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TOBACCO USE DISORDER AND SMOKING
CESSATION
ABSTRACT
A tobacco use disorder is diagnosed according to criteria of the
Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition
(DSM-5) and current research identifies tobacco patterns and severity
of use that clinicians can reference when diagnosing and planning
treatment. Medication and behavioral-based interventions such as
direct provider to patient interaction, group therapy, specialized
clinics, self-help interventions using educational resources and
telephone resources or counseling are the mainstay of smoking
cessation. Risk factors related to tobacco use, smoking cessation
options and relapse prevention are discussed.
Introduction
Tobacco use and its attendant health consequences are enormous
public health problems. Tobacco use is the leading cause of
preventable death in the United States. The number of Americans who
smoke has decreased by more than one-half in the past 50 years, but
tobacco and cigarette smoking are still the primary causes of, or
contributors to certain cancers, heart disease, common respiratory
diseases, and many other acute and chronic pathology. Hundreds of
thousand adults die prematurely each year as a direct result of
smoking, and a 2014 report from the Surgeon General noted that
tobacco and smoking have “ . . . killed ten times the number of
Americans who died in all of our nation’s wars combined.”1 It has also
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been proven that second-hand smoke is a significant cause of serious
acute and chronic heath problems in children and adults.
There are interventions that can prevent people from smoking and
there are behavioral counseling techniques and medications that have
been shown to be effective at helping smokers quit. But nicotine, the
primary active component of cigarette smoke, is strongly addictive and
since tobacco is legal the prevention of smoking and smoking
cessation are considerable challenges.
Smoking And Tobacco Use In The United States
Smoking and tobacco use are still common in the United States. The
statistics in Table 1 are from the Centers of Disease Control and
Prevention (CDC) and the Substance Abuse and Mental Health Services
Association (SAMHSA).2-4 It should be noted that a current smoker is
defined as a person who reported smoking at least 100 cigarettes
during his or her lifetime and, at the time the person participated in a
survey about the topic, smoking every day or some days.
Table 1: Smoking and Tobacco Use in the United States

In 2014, almost 17 of every 100 U.S. adults aged 18 years or older
(16.8%) currently smoked cigarettes. This means an estimated 40
million adults in the United States currently smoke cigarettes. There
are also of millions of people who use smokeless tobacco and ecigarettes.

Cigarette smoking is the leading cause of preventable disease and
death in the United States, accounting for more than 480,000 deaths
every year, or 1 of every 5 deaths.

More than 16 million Americans live with a smoking-related disease.

Current smoking has declined from nearly 21 of every 100 adults
(20.9%) in 2005 to nearly 17 of every 100 adults (16.8%) in 2014.
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
In 2014, an estimated 66.9 million Americans aged 12 or older were
current users of a tobacco product (25.2%). Young adults aged 18 to
25 had the highest rate of current use of a tobacco product (35%),
followed by adults aged 26 or older (25.8%), and by youths aged 12
to 17 (7%).

