CHAPTER 1 Smoking Cessation

Transcription

1 Psychiatric Disorders CHAPTER 1 Smoking Cessation Peter Selby, MBBS, CCFP Tobacco use kills approximately Canadians annually, primarily from cardiac disease, lung cancer and respiratory diseases such as COPD. 1 The toxicity of cigarette smoke is due to the inhalation of about 4000 chemicals including 50 to 60 carcinogens. 2 Cigarettes are highly addictive because of the rapid delivery of nicotine to the mesolimbic reward pathways in the brain and development of tolerance. The short half-life of nicotine (60 to 90 minutes) forces repeated administration to maintain nicotine levels. 3 Other psychoactive compounds in smoke include MAOA and MAOB inhibitors. 4 The polyaromatic hydrocarbons (PAHs) are inducers of CYP1A1, 1A2 and 2E1 enzymes that have clinical implications when smokers quit. 5 Goals of Therapy 8 The ultimate goal is to help smokers achieve complete and sustained remission from tobacco use and nicotine dependence An intermediate goal is to help them achieve complete and sustained remission from cigarette smoking and/or other forms of tobacco products such as chewing tobacco To help smokers understand that: smoking cessation is a process not a singular event; helping smokers stay engaged in the process of behaviour change is a major objective of therapy the best odds of quitting are when behavioural and pharmacologic interventions complement each other reduction in smoking by 50% in those unable or unwilling to quit is controversial because there is no long-term health benefit. 9 However, reduction is associated with subsequent successful quitting 10 Investigations (Figure 1) Figure 1 provides a general assessment questionnaire for patients who have not previously stopped smoking for more than 24 hours Measures of physical dependence include the Fagerström Test of Nicotine Dependence 11. A shorter version is the Heaviness of Smoking Index, which asks about the time to first cigarette of the day and the number of cigarettes smoked per day 12 Motivation can be assessed by asking the following two questions: 3 Given everything going on in your life right now, on a scale of 1 to 10, where 10 is the most important thing to do right now, how important is it for you to quit smoking altogether?

2 2 Psychiatric Disorders Given everything going on in your life right now, on a scale of 1 to 10, where 10 is the most confident you have felt about anything, how confident do you feel you will be able to quit smoking altogether? Therapeutic Choices (Figure 2, Table 2) This chapter will focus on smokers who want to quit in the next 30 days. Nonpharmacologic Choices Most smokers try to quit on several occasions though success rates over the long term are generally low. Many methods for quitting smoking have been advocated; however, few have been demonstrated to be effective. This type of evidence generally requires randomized controlled trials with a minimum follow-up assessment of self-reported quit rates at six months along with supportive objective evidence, e.g., measurement of exhaled carbon monoxide or cotinine levels in urine, saliva or serum. 8 Though widely promoted, there is no evidence for the efficacy of hypnosis or acupuncture. The five evidence-based steps required to successfully quit include the following 8 setting a target quit date getting professional help enlisting social support using medication to quit smoking using problem-solving methods of counselling to quit and remain smoke free. There is a dose-response relationship between counselling and quit success. 8 Estimated abstinence rates increase from 13.4% with minimal counselling contact time (< 3 minutes) to an average of 22% with contact time > 10 minutes. Optimal total contact time is minutes, yielding abstinence rates of approximately 28%. 8 Smokers who are attempting to quit should be counselled at least once prior to their quit date, the week following their quit date and weekly thereafter as necessary to optimize therapy and to identify and manage early relapse. 8 Formats that have been shown to be effective include face-to-face (individual or group) counselling as well as contact by telephone, Internet and mail. Pharmacologic Choices The addition of pharmacotherapy increases the odds of quitting (see Table 1) and should be offered to all patients who smoke 10 or more cigarettes per day and are attempting to quit. Pharmacotherapy can be divided into first-line and second-line medications. 8 First-line medications include all forms of nicotine replacement therapy and bupropion. Second-line pharmacotherapies have evidence of efficacy but are not officially indicated for smoking cessation. These include nortriptyline and clonidine. 14,15,16,17 Varenicline,analpha 4 beta 2 -nicotinic receptor

