Psychology of Addictive Behaviors 2005, Vol. 19, No.

2, 192198

Copyright 2005 by the American Psychological Association 0893-164X/05/$12.00 DOI: 10.1037/0893-164X.19.2.192

Effects of Transdermal Nicotine During Imaginal Exposure to Anxiety and Smoking Cues in College Smokers
Sandra Baker Morissette and Tibor P. Palfai
Boston University

Suzy Bird Gulliver

Veterans Affairs Boston Health Care System, Boston University School of Medicine, and Boston University

David A. Spiegel and David H. Barlow

Boston University and Boston University School of Medicine
In a 2 (patch) 2 (smoking) 2 (anxiety) mixed design, 52 undergraduate smokers randomly received a nicotine (21 mg) or placebo patch. After a 4-hr nicotine absorption/deprivation period, participants imagined several scenarios varying in cue content: (a) anxiety plus smoking, (b) anxiety, (c) smoking, and (d) neutral. Although smoking urge increased in both the nicotine and placebo conditions after the absorption/deprivation period, those who received the placebo reported significantly greater urge. During the cue reactivity trials, a significant Patch Smoking Anxiety interaction effect was observed for urge. However, participants who received nicotine still experienced moderate urges, indicating that nicotine did not attenuate cue-elicited urge. Transdermal nicotine did not diminish anxiety during the absorption/deprivation period or in response to the cues.

Transdermal nicotine is frequently prescribed to assist individuals with smoking cessation. The rationale for nicotine replacement therapies (NRTs), such as the nicotine patch, is that smokers may slowly taper from nicotine, the primary addictive component of smoking (Ashton & Golding, 1989; Balfour, 1990). Transdermal nicotine is marketed as a means of curbing subjective withdrawal symptoms, including urge to smoke and anxiety. Urge to smoke is commonly perceived as the most aversive part of tobacco abstinence (e.g., Gritz, Carr, & Marcus, 1991; Shiffman & Jarvik, 1976), making NRT appealing. Although NRT may aid physiological and subjective withdrawal from nicotine, the extent to

Sandra Baker Morissette, Center for Anxiety and Related Disorders, Boston University. Tibor P. Palfai, Department of Psychology, Boston University. Suzy Bird Gulliver, Psychology Service, Veterans Affairs Boston Health Care System; Department of Psychiatry, Boston University School of Medicine; and Department of Psychology, Boston University. David Spiegel and David H. Barlow, Center for Anxiety and Related Disorders, Boston University; Department of Psychology, Boston University; and Department of Psychiatry, Boston University School of Medicine. Sandra Baker Morissette is now at the Psychology Service, Veterans Affairs Boston Health Care System, and the Department of Psychiatry, Boston University School of Medicine. These data were originally presented at the annual meeting of the Association for the Advancement of Behavior Therapy, Philadelphia, Pennsylvania, November 2000. This research was supported by an American Psychological Association Dissertation Award and a Clara Mayo Dissertation Award. Nicotine and placebo patches were provided by SmithKline Beecham (now GlaxoSmithKline). We thank Stephen T. Tiffany and Brian Carter for their availability in responding to questions about the imaginal cue exposure procedures. Correspondence concerning this article should be addressed to Sandra Baker Morissette, Veterans Affairs Boston Health Care System, Psychology Service (116B), 251 Causeway Street, Boston, MA 02114. E-mail: sandra.morissette@med.va.gov 192

