Pharmacological treatments for tobacco dependence

There are currently three licensed therapies for smoking cessation: nicotine replacement (NR), bupropion and varenicline. NR can be indicated for: 1) aid in abrupt cessation; 2) gradual reduction in order to quit smoking; 3) temporary abstinence; and 4) smoking reduction maintenance. A meta-analysis has found that the relative risk of abstinence for any form of NR relative to control was 1.6. It has been found that starting NR treatment 1–3 weeks before smoking cessation and combining NR products, usually patch and gum, increases efficacy. Recently some new nicotine administration forms, i.e. lozenge, mouth spray and a pouch, have been developed. They seem to have the potential to relieve cravings faster than the current high-dose gum, and also be more preferred. Varenicline is a selective partial agonist at the α 4 β 2 nicotinic acetylcholine receptors (nAChR). It decreases cravings and alleviates the symptoms of withdrawal. It can also reduce the rewarding and reinforcing effects of nicotine. Trials have shown varenicline to have increased efficacy relative to bupropion. Varenicline has also been compared with NR (21 mg transdermal patch) in one randomised study. Abstinence at the end of treatment at 12 weeks was significantly increased for varenicline (56%) compared with for nicotine patch (43%). Some post-marketing reports have expressed concern about psychiatric adverse effects, such as aggression, depression and suicides. The European Medicines Agency and the Food and Drug Administration of the USA are monitoring reported side-effects, but so far no confirmed casual relationship between these adverse effects and varenicline has been established. Bupropion inhibits neuronal re-uptake of dopamine and norepinephrine and is an antagonist on the nAChR. Its efficacy, compared with placebo, has been proved in several meta-analyses. A recent study suggests that longer pre-cessation use of bupropion, e.g. for 4 weeks, can improve efficacy results. Under development for the treatment of tobacco dependence are cannabinoid antagonists, immunotherapy against nicotine, monoaminooxidase inhibitors, dopamine receptor D3 receptor antagonists and partial agonists, glutamatergic and GABA-ergic compounds and novel selective nicotine cholinergic receptor agonists and antagonists.