3 Chapter 1: Smoking Cessation 3 partial agonist, with quit rates higher than previously existing therapies, recently became available. 18,19,20 In two comparative trials, varenicline increased the odds of successfully quitting over bupropion and placebo at 12 weeks (varenicline 44%, bupropion 29.5% and placebo 17.7%). 21,22 However, differences at 6 months (i.e., 3 months after treatment was stopped) were smaller (varenicline 22%, bupropion 16%, placebo 8.4%). Table 1: Estimated Abstinence Rates with Pharmacotherapy Estimated 6-month Abstinence Rate (%) a Drug Drug Placebo Nicotine replacement 17 a 10 therapy 23 Varenicline 21, Bupropion 21, Nortriptyline Clonidine Pooled data from any form of nicotine replacement therapy Nortriptyline can be used in otherwise healthy individuals with minimal risk for overdose or cardiac disease when first-line therapies are either unaffordable or have not worked. Clonidine may be used in those with coexisting hypertension. However, postural hypotension can be problematic and the drug must be tapered to prevent rebound hypertension. Choice of medication should depend on patient preference and absence of contraindications. Monotherapy is the norm. There is evidence that combination therapy such as the nicotine patch combined with either nicotine gum 24, nicotine inhaler, 25 nicotine spray 25 or bupropion 26 is better in the short term than monotherapy. However, cost is a limiting factor and combination therapy should be reserved for those in whom quitting immediately is essential. Varenicline has not been studied in combination with other medications and is contraindicated in combination with nicotine replacement therapy. The nicotine lozenge, nasal spray and sublingual tablet are not available in Canada. Rimonabant, a cannabinoid receptor 1 antagonist approved in Europe for weight loss, has shown mixed results in two smoking cessation trials. 27,28 It is not approved for smoking cessation in either Europe or the United States and is not available in Canada. Therapeutic Tips Encourage smokers who have slips while on medication to continue medication for at least four weeks and use behavioural interventions to help them to stop smoking. 29

4 4 Psychiatric Disorders If smokers using the patch complain of unmanageable cravings and smoke cigarettes, add nicotine gum or inhaler as a breakthrough medication. 8 It is important to monitor for low mood and emergence of depression in smokers who quit. 30 Potential weight gain following smoking cessation should be addressed before quitting and practical advice should be offered to help the smoker avoid gaining weight, i.e., healthy diet and exercise and avoidance of high-sugar products which the patient craves when quitting smoking. 31,32 Create a therapeutic relationship in which the patient can report back at the first signs of a relapse to abort it as soon as possible.

5 Chapter 1: Smoking Cessation 5 Figure 1: Tobacco-smoking History Questionnaire

6 6 Psychiatric Disorders Figure 2: Management of Smoking Cessation

7 Chapter 1: Smoking Cessation 7 Table 2: Pharmacologic Agents Used for Smoking Cessation Class Drug Dose Adverse Effects Drug Interactions a Comments Cost b Nicotine Replacement, immediaterelease nicotine inhaler Nicorette Inhaler First 6 12 wk: 1 cartridge delivering 4 mg nicotine, as needed Encourage patient to use at least 6 doses/day for the first 3 6 wk Max 12/day Tapering: gradual reduction in use over next 6 12 wk, stopping when reduced to 1 2/day Mild local irritation (cough, throat irritation, stomatitis, rhinitis) that may decline with continued use; headache, nausea, dyspepsia. Not a true inhaler the nicotine is delivered and absorbed buccally. Hand mouth activity from using the inhaler is preferred by some quitters while others find it to be a trigger. Useful in those with poor oral health or dentures and in those who cannot chew gum. $$ nicotine polacrilex gum Nicorette Gum pieces/day initially (2 or 4 mg/piece) to max of 20 pieces/day, for 12 wk Tapering: 1 piece/day each wk, as withdrawal symptoms allow Hiccoughs, GI disturbances, jaw pain and orodental problems. Use 4 mg in heavily dependent smokers. May be used for temporary abstinence, e.g., to comply with smoking restrictions on airplanes. $$ (cont d)