which it reduces urges in response to everyday smoking cues is unclear. For example, common triggers of smoking urge include negative affect (Payne, Schare, Levis, & Colletti, 1991; Tiffany & Drobes, 1990; Zinser, Baker, Sherman, & Cannon, 1992), smoking-related thoughts, and environmental cues for smoking (Drobes & Tiffany, 1997; Elash, Tiffany, & Vrana, 1995; MaudeGriffin & Tiffany, 1996). Despite the common use of the nicotine patch, little controlled research has investigated how transdermal nicotine influences urge response to these salient triggers. In the current study, we explored how the nicotine patch affected both smoking urge and anxiety responses during imaginal exposure to smoking and anxiety cues. Although negative affect in general has been documented to influence smoking, of particular interest in the present study was the influence of anxiety cues and responses, due to the common occurrence of anxiety during nicotine withdrawal and its role as a risk factor for relapse (Shiffman, 1982). Smokers often anecdotally indicate that they smoke in response to feeling anxious. Data also indicate that anxiety influences smoking topography (i.e., increased puff volume; C. S. Pomerleau & Pomerleau, 1987). Thus, anxiety not only is a common symptom of nicotine withdrawal, but it can also serve as a salient trigger of smoking behavior. Knowledge of how nicotine affects anxiety and smoking urges during high-risk trigger situations, such as those involving anxiety and smoking cues, may help specify the conditions under which NRT is or is not effective. Several studies have investigated whether nicotine from cigarettes, and not smoking per se, is anxiolytic (Gilbert, Robinson, Chamberlin, & Spielberger, 1989; Hatch, Bierner, & Fisher, 1983; Juliano & Brandon, 2002; Kassel & Unrod, 2000; O. F. Pomerleau, Turk, & Fertig, 1984). However, to date, no studies have examined the potential anxiolytic effects of nicotine when administered transdermally. Because transdermal nicotine is administered continuously, and results in much slower absorption than tobacco smoking, it may or may not affect anxiety in the same manner.

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Indeed, only one published study to date investigated the effects of transdermal nicotine during exposure to smoking cues (Tiffany, Cox, & Elash, 2000). Although this study did not examine the influence of transdermal nicotine on anxiety, it did investigate the effects of transdermal nicotine on negative affect, a broader construct that can include anxiety (Brown, Chorpita, & Barlow, 1998). In Tiffany et al.s (2000) study, participants completed two cue reactivity sessions separated by 6 hr. During each session, they were exposed to both imaginal and in vivo cues, containing either smoking or neutral content. Participants were unmedicated during the first session and wore either a nicotine (21 mg) patch or placebo patch during the second session. Overall, smoking urge increased in both patch groups across the 6-hr experimental period, but significantly more so in the placebo group. The placebo group also experienced increases in negative mood levels across the 6-hr experimental period, whereas the nicotine group experienced no change in negative mood. With regard to the cue reactivity trials, cigarette stimuli generated greater negative affect ratings than neutral stimuli, but no significant interaction effects were observed by patch type. Participants reported significantly more craving in response to cigarette cues than in response to neutral cues, regardless of patch type. During the second session, the nicotine group reported lower craving levels across each of the cigarette and neutral trials. However, a comparison of changes in craving in response to cigarette and neutral cues across the two sessions revealed that the placebo group experienced an increase in craving, whereas the nicotine group experienced no change in craving reactivity to the cues. Thus, although nicotine appeared to reduce craving elicited by deprivation, it did not have a significant impact on craving elicited by the smoking cues. The current study expanded on Tiffany et al.s (2000) research by incorporating explicit mood triggers into the experimental paradigm and by specifically examining the effects of transdermal nicotine on anxiety responses. Our primary aim was to evaluate whether transdermal nicotine would attenuate smoking urge and anxiety in response to smoking and anxiety cues. We predicted that if this were true, then nicotine-deprived smokers (placebo) would have a greater urge and anxiety responses to the imaginal cues than nondeprived (nicotine) smokers. Although Tiffany et al. did not find that the nicotine patch selectively inhibited urge or negative affect responses to smoking cues, this has not been examined with anxiety ratings or when participants are confronted with specific anxiety cues. An accumulating body of research suggests that nicotine can be anxiolytic when administered via cigarettes, but this has yet to be established with transdermal nicotine.

