Objective To describe the relapse curve and rate of long-term prolonged abstinence among smokers who try to quit without treatment.

Method  Systematic literature review.

Data sources  Cochrane Reviews, Dissertation Abstracts, Excerpt Medica, Medline, Psych Abstracts and US Center for Disease Control databases plus bibliographies of articles and requests of scientists.

Study selection  Prospective studies of self-quitters or studies that included a no-treatment control group.

Data extraction  Two reviewers independently extracted data in a non-blind manner.

Data synthesis  The number of studies was too small and the data too heterogeneous for meta-analysis or other statistical techniques.

Results  There is a paucity of studies reporting relapse curves of self-quitters. The existing eight relapse curves from two studies of self-quitters and five no-treatment control groups indicate most relapse occurs in the first 8 days. These relapse curves were heterogeneous even when the final outcome was made similar. In terms of prolonged abstinence rates, a prior summary of 10 self-quitting studies, two other studies of self-quitters and three no-treatment control groups indicate 3–5% of self-quitters achieve prolonged abstinence for 6–12 month after a given quit attempt.

Conclusions  More reports of relapse curves of self-quitters are needed. Smoking cessation interventions should focus on the first week of abstinence. Interventions that produce abstinence rates of 5–10% may be effective. Cessation studies should report relapse curves.

Shape of the relapse curve and long-term abstinence among untreated smokers

A workgroup formed by the Society for Research on Nicotine and Tobacco reviewed the literature on abstinence measures used in trials of smoking cessation interventions. We recommend that trials report multiple measures of abstinence. However, at a minimum we recommend that trial: (a) report prolonged abstinence (i.e., sustained abstinence after an initial period in which smoking is not counted as a failure) as the preferred measure, plus point prevalence as a secondary measure; (b) use 7 consecutive days of smoking or smoking on > or = 1 day of 2 consecutive weeks to define treatment failure; (c) include non-cigarette tobacco use, but not nicotine medications in definitions of failure; and (d) report results from survival analysis to describe outcomes more fully. Trials of smokers willing to set a quit date should tie all follow-ups to the quit date and report 6- and/or 12-month abstinence rates. For these trials, we recommend an initial 2-week grace period for prolonged abstinence definitions; however, the period may vary, depending on the presumed mechanism of the treatment. Trials of smokers who may not be currently trying to quit should tie follow-up to the initiation of the intervention and should report a prolonged abstinence measure of > or = 6-month duration and point prevalence rates at 6- and 12-month follow-ups. The grace period for these trials will depend on the time necessary for treatment dissemination, which will vary depending on the treatment, setting, and population. Trials that use short-term follow-ups ( or = 4 weeks. We again recommend a 2-week grace period; however, that period can vary.

/pdf/measures-of-abstinence-in-clinical-trials-issues-and-4v9yredvpa.pdf

Measures of abstinence in clinical trials: issues and recommendations.

Tobacco smoking is a worldwide public health problem. In the United States alone, over 400,000 deaths and $50 billion in medical costs annually are directly attributed to smoking. Accumulated evidence indicates that nicotine is the component of tobacco smoke that leads to addiction, but the means by which nicotine produces addiction remain unclear. Nicotine is less effective as a positive reinforcer than other drugs of abuse in non-dependent animals. Nevertheless, nicotine-withdrawal symptoms, including depressed mood, anxiety, irritability and craving in dependent subjects may contribute to the addictive liability of nicotine. We show here that spontaneous nicotine withdrawal in rats resulted in a significant decrease in brain reward function, as measured by elevations in brain reward thresholds, which persisted for four days. Further, systemic injections of a competitive nicotinic-receptor antagonist led to a dose-dependent increase in brain reward thresholds in chronic nicotine-treated rats. The decreased function in brain reward systems during nicotine withdrawal is comparable in magnitude and duration to that of other major drugs of abuse, and may constitute an important motivational factor that contributes to craving, relapse and continued tobacco consumption in humans.

Dramatic decreases in brain reward function during nicotine withdrawal

Despite the wide-ranging and authoritative 1988 review by the US Surgeon General, views questioning the addictiveness of nicotine contine to be expressed in some quarters. This lack of complete consensus is not unexpected, since no universally agreed scientific definition of addiction exists. In this paper we briefly consider a number of lines of evidence from both the human and animal literature bearing on the addictiveness of nicotine. Patterns of use by smokers and the remarkable intractability of the smoking habit point to compulsive use as the norm. Studies in both animal and human subjects have shown that nicotine can function as reinforcer, albeit under a more limited range of conditions than with some other drugs of abuse. In drug discrimination paradigms there is some cross-generalisation between nicotine on the one hand, and amphetamine and cocaine on the other. A well-defined nicotine withdrawal syndrome has been delineated which is alleviated by nicotine replacement. Nicotine replacement also enhances outcomes in smoking cessation, roughly doubling success rates. In total, the evidence clearly identifies nicotine as a powerful drug of addiction, comparable to heroin, cocaine and alcohol.

The scientific case that nicotine is addictive

https://boerenlandvogels.nl/sites/default/files/Dwyer%20et%20al_%20Pharmacol%20Ther_2009.pdf

The Dynamic Effects of Nicotine on the Developing Brain

We examined cessation among 630 smokers who quit abruptly on their own. Continuous, complete abstinence rates were 33% at 2 days, 24% at 7 days, 22% at 14 days, 19% at 1 month, 11% at 3 months, 8% at 6 months postcessation, and 3% at 6 months with biochemical verification. Slipping (smoking an average of less than 1 cigarette/day) was common (9% to 15% of subjects) and was a strong predictor of relapse; however, 23% of long-term abstainers slipped at some point. These results challenge beliefs that most smokers can initially stop smoking and that most relapse occurs later on postcessation.

Smoking cessation among self-quitters.

Caffeine as a discriminative stimulus in humans

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Smoking cessation among self-quitters.

Caffeine as a discriminative stimulus in humans