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Divalproex, a GABA agonist, may be a useful agent in the treatment of tobacco dependence. Cue reactivity assessment paradigms are ideally suited to explore basic mechanisms underlying the pharmacological effects of medications that purport to have efficacy for smoking cessation. Our primary goal in the current study was to examine the effects of divalproex on in-treatment reactivity to smoking-relevant and affective cues, and to determine if these reactions were predictive of posttreatment smoking behavior. There were 120 nicotine dependent smokers enrolled in an 8-week double-blind clinical trial and randomly assigned to either divalproex or placebo conditions. Of these, 72 smokers (60% female) who achieved a minimal level of abstinence underwent an in-treatment cue reactivity assessment. Contrary to expectations, divalproex was associated with greater craving and arousal during smoking cue presentation. Divalproex also inhibited cardiovascular response to pleasant cues. Although no significant differences in cessation-related outcomes between divalproex- and placebo-treated participants were observed, cue-elicited craving to smoke predicted end-of-treatment and posttreatment smoking rates. These findings suggest that in-treatment cue reactivity assessment may proactively and dynamically inform ongoing treatment as well as provide a tool for screening potential medications for smoking cessation.

Effects of divalproex on smoking cue reactivity and cessation outcomes among smokers achieving initial abstinence.