history that contraindicated use of the nicotine patch (e.g., heart disease, high blood pressure, allergy to adhesive tape, pregnancy); or were currently taking anxiolytics, antidepressants, cardiac medications (e.g., beta blockers), asthma medication, or over-the-counter diet medications. Participants were also ruled out for possible alcohol or substance disorders by scoring 6 or higher on the Drug Abuse Screening Test (Skinner, 1982) or greater than 12 on the Alcohol Dependence Scale (Skinner & Allen, 1982). Finally, participants who endorsed current Axis I disorders were excluded. A diagnostic interview (described below) conducted during the course of the assessment determined final eligibility. On the basis of this interview, 2 participants who had multiple comorbid diagnoses were excluded with replacement. Both received a placebo patch. One additional participant, who had received a nicotine patch, was discontinued from the study when she became ill (i.e., vomited) during the assessment. Thus, of the 55 undergraduate, daily smokers who participated in the study, 52 were included in the final analyses (26 per patch group). No significant differences were observed between patch groups on demographic characteristics. Overall, participants were largely Caucasian (78.9%; Asian, 11.5%; Latino, 9.6%) and had an average age of 20.6 years (SD 1.7). Gender was evenly distributed across groups (female 55.8%). Participants smoked an average of 19.8 cigarettes per day (SD 4.2) for 5.1 years (SD 3.1), and had made 2.1 quit attempts (SD 2.6). A 2 2 2 mixed, between- and within-subjects design was used, with patch group (nicotine vs. placebo) as the between-subjects factor and anxiety cues (presence or absence) and smoking cues (presence or absence) as the within-subject factors.

Measures and Apparatus

Pre- and postpatch absorption measures. Prior to and following a 4-hr patch absorption period (or nicotine deprivation period, in the case of the placebo group), participants completed measures of urge and withdrawal. Replicating Tiffany et al. (2000), we administered the Questionnaire of Smoking Urges (QSU; Tiffany & Drobes, 1991) and the Smoking Withdrawal Questionnaire (SWQ; Shiffman & Jarvik, 1976). The QSU is a 32-item measure that comprises two factors demonstrating good internal consistency: Factor 1 includes items related to intention/desire to smoke and anticipation of pleasure. Factor 2 includes items related to anticipation of relief of negative affect/withdrawal and urgent desire to smoke. The SWQ is a 25-item measure containing four factors, including Stimulation, Desire to Smoke, Physical Symptoms, and Psychological Symptoms. Participants also completed ratings of current anxiety on a Likert scale that ranged from 0 (none) to 100 (as intense as imaginable). This single-item measure of anxiety is commonly used in the anxiety literature (e.g., Craske, Street, & Barlow, 1989; Turner, Beidel, & Jacob, 1994; Wilhelm & Roth, 1997) and was chosen because of the studys use of multiple assessments. Patch absorption/deprivation period. Several measures were administered during the first half of the 4-hr patch absorption/deprivation period to assess stable smoking and anxiety characteristics. The Anxiety Disorders Interview ScheduleIV (Brown, DiNardo, & Barlow, 1994) was administered to verify absence of current anxiety, mood, or substance disorders. Separate analyses exploring interrater reliability of the Anxiety Disorders Interview ScheduleIV have shown good to excellent diagnostic agreement (Brown, DiNardo, Lehman, & Campbell, 2001). Self-report measures were selected from those used extensively in past research using imaginal cue reactivity procedures (e.g., Drobes & Tiffany, 1997; Tiffany et al., 2000) for comparability across studies. The Fagerstro m Test for Nicotine Dependence (FTND; Heatherton, Kozlowski, Frecker, & Fagerstro m, 1991) is a 6-item measure of nicotine dependence that has demonstrated convergent validity with biochemical indices of heaviness of smoking. An 18-item measure identifying various types of smoking, the Reasons for Smoking Questionnaire (Ikard, Green, & Horn, 1969) includes six factors with good internal consistency: (a) Habitual, (b) Addictive, (c) Negative Affect Reduction, (d) Pleasurable Relaxation, (e) Stimulation, and (f) Sensorimotor Manipulation. Although the construct validity of this mea-

Method Participants and Design

Participants were undergraduate, daily smokers who were recruited through flyers and newspaper and Web site advertisements distributed throughout local universities and the community. Participants were screened by telephone to determine inclusion and exclusion criteria. Participants were eligible if they were at least 18 years of age, daily moderate to heavy smokers (15 40 cigarettes per day [cpd]), not currently considering quitting or changing their smoking (to minimize fluctuations in daily smoking), and willing to deprive themselves of smoking during the study and wear a nicotine or placebo patch. Participants were excluded if they had a previous history of using the nicotine patch; endorsed a medical

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MORISSETTE, PALFAI, GULLIVER, SPIEGEL, AND BARLOW ted. Pilot testing of the revised scripts indicated that they effectively induced anxiety (vs. depression, anger, or other mood). After presentation of the scripts, the patch was removed. To assess the integrity of the double-blind procedure, participants and the clinician were then asked to guess whether they had received a nicotine patch or a placebo patch.

