New medications for nicotine dependence treatment

For several years, nicotine replacement therapy (nicotine gum, patches, and nasal spray) has been the mainstay for the treatment of nicotine dependence. The nicotine vapor inhaler is a new pharmacological adjunct shown to be effective in placebo-controlled trials. It delivers a vaporized form of nicotine to the oral mucosa. Bupropion sustained release (SR) is the first non-nicotine pharmacological treatment approved for smoking cessation and is thought to be effective because of its dopaminergic activity on the pleasure and reward pathways in the mesolimbic system and nucleus accumbens. Though few studies have been reported, there is pharmacological rationale to use combined pharmacotherapies for the treatment of nicotine dependence. While there are a limited number of reported studies with mixed findings using higher than the standard nicotine patch dose, use of higher doses of nicotine patch therapy (i.e., more than one patch at a time) may be appropriate for smokers who previously failed single dose patch therapy or in those whose nicotine withdrawal symptoms were not adequately relieved with standard therapy. The concept of therapeutic drug monitoring can be applied to nicotine replacement therapy. A new product, a sublingual nicotine tablet, has shown efficacy in a double-blind placebo-controlled trial and will likely be approved in the future. The anti-hypertensive, mecamylamine, has been found to have efficacy for smoking cessation in a small trial. Nicotine and mecamylamine both occupy receptors that would otherwise be acted upon by nicotine from cigarettes, thus, when administered in combination, would be expected to occupy more receptors than either drug alone, thereby attenuating smoking reward and facilitating extinction of the smoking behavior. Pivotal trials of this combination are underway. Remaining questions include: (1) what is the optimal dose and duration of treatment using nicotine replacement therapy? (2) What is the optimal duration of treatment using bupropion? (3) What are the best combination treatments and which smokers are best suited for combination treatment? (4) Will other similar pharmacological agents with dopaminergic/noradrenergic activity have efficacy similar to bupropion?