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Nicotine patch therapy in adolescent smokers

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Title:
Nicotine patch therapy in adolescent smokers
Creator:
Wold, Angi Lynn
Publication Date:
Language:
English
Physical Description:
xiii, 126 leaves : ; 28 cm

Subjects

Subjects / Keywords:
Nicotine addiction -- Treatment ( lcsh )
Teenagers -- Tobacco use ( lcsh )
Smoking cessation ( lcsh )
Nicotine addiction -- Treatment ( fast )
Smoking cessation ( fast )
Teenagers -- Tobacco use ( fast )
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bibliography ( marcgt )
theses ( marcgt )
non-fiction ( marcgt )

Notes

Bibliography:
Includes bibliographical references (leaves 113-126).
General Note:
Integrated Sciences Program
Statement of Responsibility:
Angi Lynn Wold.

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Source Institution:
|Auraria Library
Holding Location:
|University of Colorado Denver
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All applicable rights reserved by the source institution and holding location.
Resource Identifier:
62774973 ( OCLC )
ocm62774973
Classification:
LD1193.L584 2005m W64 ( lcc )

Full Text
NICOTINE PATCH THERAPY IN ADOLESCENT SMOKERS
by
Angi Lynn Wold
B.A., University of Arkansas at Little Rock, 1997
A thesis submitted to the
University of Colorado at Denver
in partial fulfillment
of the requirements for the degree of
Master of Integrated Sciences
2005


2005 by Angi Lynn Wold
All rights reserved.


This thesis for the Master of Integrated Sciences
degree by
Angi Lynn Wold
has been approved
by
Richard Allen
Susan Mikulich-Gilbertson
1\p 105
Date


Wold, Angi Lynn (M.I.S., Integrated Sciences)
Nicotine Patch Therapy in Adolescent Smokers
Thesis directed by Assistant Professor Richard Allen
ABSTRACT
Introduction: Almost 90% of smokers begin smoking in their teens,
suggesting that treatment efforts should focus on early and effective
intervention for adolescent smokers. Nicotine patch therapy has been proven
to be an effective aid to smoking cessation in adult smokers, but the lack of
research in adolescents has prevented the Food and Drug Administration
(FDA) from approving nicotine patch therapy for use with adolescent
smokers. The aims of this study were to examine the safety, feasibility, and
efficacy of nicotine patch therapy in a population of adolescents in treatment
for substance and behavioral problems. In addition, variables that predict
smoking cessation were investigated. Demographic and descriptive variables
were also compared among males and females. Methods: This double-blind,
placebo-controlled, pilot study compared 50 adolescent clients who were in a
standard day treatment program for substance and behavioral problems.
Clients were randomly assigned to nicotine patch (NP) or placebo patch (PP)
therapy. Participants participated in a 10-week treatment phase and were
assessed at intake for substance dependence diagnoses, patterns of
cigarette use and dependence symptoms, and other demographic and
descriptive variables. Participants also completed a one-month follow-up
interview. Results: The majority of participants (68%) completed the 10-week
IV


protocol and 72% of participants were compliant with the treatment regimen.
There were no reports of serious or life-threatening adverse events and no
participant withdrew from the study because of problems related to the patch.
Only 8% of participants (4% in each group) reported smoking abstinence
during the study, but 72% of the NP group and 48% of the PP group reduced
their daily smoking by more than 80%. Daily cigarette use and carbon
monoxide (CO) levels were significantly reduced by the end of the study for
each group, and the NP group showed a greater reduction of cigarettes
smoked a day than the PP group. Conclusion: Use of nicotine patch therapy
is a safe and feasible option for adolescents interested in smoking cessation.
Pairing nicotine patch therapy with behavioral treatment (i.e., cognitive
behavioral therapy or contingency management) or other pharmacological
treatments may improve efficacy rates.
This abstract accurately represents the content of the candidates thesis. I
recommend its publication.
Signed
Richard Allen
v


DEDICATION
I dedicate this thesis to my husband, Andy, and daughter, Anais, for their
incredible patience and understanding while I spent many nights and
weekends writing this document.


ACKNOWLEDGEMENT
I would like to thank my mentor, Elizabeth Whitmore, for her guidance and
support throughout the evolution of this project. I would also like to thank Drs.
Richard Allen and Susan Mikulich-Gilbertson for their assistance with the final
stages of this manuscript. This study was made possible by a grant provided
by the University of Colorado Cancer Center or the donation of nicotine
patches by Glaxo SmithKIine. Thanks also to staff at Synergy and the clients
that participated in this study. I would further like to thank Emma Gianani for
her assistance with this study and for her dedication to the clients at Synergy.


CONTENTS
Figures.................................................xi
Tables.................................................xii
CHAPTER
1. INTRODUCTION................................................1
Nicotine and its Function................................3
Nicotine and the Adolescent Brain........................8
Nicotine Dependence in Adolescents.......................8
Nicotine and Other Substance Use........................10
Smoking Cessation.......................................12
Gender Differences......................................13
Nicotine Replacement Therapy............................14
Adolescents and Nicotine Patch Therapy..................18
Study Aims..............................................22
2. METHODS....................................................24
Recruitment.............................................24
viii
Participants
26


Study Protocol..............................................27
Measures....................................................32
Diagnostic Interview Schedule for Children............32
Composite International Diagnostic Inventory-
Substance Abuse Module................................33
Revised Hollingshead-Redlich
Socioeconomic Status..................................34
Biological Measures...................................34
Urinalysis.....................................34
Body Weight....................................35
Expired Air Carbon Monoxide....................35
Study Specific Measures...............................36
Fagerstrom Tolerance Questionnaire.............36
Smoking History Questionnaire..................36
Hughes-Hatsukami Nicotine Withdrawal
Symptom Questionnaire..........................36
Carroll Rating Scale for Depression............37
Pre-Study Symptom Checklist....................37
Nicotine Patch Questionnaire...................37
Weekly Record Questionnaire....................38
Observer Rating................................38
Data Management and Analysis...............................38
ix


3. RESULTS
42
Safety of Nicotine Patch................................51
Feasibility of Nicotine Patch Therapy...................56
Efficacy of Nicotine Patch Therapy......................57
Predictors of Smoking Cessation/Reduction...............71
Gender Differences......................................75
4. DISCUSSION.................................................79
Conclusions.............................................87
Limitations.............................................88
Future Directions.......................................89
APPENDIX
A. CONSENT FORM........................................91
B. MEASURES............................................96
REFERENCES...................................................113
x


FIGURES
Figure
3.1 Weekly Cigarette Average..............................59
3.2 Weekly CO Level Average...............................63
XI


TABLES
Table
3.1 Demographics........................................
3.2 DISC-IV.............................................
3.3 Carroll Scores......................................
3.4 Change in Carroll Score within Groups...............
3.5 Cl DI-SAM...........................................
3.6 Positive Urinalysis Results.........................
3.7 Nicotine Dependence.................................
3.8 Weight..............................................
3.9 Weight by Gender....................................
3.10 Smoking Variables...................................
3.11 Adverse Events......................................
3.12 Baseline Symptoms...................................
3.13 Comparison of Baseline Symptoms and Adverse Events...
3.14 Medications and Adverse Events in the NP Group......
3.15 Reasons Why Patch Was Removed.......................
3.16 Daily Cigarette Use.................................
3.17 Reduction in Daily Cigarette Use within Groups......
43
43
44
45
46
47
48
49
49
50
52
53
54
55
57
58
.60
XII


3.18 CO Levels..............................................62
3.19 Reduction of CO Level within Groups....................64
3.20 Smoking Abstinence and Reduction.......................65
3.21 Withdrawal Scores......................................66
3.22 Observer Rating........................................69
3.23 Efficacy...............................................70
3.24 Reasons Why Participants Continued to Smoke............71
3.25 Predictors of Smoking Cessation........................72
3.26 Predictors of Smoking Reduction........................73
3.27 Smoking Variables by Gender............................75
3.28 Nicotine Dependence by Gender..........................77
3.29 Total Baseline Symptoms and Adverse Events by Gender 77
3.30 Weekly Average of Withdrawal Symptoms by Gender.......78
xiii


CHAPTER 1
INTRODUCTION
Smoking continues to be a major health concern in the United States
with approximately 70.8 million Americans reporting current use of tobacco in
2003 (SAMHSA, 2004). It is estimated that 89% of current adult smokers
started their habit before age 19 (Lantz, Jacobson, & Warner, 2001),
providing support for the belief that experimentation with cigarette smoking
often begins during adolescence. In the United States, about 3,000
adolescents begin smoking every day and about 1,000 of those will become
daily smokers (Van Den Bree, Whitmer, & Pickworth, 2004). Although only a
minority of adolescents who experiment with cigarettes become regular
smokers (Clark & Cornelius, 2004; Shadel, Shiftman, Niaura, Nichter, &
Abrams, 2000), most adolescents who smoke regularly continue as regular
smokers into adulthood (Chassin, Presson, Rose, & Sherman, 1996).
Federal agencies, such as the Centers for Disease Control and United
States Department of Health and Human Services have recently started to
focus on the problem of adolescent smoking by implementing school-based
prevention programs and abstinence campaigns. Since then, the prevalence
1


of adolescent cigarette use has generally been on the decline. From 2002 to
2004, however there was not a significant decline in the use of tobacco
products among high school students (Grunbaum et al., 2004). The 2003
Monitoring the Future Study reported that 26.7% of high school seniors
reported past month cigarette use (Johnston, O'Malley, Bachman, &
Schulenberg, 2004) and the lifetime prevalence of ever having smoked a
cigarette was 58.5% (Grunbaum et al., 2004).
The implementation of school-based prevention programs and
abstinence campaigns has not been completely beneficial with adolescent
smokers. In order to develop effective prevention and cessation programs for
adolescents, it is important to understand the factors involved in adolescent
smoking. In the past, researchers and medical personnel have used adult
cessation programs to address the problem of adolescent smoking
(Backinger & Leischow, 2001) and these programs have not been effective
with this population. Adult programs may not be suitable for teens because
adolescents smoke for different reasons and they have different patterns of
smoking than adults.
Finding effective programs to reduce smoking in adolescents is
important, especially since almost 90% of adult smokers state that their
smoking began in their teens. Tobacco remains the leading cause of death in
the United States, accounting for 444,000 deaths per year (CDC, 2002). If
2


current patterns of smoking behaviors continue, an estimated 6.4 million of
todays children are expected to die prematurely from a smoking-related
disease (CDC, 1997).
Nicotine and its Function
Nicotine is one of the most widely-used psychoactive drugs in our
society and is the primary active ingredient in tobacco. Nicotine is a colorless,
highly volatile liquid alkaloid that was first separated from tobacco leaves in
1828. Over 4,000 compounds, including nicotine, are released by the burning
of a tobacco cigarette (Julien, 2001). Cigarettes are the most commonly used
tobacco product, which is of concern because although nicotine has some
adverse effects, the cigarette itself is responsible for much of its toxicity (e.g.,
tobacco and nicotine are combined with numerous chemical additives,
including carcinogens and pesticides, to form a cigarette).
Most cigarettes contain between 0.5 and 2.0 milligrams of nicotine, but
only about 20 percent of the nicotine in a cigarette is actually inhaled and
absorbed into the bloodstream. Smoking with frequent or deep inhalation is
the route of administration provides for the most rapid delivery of nicotine to
the brain. Nicotine is suspended in cigarette smoke in the form of minute
particles, known as tars, and it enters the lungs, as a water-soluble liquid
contained in the watery portion of the mucous membranes. As nicotine is
3


absorbed in the lungs it begins its ascent to the brain via arterial blood.
Arterial nicotine concentrations peak approximately 20 seconds after each
puff, and nicotine reaches the brain in a matter of seconds (Rose, Behm,
Westman, & Coleman, 1999). The remainder is rapidly metabolized by the
hepatic enzyme CYP2A6, and is rapidly oxidized into cotinine, a major
metabolite eliminated in the urine. The elimination half-life of nicotine in a
chronic smoker is about two hours, necessitating frequent administration of
the drug to avoid withdrawal symptoms or drug craving (Julien, 2001). This
pattern is consistent with other drugs that have a high abuse potential (Quinn,
Wodak, &Day, 1997).
Nicotine first stimulates and then depresses the nervous system. The
stimulant effect is due to the release of norepinephrine and the fact that
nicotine mimics the action of acetylcholine. Nicotine stimulates cholinergic
receptors first, but it is not removed from the receptors very rapidly. In early
stages of smoking, nicotine can cause nausea and vomiting by stimulating
both the area postrema, the vomiting center in the brain stem, and the
sensory receptors in the stomach. Tolerance to this effect develops rapidly.
Nicotine stimulates the hypothalamus to release antidiuretic hormone (ADH),
which causes fluid retention. Nicotine increases the respiration rate at low
dose levels because it stimulates the receptors in the carotid artery that
monitor the brains need for oxygen. It stimulates the cardiovascular system
4


by releasing epinephrine, which increases coronary blood flow, heart rate,
and blood pressure. The heart muscle requires an increase in oxygen, but
the overall oxygen supply is not increased (Hanson & Venturelli, 1998).
The next effect of nicotine is the depression of the central nervous
system, caused by blocked nerve activity. Nicotine reduces the activity of
afferent nerve fibers coming from the muscles, leading to a reduction in
muscle tone. This action may be involved in the relaxation effect that a
person may experience as a result of smoking. Nicotine also reduces weight
gain, most likely by reducing appetite (Julien, 2001).
Nicotine from tobacco bathes all of the brain and its action is initiated
by activating specific acetylcholine receptors (nicotinic receptors). Nicotinic
acetylcholine receptors are widely distributed in the nervous system and are
involved in neuronal communication and excitability. This activation results in
powerful effects on the brain, the spinal cord, the peripheral nervous system,
the heart, and various other body structures. The diverse distribution and
roles of nicotinic acetylcholine receptors ensures that nicotine will influence
many neuronal regions and functions (Dani & DeBiasi, 2001).
Nicotinic receptors play a role in the release of many
neurotransmitters. Nicotinic acetylcholine receptors may be located on
presynaptic nerve terminals of dopamine-, acetylcholine-, and glutamine-
5