sure has been questioned (Shiffman, 1993), we chose it for its comparability to Tiffany et al. (2000). The Affect Intensity Measure (Larsen & Diener, 1987) is a 40-item measure of strength of affective reactions with good testretest reliability and convergent validity. The Questionnaire Upon Mental Imagery (Sheehan, 1967) contains 35 items designed to measure a persons ability to use imagery in seven sensory modalities (visual, auditory, cutaneous, kinaesthetic, gustatory, olfactory, and organic). Postexposure trial ratings. Following each exposure, participants completed a 10-item, brief version of the QSU (QSUBrief; Cox, Tiffany, & Christen, 2001) to determine how they responded during the most recent exposure scenario. This measure has high internal consistency and a factor structure similar to that of the QSU (Tiffany & Drobes, 1991). We selected the briefer version to facilitate repeated assessment. Participants also completed average anxiety ratings experienced during the script using a 0-to-100-point scale (0 none, 100 as much as imaginable). Vividness ratings were obtained to measure how clearly participants were able to imagine the scripts (0-to-100-point scale; 0 not vivid at all, 100 extremely vivid).

Data Analyses
Ratings from each of the two script presentations from each category were averaged to create dependent measures of responses to the four script types (smoking plus anxiety, anxiety, smoking, neutral). The primary data-analytic strategy focused on the effect of the nicotine patch on measures of cue reactivity. We conducted separate 2 2 2 (Group Smoking Cues Anxiety Cues) mixed-design analyses of variance to analyze the study hypotheses using each of the postexposure trial measures.

Results Manipulation Check

Double blind. We calculated percentage accuracy scores to determine whether participants and the investigator were able to accurately guess whether the participant had received a nicotine patch or a placebo patch. Participants and the investigator were accurate 53.8% and 65.4% of the time, respectively. Thus, the medication blind appeared to be adequately maintained. Vividness. Comparisons between patch groups across script types were conducted to ensure that the results could not be attributed to differences in how clearly participants were able to imagine the scripts. Results did not support differences between patch groups in script vividness ratings (Patch Smoking Anxiety), F(1, 50) 0.45, p .50, supporting the equivalence of the imaginal procedures for both groups. Average vividness scores for each of the scripts (100 extremely vivid) were as follows: anxiety plus smoking cues: 74.8, SD 14.0; anxiety cues alone: 78.0, SD 13.4; smoking cues alone: 80.6, SD 14.0; and neutral cues: 75.4, SD 15.7. Anxiety manipulation. We conducted paired samples t tests to determine whether the anxiety script sufficiently induced anxiety in comparison to the neutral script. Scripts that included smoking cues were not included in this analysis because previous studies have demonstrated that smoking cues are also powerful elicitors of negative affect (e.g., Burton & Tiffany, 1997). Average anxiety ratings were significantly higher in response to the anxiety script than in response to the neutral script, t(51) 11.70, p .01 (Ms 50.8 and 14.6 for the anxiety and neutral scripts, respectively). Thus, the anxiety script appeared to elicit moderate levels of anxiety, supporting the anxiety-inducing utility of the script.