In 2014, the prevalence of current use of a tobacco product was
37.8% for American Indians or Alaska Natives, 27.6% for whites,
26.6% for blacks, 30.6% for Native Hawaiians or other Pacific
Islanders, 18.8% for Hispanics, and 10.2% for Asians.
The incidence of tobacco use disorder (defined and explained in a
subsequent section of this learning module) cannot be accurately
determined, but given the common occurrence of nicotine craving and
addiction it is clear that tobacco use disorder is widespread.5
As mentioned in the introduction, second-hand smoke (also called side
stream smoke) is very dangerous. Second-hand smoke is smoke that
is produced from burning tobacco or smoke that has been exhaled by
someone using a cigarette and there is no safe level of second-hand
smoke. The health effects of second-hand smoke that are listed in
Table 2 are from the CDC and several other sources.6,7
Table 2: Health Effects of Second-Hand Smoke
Asthma attacks
Bronchitis
COPD
Ear infections
Heart disease
Lung cancer
Pneumonia
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Stroke
Sudden infant death syndrome (SIDS)
Second-hand smoke has been estimated to increase the relative risk of
developing chronic obstructive pulmonary disease (COPD), stroke, and
ischemic heart disease by 1.66, 1.35, and 1.22, respectively.8 Children
are especially vulnerable to the harmful effects of second-hand-smoke7
and pre-natal exposure to second-hand smoke has been identified as a
risk factor for developing asthma.9 Also, close proximity is not
necessary for exposure to second-hand smoke; many studies have
shown that living in a multi-residential building can expose nonsmokers to second-hand smoke.10 Smoking bans have reduced
exposure to second-hand smoke in public areas but private homes are
still an important source of second-hand smoke exposure.
Nicotine
Tobacco and tobacco smoke contain many harmful compounds but
nicotine has been identified as the one that is primarily responsible for
addiction to tobacco. Nicotine in cigarette smoke and in products such
as chewing tobacco and snuff is rapidly absorbed across the alveoli
and through mucous membranes. Nicotine can also be absorbed
through certain sections of the gastrointestinal tract. Once nicotine has
passed through the lungs, mucous membranes, or gastrointestinal
tract it quickly enters the blood stream and then binds to the nicotinic
acetylcholine receptors, which are located in the central nervous
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system, the autonomic nervous system, neuromuscular junctions, and
other areas of the nervous system.
The acute effects of nicotine depend on the dose and how habituated
someone is to its effects. The amount of nicotine in an average
cigarette is approximately 13-20 mg, but this “dose” is delivered
somewhat slowly and the total absorbed and that reaches the central
nervous system is much less.
People smoke, in part, because the effects of nicotine are pleasurable
and the smoker is given reinforcement each time he or she has a
cigarette. Nicotine is a stimulant and it has powerful actions on the
brain’s mesolimbic dopamine center, otherwise known as the rewards
or pleasure center, and inhaled nicotine produces a mild level of
euphoria, it decreases fatigue, increases alertness, and it also can be
very relaxing.
An excess of nicotine and/or small amounts delivered to a child or a
nicotine-naïve adult can be very toxic. A dose of 2-5 mg may produce
signs and symptoms in a nicotine-naïve adult11 and a large amount of
nicotine can cause death. Nicotine is a stimulant and most cases of
nicotine poisoning reflect that but severe cases can cause depressant
effects. Some of the common signs and symptoms of acute nicotine
poisoning are listed in Table 3.
Table 3: Signs And Symptoms Of Acute Nicotine Poisoning
Agitation
Bradycardia
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Cholinergic syndrome
Coma
Diaphoresis
Diarrhea
Drowsiness
Hyperpnea
Hypertension
Nausea
Pallor
Respiratory depression
Seizures
Tachycardia
Vomiting
Nicotine can also affect the metabolism of drugs. Some of the
components of cigarette smoke have been proven to increase the
activity of certain cytochrome p450 enzymes. This enzyme induction
can significantly increase the metabolism of commonly used drugs
such as β-adrenergic antagonists, benzodiazepines, and cyclic
antidepressants, and some who smoke and are taking one of these
medications may be receiving a sub-therapeutic dose.11,12
Pathophysiology Of Acute Nicotine Addiction
Nicotine is addictive. After years of study the Surgeon General
declared in 1988 that “ . . . cigarettes are addicting, similar to heroin
and cocaine, and nicotine is the primary agent of addiction.”1,13
Nicotine addiction is very complex and a detailed discussion of the
subject is beyond the scope of this module and this author’s
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knowledge base. However, several basic points about the process are
useful for an understanding of tobacco use disorder.1,14-16
Tobacco Use Disorder and Addiction
Tobacco use disorder is a substance use disorder and a crucial aspect
of substance use disorders is “ . . . an underlying change in brain
circuits that may persist beyond detoxification, particularly in
individuals with severe disorders. The behavioral effects of these brain
changes may be exhibited in the repeated relapses and intense drug
craving when the individuals are exposed to drug-related stimuli.”17 In
basic terms, smoking produces structural changes in the brain that
make it very difficult to quit the habit.
Chronic nicotine use produces drug-taking behavior and tolerance and
