Validation of a paradigm for screening medications for nicotine dependence.

A33

Research to improve pharmacotherapy for nicotine dependence is hindered by a lack of validated early screening paradigms to predict likely efficacy in the clinical setting. This within-subject behavioral pharmacology study sought to validate a paradigm to assess medication effects on smoking relapse following a programmed lapse (based on the paradigm by Juliano, Stitzer and colleagues). Using varenicline as a positive control, 48 smokers completed two 21-day experimental phases separated by a ≈7-day wash-out period. Treatment order (varenicline vs. placebo) was randomized. Each experimental period included medication run-up (days 1-10), monitored abstinence (days 11-13), programmed smoking lapse (day 14), and observation days (15-21) during which participants were encouraged to stay quit. The primary outcomes were number of days abstinent during the 7-day observation period and 7-day abstinence, both confirmed by CO. Secondary outcomes were changes in negative affect, smoking urges, and withdrawal symptoms during monitored abstinence (day 13 - day 10). In the mixed effects model of number of days to relapse, there was a significant drug by order interaction (p<.01). Among participants receiving varenicline first, mean days to relapse were 4.1 and 5.0 for the varenicline and placebo phases, respectively; among those receiving placebo first, mean days to relapse were 4.7 and 2.7 for varenicline and placebo. There was also was a significant drug by order interaction for 7-day abstinence (p<.01). Among participants receiving varenicline first, abstinence rates were 48% for varenicline and 62% for placebo, respectively; among those receiving placebo first, rates were 52% for varenicline and 22% for placebo. Main effects of treatment were observed for abstinence-induced changes in negative affect (p<.01), and total withdrawal symptoms (p<.05); effects on smoking urges were marginal (p=.08). These data indicate that this paradigm is sensitive to medication effects on abstinence; however, the observed drug by order interaction suggests that a between-subjects design may be preferable for early screening of medication effects on abstinence.
 >Funding for this study was provided by AstraZeneca and a grant from NCI and NIDA (P50 CA/DA84718). *Corresponding Author