Efficacy of pharmacotherapy for nicotine dependence: A narrative analysis of contemporary evidence

Abstract

Nicotine dependence is a chronic relapsing disorder, and pharmacotherapy increases the likelihood of long-term abstinence. The aim was to compare the mechanisms of action and efficacy of contemporary pharmacological options for smoking cessation. A targeted narrative review was conducted by searching PubMed/MEDLINE, the Cochrane Library, and World Health Organization documents published from January 2018 to July 2026. Search terms were "nicotine dependence", "smoking cessation", "nicotine replacement therapy", "bupropion", "varenicline", and "cytisine". Priority was given to guidelines, systematic reviews, and meta-analyses evaluating abstinence at six months or longer. The analysed options were nicotine replacement therapy (NRT), the α4β2 nicotinic acetylcholine receptor partial agonists varenicline and cytisine, and bupropion, an inhibitor of neuronal norepinephrine and Dopamine reuptake. Compared with placebo or no pharmacotherapy, long-term abstinence was more likely with NRT (risk ratio [RR] 1.55; 95% confidence interval [CI] 1.49-1.61), bupropion (RR 1.60; 95% CI 1.49-1.72), varenicline (RR 2.32; 95% CI 2.15-2.51), and cytisine (RR 2.61; 95% CI 1.50-4.67). Combination NRT, a patch plus a short-acting formulation, was more effective than monotherapy (RR 1.25; 95% CI 1.15-1.36). Varenicline was more effective than bupropion and single-form NRT, while no clear difference was found compared with combination NRT. The findings confirm the efficacy of all analysed medications, with larger effects for varenicline and cytisine versus control. Treatment should be individualized according to contraindications, tolerability, previous quit attempts, and medicine availability, with concurrent behavioural support.