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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 e-

cigarettes.

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 non-

smokers 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 first-

line 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 e-

cigarettes 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 e-

cigarettes discourages or encourages the use of other nicotine-

containing 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 e-

cigarettes.

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/stop-

smoking/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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