secreting neurons. The activation of these presynaptic nicotinic acetylcholine
receptors has been shown to initiate a calcium increase in presynaptic
terminals, which in turn stimulates the release of several neurotransmitters,
including acetylcholine, norepinephrine, dopamine, and serotonin (Dani &
DeBiasi, 2001). Evidence suggests that nicotine addiction, or chronic
administration may alter the function of most, if not all, of the various
neurotransmitter systems (Mathieu-Kia, Butelman, & Kreek, 2002). Nicotine
administration causes an increase in endogenous acetylcholine release. This
release is believed to play a role in nicotine addiction as well as playing a role
in the cognitive potentiation and memory facilitation properties of the drug. It
may also be responsible for the arousal effects (e.g., pleasure and euphoria)
commonly seen with smoking (Brautbar, 1995; Julien, 2001).
Although numerous neurotransmitters are activated by nicotine, the
mesolimbic and mesocortical dopamine systems have been identified as the
systems responsible for the initial reinforcing properties of this drug. Nicotine
increases the activity of dopamine neurons in the ventral tegmental area that
project to various cerebral regions, such as the nucleus accumbens and
forebrain. These brain areas are thought to be involved in reward functions
and mediate the actions of natural reinforcers as well as many drugs of abuse
(Mathieu-Kia et al., 2002). As nicotine binds at the nicotinic acetylcholine
receptors, profound modifications in the functioning of the dopamine neurons
6


occur on the ventral tegmental area-accumbens pathway (Mathieu-Kia et al.,
2002). Acute, as well as chronic, intermittent administration of nicotine leads
to an increase in the activity of midbrain dopamine neurons by accelerating
the firing of neurons and by switching their activity from regular to burst-firing
patterns (Mathieu-Kia et al., 2002).
Increases in the concentration of nicotinic acetylcholine receptors are a
hallmark of the development of nicotine dependence (Sanderson, Drasdo,
McCrea, & Wonnacotts, 1993). Through nicotinic acetylcholine receptor
activation, nicotine enhances the actions of glutamate and dopamine, thus
providing a potential mechanism of action for the addictive properties of the
drug (Kelley, 2002). Laboratory studies have shown that the administration of
nicotine results in behaviors (e.g., cannot quit or cut down, tolerance,
developing dependence and physical withdrawal) that are associated with
other addictive substances, such as amphetamines and cocaine (Brautbar,
1995; Dani & DeBiasi, 2001). In animals, nicotine increases locomotor
activity, enhances reward from brain stimulation, supports the development of
place preferences, and can function as a reinforcer in the drug self-
administration procedure (DiChiara, 2000). Although the molecular
mechanisms that lead to and maintain nicotine addiction are poorly
understood, they are known to involve the regulation of brain monoamines
(Buisson & Bertrand, 2002).
7


Nicotine and the Adolescent Brain
Although little is known about the effects of nicotine on the human
adolescent brain, research using animal models may contribute to a better
understanding of this area. Recent research indicates that administration of
nicotine to adolescent rats elicits a different pattern of nicotinic acetylcholine
receptor upregulation in the midbrain from that seen when nicotine is given to
adults (Slotkin, 2002). In addition, hippocampal precursor cells of adolescent
rats undergo apoptosis when exposed to nicotine in concentrations similar to
the levels achieved in smoking. This suggests that adolescents may display a
greater and more lasting behavioral disruption from nicotine administration
(Slotkin, 2002). Basic biological differences between the adult and adolescent
brain may underlie at least some of the unique susceptibility of teens to
smoking (Slotkin, 2002), and adolescents brains appear to be particularly
susceptible to the neurological effects of nicotine (Faraday, Elliott, Phillips, &
Grunberg, 2003).
Nicotine Dependence in Adolescents
With the majority of smokers beginning their habit in adolescence, it is
important to acknowledge the important role adolescent smoking has in the
development of nicotine dependence. Nicotine has strong positive
8


reinforcement properties, and this is implicated in the initial development of
regular tobacco use. Chronic administration generally results in a state of
physical dependence (Malin, 2001). However, in the veteran smoker, this
reinforcing potential diminishes, and the user smokes primarily to relieve or
avoid withdrawal symptoms (Julien, 2001).
Adolescent experiences with nicotine dependence are qualitatively
different from those of adults (Colby, Tiffany, Shiffman, & Niaura, 2000). In
the past, researchers thought that lengthy and regular tobacco use was
necessary for nicotine dependence to develop (USDHHS, 1994), and the
trajectory from nonsmoking or experimental smoking to regular smoking in
children was described as an orderly progression of about two years (Russell,
1971; Stern, Prochaska, Velicer, & Elder, 1987; USDHHS, 1994). Recent
reports have raised concerns that nicotine dependence symptoms in
adolescents can develop soon after initiation (DiFranza et al., 2002; DiFranza,
et al., 2000), however, and other studies have shown a more rapid and less
orderly development of nicotine dependence (McNeill, 1991) than previously
thought. In 2003, among youth aged 12 to 17 who were current smokers,
38.4% were dependent on nicotine (SAMHSA, 2004). Although most youth do
not develop full-blown nicotine dependence until after two to three years of
use (USDHHS, 1994), addiction can occur after smoking as few as 100
cigarettes (AAPCSA, 2001). Many adolescent smokers exhibit signs of
9


nicotine dependence in a matter of days to weeks after initiation of occasional
tobacco use, often well before the development of daily smoking (DiFranza et
al., 2000). Van Den Bree et al. (2004) found that a substantial proportion of
experimental adolescent smokers progress rapidly to a dependent pattern of
smoking, and Robinson (2004) found that, among teenagers reporting for
treatment of nicotine dependence, the transition from experimental to regular
smoking averaged 12 months.
Nicotine and Other Substance Use
Substance-abusing adolescents represent a subgroup with particularly
high rates of regular tobacco use. For example, in a study of smoking among
adolescents in treatment for substance abuse, Myers and Brown (1990) found
that of 132 adolescent participants aged 14 to 19, 86% (n=113) reported
current cigarette smoking, with 75% smoking daily, and 65% smoking 10 or
more cigarettes a day. Studies to date demonstrate that this group of youth
continues cigarette smoking following treatment for substance abuse and they
evidence smoking-related health problems during adolescence (Myers &
Brown, 1994). Unfortunately, few adolescent substance abuse treatment
programs directly address tobacco use or nicotine dependence. Rates of
smoking in adolescent drug treatment facilities are much higher than those
10


found in the general population (Myers, 1999), suggesting an even greater
need to provide smoking cessation programs in these settings.
Given the overwhelming evidence regarding the addictive properties of
nicotine and the significant long-term health consequences of tobacco use,
the failure of substance abuse treatment programs to consistently address
tobacco along with other drug and alcohol use is an important omission
(Myers, 1999). The importance of addressing nicotine along with alcohol and
other drug dependence is highlighted by recent evidence that tobacco-related
disease is the leading cause of death among individuals treated for alcohol
abuse and dependence (Hurt et al., 1996). One potential consequence of the
failure to address nicotine in the context of substance abuse treatment is that
this practice may inadvertently serve to reinforce tobacco use (Myers and
Brown, 1994). Adolescents may perceive this omission as tacit approval of
tobacco use; it may lead them to minimize the dangers associated with
tobacco, relative to alcohol and other drugs; and it may result in increased
resistance to smoking cessation. Addressing tobacco use along with alcohol
and other drugs during treatment would provide a more consistent message
to adolescents regarding treatment of addiction (Myers, 1999) and would
provide a more comprehensive approach to substance treatment.
11


Smoking Cessation
Studies of adolescent smoking reveal that many adolescents report a
desire to stop smoking (CDC, 2001; Hurt, Croghan, Beede, Wolter, Croghan,
& Patten, 2000; Karle, Shenassa, Edwards, Werden, Elder, & Whitehorse,
1994), and nearly 67% of youth wish they had never started smoking (CDC,
1994). Unfortunately, 75% of adolescent smokers who try to quit fail (Moss,
Allen, Giovino, & Mills, 1992). Therefore, the development of efficacious
smoking cessation programs that are safe and feasible for use in adolescents
is greatly needed.
In the area of youth tobacco-use cessation, fewer than 80 studies have
been published in scientific journals as of the spring of 2001 (CDC, 2004) and
thus far, there is little evidence to support the efficacy of smoking-cessation
interventions in adolescents (Garrison, Christakis, Ebel, Wiehe, & Rivara,
2003). Several factors, such as lack of motivation, concerns about admitting
cigarette use, and the relatively low overall prevalence of adolescent smoking
contribute to difficulties in the recruitment of adolescents into smoking
cessation programs (USDHHS, 1994). An alternative solution to these
problems is to focus on settings that service heavy smoking subgroups with
demonstrated health risks (such as substance-abusing youth). There are
several advantages of focusing treatment on substance-abusing adolescents:
(1) the high prevalence of smoking will increase the pool of potential at-risk
12


participants; (2) youth identified as substance abusers are less likely to be
concerned about concealing their smoking from adults; (3) substance-abusing
adolescent smokers more often report negative consequences from cigarette
use (Myers, Kelly, & Lennox, 1997); and (4) they may be more motivated to
attempt cessation than lighter-smoking adolescents (Myers, 1999). One
barrier to implementing smoking-cessation interventions for substance
abusers is the concern that quitting smoking may make it more difficult to
become abstinent from alcohol and other drugs. Some clinicians believe that
alcohol and other drug abusers should not attempt smoking cessation since it
may hinder efforts at abstinence and recovery from other drug abuse (Bobo &
Gilchrist, 1983; Bobo, Gilchrist, Schilling, Noach, & Schinke, 1987). Available
studies examining smoking cessation among drug and alcohol abusers do not
support the belief of increased risk for relapse, however (Hughes, 1993;
Martin et al., 1997; Sees & Clark, 1993).
Gender Differences
Evidence suggests that female smokers are less nicotine-dependent
than males (Perkins, 1999). Female smokers also tend to smoke fewer
cigarettes per day, tend to smoke brands with lower nicotine yields, and tend
to be less likely to inhale deeply, as compared to males (Perkins, 1999).
Although their average smoking rates are lower than males, a number of
13


studies have shown that females find it more difficult than do males to quit
smoking cigarettes (Hatsukami, Skoog, Allen & Bliss, 1995; Perkins, 1999).
This is partially due to the fact that factors such as acquiring pleasure from
the smoke, social reinforcements for smoking, comfort from having something
to manipulate in social situations, and gratification from oral stimulation that is
involved in smoking behavior, are greater in females than in males (Mathieu-
Kia et al., 2002). Females are also more likely to see smoking as a useful
mechanism for coping with social situations or unpleasant affective states
(Faraday, Scheufele, Rahman, & Grunberg, 1999). In addition, females report
greater withdrawal stress compared to males (Pomerleau, Tate, Lumley, &
Pomerleau, 1994). It has been suggested that the lower cessation success
with nicotine replacement in females may be attributed to the reduced
effectiveness of the replacement therapy in relieving nicotine withdrawal
symptoms in females (Hatsukami et al., 1995), but further research is needed
to identify other gender and biological differences in relation to smoking and
smoking cessation.
Nicotine Replacement Therapy
Nonpharmacologic treatments such as self-help materials and
behavioral therapy were the first available treatments for nicotine
dependence, and they continue to be used by up to 90% of smokers wanting
14


to quit (Cunningham, Ferrence, Cohen, & Adlaf, 2003; Fiore etal, 2000; Fiore
et al., 1990; Haxby, 1995). Behavioral therapies, which include elements of
nicotine fading, quit dates, contracting, management of smoking triggers, and
relaxation techniques, have been reported to produce quit rates of seven to
20 percent (Coleman, 2004; Prochazka, 2000) in adult smokers.
The current standard of care is for counseling to be delivered in
conjunction with pharmacologic treatments (Fiore et al., 2000). Nicotine
replacement therapy (NRT), such as nicotine gum, patch, spray, inhaler, and
lozenge, are the United States Food and Drug Administrations (US FDA) -
approved first-line treatments for nicotine-dependence (Fiore et al., 2000;
Silagy, Lancaster, Stead, Mant, & Fowler, 2004). NRT is believed to facilitate
abstinence through two primary mechanisms. First, on a physical level,
nicotine replacement provides the smoker with a lower, relatively safer dose
of nicotine to attenuate withdrawal symptoms (Hughes, 1993) and ease the
transition to becoming a nonsmoker. Secondly, on a behavioral level, the use
of NRT allows the smoker to develop coping and other strategies for the
behavioral aspects of their addiction (Niaura et al., 1996).
Nicotine replacement therapy has been suggested by the Center for
Disease Control as a possible cessation option for adolescents with nicotine
dependence (CDC, 2004). NRT may be beneficial for adolescents who try to
quit smoking because it may help relieve physical and/or psychological
15


