Combined NRT with patch and a more immediate acting product results in higher quit rates than single NRT [Cochrane meta-analysis: risk ratio , 1.34; 95% confidence interval , 1.18 to 1.48] . The combination of varenicline and nicotine patch has been evaluated with mixed results . The mechanism for why NRT should augment effects of varenicline is unclear, but the combination appears to be safe. The combination can be considered in a smoker who does not quit with dual NRT or varenicline. Bupropion in combination with nicotine patch or dual NRT increases quit rates compared to these drugs given alone . One trial reported promising results with the combination of varenicline and bupropion, although neuropsychiatric adverse effects were greater in the first 2 weeks compared to varenicline alone .Many smokers would like to quit but are not prepared to commit to a quit date when seen by a healthcare provider. Starting pharmaco therapy while the smoker is still smoking with the expectation that quitting will be easier at a later date has been studied with the use of nicotine patches and varenicline. The pharmacological basis for this approach is that NRT, by desensitizing nicotinic receptors and reducing withdrawal symptoms between cigarettes, and varenicline, by antagonizing effects of nicotine from cigarettes and also providing relief of withdrawal symptoms, will reduce satisfaction from smoking and decrease the number of cigarettes smoked per day. Preloading trials with nicotine patches have shown mixed benefit on quitting with a weak overall effect, although some trials showed large beneficial effects.Varenicline trials have shown benefit with a flexible quit date, and this approach is approved by the FDA .
The attraction of precessation pharmacotherapy is that the clinician can now approach every patient who smokes,trim tray pollen regardless of whether they are prepared to quit at the time of the visit, with a pharmacological intervention along with communication that this will help with quitting smoking in time, just as the clinician would advise every patient with hypertension to take medication to prevent future disease. In this regard, a small trial involving heavy smokers with COPD, who were initially unprepared to quit, prescribed varenicline for as long as they wanted, without a fixed quit date, and by 18 months, most had quit .Personalized medicine aims to use individual patient characteristics to select the most effective and/or safest medications for their medical problem. With long-term quit rates of 30% or less in most smoking cessation trials, there is interest in individualizing treatment to enhance efficacy.Rapid metabolizers of nicotine, on average, smoke more cigarettes and take in more nicotine per day compared to slower metabolizers, presumably to maintain desired levels of nicotine in the body . Rapid metabolizers also have more severe withdrawal symptoms when not smoking . The nicotine metabolite ratio is a phenotypic marker of the rate of nico tine metabolism, which can be measured in blood, saliva, or urine . In a prospective clinical trial, smokers were stratified as slow or normal metabolizers and treated with nicotine patch, varenicline, or placebo. In slow metabolizers, varenicline and nicotine patch were equally effective [odds ratio , 1.13; P = 0.56], but in rapid metabolizers, varenicline was more effective . Side effects were greater for varenicline in slow metabolizers. The results indicate that slow metabolizers can be successfully treated with nicotine patch, at lower cost and with fewer side effects, but normal metabolizers are better treated with varenicline.
More research is needed for confirmation.While not approved by the FDA, nortriptyline and clonidine have demonstrated efficacy in clinical trials for smoking cessation . These drugs are used primarily by smoking cessation specialists for patients who have not responded to other treatment. Nortriptyline is a tricyclic antidepressant that blocks neuronal reuptake of nor epinephrine, thereby increasing levels of the neurotransmitter in the brain. These actions simulate some of the actions of nicotine on brain neurotransmitters. Clonidine is a central 2 adrenergic receptor agonist that reduces sympathetic activity, resulting in sedation and anxiolysis. The benefit of clonidine is thought to be mediated by its anxiolytic and calming effects and appears to be most useful in smokers with anxiety as a major withdrawal symptom.A number of medications have been considered as possible candidates for smoking cessation . While animal and/or small studies in people show effects on nicotine reward or smoking behavior, none of these medications alone has been shown in adequately sized clinical trials to be effective in promoting cessation, including serotonin agonists , acetylcholinesterase inhibitors , drugs affecting GABA recep tors , and N-methyl-daspartate receptor modulators . A promising new medication is lorcaserin, a selective 5-hydroxytryptamine 2c receptor agonist. The drug induces food satiety by increasing pro-opiomelanocortin production in the hypo thalamus and is FDA approved for weight loss in overweight individuals. Lorcaserin has also been reported to reduce nicotine self-administration in rodents. Because weight gain after stopping smoking is common and sometimes triggers relapse, lorcaserin alone or in combination with other smoking cessation medications has been of interest. In a placebo-controlled trial combining lorcaserin with varenicline, the combination significantly increased 3-month continuous abstinence versus placebo , and weight gain was significantly less.