Procedure
Participants attended one experimental session that lasted 6.5 hr. They were each paid $70 for their participation plus an additional $5 reimbursement for lunch. At the start of each session, participants completed an informed consent form. They then smoked one cigarette and waited a standardized period of 30 min, at the end of which a nicotine (21 mg; n 26) or placebo (n 26) patch was randomly applied to the upper dominant smoking arm in a double-blind fashion. A Nicoderm 21 mg patch (SmithKline Beecham, now GlaxoSmithKline; Research Triangle Park, NC) was used. Participants then waited a period of 4 hr (nicotine absorption/ deprivation period). The 4-hr absorption period was selected on the basis of the manufacturers suggestions of a period of 2 hr to 4 hr for transdermal nicotine to reach constant levels in the blood (Physician Representative, SmithKline Beecham [now GlaxoSmithKline], personal communication, December 14, 1999). During the first half of the nicotine absorption/ deprivation period, a diagnostic interview was conducted, and self-report measures were completed. Participants were allowed to read, study, or watch a movie during the remaining time. The exposure procedures were based on those validated by Tiffany and Drobes (1990). After the absorption period, participants were seated in a reclining chair. A white-noise machine was used to minimize outside noise during the imaginal procedures. The scripts were then presented over headphones. Participants listened to and imagined each of the scripts with their eyes closed. For demonstration purposes, a practice script was first presented. Four types of experimental imagery scripts were then presented: (a) anxiety plus smoking cues, (b) anxiety cues alone, (c) smoking cues alone, and (d) neutral cues. Two scripts of each type were used, totaling eight imaginal scenarios. Scripts were counterbalanced for both order and sequence. Each script sequence consisted of a 30-s baseline period, 50-s script presentation period, and 30 s of active imagery by the participant terminated with the word stop. Participants were then asked to open their eyes and complete postexposure trial questionnaires asking them about how they felt during the most recent scenario. The scripts were selected from a series of scripts developed by MaudeGriffin and Tiffany (1996). Scenarios that contained anxiety content (i.e., words such as tense, anxious, and worried) were specifically chosen from the series of negative affect scripts. The scripts were slightly modified from the originals by Maude-Griffin and Tiffany and are available from Sandra Morissette. Specifically, words that suggested presence or degree of urge were removed (e.g., your desire to smoke grows stronger and stronger, your desire to smoke does not seem to be going away). In addition, words and phrases in the neutral scripts that might have suggested an anxiety response (e.g., suddenly, and your fingers slip) were omit-

Between-Groups Differences
Smoking characteristics are presented in Table 1, along with relevant indices of affect intensity and mental imagery ability. No significant differences were observed between patch groups on smoking characteristics, strength in affective reactions, or mental imagery ability.

Patch Absorption/Deprivation Phase

Mean scores and standard deviations of measures completed prior to and following the patch absorption phase are presented in

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Table 1 Means of Smoking Characteristics and Other Measures by Patch Status

Nicotine (n 26) Index CSR nicotine abuse/dependence FTND RFS Nicotine Habitual Psychological AIM QMI M 2.4 3.7 17.6 16.4 23.0 3.7 2.5 SD 1.4 1.8 4.8 3.8 3.5 0.46 0.78 Placebo (n 26) M 3.0 4.2 16.6 15.2 21.7 3.5 2.4 SD 1.5 1.7 3.7 3.1 3.4 0.43 0.69

Sedation subscale), F(1, 50) 4.21, p .05. Specifically, ratings on QSU Factor 1 and the SWQ Craving subscale increased over time in both groups, but to a greater magnitude in the placebo group. In comparison, the SWQ Physical Symptoms and StimulationSedation subscales increased over time in the nicotine group, but decreased in the placebo group. The symptomatic increase in the nicotine group may be a product of its stimulant properties (e.g., leading to endorsement of increased heart rate, vs. decreased heart rate in the placebo group due to withdrawal; Carter & Tiffany, 1999). A significant two-way interaction was not observed for anxiety ratings, F(1, 50) 0.004, p .95.

Cue Reactivity Indices

Smoking urge. A significant three-way interaction (Patch Smoking Anxiety) was found, F(1, 50) 5.79, p .05, for smoking urge, as measured by the QSUBrief (see Figure 1, left panel). We conducted follow-up tests using interaction contrasts to examine the nature of the three-way interaction. We used a modified Bonferroni technique (Holland & Copenhaver, 1988) to control for error related to conducting multiple follow-up contrasts. Results indicated that both the Patch Smoking interaction, F(1, 50) 2.97, p .09, and the Patch Anxiety interaction, F(1, 50) 1.13, p .29, were nonsignificant. However, significant Smoking Anxiety interactions were found within both the nicotine group, F(1, 25) 44.91, p .001, and the placebo group, F(1, 25) 20.32, p .001. These findings suggest that the presence of anxiety cues moderated the effect of smoking cues on urge response, although the overarching three-way interaction indicated that the nature of this interaction differed by patch group. Thus, patch group did not alter response to each cue alone (as per nonsignificant Patch Smoking and Patch Anxiety interactions) but, rather, moderated the interaction between smoking and anxiety cues. We also conducted t-test comparisons to determine whether there were between-groups differences in absolute levels of urge response to the script types. No significant differences were ob-

