??s??
• Patch
• ??a?e?a? d??s??
• Gum
• Inhaler
• Nasal spray
• Sublingual tablets/lozenges
• Bupropion
• S???st?µe?? ?e?ape?a p??t?? ??aµµ?? (WHO, US,
  Europe, UK)
• Varenikline p??t?? ??aµ??

S???st?µe?? ?e?ape?a de?te??? ??aµ Nortriptyline C
lonidine
Henningfield JE. CA Cancer J Clin
200555281 Hughes JR. Nicotine Tob Res
20057491 West R. Smoking cessation guidelines
an update. Thorax 200055987
10
Te?ape?a µe ?p??at?stata ????t???? (?R?)
11
?p??at?stata ????t???? ??? d????

• ??e?e??e? t??? ????t??????? ?a? ?t?paµ???????
  ?p?d??e?? ? ape?e?????s?
  ?e???µetaß?ßast??
• ?e?t???? d??s?
• ?e??fe???? d??s?
• ?e? e?afa?????? e?te??? ta s?µpt?µata st???s??
• ??a ta d?a??s?µa s?e??sµata ??????s?? ????t????
  e?a?t??ta? ap? t?? f?eß??? ap????f?s?
• ?e? ep?t?????eta? ? ??????? ?a? ????? s?????t??s?
  st? a?t???a?? a?µa p?? ep?t?????eta? ?ta?
  e?sp??eta? ? ?ap??? t?? ts??????

A.Molyneux, ?MJ 3282004 454-58
12
S?????t??s? ????t???? st? a?µa
13
?p??at?stata ????t???? (t?p??)

• ??t??????ta
• Patch 16h 15, 10 ? 5mg
• Patch 24h 21, 14 ? 7mg
• ?s???e?
• 2 ? 4mg/teµ????
• ??sp?e?µe?a
• Inhaler 10mg /e?sp???
• Nasal spray 10mg /ml, 0,5mg/?e?asµ?
• ?p????ss?a d?s??a / ??a???µe?e? past???e?
  (lozenge)
• 1, 2 ? 4mg / d?s???

14
?p?peda ????t???? st? p??sµa s?????s? µeta??
ts?????? ?a? NRT
?s????? (ape?e?????s? ????t????, 1-2 mg) ?s???a
(ape?e?????s? ????t????, 4 mg) ?????? e???f?µa
(ape?e?????s? ????t????, 1 mg) ??ade?µ??? ep??eµa
S?????t??s? ????t???? st? ???sµa (µg/L)
?????? µet? t? ??????s? (?ept?)
1. Sweeney CT, et al. CNS Drugs. 200115453-467.
15
?p??at?stata ????t???? 3 ?a? 12 µ??e?
?eta a????s? BMC 2007
16
Effectiveness of different types of NRT
Odds ratio
Marlow SP Respir Care 2003 48(12) 1238
17
?p??at?stata ????t???? ???a? asfa??

• ???µ? ?a? µa????????a ?e?ape?a de? ??e?
  s?s?et?s?e? µe s?ßa??? pa?e????e?e?
• S????te?e? pa?e????e?e?
• ????st?µ?a / Ste???? ?a?µ??
• ??????a?
• ????e? e????? / ?a?t?a
• ?f???te? ?e?µat???? e?e??sµ?? (patch)
• ??????fa???
• A?s??µa p???a?d??? pa?µ??

West R. Thorax 200055987-99
18
?p??at?stata ????t???? ?????e?a ?e?ape?a?
gt 8 eßd?µ

• ??t??????ta
• ? a????? d?s? (15 ? 21mg/24h) p??pe? ?a
  d?at??e?ta? ??a 2-4 eßd?µ?de?
• ????de?t??? µe??s? ???e 2 ? 1 ßd?µ?da
• ?s???e?
• 2mg (lt25 ts????a t?? ?µ??a)
• 4mg (gt25 ts????a t?? ?µ??a)
• 1 ts???a t?? ??a max 24 ts???e? t? 24???
• ??sp?e?µe?a
• Inhalers 6-16 e?s???? /24h (4mg/e?sp???)
• Nasal spray 1-2 (0.5mg each)d?se??/h

