However, a 2015 review of 225 Android apps for quitting smoking found that most provide simplistic tools ; use of tailoring was limited, although positively related to app popularity and user ratings of quality .Notably, one randomized trial found that a simpler, direct texting program outperformed a smoking cessation app . Social media. Social media, such as Twitter and Facebook, are being explored for delivering cessation treatment. In the United States, 74% of online adults use social media, 80% of whom are seeking health information, and a majority access the sites daily . A promising technology, efforts to sustain engagement are key and can be challenging; like predecessor technologies such as bulletin boards and listservs, initial interest may be high but then tends to wane . There is preliminary evidence, however, of good acceptability and efficacy. Using Twitter, small, private groups of 20 smokers, who interact for 100 days, have been studied. The intervention seeds the groups with twice-daily automessages to encourage group sharing and support.Similar efforts are being developed on Facebook, with a focus on engaging young adults into cessation treatment. In a randomized trial, a novel Facebook smoking cessation intervention increased abstinence at the end of treatment, although effects were not sustained out to 1-year follow-up .Having tried and failed to quit smoking in the past,planting racks smokers may not initially publicize their quit attempts within their main social circle . With social media sites that are largely uncurated or expert moderated, however, users should be forewarned that inaccurate information may be posted. For example, online communities may encourage use of non–evidence-based treatments .
A heterogeneous group of emerging applications and knowledge gaps remain concerning best strategies for maximizing the reach and efficacy of mobile technologies for treating nicotine addiction as well as the comparative effectiveness relative to in-person approaches.Monetary incentives that reward outcome or engagement have been evaluated in 33 trials, with a meta-analysis finding evidence of increased abstinence that persisted after the incentives ceased . The level of the incentives ranged from zero to between $45 and $1185, with no clear direction of effect by level of incentive. Conditional payments outperformed non conditional payments. Findings from a subgroup analysis of eight trials conducted with smokers with substance use problems were consistent with the overall analysis. A summary of nine trials with pregnant smokers reported more than twofold greater odds of abstinence at longest follow-up assessment . The findings are particularly important given the substantial health harms of smoking to mother and baby and that, currently, there is no other effective cessation intervention for pregnant smokers.While counseling and psychosocial treatments help promote cessation, medications that address the neuropharmacological effects of nicotine and nicotine withdrawal further enhance the likelihood of quitting. E-cigarettes, which allow continued self-administration of nicotine without combustion, can also promote quitting smoking. Smoking cessation guidelines, such as those from the U.S. Public Health Service and National Cancer Center Network, recommend smoking cessation medications for all daily smokers where feasible and safe . Pharmacotherapy can be considered fornondaily smokers as well, although there are few clinical trials to guide treatment in this group. The mechanism of benefit innondaily smokers would be reduction of nicotine reward from cigarettes by nicotinic receptor desensitization or antagonism, as discussed below. Table 2 presents the FDA-approved smoking cessation medications, including dosing guidelines, advantages, disadvantages, adverse effects, and precautions. FDA-approved medications are NRT in the form of gum, patches, lozenge, nasal spray and inhaler, varenicline, and bupropion. Nicotine gums, lozenges, and patches are available over the counter in the United States, while the nicotine nasal spray, nicotine inhaler, varenicline, and bupropion are by prescription only.
Nicotine mouth spray is available outside of the United States and has evidence of acceptability, efficacy, and safety, including with minimal behavioral support . In general, medications serve to make smokers more comfortable while they learn to live and cope with daily cues/triggers and life stressors without smoking cigarettes. There are three main mechanisms by which medications can facilitate smoking cessation: reduction of nicotine withdrawal symptoms, reduction of the rewarding effects of nicotine from smoking by blocking or desensitizing nicotine receptors, and providing an alternative source of nicotine with the desired pharmacologic effect previously provided by nicotine from cigarettes. NRT medications are not as satisfying as cigarette smoking because of slower absorption of nicotine; nicotine delivery from e-cigarettes can resemble that of a cigarette, and these devices tend to be much more satisfying. Most smoking cessation medications are recommended for 8 to 12 weeks, although use for 6 months or longer may be necessary to achieve optimal quit rates. It makes sense to use medications to support smoking cessation for as long as the individual feels at risk for relapse. For those switching to e-cigarettes as a less harmful substitute for cigarette smoking, use sometimes continues for many months or years.Nicotine medications consist of purified nicotine that is administered to ameliorate symptoms of physical dependence on nicotine. The particular actions of different products vary according to route of administration and rate of nicotine absorption into the bloodstream. For example, nicotine patches deliver nicotine slowly, relieving nicotine withdrawal symptoms and reducing positive effects of cigarette smoking, without providing much, if any, direct positive effects of nicotine. Nicotine gums, lozenges, sprays, and inhalers deliver nic otine more rapidly, providing some acute nicotine effects that may serve as a substitute for smoking a cigarette. Combining a short-acting with a long-acting NRT results in superior quit rates compared to any NRT product alone and is recommended as a first-line treatment .