Note. CSR clinical severity rating (0 8; 4 or higher clinical diagnosis, 3 or lower subclinical diagnosis); FTND Fagerstro m Test for Nicotine Dependence (Heatherton et al., 1991; range of possible scores 0 10; higher scores indicate more physical dependence); RFS Reasons for Smoking (Ikard et al., 1969; range of possible scores for each scale 6 30; higher scores indicate more inclination to smoke for nicotine, out of habit, or for psychological reasons); AIM Affect Intensity Measure (Larsen & Diener, 1987; range of possible scores 1 6; higher scores indicate greater intensity of emotions); QMI Questionnaire of Mental Imagery (Sheehan, 1967; range of possible scores 17; lower scores indicate more imagery vividness).

Table 2. We conducted repeated measures analyses of variance to determine whether the nicotine and placebo groups differed significantly on measures prior to and following the 4-hr patch absorption/deprivation phase. Before patch administration and the absorption phase, the two groups did not significantly differ on any measures. Significant Patch (nicotine vs. placebo) Time (prevs. postabsorption) interactions were found for desire to smoke/ anticipation of pleasure (QSU Factor 1), F(1, 50) 9.44, p .01; craving (SWQ Craving subscale), F(1, 49) 12.07, p .01; physical symptoms (SWQ Physical Symptoms subscale), F(1, 50) 5.27, p .05; and stimulation/sedation (SWQ/Stimulation

Table 2 Means of Measures Completed Prior to and Following the Patch Absorption Phase
Nicotine (n 26) Pre Measure QSU32 Factor 1a Factor 2 SWQ Cravingb Psych. Discomfort Physical Symptomsa Stimulation/Sedationa Anxiety M 3.36 1.95 3.91 4.03 2.17 4.60 11.54 SD 1.41 0.96 1.22 0.71 0.89 1.22 15.92 M 4.26 2.65 4.41 4.10 2.65 5.00 23.46 Post SD 1.23 1.20 1.11 0.91 1.19 1.17 26.37 M 3.14 2.04 3.70 4.23 2.50 4.35 12.31 Pre SD 1.24 0.81 0.99 0.77 0.95 1.30 13.94 M 5.09 2.94 5.21 4.19 2.33 3.90 24.62 Placebo (n 26) Post SD 1.27 0.92 1.08 0.76 0.85 1.37 19.64

Note. QSU32 Questionnaire of Smoking Urges (Tiffany & Drobes, 1991; Factor 1 intention/desire to smoke and anticipation of pleasure; Factor 2 anticipation of relief of negative affect/withdrawal and urgent desire to smoke; range of possible scores for each factor: 17; higher scores indicate greater levels of Factors 1 and 2); SWQ Symptom Withdrawal Questionnaire (Shiffman & Jarvik, 1976; range of possible scores: 0 7; higher scores signify more withdrawal symptoms present, 4 neutral). Anxiety ratings could range from 0 to 100 (0 none, 100 as much as imaginable). a Significant Patch Time interaction at p .05. b Significant Patch Time interaction at p .01.

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Figure 1. Average Questionnaire of Smoking UrgesBrief (QSU-Brief) and anxiety scores by patch and script type.

served (all ps .15), suggesting that participants who received a nicotine patch experienced levels of urge similar to those given a placebo patch. Thus, transdermal nicotine had no benefit whatsoever on alleviating urge in response to smoking and anxiety cues. Anxiety/negative affect. Ratings of anxiety exhibited a different pattern (see Figure 1, right panel). The three-way interaction (Patch Smoking Anxiety), F(1, 50) 1.51, p .23, was not significant. Two-way Patch Smoking, F(1, 50) 2.38, p .13, and Patch Anxiety interactions, F(1, 50) 1.91, p .17, were also not supported for anxiety ratings, suggesting that patch condition did not moderate the effects of smoking and anxiety cues on anxiety levels. As with urge, a significant Smoking Anxiety Cues interaction was found, F(1, 51) 45.73, p .01. As can be seen in Figure 1 (right panel), scripts that contained specific anxiety cues elicited greater anxiety ratings than scripts that contained either smoking or neutral cues, supporting the utility of the anxiety scripts in inducing anxiety. Moreover, smoking cue scripts also induced anxiety, albeit less so than scripts that contained explicit anxiety cues. No significant differences were observed between patch groups by script type (all ps .33).

