Research paper Tob Control: first published as 10.1136/tc.2008.025635 on 9 October 2008. Downloaded from An algorithm for tailoring pharmacotherapy for smoking cessation: results from a Delphi panel of international experts P Bader,1 P McDonald,2 P Selby3 1 Consultants in Behavior ABSTRACT medication, limited data are available to guide Change, Toronto, Ontario; Background: Evidence-based smoking cessation guide- clinicians in selecting specific forms of pharma- Ontario Tobacco Research Unit, Canada; 2 University of lines recommend nicotine replacement therapy (NRT), cotherapy for individual smokers. While vareni- Waterloo; Population Health bupropion SR and varenicline as first-line therapy in cline, a new pharmacotherapeutic option, has Research Group, Waterloo, combination with behavioural interventions. However, demonstrated therapeutic superiority over existing Ontario; Ontario Tobacco there are limited data to guide clinicians in recommending first-line medications,9–12 post-marketing reviews Research Unit, Canada; 3 one form over another, using combinations, or matching have recently raised safety concerns regarding Departments of Family and 13 Community Medicine and individual smokers to particular forms. varenicline. Psychiatry, Faculty of Medicine Objective: To develop decision rules for clinicians to The health benefits of smoking cessation are and the Dalla Lana School of guide differential prescribing practices and tailoring of well documented. Smokers who quit reduce their Public Health, University of pharmacotherapy for smoking cessation. risk of cardiovascular disease, lung disease, and Toronto; Addictions Program, Centre for Addiction and Mental Methods: A Delphi approach was used to build cancer and increase their life expectancy substan- Health, Toronto, Ontario; Ontario consensus among a panel of 37 international experts from tially.14 While most smokers make several quit Tobacco Research Unit, Canada various health disciplines. Through an iterative process, attempts before they succeed, about one in four panellists responded to three rounds of questionnaires. who use any pharmacotherapy will eventually quit Correspondence to: 15 Dr Peter Selby, Centre for Participants identified and ranked ‘‘best practices’’ used smoking. Evidence indicates that pharmacother- Addiction and Mental Health, 33 by them to tailor pharmacotherapy to aid smoking apy increases the odds of success and may reduce Russell Street, Toronto, Ontario, cessation. An independent panel of 10 experts provided symptoms of withdrawal for those who smoke 10 Canada M5S 2S1; 815 [email protected] cross-validation of findings. or more cigarettes per day. While a few studies Results: There was a 100% response rate to all three have shown that pharmacotherapy works even in 16 17 Received 28 March 2008 rounds. A high level of consensus was achieved in the absence of psychosocial therapies, most Accepted 20 September 2008 determining the most important priorities: (1) factors to studies show that combining pharmacotherapy Published Online First consider in prescribing pharmacotherapy: evidence, and psychosocial treatments increases quit rates.38 http://tobaccocontrol.bmj.com/ 13 October 2008 patient preference, patient experience; (2) combinations A Cochrane review16 including 123 trials con- based on: failed attempt with monotherapy, patients with cluded that all types of NRT increased the odds of breakthrough cravings, level of tobacco dependence; (3) quitting by approximately one-and-a-half to two- specific combinations, main categories: (a) two or more fold. In addition, the effectiveness of NRT was forms of NRT, (b) bupropion + form of NRT; (4) specific independent of the intensity of behavioural sup- combinations, subcategories: (1a) patch + gum, (1b) port provided to the smoker. Bupropion SR and patch + inhaler, (1c) patch + lozenge; (2a) bupropion + nortriptyline (antidepressants) were found to patch, (2b) bupropion + gum; (5) impact of comorbidities increase rates of smoking cessation in a Cochrane on selection of pharmacotherapy: contraindications, review of antidepressants including 53 trials.18 specific pharmacotherapy useful for certain comorbidities, When prescribed as monotherapy, bupropion (31 dual purpose medications; (6) frequency of monitoring trials) and nortriptyline (four trials) both doubled on September 25, 2021 by guest. Protected copyright. determined by patient needs and type of pharmacother- the odds of cessation. Bupropion and nortriptyline apy. appear to have similar effectiveness to NRT. Other Conclusion: An algorithm and guide were developed to antidepressants (fluoxetine, sertraline, paroxetine, assist clinicians in prescribing pharmacotherapy for moclobemide, venlafaxine) have not shown sig- smoking