8 8 Psychiatric Disorders Table 2: Pharmacologic Agents Used for Smoking Cessation (cont d) Class Drug Dose Adverse Effects Drug Interactions a Comments Cost b Nicotine Replacement, sustainedrelease nicotine transdermal patch Habitrol, Nicoderm, generics Habitrol: > 20 cigarettes/day: 1 patch (21 mg/24 h) daily 3 4 wk 20 cigarettes/day: 1 patch (14 mg/24 h) daily 3 4 wk Tapering: reduce strength of patch (i.e., from 21 to 14 to 7 mg/24 h) every 3 4 wk Nicoderm: 21 mg/24 h 6 wk then 14 mg/24 h 2 wk then 7mg/24h 2wk If patient has cardiovascular disease, weighs less than 45 kg or smokes < ½ pack/day begin with 14 mg/24 h 6 wk then to 7 mg/24 h 2wk Skin sensitivity and irritation (most common); abnormal dreams; insomnia; nausea, dyspepsia. Start patch on the quit date. Advise not to smoke cigarettes while using the patch, though this is generally safe and does not indicate treatment failure. Educate users on the signs and symptoms of nicotine toxicity. Habitrol: Takes longer to reach peak levels than Nicoderm; should not use while exercising; major supplier of the generic/store brands. Nicoderm: More rapid onset and shorter time to peak effects; maybewornwhile exercising; although not recommended by the manufacturer, can be cut without damaging the delivery device. $$$$

9 Chapter 1: Smoking Cessation 9 Class Drug Dose Adverse Effects Drug Interactions a Comments Cost b Nicotine Receptor Partial Agonists varenicline Champix 0.5 mg daily for 3 days then BID for 3 days then 1mgpoBIDfor12wk. Patient should quit smoking 1 2 wk after starting the medication. Reassess if patient is still smoking 4 wk after starting medication; can be continued for an additional 12 wk if patient has benefited. No tapering necessary Nausea (30%); can be mitigated by increasing water intake or dosage reduction. Should not be combined with nicotine replacement therapy due to increased risk of adverse effects. Does not induce cytochrome P450 enzymes; excreted renally unchanged. $$$$$ Antidepressants bupropion Zyban, generics 150 mg daily 3 days then 150 mg BID 7 12 wk. Begin 1 2 wk before the selected quit date Usual: insomnia, dry mouth, dizziness, restlessness, difficulty concentrating. Unusual: hypersensitivity reactions, risk of seizures at higher dosages. Clearance of bupropion may be by inhibitors (e.g., ticlopidine) or by inducers (e.g., phenobarbital, phenytoin, primidone) of CYP2B6. May clearance of other substrates of CYP2B6 (e.g., cyclophosphamide, ketamine, promethazine, propofol, selegiline). MAOIs, levodopa, amantadine may toxicity. May be safely combined with NRT (monitor for treatment-emergent hypertension). Not recommended in patients with conditions predisposing to seizures, history of seizures, current eating disorder or severe hepatic impairment. Least expensive of oral medications officially indicated for smoking cessation. $$$ (cont d)

