Psychopharmacology (2006) 184: 608–618 DOI 10.1007/s00213-005-0175-4 ORIGINAL INVESTIGATION Saul Shiffman . Stuart G. Ferguson . Chad J. Gwaltney Immediate hedonic response to smoking lapses: relationship to smoking relapse, and effects of nicotine replacement therapy Received: 14 August 2005 / Accepted: 18 August 2005 / Published online: 11 November 2005 # Springer-Verlag 2005 Abstract Objective and rationale: Smoking lapses re- present an important juncture between smoking cessation and relapse. Nicotine replacement therapy (NRT) has been shown to decrease the risk of progression from lapse to relapse. We hypothesized that this effect might be medi- ated via decreases in reinforcement from smoking lapses. Method: We assessed 169 subjects who lapsed during treatment in a double-blind placebo-controlled study of high-dose (35 mg) nicotine patch. Following their first lapse, using an electronic diary, subjects recorded the amount they smoked, and rated the pleasantness and satisfaction (“hedonic rating”) and the aversiveness of smoking. Subjects were then followed and assessed for further lapses and relapses. Results: Subjects who smoked more during the first lapse had greater risk of progression [second lapse: hazard ratio (HR)=1.16, confidence interval (CI)=1.01–1.32; relapse: HR=1.22, CI=0.97–1.54]. Sub- jects with higher hedonic ratings of the first lapse also had a greater risk of progression to the second lapse (HR=1.08, CI=1.02–1.14) and to relapse (HR=1.26, CI=1.11–1.41). Aversive ratings had no bearing on progression. As ex- pected, active treatment reduced the risk of both a second lapse (HR=0.54, CI=0.39–0.78) and a relapse (HR=0.22, CI=0.11–0.45). Importantly, however, NRT had no effect on hedonic ratings, amount smoked during the first lapse, or aversive ratings. Conclusions: Hedonic response to an ini- tial lapse predicted progression to relapse, but this did not mediate the effect of NRT on progression. Introduction Addictions are relapsing disorders: the majority of those who achieve abstinence ultimately relapse (Brownell et al. 1986). Despite considerable theoretical and empirical work on relapse (Shiffman 1982; Marlatt and Gordon 1985), addictive relapse (i.e., the resumption of regular drug taking following a period of abstinence) is still not well understood, and relapse prevention interventions have not generally proven successful (Lichtenstein and Glasgow 1992; Hajek et al. 2005). One of the unsolved questions concerns the apparently inexorable progression from an initial lapse to a full-blown relapse. Even a single episode of postcessation smoking almost inevitably leads to relapse (95%, according to Kenford et al. 1994; see also Brandon et al. 1990). Better understanding of the progression from lapse to relapse in smoking could suggest opportunities for intervention. Why does a lapse in abstinence lead so readily to relapse? Marlatt and Gordon (1985) emphasized a smoker’ s psycho- logical reaction of demoralization in response to a lapse. However, analysis of real-time reports of lapses has not supported this hypothesis (Shiffman et al. 1996a). In ad- dition, laboratory studies have shown that reexposure to smoking, even in contexts that should not invoke these psychological reactions, still predisposes smokers to relapse (Chornock et al. 1992). An alternative hypothesis is that lapses lead to repeated smoking because they reintroduce the smoker to reinforce- ment associated with smoking (deWit and Stewart 1981, 1983). Several theories (Stewart et al. 1984; Wise 1996) explain drug use primarily in terms of positive reinforce- Saul Shiffman and Stuart Ferguson consult exclusively for GlaxoSmithKline Consumer Healthcare on matters relating to existing smoking cessation products. Dr. Shiffman also has an interest in a new smoking cessation product and is a founder of invivodata, which provides electronic diaries for clinical trials. S. Shiffman . S. G. Ferguson University of Pittsburgh and Pinney Associates, Pittsburgh, PA, USA C. J. Gwaltney Brown University, Providence, RI, USA S. Shiffman (*) Smoking Research Group, 130 North Bellefield Avenue, Suite 510, Pittsburgh, PA 15260, USA e-mail: Shiffman@pinneyassociates.com Tel.: +1-412-3832050 Fax: +1-412-3832041