withdrawal symptoms. Using NRT as a form of smoking cessation is thought
to help relieve the withdrawal syndrome: anxiety, irritability, difficulty
concentrating, restlessness, sleep disturbance, and other symptoms (Hughes
& Hatsukami, 1986). Not surprisingly, many adolescent smokers report
craving tobacco, which may precipitate a return to smoking (Gritz, Carr, &
Marcus, 1991). By providing nicotine via a route other than smoking, it is
possible to ameliorate the severity of the withdrawal syndrome and craving
while avoiding many of the health risks associated with smoking tobacco
(Fiore, Jorenby, Baker, & Kenford, 1992). Because withdrawal symptoms are
thought to be a main reason why people continue to smoke, replacing
nicotine and gradually tapering the level via NRT is an appealing method.
The efficacy of transdermal nicotine with use in adults has been well
established in placebo-controlled trials. In a meta-analysis of 17 studies with
over 5,000 total participants, quit rates among patch users were found to be
more than double those for placebo at the end of treatment (27% vs. 13%
respectively) and at six-month follow-up (22% vs. 9% respectively) (Fiore,
Smith, Jorenby, & Baker, 1994). Several, more recent randomized controlled
trials have yielded similar results (Daughton et al., 1999; Lewis, Piasecki,
Fiore, Anderson, & Baker, 1998). When compared to placebo, nicotine patch
has been shown to reduce relapse rates, especially in the first two weeks of
16


quitting, during which complete abstinence is a powerful predictor of long-
term abstinence (Kenford, Fiore, Jorenby, Smith, Wetter, & Baker, 1994).
Establishing the safety of NRT with adolescents is now a primary
concern among researchers, and examining findings from the adult use of the
nicotine patch, a popular form of NRT, has provided insight into possible
adverse events that may be exhibited in adolescents. Studies with adult
smokers have found that skin irritation at the patch site was generally the
most reported adverse event (Bohadana, Nilsson, Rasmussen, & Martinet,
2000; Davidson, Epstein, Burt, Schaefer, Whitworth, & McDonald, 1998; Fiore
et al., 1994; Lavelle, Birek, & Scott, 2003; Schuurmans, Diacon, Van Biljon, &
Bolliger, 2004), followed by headaches, and other symptoms such as
weakness, sleep disturbances, and nausea/vomiting (Jorenby et al., 1995;
Paoletti et al., 1996; Schuurmans et al., 2004). Few subjects withdrew from
the treatment due to adverse events (Davidson et al., 1998; Gourlay, 1994).
Overall, research suggests that nicotine patch therapy is safe for use in adults
(Davidson et al., 1998; Fiore et al., 1992; Fredrickson et al., 1995; Lavelle et
al., 2003; Hughes et al., 1999; Hughes, 2000; Stapleton et al., 1995;
Transdermal Nicotine Study Group, 1991).
Although NRT has been utilized with adult smokers, these techniques
have not been well studied in adolescents. Fiore et al. (1994) encouraged the
study of NRT in adolescent smokers to increase quit rates after he found that
17


NRT increased the odds of cessation by a factor of three in adults. Because
there are many reasons to believe that cessation processes might be different
behaviorally for adolescents as compared with adults (Evans, Farkas, Gilpin,
Berry, & Pierce, 1995; Pierce & Gilpin, 1995; Pierce et at., 1991; Sargent,
Dalton, Beach, Bernhardt, Pullin & Stevens, 1997), a more thorough
investigation of NRT in adolescent smokers is needed.
Adolescents and Nicotine Patch Therapy
To date, there have only been a handful of studies conducted with
adolescent smokers utilizing nicotine patch therapy. Therefore, there are
many unanswered questions about its safety, feasibility, and efficacy in
adolescent smokers. Because the use of the nicotine patch with adolescents
has not yet been approved by the Food and Drug Administration, researchers
are still actively working to uncover answers to these questions.
Smith et al. (1996) conducted a non-randomized, open-label study of
the nicotine patch with 22 adolescent smokers aged 13-17 years who were
recruited from a public high school. Participants were required to smoke at
least 20 cigarettes a day to qualify. They wore 22 milligram (mg) patches for
six weeks, and then 11 mg patches for two weeks, as well as receiving
weekly behavioral counseling and group support. Participants were contacted
for a three-month, six-month, and 12-month follow-up. The group reported
18


that, although 86% of participants completed eight weeks of therapy, only
14% were abstinent from smoking at study end, and only one participant
remained abstinent at the three- and six-month follow-up interviews. The
patch was found to be effective in significantly reducing withdrawal symptom
scores. Skin reactions were the most common adverse event reported. There
were no life threatening adverse events reported and no adverse events led
to discontinuation of the patch. The authors concluded that the patch was
safe for use in adolescents, although efficacy appeared to be less than that
seen in adult studies.
Hurt et al. (2000) also conducted a non-randomized, open-label trial of
the nicotine patch in adolescent smokers. Recruitment occurred in two
Midwestern cities and a total of 101 adolescent smokers aged 13-17 years
participated in the six-week study. Participants were also contacted for a 12-
week and six-month follow-up interview. Participants had to smoke a
minimum of 10 cigarettes a day to qualify for participation. All participants
wore 15 mg patches for 16 hours a day for all six weeks of the study. The
authors reported that 71% of participants completed six weeks of treatment
and 17% stopped participating because of an adverse event. The most
commonly reported adverse events were upper respiratory tract infections
and headaches. Participants did reduce their smoking, carbon monoxide
levels, and withdrawal symptom scores by the end of the study, but only
19


10.9% reported abstinence at the end of the study and only five percent were
abstinent at the six-month follow-up. The authors concluded that nicotine
patch therapy plus minimal behavioral intervention was not effective for
smoking cessation in adolescent smokers.
Hanson, Allen, Jensen, and Hatsukami (2003) published the first
double-blind, placebo-controlled randomized trial of nicotine patch therapy in
adolescent smokers. Participants, recruited from the community, were 100
adolescents aged 13-19 who smoked at least 10 cigarettes a day.
Participants who smoked more than 15 cigarettes a day wore the 21 mg
patch for six weeks, then the 14 mg patch for two weeks, and then the seven
mg patch for two weeks. For those who smoked 10-14 cigarettes per day, 14
mg patches were worn for six weeks and the seven mg patches were worn for
the next four weeks. Intensive cognitive behavioral therapy and contingency
management procedures were combined with patch therapy for both the
placebo and patch group. The nicotine patch group had a significant reduction
in craving score and withdrawal symptom scores when compared to the
placebo group. There was not a significant difference between the two groups
in reported adverse events, and itching at the patch site was the symptom
reported most often. In addition, there were no life threatening or severe
adverse events reported by either group. Daily cigarette smoking and carbon
monoxide levels were reduced in both groups and participants were generally
20


compliant with treatment. The patch group had an end-of-study abstinence
rate of 20% and the placebo patch group had a rate of 18%. The authors
concluded that nicotine patch therapy is safe for adolescents.
Recently, Moolchan and his associates (2005) completed a double-
blind study that examined the safety and efficacy of the nicotine patch and
nicotine gum in adolescent smokers. A total of 120 adolescents were
randomized into one of three groups: (1) active patch and placebo gum; (2)
active gum and placebo patch; and (3) placebo gum and placebo patch.
Treatment lasted 12 weeks and was combined with cognitive behavioral
therapy. Both the patch and gum were well tolerated by the participants. The
nicotine patch group had a higher abstinence rate (18%) than the nicotine
gum group (6.5%), and both had higher rates than the placebo group (2.5%).
Adverse events were similar to those reported in studies of adult nicotine
replacement therapy. The results suggest that nicotine patch therapy
combined with cognitive behavioral therapy is safe and effective for treatment
of tobacco dependence among adolescent smokers.
Together, these studies have reported abstinence rates ranging from
10% to 20% at study end, rates lower than those found in adult samples. This
indicates that adolescent smoking characteristics may be different than that of
adults. Furthermore, this suggests the need for developing smoking cessation
programs that are specifically designed for teens. On a positive note, the
21


studies that have been conducted thus far have shown that nicotine patches
are safe for adolescents, with no serious or life threatening adverse events
being reported. In addition, adolescent smokers appear to be willing to
participate in nicotine patch therapy and the majority of participants are
compliant with the treatment regimen.
Although overall abstinence rates achieved with adolescents have
been discouraging, further evidence to support the safety and feasibility of
nicotine patch therapy in adolescents is warranted. In addition, because
substance-abusing adolescents represent the largest group of adolescent
smokers, identifying a safe and effective treatment to curb, and hopefully
eliminate, their smoking is needed.
Study Aims
In a sample of adolescents who are in treatment for substance and
behavioral problems, this study aims to demonstrate that (1) nicotine patch
therapy will be safe for adolescent smokers; (2) nicotine patch therapy will be
feasible in adolescent smokers; (3) nicotine patch therapy will be an effective
form of treatment when compared to placebo for nicotine dependence; (4)
fewer nicotine dependence symptoms, older age of regular smoking, fewer
cigarettes smoked per day, and higher levels of motivation will be predictive
of smoking cessation in this sample; and (5) females will have fewer nicotine
22


dependence symptoms, will be less motivated to quit smoking, will report a
later age of smoking initiation, will smoke fewer cigarettes per day, will report
more adverse events, and will have higher withdrawal symptom scores when
compared to males in the study.
23


CHAPTER 2
METHODS
Recruitment
Fifty adolescents (25 experimental, 25 control) were recruited from
Synergy Day Treatment, a treatment program of the University of Colorado
School of Medicine, Department of Psychiatry for male and female
adolescents with substance dependence and behavioral disorders. The
inclusion criteria for the study were: (1) ages of 13 to 17 years; (2) self-
reported smoking of 10 cigarettes or more a day; (3) a breath carbon
monoxide (CO) level of at least 10 parts per million (ppm); and (4) willingness
to give up using tobacco. Adolescents were excluded if they had: (1) a pre-
existing contraindicated medical condition as determined by medical exam;
(2) pregnancy; (3) current psychosis, risk of homicide, suicide, or a significant
primary disorder other than conduct disorder or substance use disorder; (4) a
borderline or lower IQ (<80) or functional impairments; (5) they or their family
did not speak fluent English to effectively participate in treatment or research;
(6) circumstances that would reduce their length of stay in treatment and
research (e.g., going to jail); or (7) current use of bupropion for smoking
24


cessation, depression, or ADHD. Participants in this study were allowed to
take other psychotropic medications (except bupropion) because: (1) there
are no known interactions between the nicotine patch and psychotropic
medications, (2) this study was primarily concerned with safety and feasibility
of the nicotine patch in adolescent drug abusers, many of whom take
psychotropic medications for comorbid disorders, so excluding these
individuals would severely limit the recruitment population and generalizability
of the results, and (3) medications that were taken by each individual were
tracked so that they could be analyzed, and any effects these medications
may have had on the results of the study were documented.
Clients interested in the study completed a screening questionnaire to
assess inclusion and exclusion criteria (see Appendix B). The study was
explained to potential participants and their parents, and questions about the
study were addressed. As required by the Colorado Multiple Institutional
Review Board (COMIRB), written informed assent from patients, and written
informed consent from their parents/guardians for participation in this study
was obtained (see Appendix A). A Federal Certificate of Confidentiality was
also obtained to protect participants data.
25


Participants
Participants were recruited from Synergy Day Treatment from 2001-
2004. A total of 185 clients were screened, but only 92 met criteria for
participation. Clients did not meet eligibility requirements for the following
reasons: 29 did not smoke at least 10 cigarettes a day; 23 were not expected
to be in treatment for 10 or more weeks (duration of study); 19 had a CO level
below the required (10 ppm) level; 11 clients/parents declined participation
after initial interest; nine were taking bupropion; and two were pregnant or
thought they might be pregnant.
Of those 92 eligible clients, 62 signed consent for participation forms.
There were 12 participants who were consented, but they did not start the
treatment phase of the study. Reasons for non-enrollment include being
discharged from the treatment program before the study started (n=7),
stopping smoking before the study began (n=2), having suicidal ideation
(n=1), initial CO level being too low (n=1), or being placed in a detention
facility where access to cigarettes were prohibited (n=1).
Sixty-eight percent (34/50) of participants completed all 10 weeks of
the study. No participants formally withdrew their consent for participation and
no participants stopped participating because of adverse events or any other
study-related reasons. Fifteen participants were discharged prematurely from
the treatment program and their study participation was terminated as a
26


result. One participant was withdrawn by the investigator because he began
taking bupropion (an exclusion criterion) while enrolled in the study.
An attempt was made to contact all participants, but the one withdrawn
by the investigator, for a follow-up interview one-month after their scheduled
last day of the study. Seventy-eight percent (39/50) of participants completed
the one-month follow-up assessment. Some participants were not able to
meet in person with research staff for the follow-up interview, so
questionnaires were completed over the phone. Carbon monoxide levels and
urinalyses were not obtained for these clients.
Study Protocol
Fifty participants (25 in each group) who met inclusion criteria
participated in a 10-week, double-blind, placebo-controlled study. Stratifying
by gender, participants were randomly assigned to either nicotine patch
therapy (NP) or placebo patch therapy (PP). Participants in both groups
received standard day treatment services to address substance dependence.
They also received background treatment for tobacco use, including Not-On-
Tobacco (N-O-T), an educational program sponsored by the American Lung
Association (Horn & Dino, 1997), and encouragement from their drug and
alcohol counselor to abstain from tobacco use. Participants were allowed to
refuse or discontinue their participation at any time in the study, and if so,
27