A.Molyneux, ?MJ 3282004 454-58
19
?a?e????e?e? p?? s?et????ta? µe t? ???s?
NRT 177.390 ?ap??st??
?aµ?a pa?e????e?a de? ap?te?e? ???? d?a??p?? t??
a????? ?a? ?e? e??a? ?d?a?te?a s?ßa??
Mills EJ Tob Ind Diseas 201088
20
???e???µ??? Fa?µa???e?ape?a st?
d?a??p? t?? ?ap??sµat??

• ?p??at?stata ????t????
• S???st?µe?? ?e?ape?a p??t?? ??aµµ??
• ?a???? d??s??
• Patch
• ??a?e?a? d??s??
• Gum
• Inhaler
• Nasal spray
• Sublingual tablets/lozenges
• Bupropion
• S???st?µe?? ?e?ape?a p??t?? ??aµµ?? (WHO, US,
  Europe, UK)
• Varenikline

Henningfield JE. CA Cancer J Clin
200555281 Hughes JR. Nicotine Tob Res
20057491 West R. Smoking cessation guidelines
an update. Thorax 200055987
21
Bupropion SR (?d????????? ß??p??p????)

• ?µ????et???
• ?p?? a?t??ata???pt???
• ? a???ß?? µ??a??sµ?? d??s?? t?? st? d?a??p? t??
  ?ap??sµat?? e??a? ????st??
• ??e? ???ad?e?e????? ?????? ?a? ????te??
  ?t?paµ????? d??s? ? ?p??a p??a??tata p???a?e?
  d???e?s? ?a? ße?t??s? t?? d???es?? ? p??a?? se
  ??p??? ßa?µ? µ?µe?ta? t? d??s? t?? ????t????

22
?? ?upropion HCl SR p?ste?eta? ?t? ?a??ste?e? t??
epa?ap??s???? ?????? ???ad?e?a????? ?a? t??
?t?paµ????
?etaß???e? ta ep?peda ?t?paµ????
?etaß???e? t? ???ad?e?e????? d?ast????t?ta
23
?p?te??sµata µe??t?? ??s??- ??tap????s??
of subjects not smoking
Hurt et al, N Engl J Med 1997
24
?d????????? ß??p??p???? (Zyban) 3 ?a? 12 µ??e?
?eta a????s? BMC 2007
25
??s?????a ?a? ??????s?

• ?????e?ta? per-os
• ??a??? t?? ?upropion HCl SR ? 7 ?µ??e? p??? ap?
  t?? ?µe??µ???a-st??? t?? d?a??p??, p.?. 8? ?µ??a
• 150mg t?? 6 p??te? µ??e?, 300mg (150 x 2) st?
  s????e?a
• ? d????e?a ?e?ape?a? t?? ?upropion HCl SR e??a? 2
  µ??e????a? s?µa?t??? ?a ?????????e? ? ?e?ape?a
  epe?d? ?p???e? p??a??t?ta ?a a???s??? ?a
  eµfa??s???? s?µe?a ep?t???a?
• ?pa???e?eta? ? ???s? d?s?? µe?a??te??? t?? 300
  mg/?µe??s???

26
?????ep?d??se?? µe f??µa?a

• ?e? e??a? ??e? ???st??
• ?p???e? d??aµ??? a????ep?d?as? µe f??µa?a p??
  ep??e????? t? ??tt????µa P450
• ??ast???e? t? d??s? t?? ?s?e???µ?? CYP2D6 t?
  ?p??? µetaß????e?
• ???sµ??a a?t??ata???pt???
• ?-a?ast??e??
• ??t?a????µ???
• ??t?????s???
• (CYP2B6 ?s?????µ? t? ?p??? µetaß????e? ???sµ??a
  a?t?pa?as?t???)