smoking cessation can cause a withdrawal syndrome. Notably, nicotine
addiction is the result of neurological and biological adaptations to the
chronic administration of nicotine and a change in the number of
nicotinic receptors.
The dopaminergic system is the main part of the central nervous
system (CNS) that is involved in drug addiction and over time and as
someone is continually exposed to nicotine, the CNS becomes adapted
to and seeks out the high levels of dopamine that are produced by
nicotine. The physical and psychoactive effects of nicotine are primarily
mediated through dopamine release in the reward center of the brain,
and the release of dopamine produces the immediate pleasurable
sensations and it acts to reinforce the act of smoking.
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Nicotine binding to the nicotinic receptors also stimulates the release
of GABA, glutamate, serotonin, and other neurotransmitters. The firstline smoking cessation medications work by their action on the
nicotinic receptors, but because other neurotransmitters are influenced
by nicotine, alternative medications may be needed for successful
smoking cessation.
The daily nicotine intake and the blood nicotine level of a smoker
depends on: 1) how many cigarettes are smoked; 2) how the cigarette
is smoked (inhalation depth and pattern, etc.); and, 3) the smoker’s
rate of metabolizing nicotine. Some metabolize nicotine faster than
others do and this is an inducement to smoke more cigarettes to
obtain the pleasure of smoking and to avoid cravings.
The Definition And Diagnosis Of Tobacco Use Disorder
Tobacco use disorder is considered to be a substance use disorder
(SUD). The DSM-5 criteria for substance use disorders are listed in
Table 4.
Table 4: DSM-5 Criteria for Substance Use Disorders
Continued use despite negative interpersonal consequences
Craving or urge to use the substance
Failure to fulfill obligations
Persistent desire to cut down or quit
Reduced social or recreational activities
Significant time spent taking or obtaining substance
Tolerance (excludes prescription medication)
Use in physically hazardous situations
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Use despite knowledge of harms
Using larger amounts than intended
Withdrawal (excludes prescription medication)
0–1 criteria 5 no SUD
2–3 criteria 5 mild SUD
4–5 criteria 5 moderate SUD
>5 criteria 5 severe SUD
These criteria provide a basic picture of a substance use disorder. The
DSM-5 definition of tobacco use disorder and the diagnostic criteria for
it are listed in Table 5. It should be noted that these have been
changed slightly from the original version but nothing substantive has
been omitted.
Table 5: DSM-5 Definition of Tobacco Use Disorder
A problematic pattern of tobacco use that causes clinically significant
impairment or distress, as manifested by at least two of the following,
occurring within a 12-month period:
1.
Tobacco is often taken in larger amounts or over a longer period
than the user intended.
2.
The user has a persistent desire to cut down or control his or her
tobacco use or he or she makes persistent, unsuccessful efforts to
cut down or control tobacco use.
3.
A great deal of time is spent in activities that are needed to obtain
or use tobacco.
4.
The user has a craving, a strong desire, or a strong urge to use
tobacco.
5.
Recurrent tobacco use that is a direct cause of failure to fulfill
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major role obligations at work, school, or home (i.e., interference
with work).
6.
Continued tobacco use despite having persistent or recurrent social
or interpersonal problems caused or exacerbated by the effects of
tobacco (i.e., arguments with others about tobacco use).
7.
The user gives up or reduces important social, occupational, or
recreational activities because of tobacco use.
8.
Recurrent tobacco use in situations in which it is physically
hazardous (i.e., smoking in bed).
9.
Tobacco use is continued despite knowledge of having a persistent
or recurrent physical or psychological problem that is likely to have
been caused or exacerbated by tobacco.
10.
Tolerance, which is defines as either; a) A need for a markedly
larger amount of tobacco to achieve the desired effect; or, b) A
markedly diminished effect from the same amount of tobacco.
11.
Withdrawal, which is evidenced by either: a) Characteristic criteria
for tobacco withdrawal syndrome; or, b) the use of tobacco or a
nicotine-containing product to alleviate signs and symptoms of
tobacco withdrawal.
The clinician should also determine if the patient is in early remission
or sustained remission and if the patient is on maintenance therapy,
and in a controlled environment.
Early Remission
The patient had met the full criteria for tobacco use disorder; none of
these have been present for at least three months but for less than 12
months; and, criteria number 4 may be present.
Sustained Remission
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The patient had met the full criteria for tobacco use disorder; none of
these have been present for at least 12 months; and, criteria number
4 may be present.
Maintenance Therapy
The patient is taking a long-term maintenance medication. In a
controlled environment the patient is in an environment where access
to tobacco is restricted.
A mild tobacco use disorder is diagnosed if the patient has two to three
symptoms. Moderate tobacco use disorder is diagnosed if the patient
has four to five symptoms, and a severe tobacco use disorder is
diagnosed if the patient has six or more symptoms. People who have
