Smoking Cessation

Smoking cessation (colloquially quitting smoking) is the process of discontinuing the practice of inhaling a smoked substance. This article focuses exclusively on cessation of tobacco smoking; however, the methods described may apply to cessation of smoking other substances that can be difficult to stop using due to the development of strong physical substance dependence or psychological dependence (in more common parlance, addiction).

Smoking cessation can be achieved with or without assistance from healthcare professionals or the use of medications.[2] Methods that have been found to be effective include interventions directed at or via health care providers and health care systems; medications including nicotine replacement therapy (NRT) and varenicline; individual and group counselling; and Web-based or stand-alone and computer programs. Although stopping smoking can cause short-term side effects such as reversible weight gain, smoking cessation services and activities are cost-effective because of the positive health benefits.

In a growing number of countries, there are more ex-smokers than smokers.
Early "failure" is a normal part of trying to stop, and more than one attempt at stopping smoking prior to longer-term success is common.

NRT, other prescribed pharmaceuticals, and professional counselling or support also help many smokers.
However, up to three-quarters of ex-smokers report having quit without assistance ("cold turkey" or cut down then quit), and cessation without professional support or medication may be the most common method used by ex-smokers.

Nicotine addiction

Tobacco contains the chemical nicotine. Smoking cigarettes can lead to nicotine addiction.:2300–2301 The addiction begins when nicotine acts on nicotinic acetylcholine receptors to release neurotransmitters such as dopamine, glutamate, and gamma-aminobutyric acid.:2296 Cessation of smoking leads to symptoms of nicotine withdrawal such as anxiety and irritability.:2298 Professional smoking cessation support methods generally endeavour to address both nicotine addiction and nicotine withdrawal symptoms.
Studies have shown that it takes between 6 to 12 weeks post quitting before the amount of nicotinic receptors in the brain return to the level that of a non smoker.

Methods of smoking cessation

Major reviews of the scientific literature on smoking cessation include:
Systematic reviews of the Cochrane Tobacco Addiction Group of the Cochrane Collaboration. As of 2012, this independent, international, not-for-profit organization has published over 60 systematic reviews "on interventions to prevent and treat tobacco addiction" which will be referred to as "Cochrane reviews."

Clinical Practice Guideline: Treating Tobacco Use and Dependence: 2008 Update of the United States Department of Health and Human Services, which will be referred to as the "2008 Guideline." The Guideline was originally published in 1996 and revised in 2000. For the 2008 Guideline, experts screened over 8700 research articles published between 1975 and 2007.:13–14 More than 300 studies were used in meta-analyses of relevant treatments; an additional 600 reports were not included in meta-analyses, but helped formulate the recommendations.[6]:22 Limitations of the 2008 Guideline include its not evaluating studies of "cold turkey" methods ("unaided quit attempts") and its focus on studies that followed up subjects only to about 6 months after the "quit date" (even though almost one-third of former smokers who relapse before one year will do so 7–12 months after the "quit date").

Unassisted methods
As it is common for ex-smokers to have made a number of attempts (often using different approaches on each occasion) to stop smoking before achieving long-term abstinence, identifying which approach or technique is eventually most successful is difficult; it has been estimated, for example, that "only about 4% to 7% of people are able to quit smoking on any given attempt without medicines or other help."[11]. However, in analysing a 1986 U.S. survey, Fiore et al. (1990) found that 95% of former smokers who had been abstinent for 1–10 years had made an unassisted last quit attempt. The most frequent unassisted methods were "cold turkey" and "gradually decreased number" of cigarettes. A 1995 meta-analysis estimated that the quit rate from unaided methods was 7.3% after an average of 10 months of follow-up.

Cold turkey
"Cold turkey" is a colloquial term indicating abrupt withdrawal from an addictive drug, and in this context indicates sudden and complete cessation of all nicotine use. In three studies, it was the quitting method cited by 76%, 85%, or 88% of long-term successful quitters. In a large British study of ex-smokers in the 1980s, before the advent of pharmacotherapy, 53% of the ex-smokers said that it was "not at all difficult" to stop, 27% said it was "fairly difficult", and the remaining 20% found it very difficult.[2] Cold turkey methods have been advanced by J. Wayne McFarland and Elman J. Folkenburg; Joel Spitzer and John R. Polito; and Allen Carr.

Healthcare provider and system interventions
Interventions delivered via healthcare providers and healthcare systems have been shown to improve smoking cessation among people who visit those providers.

