Tabagismo: tratamento expandido Prof. Dr. José Miguel Chatkin Faculdade de Medicina PUCRS Progama de Auxílio à Cessação do Tabagismo Data: 23 novembro 2008 Horário: 16:40 – 17:05

Different determinants for individual smoking and for populatin smoking

1. Effectiveness of proactive quitlines 2. Effectiveness of combining counseling and medication relative to either counseling or medication alone 3. Effectiveness of varenicline 4. Effectiveness of various medication combinations 5. Effectiveness of long-term medication use 6. Effectiveness of tobacco use interventions for individuals with low SES/limited formal education 7. Effectiveness of tobacco use interventions for adolescent smokers 8. Effectiveness of tobacco use interventions for pregnant smokers 9. Effectiveness of tobacco use interventions for individuals with psychiatric disorders, including substance use disorders 10. Effectiveness of providing tobacco use interventions as a health benefit 11. Effectiveness of systems interventions, including provider training and the combination of training and systems interventions Table 1.1: Topics chosen by the USPHS 2008 Guideline Panel for updated meta-analysis

Tratamento expandido: terapia cognitivo-comportamental terapia de reposição nicotínica bupropiona nortriptilina vareniclina

Terapia cognitivo-comportamental

; 2008 Terapia cognitivo-comportamental

Adesivos de nicotina Collaborative European Anti-Smoking Evaluation: ERS 1999 CEASE trial

goma nicotina

For some patients, it may be appropriate to continue medication treatment for periods longer than is usually recommended. Results of meta-analysis indicated that long-term patch and gum use are effective. Evidence indicates that the long-term use of gum may be more effective than a shorter course of gum therapy. The Lung Health Study reported that 1/3 of long-term quitters still were using nicotine gum at 12 months and some for as long as 5 years, with no serious side effects. Extended Use: USPHS 2008 Update

Among patients given free access to nicotine gum, 15-20% of successful abstainers continue to use the gum for a year or longer. Thus, certain groups of smokers may benefit from long-term medication use. Although weaning should be encouraged for all patients using medications, continued use of such medication clearly is preferable to a return to smoking with respect to health consequences. Finally, it should be noted that the medication treatment that produced the largest effects on abstinence rates, of those analyzed, involved long-term nicotine patch therapy + ad libitum NRT Extended Use: USPHS 2008 Update

Bupropiona por 7 semanas – fase aberta 59% abstinentes: eram então randomizados para TCC + BUP ou TCC + PLAC tratamento por 45 sem seguimento 52, 78, 104 semanas Bupropiona

Resultados: BUP 52 : 55,1%Plac 52 : 42,3% P=0,008 BUP 78 : 47,7% Plac 78 : 37,7% P= 0,034 BUP 104 : 41,6% Plac 104 : 40,0% P>0,05 não controlado para TCC

J Clin Oncol, % Plac3% Bup P=0.12 BUP/PLA 26 sem 28% Bup25% Plac P=0.73 BUP/PLA 26 sem 578 fumantes: TRN 8 semanas 31% abstinentes 69% fumantes Bupropiona

J Consult Clin Psychol, 2006 Bupropiona

1700 smokers: 566 TRN; 567 BUP; 567 BUP+TRN Bupropiona / TRN Croghan, Mayo Clin Proc 2007

Bupropiona / TRN Croghan, Mayo Clin Proc 2007

Bupropiona / TRN Croghan, Mayo Clin Proc 2007

Bupropiona / TRN Croghan, Mayo Clin Proc 2007

8-week Open PHASE I BUP Nicotine patch Counseling Success 16-wk D/Blind Maintenance 24-wk Rx-free Follow-up PHASE II PHASE III Pbo + Pbo Pbo pill + Nicotine gum BUP + Pbo gum BUP + Nicotine Gum Wk 36 Wk 48 Study Design: Single site 48 week duration Bupropiona+ TRN

Median days to relapse by treatment through 16-week maintenance and 24 week follow-up Bupropiona+ TRN

AuthorsBup N= Pbo N= Bupropion Abstinent N (%) Placebo Abstinent N (%) O.R.95% C.I. p- value Hays, (52.3) 90 (42.3)* Hurt, (28) 22 (25) Covey, (54.8) 25 (35.2)* Combined odds ratio Abstinence rate at Week 24/26 Meta-analysis of 3 maintenance trials of bupropion Bupropiona+ TRN