they were able to continue to receive the same standard day treatment
services.
Participants were blind to their treatment condition, as were the
research staff conducting the assessments. One staff member, who was not
blind, was responsible for assigning participants to their respective group.
This person was not involved in the active study phase; therefore, the double-
blind study protocol was not compromised.
Because the nicotine patch has not been approved for use in
adolescents by the Food and Drug Administration (FDA), we utilized the
following COMIRB-approved protocol for screening participants for eligibility
and administering the treatment. A complete medical exam with blood tests
was given to ensure participants did not have pre-existing medical conditions
that would interfere with the use of the patch, including heart disease, thyroid
or liver problems, and pregnancy in females. The exam was completed by a
physician with specialties in addiction and internal medicine. This physician
served as the medical director for the project and he was also blind to the
study protocol. After the examination, the medical director determined
whether the client was medically eligible to enter the study and wrote a
prescription for the patch. As stated above, the nicotine patch has not been
approved by the FDA for use in individuals under the age of 18, therefore, a
prescription was needed for its use in adolescents. FDA approval was
28


received for this study even though a physician can prescribe the nicotine
patch without it.
During the medical exam, the medical director reviewed possible
adverse events that could result from wearing the patch with each participant.
Clients were referred back to the prescribing physician if they experienced
persistent adverse events or medical problems that were related to use of the
patch (e.g., nausea, vomiting, dizziness), and he determined whether the
participant should continue using the patch. All together, five participants
were referred to the medical director due to adverse events. Two participants
were referred for nausea and vomiting, two reported having a persistent rash,
one reported a dizzy spell, and one reported chest pains. After a medical
examination by the medical director, all of these symptoms were not
determined to be serious or life threatening. It is possible that the two
participants who reported nausea and vomiting were experiencing nicotine
toxicity because they admitted to smoking on the patch and once they
stopped smoking the symptoms subsided.
Participants received intensive instruction about wearing the patches
and were given quit tips from the package insert used in the over-the-counter
product, smoking literature, and other self-help materials to aid in cessation.
Both nicotine (Nicoderm CQ) and placebo patches were provided by Glaxo
SmithKIine. Adverse events were again explained to the participants by
29


research staff so they were aware of possible symptoms and what to do if
those symptoms occurred.
As recommended by the manufacturer for heavy smokers (>10
cigarettes per day), participants wore the 21 mg nicotine patch for six weeks,
the 14 mg patch for two weeks, and the seven mg patch for two weeks.
Clients were instructed to wear the patch for 24 continuous hours before
changing to another patch. Clients who experienced adverse events were
given the option of wearing the patch for 16 continuous hours, taking it off
while they slept. Eight participants removed their patch at least one time due
to adverse events, two in the NP group and six in the PP group. During the
course of the study, if a participant stopped wearing the nicotine patch for two
consecutive weeks (usually in the event of a discharge from the treatment
program), the participant was discharged from the active study phase for non-
compliance. These participants were tracked and contacted for the follow-up
assessment, however.
Nicoderm CQ and the corresponding placebo patch was packaged to
include a child-resistant disposal mechanism. This is a small tamper-proof
box, with a slit for slipping the patch into after it has been worn. All
participants were given information about proper disposal procedures and
warnings about risks to animals, children, and other individuals who could
come in contact with the patch if they were not properly disposed. Extra
30


patches and safety disposal trays were given to the participants at the end of
each week for weekend use. They were also given a few extra patches so
that they had patches at home to use if they were absent from treatment.
Participants were instructed to wear the patch as intended and to immediately
report any serious adverse events to the research staff.
Participants visited the research office during their lunch hour on
weekdays to change their patches. On weekends, holidays, or days when
participants did not attend day treatment, they were instructed to use a new
patch from a small supply they kept at home. Reminder calls were given, as
needed, to ensure that the participant remembered to change the patch daily.
The 25 participants who were assigned to the placebo patch (PP)
group received an identical protocol to the nicotine patch group (NP), but
instead they wore a placebo patch. Although placebo patches contained trace
amounts of nicotine (to ensure that they smelled and felt like nicotine
patches), the manufacturer provided data indicating that these trace amounts
were not absorbed to any significant degree by the patient.
The study period lasted for 10 weeks per participant, followed by a
one-month follow-up assessment. Participants were paid $10 a week for 10
weeks for their participation. Payment was dependent on completion of
urinalysis and carbon monoxide samples, as well as required paperwork. The
participants were able to choose how they received their payments; either
31


weekly or in a lump sum at the end of the study. In total, the participants
could receive up to $100 for participation in this research study. In the event
that a participant was discharged from the treatment program before the
study ended, they were withdrawn from the treatment phase of the study.
Because this was an intent-to-treat design, all participants were followed
(even those who did not complete the 10 week study), and the follow-up
assessment was attempted.
Measures
As part of the regular treatment received by all clients at Synergy, all
participants completed a standard intake assessment approximately two
weeks to one month after admission to the treatment program. These
assessments were administered by trained interviewers, all of whom were
either bachelors- or masters-level research assistants who were trained by
an experienced member of the research group. The individual measures
that were used from this battery are summarized below.
Diagnostic Interview Schedule for Children
The Diagnostic Interview Schedule for Children-4th edition (DISC-IV) is
a highly structured interview developed by the National Institute of Mental
Health (NIMH) (Fisher et al., 1993; Shaffer, Fisher, Lucas, Dulcan, & Schwab-
32


Stone, 2000). It was used to obtain diagnoses and symptom counts for
generalized anxiety disorder (GAD), major depressive disorder (MDD),
dysthymic disorder (DD), attention deficit hyperactivity disorder (ADHD),
oppositional defiant disorder (ODD), and conduct disorder (CD). Diagnoses
were based on criteria published in the Diagnostic and Statistical Manual of
Mental Disorders, 4th edition (DSM-IV) (APA, 1994).
Composite International Diagnostic Inventory-
Substance Abuse Module
Drug and alcohol use, including nicotine, was assessed using the 4.1
version of the Composite International Diagnostic Inventory-Substance Abuse
Module (CIDI-SAM) (Cottier et al.,1995). Six participants were tested using an
earlier version of the CIDI-SAM. The CIDI-SAM is a structured, 30-60 minute
interview designed for trained, lay interviewers. It is a descendant of the
NIMH Diagnostic Interview Schedule. The CIDI-SAM is designed to assess
DSM-IIIR and DSM-IV symptoms and give diagnoses of substance abuse or
dependence for alcohol and each of the 10 drug categories. The seven
symptoms of nicotine dependence listed in the DSM-IV were assessed on the
CIDI-SAM interview (APA, 1994); tolerance, withdrawal, using in larger
amounts than intended, wanting or trying to quit or cut down, spending a
great deal of time smoking, giving up social activities to smoke, and
continuing to smoke despite the problems nicotine has caused. Three
33


symptoms are required to occur within the same year to get a diagnosis of
nicotine dependence.
Revised Hollinqshead-Redlich
Socioeconomic Status
Social class was estimated (updated from Hollingshead & Redlich,
1958) from the participants report about his/her parents. A socioeconomic
status (SES) score was derived from rankings of the head of households
education and occupation. Education and occupation are each assigned a
rank from one to seven according to categories established by Hollingshead
and Redlich (1958). These ranks are then weighted according to a
regression equation and summed. This yields a SES score between 11 and
77 where 11 represents the highest SES score and 77 represents the lowest.
These scores are grouped into five categories; upper class (11-17), upper
middle class (18-27), middle class (28-43), lower middle class (44-60), and
lower class (61-77).
Biological Measures
Urinalysis. Each client completed at least two random, observed
urinalyses each week, which assessed drug use for nine drug categories, not
including tobacco, as part of the standard drug and alcohol treatment.
34


Body Weight. Body weight was measured at the initiation of the study,
weekly throughout the study, and at the one-month follow-up to assess the
extent to which the use of the nicotine patch and/or smoking cessation was
associated with short-term weight changes in these adolescents.
Expired Air Carbon Monoxide. Breath carbon monoxide (CO) levels
were measured with a PiCO Carbon Monoxide monitor, manufactured by
Bedfont Scientific. Carbon monoxide results can be contaminated by
marijuana use so it was important to try to ensure that participants were not
currently using marijuana, or if they were to report recent use. Participants
were continually supervised in treatment, but participants were allowed to
smoke cigarettes during breaks at the treatment program. Drug use, including
marijuana use, was prohibited during the day and actively discouraged
otherwise, but participants did sometimes use marijuana outside of treatment.
Because the half-life of carbon monoxide is approximately six hours and the
amount of smoking that occurred during the day was monitored, this helped
assure that the readings were related to nicotine use alone. We also asked
participants about their past day nicotine and marijuana use at each reading.
Furthermore, carbon monoxide readings were measured during the lunch
hour to try to reduce the possibility of marijuana contamination.
35


Study Specific Measures
Fagerstrom Tolerance Questionnaire (Fagerstrom. 1978; Heatherton,
Kozlowski, Frecker, & Fagerstrom, 1991). Degree of nicotine dependence can
be accurately and reliably calculated with this test (Fagerstrom & Schneider,
1989). This battery of eight questions about smoking habits yields a score
from 0-11; a score of seven indicates a high degree of nicotine dependency.
This questionnaire was completed during the first research visit (see
Appendix B).
Smoking History Questionnaire. This interview was created for this
study and it asked questions about a participants smoking history, such as
age of smoking initiation, age of regular smoking, number of quit attempts,
and number of smokers in their household (see Appendix B).
Huqhes-Hatsukami Nicotine Withdrawal Symptom Questionnaire
(Hughes & Hatsukami, 1986). This eight-item questionnaire addressed
nicotine withdrawal and included the following symptoms: desire to smoke;
anger, irritability or frustration; anxiety or nervousness; difficulty
concentrating; impatience or restlessness; hunger; trouble sleeping; and
depression. Each symptom was scored as none (0), slight (1), mild (2),
moderate (3), or severe (4) (see Appendix B). Symptoms were based on
those listed in the DSM-IV.
36


Carroll Rating Scale for Depression (Carroll, Feinberg, Smouse,
Rawson, & Greden, 1981). This 52-item questionnaire was used to measure
current depressive symptoms. It is a self-rated Hamilton Scale and is thought
to be more sensitive to adolescent depression than Becks Depression
Inventory (Alessi, McManus,Grapentine, & Brickman, 1984). Participants
completed the Carroll Rating Scale for Depression at study intake, on the last
day of treatment, and at one-month follow-up to assess the effect the nicotine
patch and smoking cessation had on depression (see Appendix B). A score of
10 or higher is worthy of interpretation.
Pre-Study Symptom Checklist. This checklist was designed for this
study to identify symptoms that were present before the participant began
wearing the nicotine (or placebo) patch. Symptoms that were measured were
those that were also listed on the adverse event list (see Appendix B).
Nicotine Patch Questionnaire. An interview was created for this study
to assess the participants experiences with using the patch, adverse events,
impressions of its efficacy and problems, and issues related to compliance
with the patch protocol (see Appendix B). Severity of adverse events were
rated as being mild (1), moderate (2), severe (3), or life threatening (4). All
reported adverse events were reviewed by the medical director on a weekly
basis, with follow-up, if necessary. The medical director also rated the
37


relationship of the adverse events to the patch as being certain (1), probable
(2), possible (3), or unlikely (4).
Weekly Record Questionnaire. At each visit, the participants completed
a daily self-reported smoking history that addressed the amount of cigarettes
smoked in the past 24 hours, and whether they smoked any other substance
(e.g. marijuana) or used any other nicotine products, such as chewing
tobacco (see Appendix B).
Observer Rating. The research assistant completed an observer rating
form weekly that rated symptoms that participants may have exhibited while
wearing the patch (see Appendix B). Participants were rated on their
irritability, anxiousness, restlessness, and depression. Each symptom was
scored as none (0), slight (1), mild (2), moderate (3), or severe (4).
Data Management and Analysis
All data were analyzed using SPSS version 12.0 (SPSS, 2004).
Demographic data were collected on all participants at the beginning of the
study. Participants were monitored weekly for smoking cessation, adverse
events, withdrawal symptoms, compliance with the protocol, and other drug
use. These variables were specifically collected for the purpose of this
research study. Some data that were collected as part of their participation in
the day treatment program (i.e., psychiatric and substance
38


abuse/dependence diagnoses and symptoms) were also accessed and used,
with permission of the participant and parent.
Groups were compared on categorical variables using chi-square
tests. For continuous variables when data were approximately normally
distributed, independent t-tests were used to compare groups on intake and
demographic variables, as well as smoking and other descriptive variables.
Paired samples t-tests were used to assess the impact of treatment group on
(1) average reduction of cigarettes smoked per day; (2) average reduction of
carbon monoxide levels; (3) average change in Carroll score; and (4) average
change in weight. All continuous variables were examined for violations of
normality assumptions. When variables were non-normally distributed the
appropriate non-parametric test was substituted (i.e., Mann-Whitney U to
compare groups and Wilcoxon Sign Rank to assess change over time).
Intake and demographic variables such as gender, SES, psychiatric
comorbidity, and severity of drug use, including nicotine, were assessed to
determine if they were predictors of smoking cessation. For these exploratory
analyses, chi-square and independent t-tests (Mann-Whitney U if non-normal)
assessed the relationships between intake and demographic variables and
smoking cessation. An aim of this study was to examine whether fewer
nicotine dependence symptoms, older age of regular smoking, higher levels
of motivation to quit, and lower levels of smoking would be predictive of
39


smoking cessation. These variables were also examined using chi-square
and independent t-tests to compare those who achieved smoking cessation
and those who did not. If any variables were individually related to smoking
cessation (found to be significant at the 0.05 level), they were combined in a
multiple logistic regression model to evaluate their joint prediction of smoking
cessation. In addition, chi-square and independent t-tests were used to
determine if females and their smoking behavior were different than males.
Random assignment with stratification by gender was implemented to
help ensure that the two treatment groups did not differ significantly in
demographics, comorbidity, medication status, and other descriptive
variables. An intent to treat design was used for this study, which requires
that data from all participants who consented, but who did not formally
withdraw their consent from the study, be analyzed, regardless of their length
of stay in treatment. For example, if a participant stopped attending
treatment, but did not formally withdraw their consent from the study, he or
she was contacted for a follow-up assessment.
A Data Safety Monitoring Board was created for this study and met
quarterly at the University of Colorado Health Sciences Center, Colorado
Psychiatric Hospital to review adverse events and data safety, including
protocol adherence, participant recruitment and participation, adverse event
reports, and safety. The meetings consisted of the principal investigator, two
40


consulting psychiatrists who specialize in addictions, a statistician, and
professional research assistants. The medical director was also contacted
throughout the study in the event of any adverse events. A physical
examination was conducted by the medical director in cases where the
adverse event was causing significant discomfort.
41