A clinic screening system (e.g., computer prompts) to identify whether or not a person smokes doubled abstinence rates, from 3.1% to 6.4%.78–79 Similarly, the Task Force on Community Preventive Services determined that provider reminders alone or with provider education are effective in promoting smoking cessation.

A 2008 Guideline meta-analysis estimated that physician advice to quit smoking led to a quit rate of 10.2%, as opposed to a quit rate of 7.9% among patients who did not receive physician advice to quit smoking.:82–83 A Cochrane review found that even brief advice from physicians had "a small effect on cessation rates."[21] However, one study from Ireland involving vignettes found that physicians' probability of giving smoking cessation advice declines with the patient's age,[22] and another study from the U.S. found that only 81% of smokers age 50 or greater received advice on quitting from their physicians in the preceding year.

For one-to-one or person-to-person counselling sessions, the duration of each session, the total amount of contact time, and the number of sessions all correlated with the effectiveness of smoking cessation. For example, "Higher intensity" interventions (>10 minutes) produced a quit rate of 22.1% as opposed to 10.9% for "no contact"; over 300 minutes of contact time produced a quit rate of 25.5% as opposed to 11.0% for "no minutes"; and more than 8 sessions produced a quit rate of 24.7% as opposed to 12.4% for 0–1 sessions.[6]:83–86

Both physicians and non-physicians increased abstinence rates compared with self-help or no clinicians.:87–88 For example, a Cochrane review of 31 studies found that nursing interventions increased the likelihood of quitting by 28%.

According to the 2008 Guideline, based on two studies the training of clinicians in smoking cessation methods may increase abstinence rates:130; however, a Cochrane review found "a measurable effect" that such training decreased smoking in patients.

Reducing or eliminating the costs of cessation therapies for smokers increased quit rates in three meta-analyses.139–140:38–40

In one systematic review and meta-analysis, multi-component interventions increased quit rates in primary care settings. "Multi-component" interventions were defined as those that combined two or more of the following strategies known as the "5 A's"[6]:38–43:

Ask — Systematically identify all tobacco users at every visit
Advise — Strongly urge all tobacco users to quit
Assess — Determine willingness to make a quit attempt
Assist — Aid the patient in quitting (provide counselling-style support and medication)
Arrange — Ensure followup contact

Biochemical feedback

Breath CO monitor displaying carbon monoxide concentration of an exhaled breath sample (in ppm) with its corresponding percent concentration of carboxyhemoglobin.
Various methods exist which allow a smoker to see the impact of their tobacco use, and the immediate effects of quitting. Using biochemical feedback methods can allow tobacco-users to be identified and assessed, and the use of monitoring throughout an effort to quit can increase motivation to quit.

Breath carbon monoxide (CO) monitoring: Because carbon monoxide is a significant component of cigarette smoke, a breath carbon monoxide monitor can be used to detect recent cigarette use. Carbon monoxide concentration in breath has been shown to be directly correlated with the CO concentration in blood, known as percent carboxyhemoglobin. The value of demonstrating blood CO concentration to a smoker through a non-invasive breath sample is that it links the smoking habit with the physiological harm associated with smoking. Within hours of quitting, CO concentrations show a noticeable decrease, and this can be encouraging for someone working to quit. Breath CO monitoring has been utilized in smoking cessation as a tool to provide patients with biomarker feedback, similar to the way in which other diagnostic tools such as the stethoscope, the blood pressure cuff, and the cholesterol test have been used by treatment professionals in medicine.

Cotinine: A metabolite of nicotine, cotinine is present in smokers. Like carbon monoxide, a cotinine test can serve as a reliable biomarker to determine smoking status.[31] Cotinine levels can be tested through urine, saliva, blood, or hair samples, with one of the main concerns of cotinine testing being the invasiveness of typical sampling methods.

While both measures offer high sensitivity and specificity, they differ in usage method and cost. As an example, breath CO monitoring is non-invasive, while cotinine testing relies on a bodily fluid. These two methods can be used either alone or together, for example, in a situation where abstinence verification needs additional confirmation.