10 10 Psychiatric Disorders Table 2: Pharmacologic Agents Used for Smoking Cessation (cont d) Class Drug Dose Adverse Effects Drug Interactions a Comments Cost b nortriptyline generics 25 mg/day titrated to mg/day. Quit day is usually set between 1 and 4 wk; medication is continued for 12 wk Common: dry mouth, blurred vision, constipation, dizziness, sedation. Less common: confusion, arrhythmias, urinary retention. AvoidwithMAOIs may cause mania, excitation, hyperpyrexia. Inducers of CYP2D6 or CYP3A4 (e.g., carbamazepine, phenytoin, rifampin) may effect. Inhibitors of CYP2D6 or CYP3A4 (e.g., clarithromycin, erythromycin, grapefruit juice, fluoxetine, paroxetine) may effect and toxicity. Caution in patients with cardiovascular disease or arrhythmias. Consider measuring serum levels to reach therapeutic dose. $$ Alpha 2 -adrenergic Receptor Agonists clonidine Catapres, Dixarit, generics 0.1mgpoBIDstarting up to 3 days before or on the quit date. Increase by 0.1 mg/day once per wk if needed. Duration of therapy ranges from 3 10 wk Common: sedation, dizziness, hypotension, dry mouth. Less common: anxiety, irritability, memory problems, rebound hypertension. Avoid concurrent usewithtricyclic antidepressants. Additive effects with other CNS depressants such as ethanol. Monitor blood pressure and heart rate during treatment initiation. Taper off gradually to avoid rebound hypertension when stopping treatment. $ a Smoking is associated with increased CYP1A1/ 1A2 and 2E1 activity. Upon smoking cessation, reduced clearance of substrates of these enzymes (e.g., theophylline, clozapine, caffeine, fluvoxamine, haloperidol, olanzapine, lorazepam, alprazolam and diazepam) may necessitate dose adjustments. b Cost of 105 pieces of gum, 42 inhalations, 28 patches or 30-day supply of tablets; includes drug cost only. Dosage adjustment may be required in renal impairment; see. Abbreviations: CVS = cardiovascular; NRT = nicotine replacement therapy Legend: $ < $25 $$ $25 50 $$$ $50 75 $$$$ $ $$$$$ $

11 Chapter 1: Smoking Cessation 11 Suggested Readings Foulds J, Steinberg MB, Williams JM et al. Developments in pharmacotherapy for tobacco dependence: past, present and future. Drug Alcohol Rev 2006;25(1): George TP, editor. Medication treatments for nicotine dependence. Boca Raton (FL): CRC/Taylor & Francis; McEwen A, Hajek P, McRobbie H et al. Manual of smoking cessation: a guide for counsellors and practitioners. Malden (MA): Addiction Press, Blackwell; West R. Bupropion SR for smoking cessation. Expert Opin Pharmacother 2003;4(4): Database & educational resource for treatment of tobacco dependence. Available from: Accessed June 1, References 1. Makomaski Illing EM, Kaiserman MJ. Mortality attributable to tobacco use in Canada and its regions, Can J Public Health 2004;95(1): Hoffmann D, Djordjevic MV, Hoffmann I. The changing cigarette. Prev Med 1997;26(4): LeHouezecJ.Roleofnicotine pharmacokinetics in nicotine addiction and nicotine replacement therapy: a review. Int J Tuberc Lung Dis 2003;7(9): Fowler JS, Logan J, Wang GJ et al. Monoamine oxidase and cigarette smoking. Neurotoxicology 2003;24(1): DesaiHD,SeaboltJ,JannMW.Smokinginpatients receiving psychotropic medications: a pharmacokinetic perspective. CNS Drugs 2001;15(6): SongF,RafteryJ,Aveyard P et al. Cost-effectiveness of pharmacological interventions for smoking cessation: a literature review and a decision analytic analysis. Med Decis Making 2002;22(5 Suppl):S Parrott S, Godfrey C. Economics of smoking cessation. BMJ 2004;328(7445): Fiore MC, Bailey WC, Cohen SJ et al. Clinical practice guideline. Treating tobacco use and dependence. Washington (DC): Public Health Service, US Department of Health and Human Services; Available from: Accessed June 1, Tverdal A, Bjartveit K. Health consequences of reduced daily cigarette consumption. Tob Control 2006;15(6): Hyland A, Levy DT, Rezaishiraz H et al. Reduction in amount smoked predicts future cessation. Psychol Addict Behav 2005;19(2): Heatherton TF, Kozlowski LT, Frecker RC et al. The Fagerstrom Test for Nicotine Dependence: a revision of the Fagerstrom Tolerance Questionnaire. Br J Addict 1991;86(9): Kozlowski LT, Porter CQ, Orleans CT et al. Predicting smoking cessation with self-reported measures of nicotine dependence: FTQ, FTND, and HSI. Drug Alcohol Depend 1994;34(3): Rollnick S, Mason P, Butler C. Health behavior change: a guide for practitioners. New York (NY): Churchill Livingstone; Hughes JR, Stead LF, Lancaster T. Antidepressants for smoking cessation. Cochrane Database Syst Rev 2007;1:CD Frishman WH, Mitta W, Kupersmith A et al. Nicotine and non-nicotine smoking cessation pharmacotherapies. Cardiol Rev 2006;14(2): Gourlay S, Forbes A, Marriner T et al. A placebo-controlled study of three clonidine doses for smoking cessation. Clin Pharmacol Ther 1994;55(1): Glassman AH, Stetner F, Walsh BT et al. Heavy smokers, smoking cessation, and clonidine. Results of a double-blind, randomized trial. JAMA 1988;259(19): Keating GM, Siddiqui MA. Varenicline: a review of its use as an aid to smoking cessation therapy. CNS Drugs 2006;20(11): Oncken C, Gonzales D, Nides M et al. Efficacy and safety of the novel selective nicotinic acetylcholine receptor partial agonist, varenicline, for smoking cessation. Arch Intern Med 2006;166(15): Tonstad S, Tonnesen P, Hajek P et al. Effect of maintenance therapy with varenicline on smoking cessation: a randomized controlled trial. JAMA 2006;296(1): Jorenby DE, Hays JT, Rigotti NA et al. Efficacy of varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation: a randomized controlled trial. JAMA 2006;296(1):56-63.