NRT products are marketed in different strengths, with higher doses recommended for more dependent smokers based on the number of cigarettes smoked per day or time to first cigarette upon wakening. A 2019 Cochrane review concluded that 4-mg gum is more effective than 2-mg gum in more highly dependent smokers and that 21-mg patch is more effective than 14-mg patch in general . While clinical trials do not demonstrate superiority of 42- to 21-mg dose nicotine patch, some clinicians do use high-dose patch for smokers with particularly severe withdrawal symptoms. Tapering of nicotine doses over time is an option for nicotine patches but does not appear to affect outcome in clinical trials. All forms of NRT have shown similar efficacy in clinical trials , increasing quit rates by 50 to 100% compared to behavioral treatment alone. For the NRTs, compliance is greatest with nicotine patches,sub irrigation cannabis lower with gum and lozenge, and lowest with the nasal spray and inhaler.Some smokers experience nicotine patch–related insomnia and/or abnormal dreams and do better removing the patch at bedtime. Use of patches for 16 or 24 hours is equally effective in promoting quitting smoking. The pharmacokinetics of nicotine gum, lozenge, and inhaler are similar, with gradual absorption of relatively low doses of nicotine over 15 to 30 min. Use every 1 to 2 hours provides the best pharmacologic response. The nicotine inhaler is a plastic device inhaled like a cigarette but delivers nicotine to the oropharyngeal area rather than to the lungs, which explains its slow absorption. All oral nicotine products have an alkaline pH, which results in a high proportion of nicotine in the free base form, which is rapidly absorbed across mucous membranes. Acidicbever ages reduce the pH and reduce nicotine absorption and should be avoided for >10 min before using oral NRT products. The nicotine nasal spray is absorbed much faster than the other rapid-release products, most closely resembling a cigarette. More dependent smokers may find nicotine nasal spray to be more effective than other NRT products for smoking cessation. The spray is associated with more local toxicity, including a burning sensation, watery eyes, and sneezing; however, tolerance develops to these effects with regular use of the spray over 1 to 2 days.
Overall, NRT products are well tolerated and present few safety concerns. Safety concerns with NRT are primarily skin irritation with patches, gastrointestinal symptoms with oral products, and nasal/throat burning and irritation with nasal spray. Nicotine’s car diovascular effects raised concern about NRT cardiovascular safety. Nicotine enhances sympathetic neural activity, resulting in increased heart rate, constriction of blood vessels, induction of proatherogenic lipid profiles , development of insulin resistance, and possible promotion of arrhythmias . Cigarette smoke delivers not only nicotine but also many oxidants, prothrombotic and other toxic chemicals, making smoking much more toxic than nicotine alone. Clinical trials and other stud ies of NRT in patients with cardiovascular disease find no increase in adverse cardiovascular events due to NRT .Varenicline is a partial agonist at the nicotinic a4b2 receptor, the major receptor mediating nicotine addiction. Varenicline both activates and blocks the effects of nicotine on the a4b2 receptor . The agonist effect serves to reduce withdrawal symptoms, while the antagonist effects reduce the rewarding effects of nicotine from cigarette smoke. Varenicline treatment before smoking cessation is often associated with reduced smoking, presumably because smoking is less satisfying, an effect that can promote subsequent cessation. In clinical trials, varenicline is more effective than bupropion or nicotine patch in promoting smoking cessation and is comparably effective to combined NRT . The EAGLES trial, the largest smoking cessation trial conducted with 8000 smokers, directly com pared varenicline, bupropion, nicotine patch, and placebo. Varenicline outperformed all conditions; bupropion and nicotine patch were comparable to each other and were significantly better than placebo . EAGLES included smokers without and with psychiatric diagnoses. Quit rates were higher in those without psychiatric diagnoses, but the relative efficacy of the various treatments was similar. Extended treatment with varenicline for 6 months is superior to the standard 12-week treatment and is recommended for smokers who feel at risk of relapse . The most common adverse effect of varenicline is nausea, which is dose related and to which tolerance develops over time. Concern about nausea is the rationale for starting at lower doses for a week before starting the full dose . Some smokers cannot tolerate the normal dose but do well on continued use of the lower dose. Anecdotal reports of neuropsy chiatric adverse effects of varenicline used for smoking cessation have been reported, prompting a black box warning in the label after the drug was marketed . The putative neuropsychiatric side effects included depression, psychosis, and suicide, with potentially higher risk in smokers with psychiatric disease. However, the EAGLES trial found no evidence of increased neuropsychiatric adverse events for varenicline or bupropion relative to nicotine patch or placebo, in smokers with or without psychiatric illness, and in 2016, the black box warnings were removed for both varenicline and bupropion . Varenicline has been shown to enhance smoking cessation in patients with cardio vascular disease, including stable coronary heart disease and acute coronary syndrome . Concern was raised about possible cardiovascular toxicity due to the nicotine-like effects of varenicline and anecdotal reports of adverse cardiovascular events, but several meta analyses, a large retrospective cohort study, and clinical trials in smokers with cardiovascular disease, as well as the EAGLES trial, showed no increase in cardiovascular risk . Varenicline has also been found efficacious for cessation of smokeless tobacco use .Bupropion is a stimulant drug originally marketed as an antidepres sant. Bupropion blocks neuronal uptake of dopamine and norepinephrine and has antagonist activity on the a4b2 nicotinic receptor. By blocking reuptake, bupropion increases brain levels of dopamine and norepinephrine, simulating effects of nicotine. Bupropion is marketed for smoking cessation as a sustained-release prepara tion. The drug works in both depressed and non-depressed smok ers. The usual duration of bupropion treatment is 12 weeks, but extended bupropion therapy for a year reduces relapse and enhances long-term quit rates . With lower quit rates, bupropion is considered to be second-line, after combination NRT and varenicline. The main adverse effects of bupropion relate to its nervous system stimulant actions. Some smokers are intolerant to bupropion because of anxiety, agitation, and insomnia. Bupropion reduces the seizure threshold and should not be used in smokers who are at risk for seizures. In overdose, bupropion causes tachycardia and hyper tension, but there is no evidence of increased cardiovascular events in smokers with preexisting stable cardiovascular disease .