The available literature on smoking cessation documents a robust relationship between early and later abstinence. Studies done in community samples of self-quitters (i.e. Garvey, Bliss, Hitchcock, Heinhold & Rosner, 1992
) for example, demonstrate that it is the first weeks of a cessation attempt when relapse risk is the highest, with the relative risk decreasing the longer abstinence is sustained. Kenford et al. (1994)
described results from two independent randomized clinical trials on active and placebo transdermal nicotine replacement therapy. Participants were assessed before, during, and following six to eight weeks of patch therapy, and predictors of smoking status at the end of therapy and six-month follow-up were sought. Commonly investigated baseline characteristics such as the Fagerstrom Tolerance Questionnaire scores (Fagerstrom & Schneider, 1989
), number of cigarettes smoked per day, years smoked, breath carbon monoxide (CO) levels, and plasma cotinine and nicotine levels, as well as during-treatment nicotine withdrawal levels, failed to predict smoking status at end-of-treatment and follow-up. In contrast, smoking status during the first two weeks of treatment, especially in the second week, was a robust predictor of smoking status at end-of-treatment and six-month follow-up in both studies. Based on their findings, Kenford et al. (1994)
proposed two rules for predicting abstinence outcomes: 1) Any smoking during weeks one and two of treatment predicted short and longer-term failure, and 2) Abstinence during weeks one and two predicted short and longer-term success.
Laboratory studies of smoking abstinence have provided further evidence of the relationship between early and later abstinence. Heil, et al. (2004)
found that failure to abstain during early study periods where subjects could earn incentives for abstinence led to failure to abstain during later periods where abstinence was required for earning incentives.
Taken together, these studies described above underscore the fundamental importance of establishing abstinence in the initial weeks of a cessation effort. What has not been fully explored is whether this relationship between early and later abstinence is true for abused stimulants, most notably cocaine.
Studies exploring the relationship between early and later abstinence in cocaine treatment have focused on abstinence in treatment compared to abstinence post-treatment. Higgins and colleagues (2000)
have shown that achieving a period of continuous abstinence during cocaine treatment is associated with significantly greater odds of being abstinent at 12-month post-treatment follow-up. Further, the results show that the odds for post-treatment abstinence increase with each one-week increase in continuous abstinence (defined by both urine drug screens and self-report) during treatment (O.R. =1.14, CI = 1.09–1.20, p=.001). However, Higgins and colleagues do not provide data on where in the treatment period abstinence occurs. As such, published data on the “first two weeks of a quit attempt” during cocaine treatment that could be used to parallel the findings in the smoking literature is not available.
Prior cocaine research does show a link between baseline abstinence and later in-treatment abstinence (Alterman 1996
;Ehrman, 1998; Kampman, 2002
). In those studies, patients who presented with cocaine-positive urines during baseline had less abstinence during pharmacotherapy trials for cocaine dependence. In addition, the patients with the least baseline abstinence also failed to engage in treatment and had higher attrition rates than did individuals who were abstinent at baseline. In those studies, abstinence throughout the trial was compared to baseline abstinence without regard to what happened during the early period of treatment. As such, no conclusions about the relationship between baseline and early abstinence can be made from those studies.
More recently, investigators have examined the impact of abstinence in the week prior to randomization on subsequent abstinence in a double-blind pharmacotherapy trial (Levin et al., 2008
). Defining baseline cocaine use as negative only if all baseline urines were cocaine-negative, the investigators found that among patients without co-morbidities, those who were cocaine-negative at baseline actually showed increased probability of cocaine use during the course of the study, while those who were cocaine-positive at baseline showed decreased probability of cocaine use during the same period. This somewhat surprising finding suggests that further investigation of the relationship between early abstinence and later abstinence during cocaine trials is warranted.
Recently, studies have examined what impact abstinence during a placebo lead-in period has on later in-treatment abstinence (Bisaga et al., 2005
; Bisaga et al., 2006
). In those studies, prior to randomization to either pharmacotherapy or placebo, patients undergo a single-blind placebo lead in period of one or two weeks. During that period, patients receive manual-guided psychotherapy. Results from a double-blind study of gabapentin and relapse-prevention therapy revealed that patients able to provide at least two cocaine-negative urines during a two-week placebo lead-in period had better rates of abstinence during the trial (Bisaga et al., 2005
). Although that study includes only 50 patients, the findings dovetail nicely with the above findings regarding baseline cocaine abstinence and treatment outcome. In addition, the outcome from the larger trial revealed no medication effects (Bisaga et al., 2006
Having a placebo lead-in during which to assess early abstinence is not always feasible. In addition, providing psychosocial treatment during that placebo lead-in means that patients are not still in baseline as it has been defined in the above trials, but are also not yet receiving a full course of treatment. As such, it may be difficult to generalize the above findings to the majority of pharmacotherapy trials, which are conducted without such a lead-in period.
Therefore, in order to test whether the relationship between the first two weeks of a quit attempt, operationally defined as the first two weeks of medication in a trial of pharmacotherapy for cocaine dependence, and later abstinence mirrors that found in the smoking cessation literature, and to explore how baseline and early abstinence are related, we analyzed aggregate data from two double-blind randomized placebo-controlled pharmacotherapy trials conducted here at the Treatment Research Center.