CHAPTER 3
RESULTS
At time of admission to the study, participants in both the nicotine
patch (NP) group and the placebo patch (PP) group were on average 16
years old. Thirty percent were female (32% in the NP group and 28% in the
PP group). Gender stratification was used during randomization, but one male
was inadvertently given a female spot due to confusion caused by his name.
The ethnic breakdown of participants included 74% Caucasian, six percent
African-American, 14% Hispanic, and six percent biracial or multiracial. The
mean socioeconomic status (SES) for the NP group was 42.86 and the PP
group had a mean score of 43.09, suggesting that, on average, participants
came from middle class families. The groups did not differ on any of the
demographic variables (see Table 3.1).
42


Table 3.1
Demographics
NP (mean SD) PP (mean SD) Score(df) P
Age at Intake 16.15 0.81 16.02 0.83 t=-0.53(48) 0.60
(mean SD)
SES (mean SD) 42.86 17.53 43.09 13.70 t=0.05(42) 0.96
Gender
Male 68% 72% x2=0.10(1) 0.76
Female 32% 28%
Ethnicity
Caucasian 68% 80%
African-American 12% 0% X2=3.72(3) 0.29
Hispanic 16% 12%
Bi/Multi-Racial 4% 8%
As expected with this population, the majority of participants received a
diagnosis of Conduct Disorder. Both groups reported similar rates of
psychiatric disorders as assessed by the DISC-IV (see Table 3.2).
Table 3.2
DISC-IV
NP PP '/2(df) P
GAD 4% 4% 0.00(1) 1.00
MDD 24% 20% 0.12(1) 1.00
DD 4% 4% 0.00(1) 1.00
ADHD 20% 4% 3.03(1) 0.19
ODD 40% 28% 0.80(1) 0.55
CD 76% 64% 0.86(1) 0.54
43


Both groups reported equal rates of depressive symptoms on the
Carroll Rating Scale for Depression at study intake, last day of study, and at
the one-month follow-up. There were no group differences in the reduction of
depressive symptoms at study end or at the one-month follow-up (see Table
3.3).
Table 3.3
Carroll Scores
NP (mean SD) PP (mean SD) t(df) P
Intake Carroll (n=50) 9.40 5.36 9.60 5.97 0.13(48) 0.90
Last Day Carroll (n=39) 8.79 5.44 7.25 4.71 -0.95(37) 0.35
Follow-Up Carroll (n=39) 5.30 4.12 6.79 4.43 1.09(37) 0.28
Change in Score from Last Day to Intake (n=39) 0.90 6.93 2.55 5.72 0.82(37) 0.42
Change in Score from Follow-Up to Intake (n=39) 3.30 5.65 3.84 5.55 0.30(37) 0.76
Paired sample t-tests were used to compare the differences in the
number of depressive symptoms within groups at study intake and study end,
and at study intake and follow-up (see Table 3.4). Participants in both groups
reported fewer depressive symptoms at the one-month follow-up (NP:
t=2.6119, p=0.02; PP: t=3.0218, p=0.01).
44


Table 3.4
Change in Carroll Score within Groups
Mean SD t(df) P
NP Last Day & Intake (n=19) 0.90 6.93 0.56(18) 0.58
NP Follow-Up & Intake (n=20) 3.30 5.65 2.61(19) 0.02
PP Last Day & Intake (n=20) 2.55 5.72 2.00(38) 0.06
PP Follow-Up & Intake (n=19) 3.84 5.55 3.02(18) 0.01
On the CIDI-SAM, there were no group differences in the diagnosis of
alcohol abuse or dependence or in the diagnosis of abuse or dependence for
any of the 10 drug categories, which includes nicotine, cannabis,
amphetamines, cocaine, sedatives, inhalants, hallucinogens, opioids, PCP,
and club drugs (see Table 3.5). The rate of cocaine abuse/dependence was
higher in the NP group, a difference that was trending towards significance
(x2=7.463, p=0.06). Because there were no reports of PCP abuse or
dependence, this category was not included in the table.
45


Table 3.5
CIDI-SAM
NP PP X2(df) P
Alcohol Abuse 28% 8% 3.87(3) 0.28
Alcohol Dependence 44% 64%
Cannabis Abuse 28% 36% 0.38(3) 0.94
Cannabis Dependence 68% 60%
Amphetamine Abuse 12% 12% 1.91(3) 0.59
Amphetamine Dependence 20% 8%
Cocaine Abuse 12% 8% 7.46(3) 0.06
Cocaine Dependence 24% 0%
Sedative Abuse 4% 4% 0.00(1) 1.00
Sedative Dependence 0% 0%
Inhalant Abuse 4% 0% 2.22(3) 0.53
Inhalant Dependence 12% 12%
Hallucinogen Abuse 16% 16% 1.03(3) 0.80
Hallucinogen Dependence 8% 4%
Opioid Abuse 8% 4% 0.36(1) 0.55
Opioid Dependence 0% 0%
Club Drug Abuse 4% 0% 1.02(2) 0.60
Club Drug Dependence 4% 4%
The NP group reported a mean of 4.2 drug positive urinalyses results
throughout the study and the PP group reported a mean of 2.1 drug positive
results, a difference that was not significant. The groups did not differ on the
number of positive urine results at intake or at the one month follow-up
46


interview (see Table 3.6). Follow-up urinalyses results were not available for
participants who completed the one month follow-up interview over the
phone.
Table 3.6
Positive Urinalysis Results
NP PP score P
Intake UA (n=50) 36% 20% X2=1.59(1) 0.21
Follow-Up UA (n=27) 6% 18% X2=0.94(1) 0.55
Positive UA Results (mean SD) 4.24 5.70 2.08 3.58 U=-1.33 0.19
The majority of participants (88%) in both groups met criteria for a
diagnosis of nicotine dependence on the CIDI-SAM and both groups, on
average, reported approximately five symptoms (out of seven) of nicotine
dependence. On the Fagerstrom Tolerance Questionnaire, the average score
for the NP group (7.56) and the PP group (7.29) were similar, further
suggesting that both groups had equal rates of nicotine dependence (see
Table 3.7).
47


Table 3.7
Nicotine Dependence
NP PP X2(df) P
Nicotine Dependence 88% 88% 1.02(2) 0.60
Symptoms
Tolerance 88% 80% 0.60(1) 0.70
Withdrawal 76% 64% 0.86(1) 0.36
Used in larger amounts 56% 68% 0.76(1) 0.38
Wanted to quit/cut down 80% 88% 0.60(1) 0.70
Spent a lot of time using 88% 84% 0.17(1) 1.00
Gave up activities to use 32% 16% 1.75(1) 0.19
Used despite problems 64% 52% 0.74(1) 0.39
NP PP t(df) P
Nicotine Dep. Symptoms 4.84 1.77 4.52 1.58 -0.67(48) 0.50
(mean SD)
Fagerstrom Score 7.56 1.29 7.29 1.16 -0.76(47) 0.45
(mean SD)
Weight remained relatively stable throughout the study and at the one
month follow-up for both the NP and PP group (see Table 3.8). Weight
change was also stable for both males and females throughout the study and
at the one month follow-up interview (see Table 3.9).
48


Table 3.8
Weight
NP (mean SD) PP (mean SD) U P
Intake Weight (n=50) 147.56 35.06 139.961 17.85 -0.59 0.55
Change Last Day & Intake Weight (n=27) -0.62 9.21 -1.36 4.73 -1.15 0.25
Change Follow Up & Intake (n=37) -0.70 7.88 0.5314.99 -0.08 0.94
Table 3.9
Weight by Gender
Female (mean SD) Male (mean SD) U P
Intake Weight (n=50) 129.471 16.31 149.89 29.59 -2.87 0.004
Change Last Day & Intake (n=27) -2.43 6.55 -0.50 7.38 -0.75 0.45
Change Follow Up & Intake (n=37) -3.30 9.31 1.0415.09 -1.28 0.20
Smoking onset for participants in the NP group (average age=11.24)
and the PP group (average age=12.08) was similar. The age of regular
smoking was also similar between the two groups, with both groups reporting
an average age of initiation of regular smoking of 12 years (see Table 3.10).
49


The time between smoking initiation and regular use was about one year for
both groups.
Participants rated their motivation to quit smoking on a scale from one
to five, with one (1) being not motivated at all and five (5) being very
motivated. There was an equal interest in quitting smoking for both the NP
group (mean=3.68) and the PP group (mean=3.40). Participants in both
groups indicated similar rates of prior quit attempts, with the NP group
reporting a mean of 1.60 attempts and the PP group reporting a mean of 1.84
quit attempts. Both groups reported that they had first wanted to quit smoking
around the age of 14. Participants also had equal numbers of current
smokers living in their household (see Table 3.10).
Table 3.10
Smoking Variables
NP (mean SD) PP (mean SD) score P
Age of Smoking Initiation 11.24 2.49 12.08 2.08 U=-1.23 0.22
Age of Regular Use 12.24 2.17 12.88 1.39 U=-0.74 0.46
Initiation and Regular Use Interval -1.00 1.44 -0.80 1.00 U=-0.73 0.94
Motivation to Quit 3.68 0.90 3.40 0.91 t=-1.09(48) 0.28
Age of 1st Quit Attempt 14.27 1.83 14.48 1.12 U=-0.35 0.73
Quit Attempts 1.60 1.66 1.84 1.70 t=0.51(48) 0.62
50


Safety of Nicotine Patch
The nicotine patch has not been approved for use in adolescents by
the FDA; therefore testing the safety of the patch was identified as an aim of
this study. Adverse events were assessed weekly by self-report and these
reports were rated as mild, moderate, severe, or life threatening by the
professional research assistant. The medical director reviewed all reported
adverse events on a weekly basis, although none of the adverse events were
deemed severe or life threatening. Eighty six percent (n=43) of participants
reported at least one adverse event. Over the course of the study, the NP
group reported an average of 11.32 adverse events and the PP group
reported an average of 7.64 adverse events, however this difference was not
enough to be significant (U=-0.92, p=0.36). Overall, the most commonly
reported adverse events were redness and itching, headaches, strange
dreams, and insomnia. Other symptoms that were reported include, tiredness,
nausea/vomiting, arm pain, muscle pain, dry mouth, joint pain, sweating,
nervousness, and diarrhea (see Table 3.11).
51


Table 3.11
Adverse Events
NP
PP
X(dQ_
Redness, Itching, Burning
Diarrhea Mild 80% 64% 1.59(1) 0.17
Dry Mouth Mild 4% 8% 0.36(1) 0.50
Muscle Pain Mild 16% 24% 0.50(1) 0.36
Joint Pain Mild 36% 20% 1.59 (1) 0.17
Arm Pain Mild Moderate 12% 4% 24% 0% 2.10(2) 0.35
Strange Dreams Mild 40% 10% 3.57(1) 0.06
Nervousness Mild Moderate 24% 4% 40% 4% 1.50(2) 0.47
Insomnia Mild 4% 8% 0.36(1) 0.50
Tiredness Mild 28% 36% 0.37(1) 0.38
Sweating Mild 24% 36% 0.86(1) 0.27
Headache Mild 16% 8% 0.76(1) 0.33
NauseaA/omiting Mild Moderate 48% 0% 40% 4% 1.22(2) 0.54
Mild Moderate 20% 12% 28% 0% 3.36(2) 0.19
Baseline symptoms were recorded for 48 of the 50 participants to
compare symptoms that were present before patch initiation to adverse
events that were reported while wearing the patch. There were no differences
in reports of baseline symptoms between the two groups. Insomnia and
52


headache were the most common symptoms reported before patch initiation
(see Table 3.12).
Table 3.12
Baseline Symptoms
NP PP X2(df) P
Redness, Itching, Burning 0% 4.3% 1.11(1) 0.48
Diarrhea 4% 0% 0.94(1) 1.00
Dry Mouth 8% 13% 0.33(1) 0.66
Muscle Pain 4% 0% 0.94(1) 1.00
Arm Pain 4% 0% 0.94(1) 1.00
Strange Dreams 12% 8.7% 0.14(1) 1.00
Nervousness 4% 8.7% 0.45(1) 0.60
Insomnia 44% 39.1% 0.12(1) 0.73
Tiredness 16% 8.7% 0.58(1) 0.67
Sweating 4% 0% 0.94(1) 1.00
Headache 20% 26.1% 0.25(1) 0.62
NauseaA/omiting 4% 0% 0.94(1) 1.00
Because there were no group differences in reports of adverse events
or baseline symptoms, the NP and PP groups were combined to study the
relationship between baseline symptoms and adverse events using
53