anxiety, bipolar disorder, depression, psychosis, or another substance
use disorder are at risk for developing tobacco use disorder.5,18,19
There is evidence of an inherited trait that can predispose someone to
the development of tobacco use disorder and certain cultural and
ethnic factors may put a person at risk, as well.5,20
Tobacco use disorder is common in people who use cigarettes or
smokeless tobacco but not prescription nicotine products.5 Many
tobacco users report a craving for tobacco if they have not used it for
several hours, and cessation of tobacco can cause a well-described
withdrawal syndrome.5 Electronic cigarettes, often known as ecigarettes are quite popular and also controversial. They do not deliver
as much nicotine as a cigarette, but it is not clear if the use of ecigarettes discourages or encourages the use of other nicotinecontaining products.21,22
Tobacco Withdrawal
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This learning module will not discuss tobacco withdrawal at length, but
it is useful for the reader to know the diagnostic criteria for this
substance use disorder. The DSM-5 diagnostic criteria for tobacco
withdrawal are listed in Table 6.23
Table 6: DSM-5 Diagnostic Criteria for Tobacco Withdrawal
Daily use of tobacco for at least several weeks.
Abrupt cessation of tobacco use a reduction in the amount of tobacco
used, followed within 24 hours by four or more of these signs or
symptoms
Irritability, frustration, or anger
Anxiety
Difficulty concentrating
Increased appetite
Restlessness
Depressed mood
Insomnia
In the DSM-5 criterion, the signs or symptoms identified cause
clinically significant distress or impairment in important areas of
functioning in individuals affected by a tobacco use disorder.
Additionally, the signs or symptoms are not attributed to another
medical condition and are not better explained by another mental
disorder, including intoxication or withdrawal from another substance
Smoking Cessation: Basic Principles
Because smoking and the use of nicotine-containing products are still
so common, asking patients if they smoke or use nicotine-containing
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products should be standard protocol. The U.S. Preventive Service
Task Force recommends that clinicians ask all patients who are ≥ 18
years of age about tobacco use, and tobacco cessation interventions
should be provided for patients who use tobacco.24
The benefits of smoking cessation are clear and unequivocal.25
Someone who quits smoking will live longer and is much less likely to
develop cancer, coronary heart disease, or lung disese,25 and these
benefits extend even to people who have been smoking for decades
and then quit. Of significance, a reduced risk of mortality has been
reported for people who are > age 80 and have stopped smoking.26
Nicotine is a powerful psychoactive drug, however, and smoking
cessation does have risks.25 It should be noted that these risks are
directly related to smoking cessation, which is further highlighted in
the section below.
Risks of Smoking Cessation
Risks associated with therapies that are used as aids to smoking
cessation are discussed in this section.
Cough and Mouth Ulcers
Patients who stop smoking may notice that for several months they
are coughing more frequently than they did prior to quitting and they
may develop mouth ulcers, as well.25 Coughing and mouth ulcers
should resolve within several weeks.
Mental Illness
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Depression
A depressed mood is one of the diagnostic criteria of tobacco
withdrawal, and people who have a history of psychiatric illness are
more likely to develop depression during smoking cessation.25 But in
this patient population the benefits of smoking cessation appear to
outweigh the risks,25 and a recently published study found that most
people who stop smoking are not at risk for developing depressive
symptoms.27
Psychotrophic Medication
The rates of tobacco use among people with mental illness have been
reported to be high. Pharmacotherapy and counseling can help those
with mental illness to quit smoking. However, when individuals in a
smoking cessation program have relapsed, medical providers treating
individuals continuing to use tobacco should follow them more
consistently to evaluate the effect of smoking on medication efficacy to
treat psychiatric symptoms. Patients should be educated on the impact
of tobacco use on psychotropic medication efficacy and cost, as well as
the importance of informing their medical provider of any amount of
tobacco use while on psychotropic medication.
Weight Gain
Weight gain after smoking cessation is common, probably caused by
increased food intake, decreased metabolic rate and other
physiological changes.25 The average weight gain is 4-5 kg but much
higher weight gains are possible and there is a wide variability in how
much weight will be gained.28 The choice of medication that is used as
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an aid to smoking cessation does not appear to influence weight
gain.29
Cardiovascular Disease
Cardiovascular disease (CVD) is common among smokers and the
three drugs used as aids to smoking cessation, nicotine replacement
therapy, bupropion, and varenicline, have the potential to cause
cardiovascular events such as arrhythmias and non-fatal myocardial
infarction (MI). However, in 2015 Sharma, et al., examined the
available evidence and concluded that pharmacotherapy as an aid to
smoking cessation does not increase the risk for cardiovascular events
in patients with or without pre-existing cardiovascular disease.30 The
