Rationale The effectiveness of varenicline for smoking cessation has been established, but little is known about the psychological processes that mediate this clinical outcome. Objectives This study evaluated the effect of a single dose of varenicline on tonic and cue-provoked changes in craving, withdrawal, and affect using a randomized, double-blind, placebo-controlled, cross-over design. Methods Following overnight abstinence, 38 non-treatment-motivated smokers received either varenicline 2 mg or matched placebo, then tonic measures of craving, withdrawal, and positive and negative affect were obtained at 30-minute intervals. At 4-hours post-administration, a cue exposure session obtained the same subjective measures at three time-points following the physical handling of a lit cigarette versus the sharpening and handling of a pencil. Results At 4-hours post-administration, varenicline reduced tonic craving as well as craving across the smoking and neutral cue conditions, relative to placebo. By contrast, the capacity of the smoking cue to enhance craving relative to the neutral cue was unaffected by varenicline. Measures of withdrawal and positive and negative affect produced mixed results. Conclusions Acute varenicline selectively attenuates tonic but not cue-provoked craving. This dissociation provides insight into the specific psychological processes that might mediate the effectiveness of varenicline, and highlights cue-provoked craving as a discrete target for advancing smoking cessation pharmacotherapy.

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Associate Editor Michael G. Wyllie Editorial Board Ian Eardley, UK Jean Fourcroy, USA Sidney Glina, Brazil Julia Heiman, USA Chris McMahon, Australia Bob Millar, UK Alvaro Morales, Canada Michael Perelman, USA Marcel Waldinger, Netherlands OBJECTIVE To evaluate the effect of sildenafil citrate on each item of the 14‐item Self‐Esteem And Relationship (SEAR) questionnaire, which is used to measure self‐esteem, confidence, satisfaction with sexual relationship, and overall relationship satisfaction in men with erectile dysfunction (ED). PATIENTS AND METHODS Data were combined from two 12‐week, double‐blind, placebo‐controlled, flexible‐dose sildenafil trials having identical protocols, one conducted in the USA and the other in Mexico, Brazil, Australia and Japan. All men had ED and were aged ≥18 years. Response categories of each SEAR item used a 4‐week reference period and were based on a five‐point scale (1, almost never/never; 2, a few times; 3, sometimes; 4, most times; 5, almost always/always). The difference (sildenafil vs placebo) in the change from baseline to week 12 was evaluated with a Wilcoxon rank sum test using ridit analysis, and an analysis of covariance model that included treatment group, centre, study and baseline item score. RESULTS Compared with the 274 patients receiving placebo, the 279 receiving sildenafil reported significantly greater mean and median improvements (P < 0.001) in each of the 14 SEAR items. The probability of increased psychosocial benefit from baseline to week 12 was higher with sildenafil for each SEAR item, and ranged from 0.60 (‘My partner was unhappy with the quality of our sexual relations’[item reverse‐scored]) to 0.72 (‘I was satisfied with my sexual performance’). Across all items, the mean (sd) probability was 0.67 (0.04) that a randomly selected patient in the sildenafil group would have a more favourable change relative to a randomly selected patient in the placebo group. CONCLUSIONS Sildenafil produced substantial and meaningful improvements at the item‐specific level. This analysis complements previously published work on self‐esteem, confidence and relationship satisfaction.

Erectile dysfunction (ED) negatively impacts self-esteem and relationship satisfaction. The Self-Esteem and Relationship (SEAR) questionnaire is a validated, ED-specific, patient-reported instrument that specifically addresses self-esteem and relationship issues within the context of ED. Effective ED treatment with sildenafil in a double-blind, placebo-controlled clinical trial conducted in Brazil, Mexico, Australia and Japan showed pooled cross-cultural improvements in self-esteem, confidence and relationship satisfaction. This report focuses on the results from the subgroup of men from nine Mexican centers who participated in the multinational study. A total of 95 men aged X18 years with clinically diagnosed ED and currently in a stable relationship were randomized to placebo (n ¼ 47) or sildenafil (n ¼ 48). The SEAR results for Mexican men showed that sildenafil treatment led to significant improvements in self-esteem, confidence and relationship satisfaction. These data support an earlier study showing that Latin American men taking sildenafil have similar safety and efficacy profiles compared to non-Latin counterparts.