Discussion
Consistent with previous work (Tiffany et al., 2000), the nicotine patch attenuated urge related to deprivation. As can be seen in Table 2, the nicotine group reported lower levels of craving (SWQ) and desire to smoke/anticipation of pleasure (QSU Factor 1) than the placebo group following the 4-hr nicotine absorption/deprivation period. However, transdermal nicotine did not alleviate all forms of urge; specifically, anticipation of relief of negative affect/ urgent desire to smoke (QSU Factor 2) did not vary by patch condition over the course of the absorption/deprivation period. Correspondingly, although an increase in negative affect is a common feature of nicotine withdrawal (Piasecki, Kenford, Smith, Fiore, & Baker, 1997), anxiety ratings did not differ between patch groups. Both groups experienced a mild increase in anxiety levels from pre- to postabsorption. This finding was inconsistent with results from Tiffany et al. in which only individuals in the placebo

group, but not in the nicotine group, experienced an increase in negative affect. However, Tiffany et al.s study included a deprivation period of 6 hr, a longer withdrawal period than in the current study, which may account for the observed increase in negative affect in the placebo group. In addition, Tiffany et al. assessed negative affect in general rather than focusing explicitly on anxiety. Thus, differences may have been observed in the Tiffany et al. study due to the higher order construct of negative affect that was used, one component of which may have been anxiety. Transdermal nicotine did not significantly alleviate smoking urge during the cue reactivity procedures. Despite the significant three-way interaction, no differences were observed between scripts by patch group. Thus, when exposed to smoking-relevant stimuli (smoking and anxiety cues), any urge-attenuating effects of the nicotine patch were virtually eliminated. This finding is noteworthy given the observed (and expected) statistically significant differences between patch groups in craving and desire to smoke prior to beginning the cue reactivity procedures (i.e., post nicotine absorption/deprivation period). Despite these differences, the placebo group did not respond with greater reactivity to smoking and anxiety cues. Moreover, the nicotine group, which started with lower urge levels before the cue reactivity procedures, responded with similar levels of urge in response to the cues, suggesting that nicotine actually had a greater relative increase in urge from baseline. It is notable that the postabsorption period urge (QSU) was not used as a covariate when analyzing urge response, because this would violate the assumptions of analysis of covariance. Transdermal nicotine had no superior effect over a placebo in alleviating anxiety response to smoking and anxiety cues. Regardless of patch status, scripts that contained explicit anxiety cues or smoking plus anxiety cues elicited greater anxiety ratings than scripts that contained only smoking cues or neutral cues. These findings support the ability of the scripts to induce anxiety. Moreover, the smoking cue script, which contained no mention of anxiety, elicited greater anxiety ratings than neutral scripts, indi-