Single medications
The American Cancer Society estimates that "between about 25% and 33% of smokers who use medicines can stay smoke-free for over 6 months." Single medications include:

A 21mg dose Nicoderm CQ patch applied to the left arm.
Nicotine replacement therapy (NRT): Five medications approved by the U.S. Food and Drug Administration (FDA) deliver nicotine in a form that does not involve the risks of smoking. The five NRT medications, which in a Cochrane review increased the chances of stopping smoking by 50 to 70% compared to placebo or to no treatment, are:
transdermal nicotine patches deliver doses of the addictive chemical nicotine, thus reducing the unpleasant effects of nicotine withdrawal. These patches can give smaller and smaller doses of nicotine, slowly reducing dependence upon nicotine and thus tobacco. A Cochrane review found further increased chance of success in a combination of the nicotine patch and a faster acting form. Also, this method becomes most effective when combined with other medication and psychological support.
gum
lozenges
sprays
inhalers.

A study found that 93 percent of over-the-counter NRT users relapse and return to smoking within six months.
Antidepressant: Bupropion is FDA-approved and is marketed under the brand name Zyban. Bupropion is contraindicated in epilepsy, seizure disorder; anorexia/bulimia (eating disorders), patients' use of antidepressant drugs (MAO inhibitors) within 14 days, patients undergoing abrupt discontinuation of ethanol or sedatives (including benzodiazepines such as Valium).

Nicotinic receptor partial agonists:
Cytisine (Tabex) is a plant extract that has been in use since the 1960s in former Soviet-bloc countries.[38] It was the first medication approved as an aid to smoking cessation, and has very few side effects in small doses.

Varenicline tartrate is a prescription drug marketed by Pfizer as Chantix in the U.S. (under FDA approval) and as Champix outside the U.S. Synthesized as an improvement upon cytisine, varenicline decreases the urge to smoke and reduces withdrawal symptoms. Two systematic reviews and meta-analyses supported by unrestricted funding from Pfizer, one in 2006 and one in 2009, found varenicline more effective than NRT or bupropion. A table in the 2008 Guideline indicates that 2 mg/day of varenicline leads to the highest abstinence rate (33.2%) of any single therapy, while 1 mg/day leads to an abstinence rate of 25.4%.[6]:109 A 2011 Cochrane review of 15 studies (13 of which had been sponsored by Pfizer) found that varenicline was significantly superior to bupropion at one year but that varenicline and nicotine patches produced the same level of abstinence at 24 weeks.[4

A 2011 review of double-blind studies found that varenicline has increased risk of serious adverse cardiovascular events compared with placebo. Varenicline may cause neuropsychiatric side effects; for example, in 2008 the U.K. Medicines and Healthcare products Regulatory Agency issued a warning about possible suicidal thoughts and suicidal behavior associated with varenicline.

Moclobemide has been tested in heavy dependent smokers against placebo based on the theory that tobacco smoking could be a form of self medicating of major depression,[49] and moclobemide could therefore help increase abstinence rates due to moclobemide mimicking the MAO-A inhibiting effects of tobacco smoke. Moclobemide was administered for 3 months and then stopped; at 6 months follow-up it was found those who had taken moclobemide for 3 months had a much higher successful quit rate than those in the placebo group. However, at 12 month follow-up the difference between the placebo group and the moclobemide group was no longer significant.

Two other medications have been used in trials for smoking cessation, although they are not approved by the FDA for this purpose. They may be used under careful physician supervision if the first line medications are contraindicated for the patient.
Clonidine may reduce withdrawal symptoms and "approximately doubles abstinence rates when compared to a placebo," but its side effects include dry mouth and sedation, and abruptly stopping the drug can cause high blood pressure and other side effects.

Nortriptyline, another antidepressant, has similar success rates to bupropion but has side effects including dry mouth and sedation.

Combinations of medications
The 2008 US Guideline specifies that three combinations of medications are effective:118–120:
Long-term nicotine patch and ad libitum NRT gum or spray
Nicotine patch and nicotine inhaler
Nicotine patch and bupropion (the only combination that the US FDA has approved for smoking cessation)

Cut down to quit
Gradual reduction involves slowly reducing one's daily intake of nicotine. This can theoretically be accomplished through repeated changes to cigarettes with lower levels of nicotine, by gradually reducing the number of cigarettes smoked each day, or by smoking only a fraction of a cigarette on each occasion. A 2009 systematic review by researchers at the University of Birmingham found that gradual nicotine replacement therapy could be effective in smoking cessation. A 2010 Cochrane review found that abrupt cessation and gradual reduction with pre-quit NRT produced similar quit rates whether or not pharmacotherapy or psychological support was used.