27
???sa?µ??? d?s?? se e?d????? p????sµ????s?e?e??
µe ?ef???? a?ep???e?a

• HCL bupropion
• ?p?a ?? ? ?a?????? d?s? (300mg)
• ??t??a ?? ? 150mg / day
• ??µ??a?a???µe??? ? 150 mg ???e t?e?? µ??e?

?s?e?e?? µe Sa??a??d? ??aß?t? 150 mg /
day ??????µ???? as?e?e?? (gt70 et??) 150 mg/day
28
????? ????st?µ?a ?efa?a???a ??p??a ????t?da ?a?t?a
????
?a?e????e?e? s??d?asµ???? ?e?ape?a?
29
???e???µ??? Fa?µa???e?ape?a st?
d?a??p? t?? ?ap??sµat??

• ?p??at?stata ????t????
• S???st?µe?? ?e?ape?a p??t?? ??aµµ??
• ?a???? d??s??
• Patch
• ??a?e?a? d??s??
• Gum
• Inhaler
• Nasal spray
• Sublingual tablets/lozenges
• Bupropion
• S???st?µe?? ?e?ape?a p??t?? ??aµµ?? (WHO, US,
  Europe, UK)
• Varenikline

Henningfield JE. CA Cancer J Clin
200555281 Hughes JR. Nicotine Tob Res
20057491 West R. Smoking cessation guidelines
an update. Thorax 200055987
30
Champix? (ßa?e???????) ???e?t???? ?e?????
?????st?? t?? ?4?2 ?p?d???a
?es?µeta??µ?a?? S?st?µa

?p??????? p????a? (nAcc)
????t??? ?t?paµ???
?????a?? ?a??pt???? ped?? (VTA)
Picciotto MR et al. Nicotine Tob Res. 1999 Coe JW
et al. 2006
31
???s? ßa?e????????
??att??e? t?? ep???µ?a ??a ??p??sµa ?a? ta
s?µpt?µata st???s?? (d??s? a????st?) ????a?e?
µe??s? t?? a?s??µat?? ep?ß??ße?s?? p?? p???a?e?
t? ??p??sµa ?a??? ?a? e??tt?s? t?? e??s??t????
?d??t?t?? t?? ?ap??sµat?? (a?ta????st???
d??s?) Gillian M. CNS Drugs 200620 (1) 945-60
Fould J Int J Clin Pract 2006
32
4-Week Continuous Abstinence (CA) ?ßd?µ?de? 9-12
Study 1
Study 2
60
60
50
50
44.0
44.4
40
40
CA Response rate ()
30.0
29.5
CA Response rate ()
30
30
20
17.7
20
17.7
10
10
0
0
VAR1 mg bid(n344)
BUP150 mg bid(n342)
Pbo(n341)
VAR1 mg bid(n352)
BUP150 mg bid(n329)
Pbo(n344)

1. Jorenby DE, et al. JAMA. 200629656-63.
2. Gonzales D, et al. JAMA. 200629647-55

33
?a?e??????? 4 eßd?µ?de?
Mills E Harm Reduction J 2009625
34
?a?e??????? (Champix) 3 ?a? 12 µ??e?
?eta a????s? BMC 2008
35
Chandler MA CHEST 2010137428-35
36
???p?? ??????s?? t?? fa?µ????
?µ??e? 1 3 0,5 mg µ?a f??? t?? ?µ??a
?µ??e? 4 7 0,5 mg d?? f???? t?? ?µ??a
?µ??a 8 ????????s? ?e?ape?a? 1 mg d?? f???? t?? ?µ??a
Se as?e?e?? p?? eµfa?????? ??sa?e??a 1. ????
30 ?ept? µet? ap? e?af?? ?e?µa 2. ?e??s? t??
d?s?? se ?.5 mg d?? f???? t?? ?µ??a
Keating G CNS DRUGS 200620 (11) 945-960
S????? t?? ?a?a?t???st???? t?? ??????t??
Champix. Pfizer Ltd, Sandwich, UK. 2006.
37
?????e?a ?e?ape?a?