authors did caution that “ . . . there have been no large RCTs
(randomized controlled trials) in patients in the first few weeks post
acute coronary syndrome.24 Therefore, Clinical Practice Guidelines
recommends using nicotine replacement therapy with caution in
patients with CVD — especially within 2 weeks post MI, especially if
they have serious arrhythmias or progressive angina.”12
Beginning The Process Of Smoking Cessation
Using a process called the five A’s has been advocated as an effective
way of helping people to stop smoking. The five A’s include the
following steps: Ask, Advise, Asses, Assist, and Arrange.31,32
Ask
The first step is to find out how much tobacco and nicotine-containing
products the patient uses, i.e., what is used, how much, how often,
and the duration of use. It’s important to be specific. It has been
shown that people who are intermittent smokers may not consider
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themselves to be smokers or not consider alternative types of nicotine
delivery devices to be dangerous.31 In addition, some patients may not
consider smokeless tobacco, e-cigarettes and other nicotine delivery
devices to be part of their nicotine habit so its important to be sure to
ask about these.
The interviewing clinician should also determine the patient’s level of
substance use as the higher the level of use the more difficult it will be
to quit. Does he/she begin the day with a cigarette? Has the patient
been smoking since early adolescence? Do they smoke a lot? Has the
patient tried to quit before? It should be noted that the term pack
years is often used to describe someone’s smoking history rather than
simply determining how many cigarettes are smoked each day.
Pack years is calculated by: 1) Multiplying the number of packs
smoked each day by years as a smoker; or, 2) dividing the number of
cigarettes smoked each day by 20 (the amount in a pack) and
multiplying this number by the number of years someone has been
smoking. For example, 20 cigarettes a day for 25 years = 25 pack
years. As the duration and intensity of tobacco use directly affects
health, pack years is used to approximate the risk a smoker has of
developing tobacco-related diseases.
Advise
After determining the patient’s pattern of use and level of use the
patient should be advised to quit smoking. This may seem simplistic,
especially given the difficulty of stopping smoking. But there is
evidence that even simple advice from a caregiver can influence some
patients to quit smoking and, although the reported effect may be
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small (1%-2%), if advice to quit was given to every smoker the overall
public heath benefit would be quite large.32 Advice should be clear and
unequivocal and should be accompanied by offers of help.
Assess
Smokers will differ in their readiness to quit. Some will be eager to
stop smoking and others may be ambivalent.
Assist
Provide the patient with practical assistance that he/she will need for
smoking cessation, such as formulating a plan, prescribing
medications, and/or a referral to counseling.
Arrange
Arrange for follow-ups to evaluate progress. Once the decision has
been made to quit, it is advisable for the patient to set a quit date and
several recent (2014, 2016) studies have shown that abrupt quitting
produced a higher rate of abstinence than a gradual reduction of
tobacco use.33,34
The harm from smoking is directly proportional to how many cigarettes
are used. However, as with second-hand smoke there is no safe and
harmless number of cigarettes, and simply reducing the number of
cigarettes that are smoked each day will not provide lasting heath
benefits.25,31,35 Quitting is the only answer.
Aids To Smoking Cessation
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Smoking cessation programs use behavioral interventions,
medications, or both. A program that combines both has been shown
to be the most effective.31,33,36
Behavioral Interventions
There are many behavioral-based interventions that can be helpful as
aids to smoking cessation. Direct provider to patient interaction, group
therapy, specialized clinics, self-help intervention using educational
resources like printed material or videos, web-based and text-based
resources, and telephone applications and telephone contact
counseling have all been successfully used.33,37 The specific
intervention chosen will depend on availability, cost, and patient
preference. Important aspects of behavioral interventions as aids to
smoking cessation that can increase the chance of success include the
following.37-40
Duration
There appears to be a direct relationship between the duration of the
intervention sessions and success at attaining abstinence. Longer
intervention sessions results in greater success.37,38
Completeness
The patient should be given as much information about quitting
smoking as he/she can comprehend and use.
Form
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Many behavioral interventions for smoking cessation are based on a
cognitive behavioral therapy model. With this approach patients learn
practical skills such as identifying triggers for smoking, distraction
techniques, and problem solving. For example, the smoker may
identify large social gatherings as a trigger that stimulates the desire
to smoke. In those situations the smoker can use distraction
techniques such as chewing gum or mentally reviewing the benefits of
smoking cessation.
The Five Rs
The U.S. Preventive Task Force identified five variables of behavioral
interventions that may help patients to stop smoking. These variables
are called the the Five R’s.

