Results of these analyses indicate that craving, withdrawal, and other symptoms varied by time of day while participants were smoking, generally being lower during afternoon versus morning or evening (i.e. “V”-shaped; see ). The magnitude of the difference between timepoints was approximately 20%–25% for the craving measures and 10% for the other measures. For craving, this time-of-day effect was almost as large as the overall effect of abstinence or nicotine replacement ( and ), suggesting that the time-of-day effect is clinically significant. For NA, the smaller time-of-day effect was nevertheless similar to that due to abstinence and greater than that due to nicotine replacement. For PA, the time-of-day effect was similar to that due to nicotine replacement and greater than that due to abstinence.
Perhaps more important, time of day interacted with abstinence to influence craving and with nicotine patch to influence NA, although the influences of abstinence or nicotine patch treatment on other symptoms were not altered by time of day. Abstinence increased craving less in the morning than at the other times, as craving dropped from the morning to the afternoon while participants were smoking but remained elevated in the afternoon and increased further in the evening when participants were abstinent (see ). Thus, the interaction may reflect the acute influences of midday smoking in reducing craving from the higher levels in the morning that resulted from the typical overnight decrease in blood nicotine when participants were asleep, whereas such elevated craving in the morning persisted across time when participants remained abstinent. Yet the presence of smoking cues or something else other than acute smoking or nicotine deprivation influenced the general rise in craving from afternoon to evening, since this rise occurred whether participants were abstinent or smoking and whether they were using nicotine versus placebo patch while abstinent (see ). Time of day also interacted with nicotine patch effects in alleviating NA but in a pattern different from that seen with craving. Nicotine relieved NA to a modestly, but significantly, greater degree during the evening versus morning or afternoon (see ). So, contrary to craving, the rise in NA from afternoon to evening occurred only in the absence of nicotine exposure, suggesting that nicotine per se eliminated this time-of-day effect on NA during abstinence.
Our findings were generally consistent with prior studies, noted in the introduction, showing a robust time-of-day influence on craving but less so on other symptoms and only modestly in the relief of those symptoms due to nicotine versus placebo patch during abstinence. On the other hand, time-of-day effects in the present study were more pronounced during smoking compared with abstinence (see and ). This pattern is the reverse of that observed by Teneggi et al. (2002)
, who studied smokers during brief enforced abstinence within an inpatient setting; by contrast, we studied smokers during voluntary simulated quit attempts in an outpatient setting. Therefore, environmental stimuli associated with different times of the day that are present in outpatient studies but generally absent in inpatient studies could contribute to variation in symptoms across time while smoking. These stimuli could include particular locations or people and not just explicit smoking cues (Conklin, 2006
; Conklin, Robin, Perkins, Salkeld, & McClernon, 2008
The present findings suggest that, compared with a traditional single assessment of symptoms midday in the clinic, clinical studies of smoking cessation may benefit from symptom assessments at other times of the day, such as in the morning and evening (Shiffman et al., 2004
). Such assessments may better gauge the dynamic and systematic changes in symptoms across the day, more accurately capture overall levels of symptoms and the influence of abstinence on some symptoms, and perhaps detect greater effects of medication on a few symptoms (e.g., NA). These added assessments do not need to be burdensome for either participants or researchers, as we were able to determine these effects using simple and short paper-and-pencil forms totaling 20 individual Visual Analog Scale items and taking less than 3 min to complete per occasion, on average. Where added daily assessments are impractical, our results suggest that afternoon or evening may be the best single time of day to examine symptoms in clinical trials, given that effects due to abstinence may be most pronounced then, compared with the morning. This observation also may have relevance for the timing of sessions in lab-based studies aimed specifically at understanding abstinence effects on these symptoms.
Strengths of the present study include (a) the large sample size, even for the subanalyses of abstinence effects and nicotine patch effects; (b) the fully within-subject design of each comparison, which increased statistical power by reducing random variance; and (c) the stringent CO cutoff of 5 ppm to verify abstinence during patch weeks (weeks 2 and 4), as in other studies of daily assessments of abstinence (e.g., Alessi et al., 2004
), so that we could be certain that participants had not smoked in the preceding 24 hr.