McNemars test. Participant reports of diarrhea, dry mouth, nervousness,
insomnia, tiredness, and sweating were found to be similar before nicotine
patch therapy was initiated and while wearing the nicotine patch. Therefore,
these symptoms most likely were not related to wearing of the patch (see
Table 3.13).
Table 3.13
Comparison of Baseline Symptoms and Adverse Events
Baseline Adverse Event X2(df) P
Redness, Itching, Burning 2.2% 71.7% 0.36(1) 0.005
Diarrhea 0% 6.5% 0.07(1) 0.63
Dry Mouth 6.5% 13% 5.83(1) 0.29
Muscle Pain 2.2% 26.1% 2.60(1) 0.005
Arm Pain 0% 28.3% 0.40(1) 0.002
Strange Dreams 4.3% 32.6% 0.02(1) 0.008
Nervousness 0% 6.5% 0.22(1) 1.00
Insomnia 13% 17.4% 0.12(1) 0.50
Tiredness 6.5% 23.9% 1.25(1) 0.06
Sweating 0% 13% 0.15(1) 0.13
Headache 8.7% 37% 0.17(1) 0.04
Nausea/Vomiting 2.2% 28.3% 2.34(1) 0.005
54


Many adolescents in treatment for substance use and behavioral
disorders also take psychotropic medication, therefore investigating the
interaction of these medications with the patch was important. A total of 28%
of participants in the NP group reported taking other prescription medications
during the course of the study. A chi-square analysis found that the use of
psychotropic medication by participants wearing the nicotine patch did not
result in higher rates of adverse events, although reports of nausea/vomiting
in this group was trending towards significance (x2=5.13i, p=0.06) (see Table
3.14).
Table 3.14
Medications and Adverse Events in the NP group
NP & Meds (n=8) NP no Meds (n=17) X2(df) P
Redness, Itching, Burning 75% 82% 0.18(1) 1.00
Diarrhea 0% 5% 0.49(1) 1.00
Dry Mouth 13% 18% 0.11(1) 1.00
Muscle Pain 13% 47% 2.82(1) 0.18
Joint Pain 25% 12% 0.71(1) 0.57
Arm Pain 25% 47% 1.10(1) 0.40
Strange Dreams 13% 35% 1.40(1) 0.36
Nervousness 0% 6% 0.49(1) 1.00
55


Table 3.14 (Cont.)
NP & Meds (n=8) NP no Meds (n=17) 12( df) P
Insomnia 13% 35% 1.40(1) 0.36
Tiredness 0% 35% 3.72(1) 0.13
Sweating 0% 24% 2.24(1) 0.27
Headache 50% 47% 0.02(1) 1.00
Nausea/Vomiting 63% 18% 5.13(1) 0.06
Feasibility of Nicotine Patch Therapy
Compliance was measured by two separate methods. First, the
number of treatment sessions attended was calculated. Over the course of
the 10 week study, there were 45 days that the participants were scheduled
to attend. The groups attended an equal number of days, with the NP group
attending an average of 32.84 days and the PP group attending an average
of 32.36 days (t=-0.1748, p=0.86), which resulted in a 72% attendance rate.
Second, the number of times participants removed their patch when
not medically necessary was computed. Both groups removed their patch an
equal number of times and reasons for removing their patch are listed in
Table 3.15.
56


Table 3.15
Reasons Why Patch Was Removed
NP PP X2(df) P
It fell off 64% 52% 0.74(1) 0.39
Adverse Event 8% 24% 2.38(1) 0.25
To smoke 4% 4% 0.00(1) 1.00
To sleep 8% 4% 0.36(1) 1.00
Other 20% 28% 0.44(1) 0.51
The biggest complaint by participants was the frequency with which the
patch fell off. Twenty nine participants (58%) reported that the patch fell off at
least one time during the study. This was equally a problem for both the NP
group (16 reports) and the PP group (13 reports). It is important to note that
some participants may have reported that their patch fell off, but they may
have actually removed it.
Efficacy of Nicotine Patch Therapy
As part of the smoking history questionnaire, participants reported on
the number of cigarettes they had smoked a day when smoking most often.
Both groups reported smoking a pack a day (i.e., 20 cigarettes) when
smoking the most. These numbers are slightly higher than the average daily
57


smoking rates reported on the screening questionnaire, with the NP group
smoking an average of 17.40 cigarettes a day and the PP group smoking an
average of 16.12 cigarettes a day. Both groups reduced their smoking by the
end of the study, and completers in the NP group significantly reduced their
smoking when compared to completers in the PP group at last day (U=-2.35,
p=0.02), but the difference was no longer significant at the one-month follow-
up (see Table 3.16).
Table 3.16
Daily Cigarette Use
NP (mean SD) PP (mean SD) score P
Most Cigarettes (n=50) 21.92 8.46 20.04 6.83 t=-0.87(48) 0.39
Cigarettes at Screen (n=50) 17.40 6.09 16.12 6.47 t=-0.72(48) 0.48
Completers Last Day Cigarettes (n=31) 3.38 2.84 7.28 6.96 U=-1.71 0.09
Follow Up Cigarettes (n=36) 5.63 4.61 8.06 7.57 U=-0.73 0.46
Completers Change in Cigs Last Day to Screen (n=31) -15.31 6.51 -8.39 10.63 -2.35 0.02
Change in Cigs Follow-Up to Screen (n=36) -11.63 8.11 -8.12 11.16 -1.16 0.26
58


A paired-samples t-test or Wilcoxon Sign Rank was used to compute
the average smoking reduction rates within groups. The average number of
cigarettes smoked a day as reported on the screening questionnaire was
compared to last day and follow-up smoking rates. Both completers analysis
and a last-observation carry-forward method was used to compute the
reduction of daily cigarette use, with the completers analysis listed below (the
last-observation carry-forward method data can be found in Table 3.17). Both
groups reduced their smoking by the last day of the study (see Figure 3.1).
Figure 3.1
Weekly Cigarette Average
NP
PP
Week
59


Completers in the NP group reduced their smoking from an average of
18.69 cigarettes to 3.38 cigarettes daily. This resulted in a statistically
significant reduction of 15.31 cigarettes per day (z=-3.18, p=0.005).
Completers in the PP group reduced their daily smoking from an average of
15.67 cigarettes to 7.28 cigarettes on their last day. This resulted in a
reduction of 8.39 cigarettes a day and was also statistically significant (z=-
2.99, p=0.005) (see Table 3.17).
For those who completed the one-month follow-up visit, members of
the NP group reported smoking an average of 5.63 cigarettes per day, which
was a statistically significant reduction of 11.63 cigarettes from the number of
cigarettes smoked on the screening questionnaire (t=6.25ie, p=0.005). The
PP group reported smoking an average of 8.06 cigarettes per day at the one
month follow-up interview, which was a reduction of 8.12 cigarettes per day
from the number reported on the screening questionnaire and this difference
was also significant (t=3.00i6, p=0.01) (see Table 3.17).
Table 3.17
Reduction in Daily Cigarette Use within Groups
_______________________________Mean SD________score__________p
NP CompletersChange -15.31 6.51 z=-3.18 0.005
Last Day to Screen (n=13)
NP Change Last Day to -13.92 + 6.70 t=10.40(24) 0.005
Screen (n=25)
60


Table 3.17 (Cont.)
Mean SD score P
NP Change Follow Up to Screen (n=19) -11.63 8.11 t=6.25(18) 0.005
PP Completers Change Last Day to Screen (n=18) -8.39 10.63 z=-2.99 0.005
PP Change Last Day to Screen (n=25) -9.56 10.72 t=4.46(24) 0.005
PP Change Follow-Up to Screen (n=17) -8.12 11.16 t=3.00(16) 0.01
Participants CO level was tested at screening, each research visit
throughout the study, and at the one-month follow-up interview. CO levels for
five participants were not included in the analyses because the original CO
monitor did not function properly and these clients completed the study before
the monitor was replaced. The screen CO levels were similar (and not
statistically significant) for both the NP (mean= 15.67 ppm) and PP
(mean=13.60 ppm) groups. The reduction of CO levels from screen to last
day were trending towards significance between groups (U=-1.70, p=0.09),
but this finding was no longer evident at the one-month follow-up (see Table
3.18).
61


Table 3.18
CO Levels
NP (mean SD) PP (mean SD) score P
Screen CO (n=35) 15.67 4.15 13.60 4.86 U=-1.93 0.06
Intake CO (n=45) 11.65 5.46 9.95 3.27 U=-1.18 0.24
Completers Last Day CO (n=33) 7.94 4.51 8.19 5.31 t=0.14(31) 0.89
Last Day CO (n=50) 9.04 5.53 7.32 4.92 U=-1.24 0.22
Follow-Up CO (n=38) 9.55 6.42 8.00 5.06 U=-0.62 0.54
Completers Change in CO Last Day to Screen (n=25) -8.00 7.21 -4.21 6.97 U=-1.70 0.09
Change in CO Follow-Up to -8.25 7.63 -6.15 6.63 t=0.74(23) 0.47
Screen (n=25)
A paired-samples t-test was used to compute the average CO level
reduction within groups. The average daily CO level recorded at the time of
the screening was compared to the last day and follow-up CO levels. As with
cigarette reduction, both completers analysis and a last-observation carry-
forward method was used to compute the reduction of CO levels, with the
completers analysis listed below (the last-observation carry-forward method
62


data can be found in Table 3.19). Both groups significantly reduced their daily
CO levels by the end of the study (see Figure 3.2).
Figure 3.2
Weekly CO Level Average
Completers in the NP group had a mean CO level of 7.94 ppm on the
last day, which was a significant reduction of 8.00 ppm (t=-3.68io, p=0.004).
Completers in the PP group had a mean CO level of 8.19 ppm on their last
day, which was a reduction of 4.21 ppm (t=-2.26i3, p=0.04). Those in the NP
group who completed the one-month follow-up had a mean CO level of 8.17
ppm, which was a reduction of 8.25 ppm (t=-3.75n, p=0.003). The PP group
had a mean CO level of 8.69 ppm at follow up, which was 6.15 ppm lower
than at their screening (t=-3.3512, p=0.01) (see Table 3.19).
63


Table 3.19
Reduction of CO Level within Groups
Mean SD t(df) P
NP Completers Change Last Day to Screen (n=11) -8.00 7.21 -3.68(10) 0.004
NP Change Last Day to Screen (n=15) -7.73 6.64 -4.51(14) 0.005
NP Change Follow-Up to Screen (n=12) -8.25 7.63 -3.75(11) 0.003
PP Completers Change Last Day to Screen (n=14) -4.21 6.97 -2.26(13) 0.04
PP Change Last Day to Screen (n=20) -5.90 6.78 -3.89(19) 0.001
PP Change Follow-Up to Screen (n=13) -6.15 6.63 -3.35(12) 0.006
A participant was considered abstinent from smoking if they self-
reported not smoking for seven consecutive days and had a CO level of eight
ppm or less at those visits. Four participants, two in each group, reported
achieving abstinence from nicotine during the study. All four participants
began smoking again after their period of abstinence, but had kept their
smoking to one to two cigarettes per day.
Although few participants reported achieving abstinence from nicotine,
60% (n=30) of participants reduced their daily smoking amounts by 80% or
more (a cut-off level used by Moolchan et al., 2005 for adolescents nicotine
64


patch therapy). On average, participants reduced the number of cigarettes
they smoked daily by 11.74 cigarettes. Eighteen participants (72%) in the NP
group and 12 participants (48%) in the PP group reported a daily cigarette
reduction of 80% or more (x2=3.00-i, p=0.08) (see Table 3.20). Those in the
NP group who reduced their daily smoking by 80% or more reported an
average reduction of 16.06 cigarettes a day and the PP group reported an
average reduction of 17.75 cigarettes a day.
Table 3.20
Smoking Abstinence and Reduction
________________________NP__________PP y2(df) p
80% Reduction 72% 48% 3.00(1) 0.08
Quit 4% 4% 0.00(1) 1.00
Participants self-reported on eight withdrawal symptoms daily,
including: craving; anger, irritability, or frustration; anxiety or nervousness;
difficulty concentrating; restlessness; hunger; awakening at night; and
depression. Symptoms were rated as none (0), slight (1), mild (2), moderate
(3), or severe (4). A mean score was derived for each week, and an average
of the scores for 10 weeks was computed for each group. There were no
differences in withdrawal symptoms between the two groups, except
65


awakening at night during week four (t=-2.3636.7, p=0.02). However, this may
be a spurious chance significant finding because multiple comparisons were
made (see Table 3.21). Although other studies have compared the baseline
withdrawal score and compared it to scores for a given week, this
computation was not completed for this study because the scores in this
study were relatively consistent throughout the study.
Table 3.21
Withdrawal Scores
NP PP
(mean SD) (mean SD) t(df) P
Craving
1 2.51 0.96 2.74 0.71 0.94(48) 0.35
2 1.93 1.05 2.35 1.22 1.28(47) 0.21
3 1.95 1.01 2.13 1.23 0.56(47) 0.58
4 1.76 1.06 1.84 1.09 0.25(48) 0.81
5 1.63 1.00 1.85 1.04 0.72(45) 0.48
6 1.58 0.95 1.97 1.22 1.16(41) 0.25
7 1.62 0.97 2.01 1.31 1.08(39) 0.29
8 1.67 1.04 2.19 1.33 1.35(36) 0.19
9 1.70 0.97 2.24 1.27 1.47(36) 0.15
10 1.57 0.98 2.14 1.19 1.56(35) 0.13
Weekly Average 1.83 0.71 2.12 0.89 1.27(48) 0.21
NP (mean SD) PP (mean SD) t(df) P
Anger, Irritability, Frustration
1 0.97 1.07 1.36 1.00 1.32(48) 0.19
2 0.89 1.02 1.05 0.98 0.58(46) 0.57
3 0.63 0.90 1.06 1.25 1.34(43.6) 0.17
4 0.72 0.99 0.92 1.08 0.70(48) 0.49
66