Relevant to the patient.

The patient should be educated about the Risks of smoking that
apply to him or her.

The Rewards of smoking cessation should be outlined.

Roadblocks that may interfere with smoking cessation should be
identified.

Repetition is important – it takes time and repetition for smoking
cessation information to be absorbed and used.
Pharmacotherapy And Smoking Cessation
Pharmacotherapy (with or without behavioral interventions) can
significantly influence smoking cessation rates in adults.37,41 There are
three drugs that are approved by the Food and Administration (FDA)
for assisting patients with smoking cessation: bupropion, nicotine
replacement therapy (NRT), and varenicline.
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Bupropion
Bupropion is a commonly prescribed anti-depressant, and the
sustained-release form has FDA approval as an aid to smoking
cessation treatment. It inhibits the re-uptake of dopamine and
norepinephrine and it also acts as a competitive inhibitor at nicotinic
acetylcholine receptors. Bupropion also decreases cravings for nicotine
and prevents withdrawal signs and symptoms, and it has been shown
to be very effective at maintaining abstinence when it is used as a
monotherapy.42,43
When used for smoking cessation bupropion SR (sustained release) is
given 150 mg once a day for three days. The dose is then increased to
150 mg twice a day and the course of treatment is 7 to 12 weeks. If
needed, a longer duration of therapy can be used and for some
patients this may be necessary.42 Therapy with bupropion SR should
begin at least one week prior to the day the patient stops smoking;
this is needed because it takes five to seven days for a steady-state
blood level to be attained. The most common adverse effects of
bupropion SR are agitation, dry mouth, headache, insomnia, and
nausea.42
Bupropion reduces the seizure threshold and during clinical trials of
bupropion as an aid to smoking cessation seizures have occurred but
the risk for this is very, very low.44,45 Using bupropion is
contraindicated if a patient has a seizure disorder or a predisposition to
seizures.
A U.S. Boxed Warning has been issued on bupropion that alerts
prescribers that antidepressants can increase the risk of suicidal
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behavior and thoughts in children, adolescents, and young adults. A
recent (2016) review did not find that bupropion increased the risk of
neuropsychiatric adverse effects,46 but it does seem prudent to follow
the advice of the U.S. Boxed Warning to “ . . . monitor patients of all
ages who are started on antidepressant therapy and closely observe
them for clinical worsening, including the emergence of suicidal
thoughts and behaviors. Families and caregivers should be advised of
the need for close observation and communication with the health care
provider.”47
Nicotine Replacement Therapy
Nicotine replacement therapy delivers nicotine without exposure to the
harmful compounds of burning tobacco. Nicotine-containing gum,
inhalers, lozenges, patches, or sprays have been proven to be effective
at reducing craving, preventing withdrawal, and inducing sustained
abstinence from tobacco.41,42, 44 Compared to placebo, NRT can double
the success rate of smoking cessation efforts.48 NRT is typically used
for two to three months after someone has stopped smoking.42 These
products deliver a much lower dose of nicotine than a cigarette and a
nicotine use disorder and addiction from their use very rarely occurs.42
The optimal mode of use of NRT is combination therapy; the patches
are used for a long-acting effect and are supplemented by the gum,
lozenges, inhaler, or spray.42 The gum, lozenges, and patches can be
purchased over-the-counter; the inhaler and the sprays are available
by prescription. There is little data comparing the effectiveness of
these products. Patient preference and cost are the deciding factors as
to which one is used. The dose of the replacement product will depend
on the number of cigarettes the patient had been smoking each day.
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The duration of therapy is usually for two to three months after the
patient has stopped smoking but this can be adjusted as needed.
Details about nicotine gum, inhalers lozenges, patches, and sprays are
provided below.49
Nicotine Gum
Nicotine gum is provided as 2 mg or 4 mg, and the peak nicotine level
is attained in 20 minutes. Patients should be instructed to chew one
piece every 1 to 2 hours as needed for six weeks and then gradually
decrease the intake for the next 12 weeks. The gum should be chewed
until the nicotine flavor is noticed and then the gum should be placed
next to the buccal mucosa until the taste disappears. The gum should
be chewed and placed next to buccal mucosa again, and this cycle
repeated for 30 minutes and before the gum is finally discarded. The
gum should not be chewed very rapidly as this causes the nicotine to
be released from the gum at a rate that is too fast for it to be
absorbed.
Coffee, tea, or carbonated beverages should not be consumed while
chewing nicotine gum. Such products are acidic and concurrent use
with nicotine gum decreases the absorption of nicotine. Nicotine gum
can cause mild and temporary gastric distress.
Nicotine Inhaler
Nicotine inhalers consist of a mouthpiece and a cartridge that has 10
mg of nicotine. The inhalers deliver 4 mg of nicotine via an inhalation.
The nicotine-containing vapor is absorbed through the mucosa of the
oropharynx; only a very small percentage reaches the lungs and all of
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the nicotine should be gone after 20 minutes of inhaling. The dose
should be individualized for each patient but a typical starting dose is
6-12 cartridges each day for 6-12 weeks.
After the initial 12 weeks the number of cartridges used each day can
be decreased over the following 6-12 weeks and then therapy can be
stopped. These products are considered particularly useful because
their use mimics the behavioral and tactile sensations of smoking a
cigarette. Irritation of the mouth and throat are common during the
first few weeks of therapy.
Nicotine Lozenge
Nicotine lozenges have 2 mg or 4 mg of nicotine. The lozenge should
be allowed to dissolve over 30 minutes, and the patient should use one
lozenge every one to two hours. After six weeks of use, the number
used should slowly be decreased and use stopped after 12 weeks.
Local irritation is a common side effect.