• ?????e?a ?e?ape?a? 12 eßd?µ?de?
• ??? ? ?S? de? ??e? ep?te???e? µp????? ?a ??????
  ep?p???? 1-2 p??sp??e?e?
• ? ?e?ape?a µp??e? ?a s??e??s?e? ??a 12 ep?p????
  eßd?µ?de? se
• ?ap??st?? p?? d?????a? a??? ????? ??t??? ep???µ?a
• ?ap??st?? µe p????? ?p?t??p??

Zierler-Brown S. Annal Pharmacotherapy
20074195-9
38
???sa?µ??? d?s?? se e?d????? p????sµ???
?s?e?e?? µe ?ef???? a?ep???e?a
?a?????? d?s?
0.5 mg x 1 a??? 1 mg x 1 s????e?a
0.5 mg x 1
Zierler-Brown S. Annal Pharmacotherapy
20074195-9
39
???sa?µ??? d?s?? se e?d????? p????sµ???
?a?????? d?s?

• ?s?e?e?? µe ?pat??? a?ep???e?a
• ??????µ????
• ????µ????se? / ???????se?
• ?f?ß??

?a?????? d?s? SOS ?ef???? ?e?t?????a
?e? ?p?????? µe??te?
Keating G CNS DRUGS 200620 (11) 945-960
40
??ep???µ?te? e????e?e?
?a?t?a ?efa?a???a ??p??a ?e??e??a ??e??a
30 -10
Gonzales D JAMA 2006 296 (1) 47-55 Jorenby DE
JAMA 2006 296 56-63
41
Varenicline ?a? ?ata????s? a?????
Kamens H Psychipharmacology Jan 14 2010
42
S?µe?a p?? ??????? p??s???? st?? ??????s?
ßa?e????????
?e? a????ep?d?? µe f??µa?a ?p?ß???eta? ap? ta
???a s??dedeµ??? µe OCT2 (human organic cation
transporter) ?p?f??? ep????d????
d?ast????t?t?? µ???? ?a d?ap?st??e? ? at?µ???
a?t?d?as?

• ?pe?e?a?s??s?a st?? ??s?a ? ??p??? ??d???
• ? d?a??p? t?? ?e?ape?a? s?et??eta? µe ?? ?????,
  e?e?e??st?t?ta, ep???µ?a ??a ??p??sµa (3).
• ? d?a??p? t?? ?ap??sµat?? ep??e??e?
• t?? fa?µa??????t??? ???sµ???? fa?µ????
• Te?f??????
• ?a?fa????
• ??s??????
• ap????µ??e? ????at???? ??s?µata

Tonstad S. Exp Rev Neurother 2007 7(2) 121-7
43
Taylor J Mayo Clin Proc 200984(8) 730-36
44
Black JH J Vasc Surg 201051 Chandler MA CHEST
2010137428-35
45
Varenicline and suicidal behavior

• There was no clear evidence that varenicline was
  associated with an increased risk of fatal or
  non-fatal self harm
• No evidence of increased risk of depression or
  suicidal thoughts

Gunnell D. BMJ Oct 2009339-b3805
46
S?????s? fa?µa???e?ape?a? se d??st?µa 4
eßd?µ?d??
Mills E Harm Reduction J 2009625
47
Efficacy and safety of varenicline for sc in
patients with CVD

• 714 ?a?d??pa?e?? µe sta?e?? ??s?
• 9 eßd?µ?de?
• 47 ? 13.9
• 9 52 eßd?µ?de?
• 20 ? 3

?sfa???
Rigotti NA Circulation 19 Jan 2010
48
Odds Ratio ??a ap??? ap? t? ??p??sµa st??? 6 µ??e?
Steinberg MB An Int Med 2009 S??d?asµ?? 3
fa?µ???? ??a 6 µ??e?
Taylor J Mayo Clin Proc 200984(8) 730-36
49
?etaß??? s?µat???? ß?????
Study 1
5
Study 2
4
3.11 N60
2.91 N151
2.92 N61
3
2.42 N155
2.31 N343
2.113 N236
2.12 N97
1.91 N102
1.883 N197
Change From Baseline in Kg
1.51 N340
1.43 N198
2
1.31 N340
1
0
BUP
PBO
VAR
VAR
BUP
PBO
All Subjects (Secondary Endpoint)
Cessators (Post-hoc Analysis)
50
?????e?a ?e?ape?a?