AuthorsBup N= Pbo N= Bupropion Abstinent N (%) Placebo Abstinent N (%) O.R.95% C.I. p- value Hays, (52.3) 90 (42.3)* Hurt, (28) 22 (25) Covey, (54.8) 25 (35.2)* Combined odds ratio Abstinence rate at Week 24/26 Meta-analysis of 3 maintenance trials of bupropion Bupropiona+ TRN

Abstinence rate at Week 26/52 Meta-analysis of 3 maintenance trials of bupropion AuthorsBup N= Pbo N= Bupropion Abstinent N (%) Placebo Abstinent N (%) O.R.95% Confidence Interval p- value Hays, (35.5) 70 (32.1) Hurt, (22) 13 (15) Covey, (31.5) 13 (18.3) Combined odds ratio Bupropiona+ TRN

Main conclusions  Extended BUP exerted a moderate benefit for reducing relapse (6 mo: OR mo: OR 1.3)  This effect occurred mainly while using the drug (BUP)  Nicotine gum had limited appeal, but when used reduced relapse amongsome smokers Predictors of longer time to relapse  Older age  Low nicotine dependence (FTND)  Fewer cigarettes smoked daily  Lower cotinine at baseline  High BMI at screening (or at randomization)

Hall, Am J Psychiatry, 2004 Nortriptilina

Hall, Am J Psychiatry, 2004 Nortriptilina

12 additional weeks - VAR 1 mg bid vs placebo P<0.001 vs placebo Weeks % stayed quit varenicline  varenicline varenicline  placebo 603 subjects who quit randomized to varenicline 607 subjects who quit randomized to placebo 70.5% stayed quit Stage 1: Open Label 12 weeks - VAR 1 mg bid 35.9% did not quit (n= 692) 61.1% quit (n=1236) Week 12 Stage 2: Double Blind Vareniclina Tonstadt, JAMA 2006

The place of varenicline in smoking cessation treatment The place of varenicline in smoking cessation treatment Aveyard, Thorax Aug 2008 “While taking longer courses of VAR may prevent some relapse, lifetime VAR is unlikely to be a major solution. Instead, we need to develop cognitive-behavioral interventions together with judicious use of various medications.”

Tempo de tratamento influi na prevenção da recaída? Ineficaz: 1999: ERS– adesivo TRN 2003: Hurt – BUP+TRN 2006: Killen - BUP Eficácia limitada 2001: Hays – BUP Eficácia moderada 2006: Tonstad – VAR 2007: Covey: BUP;TRN Eficácia significativa 2000: Murray: goma TRN 2004: Hall: NOR 2005: Hajek: Cochrane 2006: Convey: vários esquemas 2006: Lancaster: revisão sistemática 2007: Crogham: BUP; TRN, BUP+TRN

Conclusões: Cochrane Stead, 2006 Hughes, 2007 Cahill, 2008 Não há evidências que suportem o tratamento estendido para cessação do tabagismo

s What is the ideal duration of therapy? s In what populations of smokers is long-term therapy an effective strategy? CNS Drugs 2002 Sims TH, Fiore MC, 2002 Pharmacotherapy for treating tobacco dependence:

s What is the ideal duration of therapy? s In what populations of smokers is long-term therapy an effective strategy? CNS Drugs 2002 Sims TH, Fiore MC, 2002 Pharmacotherapy for treating tobacco dependence: If a smoker is doing very well on nicotine replacement, with no adverse effects and full relief of withdrawal symptoms, yet has reached week 12, but states clearly that if we stop his/her NRT, they will most likely return to smoking, do we stop the treatment because the clock has struck 12 weeks? Steinberg MB 2008

s What is the ideal duration of therapy? s In what populations of smokers is long-term therapy an effective strategy? CNS Drugs 2002 Sims TH, Fiore MC, 2002 Pharmacotherapy for treating tobacco dependence: If a smoker is doing very well on nicotine replacement, with no adverse effects and full relief of withdrawal symptoms, yet has reached week 12, but states clearly that if we stop his/her NRT, they will most likely return to smoking, do we stop the treatment because the clock has struck 12 weeks? Individualized duration of treatment for this and other medical conditions is the best practice and the ethical thing to do for these few smokers. As far as I know, there are no clinical trial data supporting the use of statins for 40 or more years. However, right now, my patients can have their cholesterol lowering medications continued indefinitely. Are smokers less worthy of treatment than non-smokers? Steinberg MB 2008

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