Table 3.21 (Cont.)
NP (mean SD) PP (mean SD) t(df) P
5 0.64 0.88 0.90 1.19 0.85(45) 0.40
6 0.48 0.86 0.85 1.08 1.26(41) 0.22
7 0.62 0.93 0.54 0.82 -0.27(39) 0.79
8 0.45 0.69 0.75 0.88 1.18(36) 0.24
9 0.23 0.42 0.50 0.96 1.07(36) 0.29
10 0.42 0.76 0.60 0.86 0.64(35) 0.53
Weekly Average 0.70 0.89 0.85 0.73 0.67(48) 0.51
NP (mean SD) PP (mean SD) t(df) P
Anxiety, Nervousness 1 0.80 0.92 1.15 1.01 1.28(48) 0.21
2 0.53 0.82 0.73 0.83 0.85(46) 0.40
3 0.49 0.74 0.94 1.24 1.55(39.5) 0.13
4 0.64 1.10 0.67 0.82 0.10(48) 0.92
5 0.46 0.67 0.63 0.83 0.76(45) 0.45
6 0.31 0.53 0.55 0.81 1.10(41) 0.28
7 0.31 0.62 0.42 0.72 0.53(39) 0.60
8 0.38 0.65 0.38 0.80 -0.02(36) 0.98
9 0.17 0.34 0.34 0.53 1.20(32.6) 0.24
10 0.35 0.54 0.50 0.70 0.69(35) 0.49
Weekly Average 0.53 0.75 0.64 0.58 0.60(48) 0.55
NP PP
(mean SD) (mean SD) t(df) P
Difficulty Concentrating 1 0.81 0.94 1.34 1.18 1.75(48) 0.09
2 0.66 1.06 0.82 0.94 0.59(47) 0.56
3 0.54 0.71 0.91 0.82 1.69(47) 0.10
4 0.62 1.05 0.56 0.87 -0.22(48) 0.83
5 0.43 0.80 0.37 0.62 -0.32(45) 0.75
6 0.26 0.50 0.51 0.97 1.09(31.7) 0.28
7 0.30 0.50 0.40 0.61 0.56(39) 0.58
8 0.28 0.50 0.49 0.75 1.02(36) 0.32
9 0.27 0.43 0.35 0.70 0.42(36) 0.67
10 0.19 0.39 0.34 0.77 0.73(35) 0.47
Weekly Average 0.52 0.77 0.61 0.58 0.46(48) 0.65
67


Table 3.21 (Cont.)
NP (mean SD) PP (mean SD) t(df) P
Restlessness
1 0.97 1.09 1.40 0.97 1.48(48) 0.14
2 0.91 1.10 0.97 0.97 0.22(47) 0.83
3 0.79 1.15 0.83 0.93 0.12(48) 0.90
4 0.74 0.99 0.76 0.97 0.05(48) 0.96
5 0.48 0.63 0.64 0.83 0.71(45) 0.48
6 0.49 0.62 0.48 0.55 -0.04(41) 0.97
7 0.39 0.57 0.32 0.60 -0.38(39) 0.71
8 0.43 0.69 0.61 1.05 0.64(36) 0.53
9 0.35 0.54 0.51 0.75 0.74(36) 0.47
10 0.34 0.63 0.44 0.63 0.47(35) 0.64
Weekly Average 0.66 0.82 0.71 0.57 0.25(48) 0.80
NP (mean SD) PP (mean SD) t(df) P
Hunger
1 1.12 1.24 1.11 0.97 -0.01(48) 0.99
2 0.77 1.24 0.88 0.99 0.35(47) 0.73
3 0.60 1.11 0.78 1.09 0.58(48) 0.56
4 0.63 1.07 0.51 1.03 -0.40(48) 0.69
5 0.37 0.74 0.47 0.55 0.50(45) 0.62
6 0.40 0.76 0.44 0.46 0.25(41) 0.81
7 0.25 0.43 0.44 0.80 0.99(39) 0.33
8 0.34 0.74 0.24 0.46 -0.50(36) 0.62
9 0.36 0.78 0.28 0.61 -0.35(36) 0.73
10 0.39 0.89 0.41 0.78 0.07(34) 0.94
Weekly Average 0.61 0.96 0.56 0.50 -0.24(36.1) 0.81
NP (mean SD) PP (mean SD) t(df) P
Awakening at Night
1 1.06 1.09 1.14 0.97 0.26(48) 0.80
2 0.94 1.21 0.89 0.99 -0.14(46) 0.89
3 0.99 1.17 0.84 0.92 -0.51(47) 0.62
4 1.16 1.25 0.50 0.67 -2.36(36.7) 0.02
5 0.87 1.16 0.48 0.77 -1.34(37.9) 0.19
6 0.61 0.67 0.71 1.10 0.35(41) 0.73
7 0.52 0.68 0.71 1.15 0.64(30.6) 0.53
8 0.41 0.76 0.46 0.75 0.20(36) 0.85
9 0.37 0.60 0.45 0.85 0.34(36) 0.74
10 0.40 0.78 0.46 0.73 0.22(35) 0.83
Weekly Average 0.90 0.99 0.68 0.66 -0.93(48) 0.36
68


Table 3.21 (Cont.)
NP (mean SD) PP (mean SD) t(df) P
Depression 1 0.83 1.15 0.98 1.27 0.44(48) 0.66
2 0.70 1.12 0.66 1.13 -0.13(46) 0.90
3 0.66 1.15 0.63 0.96 -0.10(47) 0.92
4 0.72 1.26 0.53 0.91 -0.62(48) 0.54
5 0.64 1.10 0.41 0.64 -0.89(35.1) 0.39
6 0.37 0.75 0.66 0.97 1.11(41) 0.27
7 0.24 0.47 0.41 0.71 0.88(39) 0.39
8 0.27 0.48 0.64 1.00 1.43(23.8) 0.17
9 0.12 0.36 0.43 0.83 1.50(26.5) 0.15
10 0.24 0.60 0.49 0.84 1.02(35) 0.32
Weekly Average 0.62 1.01 0.57 0.73 -0.23(48) 0.82
In addition to the participants self-report of withdrawal symptoms, the
research assistant rated all participants on four symptoms, including anger,
anxiousness, restlessness, and depression. Average ratings were similar for
both groups on all measures (see Table 3.22).
Table 3.22
Observer Rating
NP (mean SD) PP (mean SD) U P
Anger 0.18 0.37 0.10 0.13 -1.00 0.32
Anxiousness 0.24 0.33 0.24 0.36 -0.12 0.99
Restlessness 0.36 0.42 0.33 0.32 -0.24 0.82
Depression 0.56 0.55 0.33 0.36 -1.75 0.19
69


At the one-month follow-up, participants were asked to discuss their
experiences, most importantly, their perceived efficacy, of the nicotine patch
(see Table 3.23). Of those who completed the follow-up interview, 70% of
those in the NP group and 47% of the PP group reported that they felt the
patch was effective. Participants were also asked to describe the reasons
why they felt the patch was or was not effective. Several explanations were
given, including 10% in the NP group and 21% in the PP group simply felt that
the patch was not working, 20% in the NP group and 32% in the PP group
reported craving tobacco while wearing the patch, and five percent in both the
NP and PP groups did not feel motivated to quit. Of those who felt the patch
was effective, 55% in the NP group and 32% in the PP group reported less
craving while wearing the patch.
Table 3.23
Efficacy
NP PP x2(df) P
Felt patch was effective 70% 47% 2.06(1) 0.15
Less Craving 55% 32%
Patch wasnt working 10% 21%
Still craving 20% 32%
Not motivated to quit 5% 5% 2.51(4) 0.64
70


Participants were also asked to describe the primary reported reason
of why they continued to smoke while wearing the patch or why they began
smoking once the patch was removed (see Table 3.24). Craving was the
primary reason for continued smoking, with 63% of the NP group and 83% of
the PP group giving this explanation.
Table 3.24
Reasons Why Participants Continued to Smoke
NP______________PP y2(df) P
Craving 63% 83%
Stress or nervousness 21% 17%
Never quit 11% 0%
Other 5% 0% 3.45(3) 0.33
Predictors of Smoking Cessation/Reduction
Intake and demographic variables, including participant ethnicity, age
at study intake, gender, SES, and psychiatric comorbidity and the variables
thought to be related to smoking cessation (e.g., fewer nicotine dependence
symptoms, older age of regular smoking, higher levels of motivation to quit,
and lower levels of smoking) were tested using chi-square and independent t-
71


tests (see Table 3.25). Only gender was found to be predictive of smoking
cessation in this sample (x2=10.15i, p=0.006).
Table 3.25
Predictors of Smoking Cessation
Quit Did Not Quit Score (df) P
(n=4) (n=46)
Gender
Male 0% 70% X2=10.15(1) 0.006
Female 8% 22%
Ethnicity
White 6% 68%
African-American 2% 4% X2=3.49(3) 0.32
Hispanic 0% 14%
SES (mean SD) 48.50 12.90 42.43 15.72 t=-0.75(42) 0.46
Nicotine Dep. 8% 80% X2=0.59(1) 1.00
Nicotine Dep. Sx (mean SD) 5.50 0.58 4.61 1.72 t=-1.02(48) 0.31
Most Cigarettes (mean SD) 25.25 12.53 20.61 7.20 t1.17(48) 0.25
Motivation (mean SD) 3.75 0.96 3.52 0.91 t=-0.48 0.64
Age Reg Smoking (mean SD) 13.75 1.71 12.46 1.82 t=-1.37(48) 0.18
GAD 0% 4% X2=0.18(1) 1.00
MDD 4% 18% x2=1.99(1) 0.21
DD 0% 4% X2=0.18(1) 1.00
72


Table 3.25 (Cont.)
Quit (n=4) Did Not Quit (n=46) Score (df) P
ADHD 2% 10% X2=0.70(1) 0.41
ODD 6% 28% x2=3.26(1) 0.11
CD 6% 64% X2=0.05(1) 1.00
Because of the low rate of smoking cessation, a similar procedure was
used to examine whether intake, demographic, and other variables (e.g.,
fewer nicotine dependence symptoms, older age of regular smoking, higher
levels of motivation to quit, and lower levels of smoking) were related to
smoking reduction, operationally defined as an 80% reduction of cigarettes
smoked a day (see Table 3.26). There were no variables that were predictive
of smoking reduction.
Table 3.26
Predictors of Smoking Reduction
80%
Reduction No Reduction Score (df) p
__________________________(n=30)________(n=20) __________________
Gender
Male 38% 32% x2=1-59(1) 0.21
Female 22% 8%
73


Table 3.26 (Cont.)
80% Reduction No Reduction Score (df) P
(n=30) (n=20)
Ethnicity
White 40% 34%
African-American 6% 0% X2=2.98(3) 0.39
Hispanic 10% 4%
Other 4% 2%
SES (mean SD) 43.75 15.38 42.05 15.90 t=-0.36(42) 0.72
Nicotine Dep. 54% 34% X2=0.28(1) 0.67
Nicotine Dep. Sx (mean SD) 4.87 1.48 4.40 1.93 t=-0.97(48) 0.34
Most Cigarettes (mean SD) 21.63 7.90 20.00 7.39 t=-0.73(48) 0.47
Motivation (mean SD) 3.70 0.84 3.30 0.98 t=-1.55(48) 0.13
Age Reg Smoking (mean SD) 12.57 2.11 12.55 1.36 t=-.03(48) 0.98
GAD 4% 0% X2=1.39(1) 0.51
MDD 14% 8% X2=0.08(1) 1.00
DD 2% 2% X2=0.09(1) 1.00
ADHD 10% 2% X2=1.55(1) 0.38
ODD 24% 10% X2=1.20(1) 0.27
CD 42% 28% N) II o o o 1.00
74


Gender Differences
Gender differences in adolescent smokers have not been widely
studied; therefore, comparisons were made to gain a better understanding of
these groups (see Table 3.27). Females began smoking significantly later
than males, reporting a mean age of smoking onset to be 12.73 years
whereas males began smoking at 11.20 years (U=-2.29, p=0.02). Age of
regular smoking was similar for both females and males and both reported
smoking a similar number of cigarettes a day (female mean=17.67; male
mean=16.37). Females had higher mean CO levels than males, 16.60 ppm
and 13.64 ppm respectively, a difference that was trending towards
significance (t=-1.7633, p=0.09). Both females and males reported an average
of 1.7 quit attempts, both rated their motivation to quit smoking to be close to
3.5, and both expressed an interest in first wanting to quit smoking at the age
of 14.
Table 3.27
Smoking Variables by Gender
Females (mean SD) Males (mean SD) score P
Age of Smoking 12.73 1.49 11.20 2.46 U=-2.29 0.02
Initiation
Age of Regular Use 13.27 1.10 12.26 2.01 U=-1.47 0.14
75