• ?p??at?stata ????t????
• 2 4 µ??e?
• ?d????????? ß??p??p???? (Zyban)
• 8 eßd?µ?de?
• 150mg x 2
• ?a?e??????? (Champix)
• 3 µ??e?
• 1mg x 2

51
???? e??a? ta f??µa?a p??t?? ??aµµ??
52

• ?p?????? 7 e??e???µ??a f??µa?a ??a t?? d?a??p?
  t?? ?ap??sµat??
• Varenicline
• Bupropion SR
• NRT
• Nicotine gum
• Nicotine inhaler
• Nicotine nasal spray
• Nicotine patch
• Nicotine sublingual

Guidelinew 2008 Fiore MC. JAMA 2002 288,14
1768-71
53

• ????? p??pe? ?a p??e? fa?µa???e?ape?a ??a ?a
  d?a???e? t? ??p??sµa

54

• ???? ?? ?ap??st?? p?? p??spa???? ?a d?a?????? t?
  ??p??sµa. ?d?a?te?? p??s??? st???
• ?ap??st?? µe ?at????? a?te?de??e??
• ?s??? ?ap?????? lt 10 ts????a/?µ??a
• ??????? / ???????se?
• ?f?ß???

Fiore MC. JAMA 2002 288,14 1768-71
55
??? ßas??? e??t?µata

• ?????? pa?????te? p??pe? ?a ??ße? ?p??? t?? ?
  ?at??? ?ta? ep????e? a??µesa ap? ta f??µa?a
  p??t?? ??aµµ?? ?
• ??te ???s?µ?p?????ta? f??µa?a de?te??? ??aµµ?? ?

?????e??s? ?at??? µe ta f??µa?a ??te?de??e??,
?a?a?t???st??? ?a? p??t?µ?s? as?e???.
???????µe?? eµpe???a (a???t??? ? ?et???)
??te?de??e?? ??a p??t?? ??aµµ?? ??ap?te?esµat???
ta p??t?? ??aµµ?? SOS Ste?? pa?a???????s?
56
??? ?a ?e?ape?s? ?a??te?a t? ?ap??st? ? ?p????
de? ??e? ???e? t? ??p??sµa pa?? t?? p??????µe??
fa?µa???e?ape?a

• ? ?a??te??? t??p?? (se ?p?t??p? ? ap?t???a
  d?a??p?? ?p? a????) e??a?
• ? ???s? ????? fa?µ???? p??t?? ??aµµ?? (p?? de?
  ??e? ???s?µ?p????e?)
• ? ???s? s??d?asµ???? a?????
• ? a???? ??a µe?a??te?? ??????? d??st?µa

Taylor J Mayo Clin Proc 200984(8) 730-36
57
S??d?asµ??? a????

• S??d?asµ?? d??f???? t?p?? ?p??at?stat?? ????t????
• S??d?asµ?? ß??p??p????? µe ?p??at?stata (?RT)
• O p?? ap?te?esµat???? s??d?asµ??
• S??d?asµ?? ß??p??p????? µe ßa?e???????
• ???a ded?µ??a

SOS OXI ?a?e??????? µe NRT
Taylor J Mayo Clin Proc 200984(8) 730-36
58
Combination treatment with vareniclineand
nicotine replacement therapyEbbert JO, Burke
MV, Hays T. Hurt RD

• Nicotine Tobacco Research11 (5) May 2009
• 572-576

59
????d?? / ?p?te??sµata

• 71 st?? ?µ?da t?? s??d?asµ???? ?e?ape?a? p??a?
  patches 32 mg/day
• 73 p??a? t??????st?? 2 t?p??? ?p??at?stat??
• St?? s??d?asµ??? ?e?ape?a
• ?e??s? d?s?? (e?ast???) t?? 2? eßd?µ?da a?????
• St?? s????? ?e?ape?a (patches SANRT)
• ?e??s? d?s?? ???e 2-4 eßd?µ?de?