Nicotine Patches
Nicotine patches deliver a continuous, low dose of nicotine over 24
hours. Because of the transdermal delivery of nicotine, nicotine levels
in the plasma rise very slowly, which is helpful for preventing
withdrawal but can leave patients vulnerable to cravings. The patches
contain 7 mg, 14 mg, or 21 mg of nicotine, and the patch is applied
and left on for 24 hours. An example of a standard approach is to use
a 21 mg patch for six weeks and then a 14 mg patch for two weeks.
Insomnia and vivid dreaming are often experienced if the patient
leaves the patch on overnight.
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Nicotine Spray
Nicotine sprays may contain 10 mg per mL of nicotine, and each spray
delivers 0.5 mg of nicotine. These products deliver nicotine to the
nasal mucosa so the nicotine plasma level increases much faster than
it does with gum, lozenges, or inhalers. Patients should use one to two
sprays an hour, one spray into each nostril, and the maximum number
of sprays should not exceed 80 per day (40 for each nostril). Nasal
irritation is very common and it may persist well into the therapy.
Varenicline
Varenicline acts as a partial agonist at the α4-β2 subunit of nicotinic
acetylcholine receptors. Varenicline binds to these receptors and by
doing so it: 1) Stimulates the release of dopamine, thus reducing the
signs and symptoms of nicotine withdrawal caused by the absence of
nicotine; and, 2) Prevents the binding of nicotine to the acetylcholine
receptors, preventing some of the pleasurable effects of nicotine.41
Controlled studies have proven the effectiveness of varenicline for
smoking cessation;42,44,50,51 and, there is evidence that suggests it is
the most effective monotherapy for smoking cessation.50 The initial
dose of varenicline is 0.5 mg/day for three days. This is followed by
0.5 mg twice/day for four days, then 1 mg twice/day for the rest of a
12 week course.52 Smokers should stop smoking seven days after
beginning therapy with the drug.
The most common adverse effect caused by varenicline is nausea.50
Approximately one-third of patients who take varenicline will become
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nauseous50 but only a small number will discontinue therapy for this
reason.50 In most cases the nausea is mild to moderate in severity and
subsides over time.50
Varenicline has been associated with an increased risk for adverse
neuropsychiatric events.50 The true risk for serious neuropsychiatric
events is not known, and several recent (2013, 2015) analyses of data
did not find evidence that the use of varenicline increased the risk of
attempted suicide, death, depression, suicidal ideation, or other
adverse neuropsychiatric events.53,54 However, the prescribing
information for varenicline contains a U.S. Boxed Warning (commonly
called a black box warning); “Serious neuropsychiatric events including
but not limited to, depression, suicidal ideation, suicide attempt, and
completed suicide have been reported in patients taking varenicline.
Some reported cases may have been complicated by the symptoms of
nicotine withdrawal in patients who stopped smoking. Depressed mood
may be a symptom of nicotine withdrawal. Depression, rarely including
suicidal ideation, has been reported in smokers undergoing a smoking
cessation attempt without medication. “52
There was also a concern for several years that the use of varenicline
increased the risk of developing serious and non-serious cardiac
events,30 but current evidence and data analysis have shown that any
increase in cardiac events caused by varenicline are insignificant, and
an FDA safety communication indicated that “ . . . the events were
uncommon in both the treatment and placebo group and the increased
risk observed was not statistically significant . . . (and) there is no
evidence from the trials so far that varenicline is linked to increased
heart and circulatory problems.”55
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Alternative Therapies For Smoking Cessation
Alternative approaches to support patients during their course of care
in a smoking cessation program have been reported to provide value
and good results of quitting smoking. This section reviews several
alternative approaches and benefits of acupuncture, hypnosis and ecigarettes.
Acupuncture
Acupuncture may help smokers to quit56 but a 2014 analysis of its
effectiveness as an aid to smoking cessation concluded that “ . . . lack
of evidence and methodological problems mean that no firm
conclusions can be drawn.”57
Hypnosis
As with acupuncture, the evidence is equivocal for the effectiveness of
hypnosis as an aid to smoking cessation and more research would be
needed to determine how well and for whom it can work.31
E-cigarettes
A popular alternative to traditional cigarettes is the e-cigarette, as the
e-cigarettes do not deliver the same amount of tar and carcinogenic
products of combustion as traditional cigarettes. However, there is no
government control of e-cigarettes, and there exists a lack of data on
their health effects.58 According to the American Heart Association: “ .
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. . in general, the health effects of e-cigarettes have not been well
studied, and the potential harm incurred by long-term use of these
devices remains completely unknown.”59 There is currently conclusive
evidence that e-cigarettes are an effective aid to smoking cessation.60
Smoking Cessation: Failure And Success
Each year approximately two out of every three smokers will try and
quit but the majority will be unsuccessful.61,62 Even when using what is
considered to be optimal treatment, only 30% or so of smokers will
still be abstinent after one year.31
There are many reasons why smokers find it difficult to quit and
difficult to maintain abstinence, including but not limited to: side
effects of cessation such as cravings and withdrawal, weight gain,
mood changes, poor social support, access problems for smoking
cessation programs, poor preparation for quitting, and incorrect use of
medications.31 These issues, along with the addictive properties of
nicotine, clearly present smokers with a considerable challenge when
they try to quit and to cease the smoking habit long-term.
If a patient is experiencing difficulty with his/her smoking cessation
program, he or she can be helped to quit and relapse can be
prevented. The use of the following techniques can prevent and treat
relapses.31