The study also had a number of limitations. First, we used traditional paper-and-pencil measures of abstinence symptoms for practical reasons, given our large sample size and the desire to demonstrate that assessments could be done with modest burden to participants. Electronic assessments can be cumbersome for participants and time consuming and expensive to analyze, making them less practical for regular use in clinical studies. However, the use of such electronic diary assessments or similar means may be more valid than written self-report forms (Stone, Shiffman, Schwartz, Broderick, & Hufford, 2002
), perhaps leading to different findings. We had participants record the time at which they completed the forms and found that these times roughly corresponded to the desired times for the three assessments per day (i.e., morning, afternoon, and evening). However, this self-report information did not verify that the forms were completed at those stated times. If the actual times of day varied much more than these recorded times of day indicate, such random variability should obscure, rather than exaggerate, our time-of-day effects. Therefore, our results may underestimate the magnitude of the effects of time of day on abstinence symptoms.
Second, and similarly, some of our specific findings may be biased by our procedures, and different approaches to assessment may reveal a pattern of effects due to time of day that differ from the results seen here. For example, the V-shape we observed across time of day may be a function of us having obtained ratings at only three timepoints per day; more frequent assessment may reveal that the influence of time of day is closer to U-shaped, J-shaped, or even more complex.
Third, because the afternoon assessment always took place during the clinic visit, whereas the morning and evening assessments took place in the subjects’ natural environments, time of day may have been confounded with the location of the assessment. Therefore, the differences due to afternoon versus morning or evening could be due to participants having completed the measures in a controlled environment (clinic) in the afternoon versus in the presence of potentially varying environmental stimuli that could influence symptoms in the morning or evening. Although a possible contributor to the difference between afternoon and evening ratings, as discussed, it seems unlikely as the primary cause of the difference between morning and afternoon. Time-of-day effects were more pronounced during smoking than during abstinence (see and ), even though the location of assessments remained the same for each time of day between the two conditions. Future research should control for assessment location in order to isolate effects due to time of day per se (Conklin et al., 2008
). Nevertheless, we would argue that, whether due to time of day or varying location, this variability in symptom level over the day warrants more frequent symptom assessments in short-term studies of smoking, abstinence, and medication responses.
Fourth, this study used a sample of smokers not intending to quit permanently during the patch weeks, thus limiting our ability to generalize the findings with regard to abstinence and nicotine patch effects by time of day (see and ). For example, nicotine patch did not significantly reduce total withdrawal, consistent with other studies of briefly abstinent smokers not trying to quit permanently (Teneggi et al., 2002
; see also Perkins, Stitzer, & Lerman, 2006
) but contrary to most clinical trial results (Jorenby, Keehn, & Fiore, 1995
). Moreover, analyses of abstinence effects by time of day were limited to the participants who self-selected to abstinence during the patch weeks, as with all cessation studies, including all outpatient and some inpatient studies of enforced abstinence (since not all are able to abstain even when paid to do so; e.g., Juliano, Donny, Houtsmuller, & Stitzer, 2006
). Yet the time-of-day effects were strongest while participants were smoking, suggesting good generalizability of our findings regarding the main effects of time of day to symptom levels in the general population of smokers while they smoke (see ). Future studies should explore the possibility of individual differences in the degree to which time of day affects symptom reports during smoking and abstinence, as well as in response to cessation medications (e.g., Cinciripini et al., 2004
; Perkins, Lerman, Grottenthaler, et al., 2008
In conclusion, assessment of tobacco abstinence symptoms just once at midday may not adequately reflect the dynamic but systematic changes in symptoms throughout the day. Time of day influences craving, withdrawal, and affect while smoking and may influence craving due to abstinence and relief of NA by nicotine patch while abstinent. These effects, as well as the modest burden of these measures, suggest that clinical research on abstinence symptoms may generate richer findings by increasing the frequency of symptom assessments each day.