Table 3.27 (Cont.)
Females (mean SD) Males (mean SD) score P
Initiation and Regular Use Interval 0.53 0.83 1.06 1.35 t=1.39(48) 0.17
Age of 1st Quit Attempt 14.87 0.99 14.11 1.69 t=-1.60(41) 0.12
Motivation to Quit 3.47 0.74 3.57 0.98 t=0.37(48) 0.71
Quit Attempts 1.73 1.58 1.71 1.73 t=-0.04(48) 0.97
Screen Cigarettes 17.62 7.53 16.37 5.70 t=-0.67(48) 0.51
Most Cigarettes 21.73 8.29 20.60 7.49 t=-0.45(48) 0.65
Screen CO 16.60 5.17 13.64 4.20 t=-1.76(33) 0.09
Females and males had equal Fagerstrom scores, suggesting that
their level of nicotine dependence was similar. On the CIDI-SAM interview,
however, 100% of the female participants received a diagnosis of nicotine
dependence whereas only 86% of males were nicotine dependent, and this
finding was trending towards significance (x2=5.042, p=0.08). In addition,
females reported significantly more symptoms of nicotine dependence
(mean=5.60) than males (mean=4.26) (t=-3.3644.3, p=0.002) (see Table 3.28).
76


Table 3.28
Nicotine Dependence by Gender
Females Males value P
Nicotine Dependence 100% 86% X2=5.04(2) 0.08
Dependence Symptoms (mean SD) 5.6 0.99 4.26 1.76 t=-3.36(44.3) 0.002
Fagerstrom (mean SD) 7.40 1.40 7.44 1.16 t=0.11(47) 0.92
In terms of adverse events, both females and males reported an equal
number at baseline (mean=1.5 symptoms), but females reported a greater
number (mean=12.93 reports) throughout the course of the study when
compared to males (mean=8.00 reports), a difference that was trending
towards significance (t=-1.7148, p=0.09) (see Table 3.29).
Table 3.29
Total Baseline Symptoms and Adverse Events by Gender
Female (mean SD) Male (mean SD) t(df) P
Baseline Symptoms 1.57 1.95 1.53 1.32 -0.08(44) 0.94
Adverse Events 12.93 11.23 8.00 8.48 -1.71(48) 0.09
Average withdrawal scores were similar for females and males on all
symptoms, except craving and depression. Females reported a significantly
77


lower craving score than males (t=3.7748, p=0.005) and a significantly higher
depression score than males (U=-2.85, p=0.004). Females also had a higher
rate of awakening at night, but this difference was not enough to reach
significance (U=-1.87, p=0.06) (see Table 3.30).
Table 3.30
Weekly Average of Withdrawal Symptoms by Gender
Females Males score (df) P
Craving 1.39 0.73 2.23 0.72 t=3.77(48) 0.005
Anger, Irritability, Frustration 0.95 0.74 0.70 0.84 U=-1.66 0.10
Anxiety, Nervousness 0.66 0.63 0.55 0.68 U=-0.70 0.48
Difficulty Concentrating 0.72 0.77 0.50 0.64 U=-0.76 0.45
Restlessness 0.73 0.67 0.67 0.72 U=-0.39 0.70
Hunger 0.44 0.56 0.65 0.83 U=-0.70 0.48
Awakening at Night 0.98 0.68 0.70 0.90 U=-1.87 0.06
Depression 1.07 0.91 0.39 0.78 U=-2.85 0.004
78


CHAPTER 4
DISCUSSION
Recruitment from a substance use treatment center yielded a large
number of adolescents who were interested in participating in a smoking
cessation study, although we did have trouble recruiting those who smoked
enough to meet criteria for nicotine patch therapy. Other researchers have
also demonstrated the desire of adolescents to stop smoking (CDC, 1994;
Karle et al., 1994; Hurt et al., 2000). As with most adolescent research,
participants had to have parental permission to enroll, which did eliminate a
few potential participants. Overall, however, parents were receptive to the
study. Because participants were compensated for their time, it is important to
note that some individuals may have enrolled seeking the monetary
compensation rather than being seriously motivated to stop smoking.
Another problem that has been identified with adolescent smoking
cessation programs is the feasibility of nicotine patch therapy. In this study,
feasibility was measured by adherence to the patch protocol and research
visit attendance. Clients in this treatment program were very interested in
smoking cessation and the majority reportedly adhered to the patch protocol.
79


It was impossible to determine whether the participants wore their patches
appropriately outside of the treatment facility, but participants were willing to
meet with researchers daily while at the treatment center. Some participants
mentioned that they had given their extra patches to friends or family
members to use; in retrospect it would have been useful to include a question
that would have addressed this issue.
Abstinence rates in this study were lower than rates reported in other
studies of adolescent nicotine patch therapy (Hanson et al., 2003; Hurt et al.,
2000; Moolchan et al., 2005; Smith et al., 1996), but this may be because the
participants in this study were more nicotine dependent, evidenced by earlier
age of regular smoking and the high number of nicotine dependence
symptoms. In addition, these adolescents may have had a harder time giving
up smoking while also trying to give up other drug use (e.g., marijuana).
Although only four participants reported smoking abstinence while in the
study, more than half of participants (60%) reduced their daily smoking by
more than 80%. Previous studies of adolescent nicotine patch therapy have
also reported a significant decrease in daily cigarette use (Hurt et al., 2000;
Smith et al., 1996).
Gender was the only variable that predicted smoking cessation;
interestingly all participants who quit smoking in this study were female. The
reasons for this finding warrant further exploration. In addition, identifying
80


other predictors of adolescent smoking cessation is needed to help develop
appropriate and effective smoking cessation programs for teens. This has a
long-term impact because more than one-half of the adolescent smokers who
quit remain abstinent as young adults (Chassin, Presson, Sherman, &
Edwards, 1990), it will be very helpful for future research to elucidate and
refine the variables related to smoking cessation in adolescents.
Participants in this study reported adverse event rates similar to other
studies that examined the safety of nicotine patch therapy with adolescents
(Hanson et al., 2003; Hurt et al., 1994; Hurt et al., 2000; Smith et al., 1996).
Interestingly, participants in both the nicotine patch and placebo groups
generally reported equal numbers of symptoms, which likely indicates that
participants were reporting symptoms that may not be related to wearing the
nicotine patch. Although the reports of adverse events in adolescents were
higher than in some of the adult literature, the symptoms that were
experienced were not considered to be as troublesome as those experienced
by adults (Bohadana et al., 2000; Davidson et al., 1998; Fiore et al., 1994;
Jorenby et al., 1995; Paoletti et al., 1996; Schuurmans et al., 2004). Two
subjects did report nausea/vomiting and it is likely that they were experiencing
nicotine toxicity. The medical director met with these participants and it was
discovered that they were smoking heavily while wearing the patch. When
they stopped smoking, their symptoms subsided. Most importantly, no
81


participants withdrew from the study because of adverse events and there
were no reports of severe or life threatening symptoms; therefore, nicotine
patch therapy did appear to be relatively safe for this sample of adolescent
smokers with substance and behavioral problems.
Teens in substance abuse treatment commonly have comorbid
conditions. Therefore, several participants in this study were also taking
psychotropic medication while wearing the patch, allowing for an examination
of the interaction of the nicotine patch with other medications. Adverse events
were not found to be higher in those who were wearing the nicotine patch and
also taking prescription medication. Thus, using the nicotine patch in
conjunction with prescription medication typically prescribed to adolescents
with co-occurring disorders appeared to be safe in these individuals, but
further investigation with a larger sample and more systematic study is
warranted.
Withdrawal symptoms are a common reason given for continued
smoking, and researchers have suggested that nicotine patch therapy is a
possible option for relieving withdrawal symptoms in smokers who are trying
to quit. Studies have shown that regular adolescent smokers experience
withdrawal symptoms when they go without nicotine (Colby et al., 2000;
DiFranza et al., 2000; Rojas et al., 1998), and it is believed that alleviating
withdrawal from nicotine may increase the chances of smoking abstinence
82


(Rose, Herskovic, Trilling, & Jarvik, 1985; West, Hajek, & Belcher, 1989).
Therefore, using a smoking cessation aid that allows a gradual reduction of
nicotine seems as if it would be advantageous to adolescents. Research on
gender differences and withdrawal symptoms has found that females often
report higher rates of symptoms than males (Hatsukami, et al., 1995; McKee,
OMalley, Salovey, Krihnan-Sarin, & Mazure, 2005; Perkins, 1999; Pomerleau
et al., 1994; Svikis, Hatsukami, Hughes, Carroll, & Pickens, 1986); however,
in this study, females generally reported similar rates of symptoms as males,
with the exception of depression and craving. Overall, the nicotine patch did
not appear to be beneficial in reducing withdrawal symptoms in this study, but
this could be due to the low number of participants who actually quit smoking.
Furthermore, participants in this study were poly-substance users enrolled in
a substance abuse treatment program; therefore, it was difficult to determine
if the withdrawal symptoms that the participants were experiencing were
related to smoking reduction or because of withdrawal from other substances
of abuse.
Participants in this study reported an average age of smoking initiation
of 11 years and regular smoking at 12 years, ages similar to those reported
for adolescents seeking treatment for smoking (Robinson, Berlin, &
Moolchan, 2004). These ages are much younger, however, than reported in
studies of adolescent smokers in the general population (Baugh, Hunter,
83


Webber, & Berenson, 1982; Breslau, 1993; Breslau, Fenn, & Peterson, 1993;
DeWit, Offord, &Wong, 1997; Giovino, 1999; Harrell, Bangdiwala, Deng,
Webb, & Bradley, 1998; Siqueira, Rolnitzky, & Rickert, 2001; Lando et al.,
1999). Previous findings have stated that there is a two- (Baugh et al., 1982)
and three-year interval (Breslau et al., 1993; DiFranza, 2002, McNeill, 1991;
Colby et al., 2000) from age of smoking initiation to age of regular smoking,
but this study suggests that adolescents in treatment for substance and
behavioral problems progress to an age of regular smoking less than one
year after they first experimented with tobacco. Others have also found that
adolescents may become regular smokers at a more rapid rate than once
thought (Robinson et al., 2004; Siqueira et al., 2001). Therefore, with younger
ages of regular smoking and rapid development of nicotine dependence, it
appears that adolescents in treatment for substance and behavioral problems
would benefit from smoking cessation programs designed for this special
subgroup of teen smokers.
Evidence suggests that an increased risk for a depressive episode
following smoking cessation among individuals with a history of major
depression is possible (Myers, 1999), so monitoring changes in depressive
symptoms during the process of smoking reduction and cessation was
important. The Carroll Rating Scale for Depression was administered at
intake, last day, and at the follow-up interview in order to monitor depressive
84


symptoms. Fewer depressive symptoms were reported at the one-month
follow-up interview in both groups. However, it is possible that participants
depression may have been affected by the substance abuse treatment and
treatment of psychiatric disorders and not from wearing the patch, therefore
further examination of the role nicotine patch therapy plays in adolescent
depression is needed.
Females reported a significantly higher number of nicotine dependence
symptoms than males, a finding that supports previous research (OLoughlin,
2003; DiFranza, 2002). There are a few reasons why females may report
more dependence symptoms than males; (1) they are more sensitive to the
effects of nicotine; (2) they experience more nicotine dependence symptoms;
and (3) simply, they are more likely to report nicotine dependence symptoms
(OLoughlin, 2003).
Males began smoking more than one year before females, but there
was not a gender difference between ages of regular smoking, suggesting
that females start smoking later than males, but progress to regular smoking
more quickly. This is an example of the telescoping effect commonly seen in
females referred for substance abuse treatment (Haas & Peters, 2000;
Institute of Medicine, 1991; Orford & Keddie, 1985; Piazza, Vrbka, & Yeager,
1989; Zilberman, Tavares, & el-Guebaly, 2003). They initiate their drug use at
a later age, but progress to abuse or dependence more quickly than males,
85


resulting in the same degree of severity of drug use overall by treatment
admission (Mezzich, Moss, Tarter, Wolfenstein, Hseih, & Mauss, 1994;
Robins & McEvoy, 1990; Whitmore, Mikulich, Thompson, Riggs, Aarons &
Crowley, 1997).
A common concern expressed by youth, particularly young women, is
that they will gain weight if they quit using tobacco. This fear has been
supported by adult literature that has shown that adult smokers generally
weigh less than nonsmokers and gain weight after they quit smoking
(SAMHSA, 2001). At this point, there have not been any studies that have
examined whether weight changes occur among adolescents who quit
smoking. Our participants were weighed before the study began, throughout
the course of the study, and at the one-month follow-up interview. There was
not a significant weight gain or reduction for any participants, but it is difficult
to conclude that adolescents who stop smoking will not gain weight because
few in this study actually achieved complete abstinence. Also, we only
measured weight change for a couple of months and lifetime weight changes
may be different. The majority of participants did significantly reduce their
smoking, however, and because there were no drastic weight changes, it can
be presumed that it is unlikely that adolescents would gain weight if they
stopped smoking. Most importantly, it should be emphasized to adolescents
that changes in body weight that occur after smoking cessation are generally
86


small, if not insignificant, and the health benefits of smoking cessation greatly
outweigh any risks associated with weight gain (Fiore et al., 2000; SAMHSA,
2001).
Conclusions
Nicotine patch therapy appears to be feasible in adolescents with
substance and behavioral problems. Reports of adverse events in this study
and past studies demonstrate that the nicotine patch is relatively safe to use
with adolescents, as well as using with adolescents with comorbid conditions
who are also taking psychotropic medication. The patch did not appear to
reduce withdrawal symptoms, but this could be because few participants quit
smoking or because participants were experiencing withdrawal symptoms
from other drugs of abuse.
Nicotine patch therapy in its current form may not be a powerful
enough program to achieve smoking abstinence with adolescents with
substance and behavioral problems, but it is important to point out that it was
effective in reducing smoking rates. Focusing on smoking reduction may be a
more realistic approach to use with this population. Because the majority of
smoking cessation programs that have been used with adolescents were
originally designed for adults, developing adolescent-specific programs may
produce higher abstinence rates. In addition, pairing nicotine patch therapy
87