Nina G. Schneider

Measuring nicotine dependence: A review of the Fagerstrom Tolerance Questionnaire

In the last decade, the importance of nicotine in maintaining smoking and in cessation difficulty has been acknowledged. Consequently, this has led to efforts to measure nicotine dependence. This paper focuses on a widely used, paper-and-pencil test of nicotine dependence- the Fagerstrom Tolerance Questionnaire (FTQ). The findings indicate that the FTQ correlates with other proposed measures of nicotine dependence (carbon monoxide, nicotine, and cotinine levels). The connection between FTQ scores and withdrawal symptoms is weak. In clinic outcome trials, the FTQ predicted success where no pharmacologic treatment was involved, while nicotine replacement appeared to mask the relation between FTQ scores and outcome. However, the FTQ may predict outcome with nicotine replacement as a function of dose. In placebo-controlled, nicotine replacement trials, FTQ scores were related to success by treatment. Problems with the FTQ are described with focus on item difficulties and analyses of the scale.

Effectiveness of nicotine patch and nicotine gum as individual versus combined treatments for tobacco withdrawal symptoms

Nicotine gum and transdermal nicotine have been shown to relieve withdrawal and double success rates over placebo in trials of smoking cessation. This study tested whether combining the two methods would relieve withdrawal more effectively compared to either treatment alone. Twenty-eight smokers served as their own controls in each of four conditions: active gum + active patch (double active), active gum + placebo patch (gum only active), placebo gum + active patch (patch active) and placebo gum+placebo patch (double placebo). This “double placebo” design controls sensory, psychological and ritual variables associated with each drug form. Withdrawal symptoms were rated four times daily for 3 days in each condition. Total baseline (smoking) withdrawal scores using visual analogue scales (VAS) averaged 101.1. During cessation, total withdrawal increased to 187.0 for the double placebo condition, 142.2 for the active gum/placebo patch treatment and 128.3 for the active patch/placebo gum treatment. The double active condition equalled smoking with score 99.2. All pairwise comparisons were significant (P<0.001) except between the two single active conditions and between smoking versus the double active condition. Significant time-of-day effects by treatment on withdrawal were observed for the double placebo condition (P<0.05) with less withdrawal in the morning. The findings suggest: 1) combining nicotine gum with transdermal nicotine may be superior to either treatment alone, 2) more symptoms may be nicotine specific (relieved by replacement) than previously thought.

Clinical pharmacokinetics of nasal nicotine delivery : A review and comparison to other nicotine systems

SummaryRapid drug delivery (arterial ‘boli’) and high drug concentrations occur with nicotine inhaled in smoke. These are believed to be key elements in producing addiction to cigarettes. Preparations which reduce the rate of delivery and/or concentration of nicotine have been introduced as treatments for smoking cessation.These nicotine medications work by relieving withdrawal and preventing relapse associated with abrupt cessation of smoking. The pharmacokinetics of each system are expected to affect efficacy and treatment dependence. Nasal administration systems have been developed to more closely approximate cigarette delivery for improved efficacy in clinical application and for more control in systematic testing of nicotine. With laboratory tested nasal application systems (clinical drug and experimental devices), venous plasma concentrations after a single dose range between 5 and 12 µg/L.Higher steady-state blood nicotine concentrations (16 to 29µg/L) have been reported for ad libitum clinical self-administration with a nicotine nasal spray. Time to peak plasma concentration (tmax) with nasal administration is around 11 to 13 minutes for 1mg doses. This rise time is slower than for cigarette delivery but faster than the other nicotine treatments. Venous plasma concentrations are considerably lower than tobacco product concentrations and fall within the range of the lower dose nicotine treatments (e.g. 2mg gum vs 4mg gum).The profile of nasal nicotine administration was designed for certain subsets of smokers. Efficacy trials show consistent superiority of nasal administration over placebo although the comparative efficacy among nicotine treatments remains to be determined. The more rapid onset and user control of nasal nicotine may impose a higher risk for treatment dependence compared with a slower, passive system such as the patch. It may not produce more dependence than other faster-acting treatment systems (e.g. nicotine gum).

The nicotine inhaler: Clinical pharmacokinetics and comparison with other nicotine treatments

