Int. J. Environ. Res. Public Health 2009, 6 215 consumption [63, 64]. Varenicline might diminish withdrawal symptoms through an agonist effect and reduce craving through an antagonist effect; with nicotine exposure, the receptor occupancy of varenicline is expected to block the reinforcing effects of nicotine [65]. The most common side effect associated with varenicline is nausea. Other side effects include insomnia and abnormal dreaming [66, 67]. Recently, several trials have demonstrated the effectiveness of varenicline, in improving cessation rates [65, 66, 68-70]. Bupropion has been compared with varenicline in recent head-to-head randomized controlled trials [66, 68, 70]. These trials consistently favored varenicline. After pooling these data, it was found that rates of smoking abstinence associated with varenicline were about twice those associated with bupropion. However, from the time of initial trials, varenicline has been associated with significant psychiatric adverse effects [71]. Recently the FDA issued two Med Watch advisories regarding reports of behavioral changes in patients taking varenicline. These have included erratic behavior, new onset of depressed mood, agitation, suicidal ideation, suicidal attempts, and completed suicides within days to weeks of initiating varenicline. Not all the individual affected had pre-existing histories of psychiatric illness [72]. There have been two recent published case reports of varenicline exacerbating symptoms of schizophrenia [73] and inducing a manic episode in a patient with bipolar disorder [74]. As mentioned, varenicline displaces nicotine from acetylcholine receptors, which in turn produces low to moderate levels of dopamine release, and stimulates the central nervous mesolimbic dopamine system. This may upset the balance in cholinergic-adrenergic tone, which has been implicated in the physiology of mania [71]. In summary varenicline seems to be the most effective of the available pharmacological agents for smoking cessation; however, the extensive exclusion criteria for most of these trials, the substantially different losses to follow up between groups, and the fact that most of these trial are funded by the industry might affect the trustworthiness and generalizability of these results [43]. Despite the early efficacy of these pharmacotherapies, the number of patients that remain abstinent from smoking at 1 year follow-up is low. Most of the randomized controlled trials report a point prevalence of abstinence at 12 months to be well under 30% among patients in the treatment groups. With continuous abstinence as the outcome measure, the rate of abstinence is even lower [64]. 8. Nonpharmacologic Treatment Nonpharmacologic cessation strategies include brief interventions, such as patient education and advice, behavioral therapy, self-help materials, and telephone counseling [65]. A review of randomized or quasi-randomized trials of individual behavioral counseling for smoking cessation by trained therapists with 6 months or longer follow-up indicated that individual counseling was more effective than no intervention at all. Counseling usually consists of one or more face-to-face sessions, often accompanied by telephone contact for support [66]. Evidence shows that group counseling is more effective than self-help and other less intensive intervention methods for smoking cessation [77]. It is unclear if group counseling is more effective than individual counseling, but it is more effective than no intervention [78]. Self-help materials might improve quit rates among smokers compared with those who receive no intervention, but the effect is generally small [79]. Proactive telephone counseling, in