Commentary on Etter et al. (2013): The ups and downs of nicotine withdrawal and methods to study the process.

Technological advances have generated an expansion of smoking-related studies using web-based designs. The study by Etter et al. [1] in this issue is timely in being one of the first studies to examine the process of nicotine withdrawal using an internet-based sample and also in informing the usefulness of items assessing nicotine withdrawal for the impeding DSM-5 [2]. Etter et al. [1] replicate the effect of increases in negative affect-related symptoms during nicotine abstinence observed previously in clinical [3–6], epidemiological [7–9] and animal studies [10], now using a web-based design. In addition, this report [1] conveys the importance of applying rigorous methods to studying nicotine withdrawal and new avenues for future research. The greatest strength of the study [1] may be the randomized-to-quit versus continuing-to-smoke design that allowed detection of abstinence-related relative increases in negative affect even though ‘Almost all symptoms decreased between subsequent surveys in participants in whom they were expected to remain stable. and many symptoms remained stable in groups in whom they were expected to change (e.g. in smokers who quit at follow-up). ’. Similar reductions in negative affect across repeated assessments is a large and robust testing effect observed in extremely well-controlled smoking cessation studies with minimal dropout [5,11]. This reduction in withdrawal symptoms would have masked the effects of abstinence, if a control group were not used by Etter et al. [1]. It is critical that such randomized controls be used in future internet and other studies characterizing withdrawal symptoms, because failure to do so fails to address the issue of decreasing negative affect and other withdrawal indices resulting from repeated testing, rather than from an actual diminution of symptoms [12]. A second strength of the Etter et al. study [1] is the reporting of the potential interpretive problems associated with the 76% subject attrition in the group randomized to quit. High levels of attrition are observed in most studies that attempt to characterize the effects of abstinence and raise the important question of who remains abstinent in such studies and how characteristic the abstainers are from the relapsers and those who fail to ever quit [12,13]. It has been hypothesized [5] that individuals who choose to initiate and maintain abstinence do so because of lower levels of negative affect and/or neurobiological dispositions to less intense withdrawal symptoms. To the degree that this hypothesis is true, one would expect that the Etter study [1] and virtually all studies to date underestimate the true severity of withdrawal if all were to maintain abstinence. A third strength of the study is the exploration of new withdrawal/abstinence symptoms and the resulting findings that abstinence leads to an increase in reported mood swings and improvement in sensory/physical symptoms. In terms of mood swings, within-subject volatility of symptoms in quitters has previously been reported to be associated with relapse to smoking [14] and history of depression [15]. This suggests that future studies of depression vulnerability in smokers, also known to be associated with more severe nicotine withdrawal [6,8,9], could critically inform our understanding of the mechanism underlying post-cessation mood swings in relation to other withdrawal symptoms and relapse to smoking. In terms of improvements in smell, taste, sore throat and wheezing, this avenue of inquiry could also be expanded. For example, do recent quitters find some increases in taste and smell pleasant and some unpleasant, and does this differentially predict successful cessation? Given that more research is needed to identify effective alternative rewards during smoking cessation, future efforts might examine whether enhancement of sensory processes covaries with reward processing. A fourth strength is having participants measure their heart rate using standard procedures that would be expected to replicate the decreased rate observed universally in studies of abstinence. One can only speculate as to why heart rate did not decrease in quitters [1]. In the near future, there is reason to believe that a range of noninvasive physiological measures will be obtainable via the internet and smart phones. The use of behavioral and physiological measures can help to overcome the numerous weakness of self-report measures, such as reactivity to experimental demands, effects of repeated testing and individual differences in self-report biases. A potential limitation to web-based data collection is the possibility of recruiting a non-representative sample of smokers. For example, those who stayed in the current study [1] were more educated and more motivated to quit. However, innovations in web-based smoking-related studies are rapidly under way, and are being augmented to potentially improve representation by providing financial incentives for low-income smokers, for instance [16]. In summary, Etter et al. [1] show that key negative affect-related symptoms associated with nicotine withdrawal can be replicated using an internet-based design, the importance of rigorous COMMENTARY bs_bs_banner