Transdermal nicotine-induced tobacco abstinence symptom suppression: nicotine dose and smokers' gender

Abstract

An aversive tobacco abstinence syndrome, thought to reflect an underlying level of nicotine dependence, contributes to cigarette smokers' failed quit attempts. Nicotine replacement therapy (NRT) suppresses tobacco abstinence, but high relapse rates suggest room for improvement. Improving NRT's efficacy might begin with identifying factors that influence tobacco abstinence symptom suppression. Two such factors are smokers' gender and NRT dose. The purpose of this study was to determine the dose-related effects of transdermal nicotine (TN) on tobacco abstinence symptoms in 75 men and 53 women who regularly smoked cigarettes but who had abstained from smoking for at least 8-12 hr. Participants completed 4 double-blind, randomized 6.5-hr laboratory sessions that differed by TN dose (0, 7, 21, or 42 mg). Each session included blood sampling for plasma nicotine level, measurement of heart rate, participants' ratings of tobacco abstinence symptoms and effects of nicotine, and psychomotor performance. Increases in plasma nicotine level were related to TN dose and were independent of gender. TN-induced abstinence symptom suppression was dose-related for items assessing craving and urge to smoke and largely was independent of gender. TN increased heart rate and ratings of aversive side effects (e.g., nausea, lightheadedness) in a dose-related manner, and women were more sensitive at higher doses. Results from this laboratory study support the continued use of TN as a pharmacotherapy. Higher doses may ameliorate some abstinence symptoms, although the side effect profile, at least in the short term, may limit effectiveness, especially for women.

Figure 1

Mean data (±1 SEM) for plasma nicotine (Panels A and B; N = 123, with 51 women), heart rate (Panels C and D; N = 128, with 53 women), irritability/frustration/anger visual analogue score (VAS; Panels E and F; N = 128), and dizzy VAS (Panels G and H; N = 128) for men (left) and women (right) by dose and time. Filled symbols indicate a significant difference between men and women at that time within that dose, and asterisks indicate a significant difference from placebo at that time. All ps < .05, Tukey’s HSD.

Figure 2

Mean area under the curve data (±1 SEM) for men and women by dose (0, 7, 21, or 42 mg transdermal nicotine), collapsed across time, for plasma nicotine (Panel A; N = 123, with 51 women), heart rate (Panel B; N = 128, with 53 women), craving visual analogue score (VAS; Panel C; N = 128), urge VAS (Panel D; N = 128), irritability/frustration/anger VAS (Panel E; N = 128), and Questionnaire of Smoking Urges (QSU; Tiffany & Drobes, 1991) Factor 1 (Panel F; N = 128). Filled symbols indicate a significant difference between men and women at that dose; asterisks indicate a significant difference from placebo for men and women; number signs indicate a significant difference from 7 mg for men and women; and daggers indicate a significant difference from 21 mg for men and women. All ps < .05, Tukey’s HSD.

Figure 3

Mean area under the curve data (±1 SEM) for men and women by dose (0, 7, 21, or 42 mg transdermal nicotine), collapsed across time, for visual analogue score (VAS) items nausea (Panel A; N = 128, with 53 (visual analogue score) women), dizzy (Panel B; N = 128), lightheaded (Panel C; N = 121, with 53 women), and weak (Panel D; N = 128). Filled symbols indicate a significant difference between men and women at that dose; asterisks indicate a significant difference from placebo for men and women; number signs indicate a significant difference from 7 mg for men and women; and daggers indicate a significant difference from 21 mg for men and women. All ps < .05, Tukey’s HSD.