12 12 Psychiatric Disorders 22. Gonzales D, Rennard SI, Nides M et al. Varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs sustained-release bupropion and placebo for smoking cessation: a randomized controlled trial. JAMA 2006;296(1): Silagy C, Lancaster T, Stead L, et al. Nicotine replacement therapy for smoking cessation. Cochrane Database Syst Rev, 2004;(3):CD Haustein KO, Krause J, Haustein H et al. Comparison of the effects of combined nicotine replacement therapy vs. cigarette smoking in males. Nicotine Tob Res 2003;5(2): Sweeney CT, Fant RV, Fagerstrom KO et al. Combination nicotine replacement therapy for smoking cessation: rationale, efficacy and tolerability. CNS Drugs 2001;15(6): Jorenby DE, Leischow SJ, Nides MA et al. A controlled trial of sustained-release bupropion, a nicotine patch, or both for smoking cessation. NEnglJMed1999;340(9): Foulds J, Steinberg MB, Williams JM et al. Developments in pharmacotherapy for tobacco dependence: past, present and future. Drug Alcohol Rev 2006;25(1): Henningfield JE, Fant RV, Buchhalter AR et al. Pharmacotherapy for nicotine dependence. CA Cancer J Clin 2005;55(5): Mallin R. Smoking cessation: integration of behavioral and drug therapies. Am Fam Physician 2002;65(6): Smith SS, Jorenby DE, Leischow SJ et al. Targeting smokers at increased risk for relapse: treating women and those with a history of depression. Nicotine Tob Res 2003;5(1): O Hara P, Connett JE, Lee WW et al. Early and late weight gain following smoking cessation in the Lung Health Study. Am J Epidemiol 1998;148(9): Fagerstrom K, Balfour DJ. Neuropharmacology and potential efficacy of new treatments for tobacco dependence. Expert Opin Investig Drugs 2006;15(2):