60
S?µp??asµa

• ?a e???µata t?? µe??t??
• ? s??d?asµ??? ?e?ape?a µe ßa?e??????? ?a?
  ?p??at?stata ????t???? e??a? asfa???
• ???a? p??? ?a?? a?e?t? ap? t??? ?ap??st??

61
?e?a??te?? d????e?a ?e?ape?a?

• NRT gt 14 eßd?µ?de? ?e??e?ta? p?? ap?te?esµat???
  ap? t?? ??as??? ?e?ape?a t?? 8 12 eßd?µ?d??
• ?p?????? ded?µ??a ??a ?e?ape?a ??? 12 µ??e? µe
  ß??p??p???? ?a? ßa?e???????
• ??att?µ??? d?s?
• ???? se ?ap??st?? µe ?p?t??p?? ? ad??aµ?a d?a??p??

Taylor J Mayo Clin Proc 200984(8) 730-36
62
Prevent Relapse Most relapses within 3 first
months Reinforce decision to quit Follow
up Assist resolving residual problem
Desire to quit smoking
The 5 As
Yes
No
Patient examination
Counselling
The 5 Rs
No
Low dependency
Breastfeeding Pregnancy Adolescents
High dependency
Repeat counselling
Discussing patients preference Evaluate
co-morbidities
No co-morbidities
Co-morbidities
No severe co-morbidities
Severe co-morbidities

Counselling Behavioural support
Counselling Behavioural support ? NRT
Counselling Behavioural support Therapy (NRT
or Bupr or Varenik)
Refer to smoking cessation clinics
Mitrouska et al. PPT 2006
63
??????st???? de??te? ?p?t??p?? µet? t? t????
ep?t????? ?e?ape?a?

• Data from two phase III varenicline trials
• ?s?? de? ????? ?ataf??e? ?a µ?? ?ap??s??? ?a?????
  t?? p??te? t?sse??? eßd?µ?de? ?e?ape?a?
• ?s?? a?af????? ?t? pa?a??te?a ?at?fe?a? ?a? t?
  ????a ??a? d??st?µa µe?a??te?? t?? 30 ?µe???

Heffner LJ Drug and Alcohol Dependence 2010 (in
press)
64
?e????t???? ?ate????se??

• ???sfate? µe??te? st?? ?ata???s? t??
  ?e???ß??????a? t?? e???t?s?? ap? t?? ????t???
  ????? de??e? p?????? ?e???µetaß?ßast?? ?? ?p????
  s?µß?????? st?? d?at???s? ? t?? ?p?t??p? t??
  ?ap??sµat??
• F??µa?a p?? ???s?µ?p?????ta? ??a ???a ??s?µata
• ?at?????? (fluoxetine)
• ???????sµ? (naltrexone)
• ??s? Parkinson
• F??µa?a p?? d???? se ????? fa?µa??????????
  st?????
• ???e?t????? ?p?d??e?? ?t?paµ????
• ????t???? a?et?????????
• GABA
• ?µß???a
• ??t?-e?e???µe?? s?st?µa ??????s?? ????t????

65
?fa?µ??? ??a 1 ????? minimal counseling
intensive counseling pharmacotherapy
Hoogendoom M Thorax 2010 65711-718
66
Hoogendoom M Thorax 2010 65711-718
67
??st?? fa?µa?e?t???? a????? ??a d?a??p?
?ap??sµat??
?ta? ? d?s? µe???eta? ???e 3 eßd?µ?de? ??a
d?? ???t?? ?ta? ? d?s? µe???eta? ???e 4
eßd?µ?de?
Tonstad S. Exp Rev Neurother 2007 7(2) 121-7
68
CONCLUSION

• Even in low-dependency smokers, a smoking
  cessation regimen requires more from the
  physician than simply writing a prescription and
  sending the patient off with admonition to read
  the package insert and try harder

Lillington G. Clin in Chest Med 200021199-208
69
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