What are the pharmacological options for smoking cessation, including medications such as Nicotine Replacement Therapy (NRT) and non-nicotine prescription drugs like Bupropion (Zyban) and Varenicline (Chantix)?

From the Guidelines

Varenicline is the most effective smoking cessation medication, with a higher cessation rate compared to nicotine replacement therapy (NRT) and bupropion, as evidenced by a 2021 study published in JAMA 1. When it comes to smoking cessation, medications can significantly improve the chances of quitting successfully. The first-line options include:

• Nicotine replacement therapy (NRT)
• Varenicline (Chantix)
• Bupropion (Zyban) NRT comes in various forms, such as patches, gum, lozenges, inhalers, and nasal sprays. Varenicline works by blocking nicotine receptors while partially stimulating them to reduce cravings, and is typically used for 12 weeks. Bupropion helps reduce cravings and withdrawal symptoms, and is usually started 1-2 weeks before the quit date and continued for 7-12 weeks. According to the 2021 study, varenicline was associated with a greater smoking cessation rate over any form of NRT, with eight studies (n = 6264) comparing varenicline and NRT 1. Additionally, six studies (n = 6286) evaluated varenicline vs bupropion SR and found that varenicline was associated with a higher cessation rate 1. Combining medications with behavioral support can significantly increase success rates, as found in a 2012 good-quality systematic review (40 studies; n = 15 021) that showed participants who received combination pharmacotherapy and intensive behavioral counseling had a higher abstinence rate at 6 months or more compared with control participants 1. It is essential to discuss with a healthcare provider which option best suits a specific situation and medical history.

From the FDA Drug Label

Based on varenicline characteristics and clinical experience to date, varenicline has no clinically meaningful pharmacokinetic drug interactions [see Clinical Pharmacology(12.3)]. Safety and efficacy of varenicline in combination with other smoking cessation therapies have not been studied. Bupropion Varenicline (1 mg twice daily) did not alterthe steady-state pharmacokinetics of bupropion (150 mg twice daily) in 46 smokers. The safety of the combination of bupropion and varenicline has not been established Nicotine replacement therapy (NRT) Although co-administration of varenicline (1 mg twice daily) and transdermal nicotine (21 mg/day) for up to 12 days did not affect nicotine pharmacokinetics, the incidence of nausea, headache, vomiting, dizziness, dyspepsia, and fatigue was greater for the combination than for NRT alone

Smoking cessation drugs like varenicline can be used in combination with other therapies, but the safety and efficacy of such combinations have not been fully studied.

• Bupropion: Varenicline does not alter the pharmacokinetics of bupropion.
• Nicotine replacement therapy (NRT): Combination of varenicline and NRT may increase the incidence of adverse events such as nausea and headache. The clinical decision to use varenicline with other smoking cessation therapies should be made with caution, considering the potential risks and benefits 2, 2, 2.

From the Research

Smoking Cessation Drugs

• Smoking cessation drugs, such as bupropion and varenicline, are effective in reducing craving and maintaining abstinence 3, 4, 5, 6.
• Varenicline has been shown to be more effective than bupropion in maintaining abstinence and reducing craving 3, 4, 5.
• Bupropion has been found to be more beneficial than nicotine replacement therapy (NRT) for smokers with a history of depression 6.
• The combination of NRT and bupropion has been found to be no more effective than either treatment alone 6.
• Both bupropion and varenicline have been found to be relatively safe, with no consistent higher risks for acute adverse outcomes such as myocardial infarction, stroke, suicide, and road traffic crashes 7.

Comparison of Bupropion and Varenicline

• Varenicline is a partial agonist at nicotinic alpha4beta2 receptors, while bupropion is a norepinephrine and dopamine reuptake inhibitor 4, 5.
• Varenicline has been found to be more effective than bupropion in reducing craving and maintaining abstinence 3, 4, 5.
• Bupropion has been found to be more beneficial than NRT for smokers with a history of depression 6.

Safety of Smoking Cessation Drugs

• Both bupropion and varenicline have been found to be relatively safe, with no consistent higher risks for acute adverse outcomes such as myocardial infarction, stroke, suicide, and road traffic crashes 7.
• The most common adverse effects of bupropion and varenicline are nausea, insomnia, anxiety, irritability, fatigue, and abnormal dreams, which are usually mild to moderate and can be managed 4.