Nicotine inhaled in smoke is the most rapid form of delivery of the drug. With smoking, arterial boli and high venous blood nicotine concentrations are produced within seconds and minutes, respectively. The potency of nicotine as the primary reinforcement in tobacco addiction is attributed to this rapid rate of delivery. By design, nicotine treatments reduce the rate and extent of drug delivery for weaning from nicotine during smoking cessation. Theoretically, they prevent relapse by reducing withdrawal and craving associated with the abrupt cessation of cigarettes.The nicotine inhaler treats the complexity of smoking through weaning both from the drug and from the sensory/ritual components associated with smoking. The inhaler is ‘puffed’ but not lit and there is considerable ‘puffing’ required to achieve slower rising and lower nicotine concentrations. These factors allow it to be used as a nicotine reduction treatment.One inhaler contains 10mg of nicotine (and 1mg of menthol) of which 4mg of nicotine can be extracted and 2mg are systemically available. Shallow or deep ‘puffing’ results in similar nicotine absorption. Nicotine is delivered mainly to the oral cavity, throat and upper respiratory tract with a minor fraction reaching the lungs. This was confirmed with positron emission tomography and by assessment of arterial concentrations. A single inhaler can be used for one 20-minute period of continuous puffing or periodic use of up to 400 puffs per inhaler.With controlled puffing in laboratory testing, venous plasma nicotine concentrations from a single inhaler puffed 80 times over 20 minutes averaged 8.1 μg/L at 30 minutes. Lower concentrations of 6.4 to 6.9 μg/L have been reported for self-administration under clinical conditions. The time to peak plasma concentrations varies but is always significantly longer than with cigarette delivery. Estimates of nicotine intake from cotinine concentrations were higher than expected (60 to 70% of baseline smoking concentrations). This elevation may be due to the swallowing of nicotine and subsequent first-pass biotransformation to cotinine. In general, venous blood nicotine concentrations are considerably lower than with smoking and are within the range observed for other nicotine reduction therapies.Efficacy trials show consistent superiority of the inhaler over placebo. Despite the ‘cigarette-like’ appearance of the inhaler and the associated sensory/ritual elements, little treatment dependence or abuse has been reported. This is attributed to the slow rise time and low nicotine blood concentrations. The inhaler is a valuable addition to treatment of tobacco dependence and can be used alone or with other treatments.

Time course of smoking withdrawal symptoms as a function of nicotine replacement.

Subjects (N=32) provided morning, afternoon, and evening data for week-1 withdrawal from smoking. Withdrawal symptoms were measured using Schneiders Smoker Complaint Scale. Twenty subjects received nicotine gum and 12 subjects received placebo gum. Carbon monoxide levels verified smoking abstinence. Results showed significantly less withdrawal for nicotine gum subjects compared to the placebo group. A significant treatment-x-time of day interaction was also observed: Placebo subjects reported increased withdrawal in the evenings compared to their morning and afternoon scores, and in contrast to nicotine-group responses. The results provide evidence for nicotine withdrawal and its alleviation by nicotine gum.

Comparative testing of 5 nicotine systems: initial use and preferences.

OBJECTIVE To test initial reactions to 5 nicotine treatments (NRTs: 2 and 4 mg gum, inhaler, nasal spray, tablet) in a crossover study (n=41). METHODS Subjects used each medication on arising (1/2 day) and resumed smoking each afternoon. Subjects rated (individually) and ranked (comparatively) treatments on use, reinforcement, withdrawal, craving, and preferences. RESULTS Overall preferences: inhaler (49%), 4 mg gum (24%), 2 mg gum (10%), 2 mg tablet (10%), nasal spray (7%). Overall results were consistent with ratings and rankings of individual characteristics of drugs. CONCLUSION Subjects had varied reactions to NRTs that may affect initiation of cessation.

Can Cigarette Size and Nicotine Content Influence Smoking and Puffing Rates

The stimuli controlling the rate at which people smoke cigarettes have not been clearly defined. On the hypothesis that smoking is basically nicotine-seeking behavior. nicotine available to the subject was experimentally manipulated through controlling cigarette size and nicotine content. In Experiment I, subjects given their own cigarettes in whole, half, quarter, and eighth lengths, increased the number of cigarettes smoked and number of puffs to compensate for reductions in size. Satisfaction was directly related to cigarette length. In Experiment II, subjects given special cigarettes delivering 0.2 or 2.0 mg nicotine/cigarette smoked significantly more of the low than of the high nicotine cigarettes and took significantly more puffs. As in Experiment I, significantly more quarter length than full length cigarettes were smoked, but total number of puffs did not differe. These results support the hypothesis that nicotine controls smoking behavior.

Smoking and Anxiety

460 of 1025 contacted individuals completed the Taylor Manifest Anxiety Scale and a questionnaire on smoking behavior. The data indicated that smokers, as a group, scored higher on the anxiety scale than nonsmokers. No support for the notion of a significant correlation between amount of smoking and level of anxiety was obtained. Ss reported increases in smoking behavior during periods of stress but indicated that these increases were usually not maintained beyond the period of stress.

Drop in heart rate following smoking cessation may be permanent

Data are reported on the heart rates of nine smokers who underwent 5 weeks of abstinence. There was an initial fall of 9.1 beats per min from 79 to 69.9 beats per min on the 1st day, with no significant change thereafter. The average heart rates after 2, 3, 4 and 5 weeks were 69.1, 69.1, 71.7 and 69.9 beats per min, respectively. Heart rate after 5 weeks was still significantly below baseline. The results indicate that the drop in heart rate which occurs open smoking abstinence is either a permanent change, or if it is a temporary withdrawal effect lasts longer than 5 weeks. If it is a permanent change then it may not make sense to consider drop in heart rate as part of a withdrawal syndrome; it could merely reflect absence of nicotines stimulant action.

Comparison of craving and withdrawal among four combination nicotine treatments

To assess the appearance of craving and withdrawal among four combination nicotine replacement treatments (NRTs).