Many patients who try and quit do so independently and have
not used medications or sought professional help. If a patient
states that he or she has tried to stop smoking be sure to find
out what efforts were made.
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
To prevent a relapse be sure to maintain close and consistent
contact with the patient to provide encouragement, support, and
ongoing education and to identify problems as they arise.

To treat a relapse it must be identified how and why the relapse
happened. When the problem(s) have been identified, the
patient should be offered practical solutions and most certainly
closely followed on his/her progress. If weight gain is a problem,
exercise and a nutritionist consultation can be recommended.
Ongoing education on the proper use of medications or the
addition of a second medication may be needed. The provider
should explore whether the patient clearly learned what
situations and triggers might cause a relapse. It can be helpful
during follow-up visits to review these with a patient.

Continuous follow up is essential. Patients who are trying to quit
smoking and those who have quit need support and follow-up.
This is a key factor for success and, because a relapse can
happen even years after quitting, some patients may need
periodic “check-ups” to help them maintain abstinence.
Patient Resources
There are many free and easily accessible resources that can help
someone who is contemplating smoking cessation or who wants to
stop. The ones listed below represent only a small number of what is
available.
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
Freedom from Smoking® is a program offered by the American
Lung Association. Use this link: http://www.lung.org/stopsmoking/i-wantto-quit/how-to-quit-smoking.htmlv and scroll
down the page to the section title Get Help.

The American Lung Association also has a help line, 1- 800 LUNG
USA.

Smokefree.gov is a website of the United States Department of
Health and Human Services. It includes information on healthy
habits, how smoking affects one's health, and tips on preparing
to quit. It also includes resources specifically for women, teens,
and Spanish-speaking patients.

1-800-QUIT Now (1-800-784-0669) is a toll free number that
connects smokers to the Quit For Life® program, sponsored by
the American Cancer Society.
Summary
Tobacco use poses enormous public health problems and is the leading
cause of preventable death in the United States. Although the number
of Americans who smoke has decreased, tobacco and cigarette
smoking are still the primary causes of or contributors to certain
cancers, heart disease, common respiratory diseases and other acute
and chronic pathology.
Tobacco use disorder is considered to be a substance use disorder
(SUD) according to DSM-5 criteria that occur over a 12-month period.
Risks associated with therapies that are used as aids to smoking
cessation are multifarious and should be closely monitored. Clinicians
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should follow patients closely during remission to determine early or
sustained remission, as well as maintenance therapy and whether the
patient is in a controlled environment.
There are three drugs that are approved by the Food and
Administration (FDA) for assisting patients with smoking cessation,
which are bupropion, nicotine replacement therapy (NRT), and
varenicline. Alternative approaches to support patients during their
course of care in a smoking cessation program, such as acupuncture,
hypnosis and e-cigarettes, have been reported to provide value and
good results of quitting smoking.
To treat relapse it is important for the patient’s provider to identify
how and why the relapse occurred. When the problem(s) have been
identified, the patient should be offered practical solutions and his or
her progress closely followed. Patients’ experiencing difficulty with
smoking cessation can be helped to quit, and relapse prevented, by
treating patients in a smoking cessation program according to
recommended techniques and free, easily accessible resources are
available to those desiring to stop smoking. Importantly, there is
evidence that even simple advice from a caregiver can influence some
patients to quit smoking and, although the reported effect may be
small, if advise to quit was given to every smoker the overall public
heath benefit would be quite large. Smoking cessation advice should
be clear and accompanied by offers of help by health care providers.
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