Medications evaluated in clinical trials and judged ineffective for quitting smoking include mecamylamine, serotonin-specific uptake inhibitors, anxiolytics , MAO inhibitors , modafenil, naltrexone, rimonabant, silver acetate, ondansetron, lobeline, nicotine vac cines, and Nicobrevin .A general discussion of e-cigarettes and other tobacco products for harm reduction, including consideration of benefits versus risks, is presented in the “Discussion: What Evidence Is Needed” section. Here, we specifically discuss evidence regarding e-cigarettes for smoking cessation. To date, no e-cigarette company has undergone FDA review and approval for use of e-cigarettes as a therapeutic aid for quitting smoking. Less than a handful of randomized controlled trials of e-cigarettes for smoking cessation have been published, and none has been conducted in the United States; hence, most of the evidence to date is observational. E-cigarettes produce an aerosol from a liquid that typically contains nicotine. The e-cigarette concept is to deliver nicotine by an inhaled route without generating products of tobacco combustion. NRT medications can aid cessation as discussed previously, but most smokers do not find NRT very satisfying, and quit rates are modest. The performance of e-cigarettes as nicotine delivery devices has evolved over time. The earliest devices looked like cigarettes but delivered very low levels of nicotine. The two clinical trials per formed with these devices were encouraging, but the quality of evidence was low . Recently, a randomized clinical trial with 886 smokers treated in the United Kingdom’s National Health Service evaluated a second-generation e-cigarette refillable tank–type device to patients’ choice of NRT provided free of cost for up to 3 months . All received standard behavioral support. At 1 year, the sustained abstinence rate in the e-cigarette group was twofold greater than the NRT group . Among participants randomized to the e-cigarette arm who quit smoking, 80% were still using e-cigarettes at 1 year; in comparison,trim bin tray among those randomized to the NRT arm, continued use of NRT was 9% for those who quit smoking. While e-cigarettes were found to significantly increase smoking cessation, some have expressed concern about the unknown health risks of long-term e-cigarette use. Adverse effects reported during the trial included greater throat or mouth irritation in the e-cigarette group and more nausea in the NRT group. Overall, adverse effects were minor in severity.Population-based observational studies report different results depending on the intention of the smokers to quit, how e-cigarettes are used, and where the study was conducted. A four-country comparison found the likelihood of quitting with e-cigarettes to differ by the regulatory environment . In Canada and Australia, which have more restrictive e-cigarette regulations, e-cigarette use was associated with a significantly lower likelihood of quitting smoking relative to unassisted quitting , whereas in the United States and United Kingdom, which have less restrictive e-cigarette regulatory environments, e-cigarette use was associated with increased quitting, consistent with other reports . The United Kingdom estimates that, annually, 22,000 to 57,000 long-term cigarette quitters are associated with e-cigarette use, more than quits attributed to NRT or other forms of pharmacotherapy .
In the United States and United Kingdom, daily use of e-cigarettes is associated with a greater likelihood of quitting smoking than nondaily use . In a study from France, e-cigarette use was associated with not only higher smoking cessation rates but also greater relapse to smoking . In conclusion, with respect to e-cigarettes, there is evidence that e-cigarettes can aid smoking cessation. This can occur both in the general population, where e-cigarette use is adopted as an acceptable and safer alternative to cigarette smoking, and in the context of a health service. The risks of long-term e-cigarette use are still unknown, and some medical professionals oppose the use of e-cigarettes for that reason. As discussed in the “Discussion: What Evidence Is Needed” section, there are also concerns about the use of e-cigarettes by children possibly creating a new epidemic of primary nicotine addiction, leading some U.S. public health professionals to conclude that the potential benefits of e-cigarettes for smoking cessation in adults are outweighed by the risks to youth.U.S. population-based and policy approaches successful for tobacco control include mass media tobacco education campaigns, expanded healthcare coverage for tobacco cessation treatment, excise taxation on tobacco products, clean air laws, and Tobacco 21 policies, which raise the minimum legal age to purchase tobacco products to age 21 . Other population-based interventions to reduce tobacco use have faced challenges in the United States at the federal level , and even state tobacco taxes and clean air laws have slowed . In contrast, interventions in the tobacco retail environment are increasing rapidly at the local level . Also gaining traction at the FDA, and discussed in the “Discussion: What Evidence Is Needed” section, is an effort to reduce the amount of nicotine in combusted tobacco products to reduce its addictive effects.An important component of comprehensive tobacco control pro grams, mass media tobacco education campaigns are composed of paid and earned media on TV, radio, community placements , magazines, newspapers, and digital/ social media platforms. Well-designed mass media campaigns implemented with sufficient reach, intensity, and duration can help counter pro-tobacco marketing, build support for tobacco control policies, increase awareness of tobacco’s harmful effects, promote quitting, and reduce smoking prevalence . Here, we describe the success of two ongoing U.S. campaigns.The CDC’s Tips national mass media tobacco education campaign has been implemented annually since 2012. Tips profiles real people living with serious long-term health consequences from smoking and secondhand smoke exposure based on evidence that messages graphically depicting the physical consequences of smoking-related diseases can encourage quit attempts . While Tips primarily targets adult smokers, secondary audiences include family members, healthcare providers, and faith communities able to reach people who smoke. Campaign goals include building public awareness of tobacco’s harms to self and others, encouraging smokers to quit, and making free help available . Tips has been effective at increasing population-level quit intentions, quit attempts, and sustained quits, with effectiveness persisting over time . In 2016, Tips ads featured Rebecca, a former smoker with depression. In a national evaluation, greater exposure to the Rebecca ads was associated with a greater likelihood of intending to quit and with making a quit attempt specifically among smokers with mental health conditions . National media campaigns are an important population-level strategy for reaching specific population groups, such as people living with mental health conditions, who are experiencing tobacco-related disparities.Healthcare reform legislation can increase receipt of tobacco cessation treatment for smokers from disparity groups. The U.S. Affordable Care Act mandated comprehensive coverage for tobacco treatment for most private health plans and newly eligible Medicaid beneficiaries in states that expanded Medicaid, including at least two tobacco cessation attempts per year and four tobacco cessation counseling sessions and prohibited cost-sharing and previous authorization restrictions for FDA-approved tobacco cessation medication. The ACA also removed coverage limits and preexisting condition exclusions. Concerning, however, was the ACA’s allowance for states to decide whether employers could charge smokers up to 50% more in premiums. Several states rejected the surcharge outright, while other states capped the maximum penalty at a lower level.