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cating that smoking cues alone were able to elicit anxiety, albeit less so than scripts containing specific anxiety cues. Several important similarities and differences have emerged between the current study and the findings of Tiffany et al. (2000), the only other published study to date that examined the acute effects of transdermal nicotine during cue reactivity. Both studies found statistically significant effects of nicotine in alleviating urge related to general smoking deprivation. This effect is consistent with other studies that have found an attenuating effect of nicotine on abstinence-related smoking urge (Leischow et al., 1997; Rose, Herskovic, Trilling, & Jarvik, 1985). With regard to the cue reactivity procedures, Tiffany and his colleagues found that the nicotine patch produced significantly lower levels of smoking urge than the placebo group across all stimulus trials, although there was no selective effect of nicotine on cue reactivity. This stands in contrast to current findings, in which the nicotine group produced equivalent levels of urge response as the placebo group across all script types. These discrepant findings may be due to the differing deprivation periods in the two studies (i.e., 2 hr longer in Tiffany et al.s study), the use of different cue content, or both. Moreover, the samples of the two studies were subtly but importantly different, which may have driven the dissimilar responses to the cues, the transdermal nicotine, or both. Whereas the current study included college smokers (average age: 20.65 years) who smoked an average of 19.8 cpd, and had an average FTND score of 3.95, the average participant in Tiffany et al.s study was 31.5 years old, smoked 29 cpd, and had an FTND score of 4.90. Previous studies have shown that individuals with higher levels of nicotine dependence exhibit greater urge responses to cues than those with low nicotine dependence (Payne & Smith, 1990). Consequently, smokers in Tiffany et al.s study, who were more dependent, may have responded differently to the cues when given transdermal nicotine versus being in a state of nicotine deprivation (i.e., placebo group). Additionally, differences in vividness ratings between the studies may have accounted for variability in findings. Although no significant between-groups differences in vividness were found across scripts in the current study, Tiffany et al. found that participants who received nicotine rated scripts as more vivid. Finally, scripts in the current study were modified slightly to control for demand characteristics. Although the scripts were pilot tested to ensure induction of smoking urge and anxiety, these small changes could have accounted for differences between studies. Note that it is unlikely that demand characteristics alone could explain the complex patterns of results found (e.g., differing patterns of urge response to script types within patch groups). There are several limitations to the current study that warrant notation. First, a nondeprived/no-patch control group was not included, which prevents analysis of response to the cue reactivity paradigm without a nicotine or placebo patch. Second, although for conceptual reasons the data were analyzed as a 2 2 2 design, technically it is not such a design, in that the four cue conditions were independent of one another (i.e., separate scenarios were used for each condition). Future research might use a true 2 2 2 design by using identical cues and varying their presence or absence with alternative cues. Third, we examined urge during a single absorption/deprivation period and during cue reactivity. Future research might use an alternating treatments design (e.g., ABAB, in which cues are added and removed systematically; Hayes, Barlow, & Nelson-Gray, 1999) to ascertain the

effects of nicotine over time during the fluctuating presence versus absence of cues. Fourth, the sample included college smokers who were not trying to quit smoking, which affects generalizability. College smokers may be different from postcollege smokers or from individuals who have differing educational backgrounds (Pierce, Fiore, Novotny, Hatziandreu, & Davis, 1989). Replication of the current findings with other samples is an important task for the future. Fifth, anxiety was measured using a single-item scale. It is possible that differences in patterns of responding between urge and anxiety could be a function of differences in the psychometrics between these two measures. A single-item Likert scale was chosen because of the repeated assessment design. Prior research indicates that, when using relatively intuitive constructs, single-item indices are as informative as multi-item scales (Burisch, 1984; Carver, Meyer, & Antoni, 2000). In support of the use of the single-item index of anxiety, this measure clearly distinguished between scripts that contained anxiety cues versus neutral-content scripts. Future research should develop and investigate the use of brief, multi-item, moment-to-moment anxiety measures. Finally, because the study involved repeated exposure to cues in close succession, carryover effects from preceding cues may have influenced subsequent cues. Participant fatigue from imagining several scenarios may have also affected cue reactivity. Methods for controlling carryover effects and participant fatigue in such paradigms deserve consideration in future research. In summary, transdermal nicotine attenuated some forms of urge following the patch absorption phase but had no beneficial effect over a placebo in alleviating smoking urge or anxiety in response to explicit smoking and anxiety cues. Individuals who received the nicotine patch still experienced moderate to strong levels of reactivity across measures in response to all smoking and anxiety cue scripts. Although possible, it seems unlikely that these small or nonsignificant findings were due to participants being underdosed. First, the 4-hr nicotine absorption period was chosen on the basis of the manufacturers suggestions for nicotine to reach constant levels. Second, scores on the QSU and SWQ after the absorption period were similar to those reported in Tiffany et al.s (2000) study, which used a 6-hr absorption period, suggesting comparable levels of urge and craving across the two time frames. Whether cue reactivity differs with prolonged use of the nicotine patch would be important to investigate. Nonetheless, findings from the current study are informative for smokers who are initiating their quit attempts. Future research is also needed to examine the influence of other forms of negative affect (e.g., anger, depression) on smoking response during nicotine replacement. Understanding the effects of mood during use of transdermal nicotine may be important for developing treatment and relapse prevention programs, particularly for smokers with comorbid psychiatric disorders.

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Received December 4, 2003 Revision received March 31, 2004 Accepted April 7, 2004