Second edition

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674 Substance use disorders
reduction in any irritability. With this intoxication there
may be a mild tachycardia, elevation of blood pressure, and
an increase in peristaltic activity, and in some cases there
may be palpitations; tobacco-naive patients may also experience
nausea and vomiting. Overall, appetite decreases
and frequent smokers may lose some weight.
Tolerance occurs rapidly and, by the end of a day spent
smoking, there is little effect from a cigarette. Such tolerance,
however, rapidly decreases, such that by the next day
intoxication may again be achieved. Despite these daily
fluctuations, however, a chronic tolerance does develop.
Whereas a tobacco-naive patient may, as noted above,
experience toxic nausea and vomiting with one cigarette,
the nicotine addict may be able to smoke dozens of cigarettes
a day without any immediate adverse effects.
Withdrawal symptoms (Hughes and Hatsukami 1986;
Hughes et al. 1991a) may appear within anywhere from
hours to a day of abstinence. There is a restless craving for
a cigarette, and patients become tense and irritable.
Headache, difficulty concentrating, and insomnia may
occur, as may increased appetite with, in some, substantial
weight gain. Withdrawal generally peaks within days and
then gradually subsides over a matter of weeks; in some,
however, mild withdrawal symptoms may persist for
months, and in many cases the craving for a cigarette may
recur intermittently for years, often at times of stress.
Other disorders may appear in association with tobacco
use, and these occur not as a result of the effects of nicotine
itself but rather of the by-products of tobacco. Smoked
tobacco produces over 4000 different compounds, in both
gaseous and particulate form. Gaseous components
include carbon monoxide and hydrogen cyanide, whereas
particulates contain a substance known as ‘tar’, which for
the most part contains polycyclic aromated hydrocarbons.
With chronic smoking, patients are at risk for cancer of the
mouth, larynx, and lung, chronic obstructive pulmonary
disease (COPD), coronary artery disease, cerebrovascular
disease, peripheral vascular disease, Raynaud’s phenomenon,
gingivitis, gastroesophageal reflux, cancer of the
esophagus, and peptic ulcer disease. Smoking during pregnancy
may cause spontaneous abortion, abruptio placentae,
and low birth weight.
Course
Recreational use of nicotine is very rare; those who start
smoking usually either stop in short order or go on to fairly
rapidly develop nicotine addiction (with craving, tolerance,
and withdrawal) and persistent use, despite the
development of one or more of the other disorders associated
with tobacco use.
Etiology
Although the mechanisms that determine which patients
will stop and which will go on to develop addiction are not
clearly understood, genetic factors appear to play a significant
role (Kendler et al. 2000).
Differential diagnosis
There is generally no diagnostic difficulty; in those who
deny smoking, but who appear to be doing so, one may
obtain a urine screen for cotinine, one of the metabolites of
nicotine, which has a half-life of about 20 hours.
Treatment
Patients should choose a ‘quit date’, which ideally should
fall during a relatively stress-free time in the not-too-distant
future. Patients should be instructed to stop smoking on
that day and to avoid, if possible, situations or gatherings
where smoking is likely to occur. Individual or group therapy
with a cognitive–behavioral approach is helpful and
should be offered to patients. Various pharmacologic
approaches are also available, including varenicline, bupropion,
nortriptyline, and various preparations of nicotine.
Importantly, both bupropion and nortriptyline are effective
regardless of whether patients are depressed or not.
Varenicline is a partial agonist at alpha4beta2 nicotinic
acetylcholine receptors, and reduces both nicotine intoxication
and craving. Treatment is begun 1 week before the
quit date with 0.5 mg/day for 3 days, then 0.5 mg twice
daily for 3 days, and finally 1 mg twice daily thereafter, with
treatment continued for 3–12 months.
Bupropion is started 1 week before the quit date at
150 mg daily and increased 3 days later to 150 mg twice
daily, and then continued for 3–12 months.
Nortriptyline is started 1 week before the quit date at
25 mg daily, increased to 50 mg daily after 3 days, and then
to 75 mg 3 days later, after which it is continued for 3–12
months. Although studies measuring blood levels have not
been performed, it would not be unreasonable to check a
blood level after a week or so of the full dose and to make
appropriate adjustments based on the results.
Nicotine is available in a 24-hour patch delivering various
strengths of nicotine (commonly 7, 14, and 21 mg) and,
for as-needed dosage, in lozenges and gum tablets (both
available in 2-mg sizes) and a nasal spray (delivering
0.5 mg). If a nicotine preparation is used, it should be
started on the quit date. If the patch is used, the 21-mg size
should be used for a ‘pack a day’ smoker, with lower doses
used for those who smoke less; the initial strength is then
continued until the patient has been abstinent for at least a
couple of weeks, after which one steps down to the next
lowest size, which is then continued until the patient has
been abstinent for at least another 2 continuous weeks,
until finally the patch is discontinued. The as-needed
preparations are utilized with the goal of gradually reducing
the number of doses until they too can be discontinued.
Overall, it appears that varenicline is superior to bupropion
(Gonzales et al. 2006), which in turn appears superior