156 Tobacco Dependence
increases the likelihood of successful quitting. In addition,
the effects of pharmaceutical agents are substantially in-
creased when coupled with behavioral interventions. When
feasible and not medically contraindicated, it is recom-
mended that tobacco cessation interventions include at least
one FDA-approved pharmaceutical aid for cessation in paral-
lel with tobacco dependence counseling (Fiore et al., 2000).
In a systematic review of relevant studies (Silagy, Mant,
Fowler, & Lancaster, 2000), meta-analyzes of outcomes re-
lated to nicotine replacement therapies (all dosage forms com-
bined) revealed an odds ratio for abstinence of 1.7, compared
with control. The odds of abstinence for the four different
forms of nicotine replacement therapy that currently are avail-
able in the United States were 1.6, 1.8, 2.3, and 2.1 for the gum,
transdermal patch, nasal spray, and inhaler, respectively.
The nicotine sublingual tablet also has been investigated
(Molander, Lunell, & Fagerström, 2000; Wallstrom, Nilsson,
& Hirsch, 2000); this has been approved for use in Europe but
not in the United States (odds ratio for quitting, 1.7).
Bupropion SR was the “rst nonnicotine pharmaceutical
product approved for smoking cessation. The mechanism of
action of this medication, originally marketed as an antide-
pressant, is not fully understood although it is hypothesized
to promote smoking cessation through its capacity to block
neural re-uptake of the neurotransmitters dopamine and
norepinephrine, reducing cravings for nicotine and symp-
toms of withdrawal (Fiore et al., 2000). The “rst four pub-
lished placebo-controlled trials of bupropion for smoking
cessation demonstrated increased odds of quitting, compared
to placebo (Ferry & Burchette, 1994; Ferry, Robbins, &
Scariati, 1992; Hurt et al., 1997; Jorenby et al., 1999). Pool-
ing the 12-month continuous abstinence rates for the four tri-
als provides an odds ratio estimate of 2.7 (Hughes, Stead, &
Lancaster, 2001).
Currently, insuf“cient data are available to rank-order the
effectiveness of the different cessation agents (Fiore et al.,
2000). Most clinical trials have examined the use of a single
agent. More recently, however, investigators have reported
enhancements in cessation rates when agents are used in
combination. For example, there is evidence that concurrent
use of two forms of nicotine replacement therapy, whereby
one form provides steady levels of nicotine in the body and
the second form is used as needed to control cravings, sup-
press nicotine withdrawal symptoms (Fagerström, 1994;
Fagerström, Schneider, & Lunell, 1993) and increase ability
to quit compared to monotherapy (Blondal, Gudmundsson,
Olafsdottir, Gustavsson, & Westin, 1999; Kornitzer, Bousten,
Dramaix, Thijs, & Gustavsson, 1995; Puska et al., 1995).
Dual nicotine replacement therapy, however, is recom-
mended only for use with patients who are unable to quit
using monotherapy, because of the inherent increased risk of
nicotine overdose (Fiore et al., 2000). Use of bupropion SR in
combination with the nicotine patch has been shown to in-
crease cessation rates 5.2 percentage points over bupropion
SR alone, from 30.3% to 35.5%, although this increase was
not statistically signi“cant (Jorenby et al., 1999). Thus,
despite the small number of trials that have examined combi-
nation therapy versus monotherapy, the results appear
promising and may be particularly applicable to refractory
patients who have been unable to quit using single agents.
Additional research is needed to delineate more clearly the
value-added effects of combination therapy, to compare the
relative effects of the different constellations of agents, and to
examine the comparative side effect pro“les and toxicities as-
sociated with combination therapy.
Despite the fact that several different classes of drugs have
been examined in recent years for their effectiveness in pro-
moting smoking cessation, quit rates remain low, with fewer
than one third of patients being abstinent at “ve or more
months posttreatment. Furthermore, because few studies ex-
tend beyond one year, it is not known whether cessation is
maintained long term. Although the nicotine transdermal
patch and nicotine gum now are available without a prescrip-
tion, it is not clear whether this increased access compro-
mises ef“cacy because patients can now self-prescribe and
self-treat their tobacco dependence without the proven posi-
tive effects of intervention from a health professional.Nonpharmaceutical Methods for CessationOf smokers attempting to quit, many give up smoking on their
own, without assistance of any kind. A variety of self-help ma-
terials are available; in general, these materials are just mar-
ginally more effective than no intervention, although tailored
materials tend to have a greater impact than do nontailored
materials (Lancaster & Stead, 2000). Social support, other
than that provided by cessation counselors, has been shown to
increase the likelihood of quitting by approximately 50%
(Fiore et al., 2000). When feasible, smoking cessation
treatment should involve some form of tobacco dependence
counseling. In a meta-analysis of trials assessing the effects of
cessation advice from medical practitioners (Silagy & Stead,
2001), it was determined that brief advice is associated with
an increased likelihood of quitting versus no advice (odds
ratio, 1.7); in addition, more intensive advice leads to a higher
likelihood of quitting when compared to more minimal advice
(odds ratio, 1.4). Although tobacco is the leading cause of
morbidity and premature mortality in the United States, al-
lied health professionals generally do not receive adequate
tobacco cessation training. The vast majority of medical