Indications and clinical context
Pharmacological treatment for smoking cessation significantly increases abstinence rates, particularly in smokers with moderate to high dependence. The main classes currently recommended include nicotine replacement therapy (NRT), varenicline, cytisinicline and bupropion. The choice should take into account the patient’s clinical profile, comorbidities, individual preferences and previous experience with quit attempts.
Nicotine replacement therapy (NRT)
NRT can be used as monotherapy or in combination. Patches provide continuous nicotine delivery throughout the day, while short-acting formulations — gum, lozenges or spray — help control cravings and triggering situations. Combining a patch with a rapid-acting formulation is more effective than monotherapy. NRT is generally well tolerated and can be used in most patients with stable cardiovascular disease, and should only be avoided in the presence of very recent cardiovascular events. Situations such as uncontrolled hypertension, pregnancy or adolescence require careful consideration and possible monitoring.
Varenicline
Varenicline is a partial agonist of nicotinic receptors and has high efficacy as monotherapy. It requires titration for one to two weeks before the planned quit date. The most common adverse effects include nausea, insomnia and vivid dreams. Current data do not show a significant increase in serious psychiatric events, but monitoring is recommended in patients with major psychiatric history. Extended treatment may be useful in cases of high dependence or previous relapses.
Cytisinicline
Cytisinicline, also a partial nicotinic agonist, is used in a 25-day regimen with progressive dose reduction, requiring the patient to stop smoking by the fifth day of treatment. It has efficacy similar to varenicline and is often superior to NRT or bupropion. The most frequent adverse effects include mild gastrointestinal symptoms, headache and irritability. Hypertension, diabetes and stable cardiovascular disease are considered precautionary situations rather than absolute contraindications.
Bupropion
Bupropion acts on noradrenaline and dopamine reuptake and may be particularly useful in patients with depressive symptoms or concerns about weight gain. It is contraindicated in situations that increase seizure risk, including epilepsy, a history of anorexia or bulimia, or recent withdrawal from alcohol or benzodiazepines. In patients with high dependence, it may be combined with NRT.
Combination strategies
Several combinations provide additional benefit in abstinence, particularly long-acting NRT with a rapid-acting formulation, and NRT with varenicline or bupropion in selected patients. The absence of clear therapeutic gain supports avoiding routine combination of varenicline with bupropion.
Behavioural intervention
Pharmacological treatment should be integrated with structured behavioural intervention. Techniques such as brief counselling, scheduled follow-up and education about cravings and relapse prevention significantly increase the overall effectiveness of smoking cessation strategies.
Follow-up and relapse prevention
After cessation, clinical monitoring should focus on managing withdrawal symptoms, providing motivational support and identifying relapse triggers early. Treatment extension or switching to another drug class may be necessary in high dependence, relapse or partial response. The decision should be individualised and guided by tolerability, preference and comorbidities.
