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Comparative EfficacyComparative Efficacyof Secondof Second--line drugsline drugs

for Smoking cessationfor Smoking cessation

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é ø  üâ : õ.  ëõ   ÿ úù

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OutlineOutline

Introduction

Second-line drugs f or smoking cessation- Nortriptyline

- ClonidineConclusions

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Introduction

å úøë öéâå ø â ãèéââ ûû   

- 42,000 å ú/ü - 115 å ú/ ú- 5 å ú/ë  è

ý   ü ø õ  ûâ úéêü úèüõ üô 10,000å úöü  ø  : ÷öù

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  Henningf ield et al, Epidemio

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âââöõû  

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Quitting methods

 Cold turkey  Counseling /behavioral therapy 

- Individual - Group - Telephone 

Pharmacological therapy-Replacement therapy eg.nicotine

-Reduction of withdrawal 

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Pharmacological Treatment

First-line drugs f or smoking cessations

Nicotine replacement therapy (NRT)Patch

GumInhaler

Nasal spray

Lozenge

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Pharmacological Treatment

Second-line drugs f or smoking cessations

Clonidine

Nortript

yline

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Other medications

SSRIs

MAOIs

Mecamylamine

Anxiolytics

Opioids antagonists Silver acetate

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Nortriptyline

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NortriptylineTricyclic 

antidepressantsUS-FDA has not 

approved

 use

 in

 smoking cessation

The US Public Health Service (USPHS) :

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 øù  øè ë øNortript

yline

 û  èââ ûâ û ü

 ûøâìõå  úèãèâ÷ú

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  ëéúöOnset : 2 wk 

Bioavailability :65%âéýúâ ã ûâ øèú úõ 

ü úÿø ö û : CY P 2D6

 ã ûâøèü 

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 ãúõ

  ùë õãúõ 25 mg/day

å ÿ éúüú75-100mg/dayúå  è ûèú 4

å  èå ö  èö 10-28 úâúúø 

éâû 

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 âÿ è

üèåâèèúú üâè öÿ

úõ  ú üå èøèýâéöúüúéè åõú öè orthostatichypotension

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Addiction 2005;100:317-326

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 ã   å è

 åéõõ üöüå è öââö

 åëâ ý  üø å èöâëâ ý  ø  åöû

âëâû MAOIs éøâõâëâø úè ãè éöúé å

Pre nanc cate or : D

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ý  ø ÿ è  úöéââ ý  ø ÿ 

 ã     ë

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Eff icacy o

f Nortriptyline

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ú å ÿøAbstinence rate :öââû  

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Cochrane 2004

Wagena 2004

âüûø

 û

Nortriptyline VS Placebo

Nortriptyline VS Placebo

éúútrial

7  5

éúúsubject1,021 å ú 861 å ú

 

â  

èú 6 õú èú 6 õú

öèüûøûââ

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Antidepressants f or smoking c

The Cochrane Librar 

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Nortriptyline is more more eff icaciouseff icacious than placebo

Pooled odd ratio = 2.14The Cochrane Librar 

Antidepressants f or smoking c

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Cochrane 2004

Wagena 2004

âüûø

 û

Nortriptyline VS Placebo

Nortriptyline VS Placebo

éúútrial

7  5

éúúsubject1,021 å ú 861 å ú

 

â  

6-12 õú èú 6 õú

öèüûøûââ

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Eff icacy of nortriptyline compared with placebo af ter at least 6-month prolonged abstinence f rom smoking

Nortriptyline is more more eff icaciouseff icacious than placebo

RR = 2.44 (95%CI :Addiction 

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0

10

20

3040

50

   %   A

  s   t                      i

   t  r  a

   t  e

12 24 36 52

ti e eek)Bupropion

Nortript line

P l ebo

øû % A sti ent rateè BupropiNortrityline Place o úöë è

Arch Gen Psychiatry.

Psychological Intervention and Antidepressant Treatment in Smok ing C

essatio

n

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Clonidine

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C lonidine

Alpha-2 adrenergic 

agonistAn antihypertensive agent

The US Public Health Service (USPHS) :second-line drug in

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 øù  øè ë ø

âö   ú peripheral alpha-adrenergic receptors 

vasoconstriction  û  èâüø

sympathetic éâ CNS å õ ú

 öõè

âö úãè

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  ëéúö

 Bioavaila

bility

:7

5-

95% å ãã úèõãè - oral : 2-4 ë è

- patch

: 2-

3  ú ýúâã ûâøèú ú ü úÿø ö ûüô 50

ã ûøèü 65-72 , øèéé 22  å å  èëöãè

  -å

 úüâö : 6-20 ë  è    

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Tablet

Patch

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âõ

ë å  õãúõ õú 2-4  ú ÿ â èâ÷ú

ø éâõã    ú ë ú âûâ é ú ú ú û üõ  

 è   â    éöú  å ú  üõâú   

â÷úââõúý   ø  ë 

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âÿ èüèå> 10% : üâè è è

 ì  úèè

1-10% : øèýâ ú üõ   õø  üâú  éü

è ýúü   ââ ã 

  úãúõö ø õ  éè      

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 ã   åè ã     ë  õèâë ú severe coronary 

insuff iciency

recent MI cerebrovascular disease chronic renal f ailure

  Pregnancy category : C      ë úý   ø  üöÿ

ûèéâõ   öèü ú

 ü øùÿãè

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Eff icacy o

f  C 

lonidine

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Clonidine is  moreefficacious  than placebo

P l   r ti = 1.The Cochrane

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Twenty-four week maintenance treatment of cigarette

smoking with nicotine gum, clonidine and naltrexone

Abstinence rate at 6 month

36.819.3

5.30

20

40

60

80

100

nicotine gum clonidine naltrexone

Dugs

   A   b  s   t   i  n  e  n  c  e  r  a   t  e

 Journal of  Substance Abuse Tr

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Dose(mg/day)

Cost/day

(Bath)

Cost/month

(Bath)

Nicotine gum 

(2 g)

60(~15

 ë   ú)

105 3,150

Bupropion

300 58 1,740Nortri ø  :   úããõúëôò 

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C onclusion

Eff icacy of  Nortriptyline &Clonidine > placebo

Clonidine not  more eff icacious than NRTNortriptyline : eff icacy  of 

nortriptyline ~ bupropionNortriptyline might be f irst-line drugs f or smoking cessation

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 Special

Thanksé ø  üâõ.  ëõ   ÿ úù