cessation. There appears to be good justification nificant benefit as an aid to smoking cessation.18 for ‘‘off-label’’ use such as higher doses of NRT or While studies of rimonabant have been com- combination therapy in certain circumstances. This pleted,19 no reviews currently exist and there have practical tool reflects best evidence to date of experts in been conflicting results regarding its efficacy in the tobacco cessation. US and Europe.20 21 Clonidine (an a-adrenergic antagonist) was found to be an effective medication for smoking Helping smokers quit is a critical, yet often cessation, although findings were based on a small perplexing role for physicians. While pharma- number of trials.22 Studies on other types of cotherapy generally doubles the odds of quitting pharmacotherapy for smoking cessation are lim- successfully, these smoking cessation aids are not ited. Cochrane reviews have been conducted on widely prescribed or used by smokers.12Although anxiolytics,23 silver acetate,24 lobeline,25 mecamyl- This paper is freely available guidelines exist in several countries (United States, amine26 and naltrexone,27 but findings are incon- online under the BMJ Journals unlocked scheme, see http:// United Kingdom, France, Australia, New clusive owing to insufficient studies. 3–8 tobaccocontrol.bmj.com/info/ Zealand) that recommend nicotine replacement Varenicline, an a4 b2 nicotine receptor partial unlocked.dtl therapy (NRT) or bupropion SR as first-line agonist, is the newest pharmacotherapy indicated 34 Tobacco Control 2009;18:34–42. doi:10.1136/tc.2008.025635 Research paper Tob Control: first published as 10.1136/tc.2008.025635 on 9 October 2008. Downloaded from for smoking cessation. It helps people to stop smoking by among a panel of experts.42 43 It is a powerful tool for making maintaining moderate levels of dopamine to counteract with- the best use of less than perfect information. The Delphi drawal symptoms and by reducing smoking satisfaction.28 consists of a multistage approach with each stage building on Developed in 1997, it was approved in 2006 by the American the results of the previous one. It allows for collecting and Food and Drug Administration under the trade name Chantix, refining combined knowledge and experience from a group of and by the European Medicines Evaluation Agency under the experts from various disciplines. This approach has been used trade name Champix. effectively by the investigators in a knowledge synthesis of In the most recent Cochrane review, Cahill and colleagues28 smoking cessation among employed and unemployed young found that varenicline ‘‘increased the chances of successful long- adults.44 term smoking cessation between two- and threefold compared The aim of this study was to develop decision rules with pharmacologically unassisted quit attempts.’’ However, (algorithm) for use by clinicians to guide prescribing practices physicians prescribing varenicline need to be aware of the of pharmacotherapy for smoking cessation. Experts in smoking possible association with behavioural changes such as depressed cessation were recruited from 13 countries to participate in a mood, agitation and suicidal thoughts and behaviours. The US Delphi consensus-building process. The results were synthesised Food and Drug Administration recently issued a public health into a clinical aid that can be widely used by clinicians who advisory, cautioning that there may be an increased risk of prescribe pharmacotherapy to smokers. neuropsychiatric symptoms among patients taking vareni- cline.13 It is important to note that these symptoms may also arise as a result of smoking cessation with or without METHODS treatment, and causality has not yet been determined. The Study design FDA is currently conducting a safety review. In particular, the A modified Delphi method was employed to identify and rank safety and efficacy of varenicline in patients with psychiatric ‘‘best practices’’ used by healthcare practitioners in tailoring disorders is unknown (this population was excluded from pre- prescribing practices of pharmacotherapy to aid smoking marketing trials). While an initial study in the UK (204 patients cessation. Three Delphi rounds were conducted from May to on NRT; 208 on varenicline) found no evidence that varenicline September 2007, using primarily email communication. Thirty- exacerbated mental illness,29 several individual case studies have seven panel members participated through an iterative process, been cited in the literature that report adverse psychiatric responding anonymously to a series of questionnaires. symptoms.30–34 The labelling of varenicline has now been Anonymity was intended to minimise ‘‘peer pressure’’ and changed to include warnings regarding adverse effects