What first-line medication is recommended for a patient seeking to quit smoking, considering their overall health status and potential contraindications?

First-Line Medication for Smoking Cessation

Varenicline is the recommended first-line medication for smoking cessation, as it demonstrates superior efficacy compared to all other single pharmacotherapies, increasing quit odds almost 3-fold versus placebo and showing significantly higher abstinence rates than bupropion or single forms of nicotine replacement therapy. 1, 2

Primary Pharmacotherapy Options

The evidence clearly establishes a hierarchy of effectiveness:

• Varenicline is the most effective single agent, with continuous abstinence rates of 43.9% at weeks 9-12 versus 29.8% with bupropion and 17.6% with placebo 1
• Combination NRT (nicotine patch plus short-acting NRT like gum or lozenge) is equally recommended as a primary therapy option 2
• Bupropion SR should be reserved for patients who have failed or cannot use varenicline or combination NRT 2

Varenicline Dosing Protocol

Start varenicline 1-2 weeks before the quit date using the following titration schedule to minimize nausea: 1

• Days 1-3: 0.5 mg once daily
• Days 4-7: 0.5 mg twice daily
• Weeks 2-12: 1 mg twice daily (target dose)

For patients who successfully quit during the initial 12 weeks, prescribe an additional 12-week course (total 24 weeks) to significantly increase long-term abstinence rates. 1

Critical Contraindications and Safety Monitoring

Absolute contraindications for varenicline: 1, 3

• History of serious hypersensitivity or skin reactions to varenicline
• Brain metastases or active seizure disorder (due to seizure risk)

Monitor for neuropsychiatric symptoms throughout treatment, including: 1, 3

• Depression, suicidal ideation/behavior
• Agitation, behavioral changes
• Psychosis, hallucinations, paranoia

However, the large EAGLES trial found no significant increase in neuropsychiatric events with varenicline compared to nicotine patch or placebo, supporting its safety profile even in patients with psychiatric history. 1

Common Side Effects and Management

Nausea occurs in 28-40% of patients, typically peaks in weeks 1-2, and diminishes over time. 1 The titration schedule specifically addresses this dose-dependent effect. 1

Other common effects include insomnia (14%) and abnormal dreams (10-13%). 1

For patients who cannot tolerate the target dose, flexible dosing between 0.5 mg/day and 1 mg twice daily may reduce adverse effects while maintaining efficacy. 4, 1

Alternative First-Line Options

Combination NRT

If varenicline is contraindicated or not tolerated, prescribe combination NRT: 2

• 21 mg nicotine patch (long-acting) PLUS
• Short-acting NRT (gum, lozenge, or inhaler) for breakthrough cravings
• Duration: minimum 12 weeks, can extend to 6-12 months 2

Combination NRT is more effective than single NRT forms. 2

Bupropion SR

Reserve bupropion for patients who failed or cannot use preferred therapies: 2

• Days 1-3: 150 mg once daily
• Days 4 through 12 weeks: 150 mg twice daily

Bupropion contraindications: 5

• Seizure disorder or conditions lowering seizure threshold
• Eating disorders (anorexia, bulimia)
• Concurrent MAO inhibitor use
• Abrupt alcohol or benzodiazepine discontinuation
• Concurrent tamoxifen use

Essential Behavioral Support Integration

Pharmacotherapy must always be combined with behavioral counseling for optimal outcomes. 4, 1, 2 This combination increases cessation rates from approximately 8% to 14% compared to usual care. 2

Provide a minimum of 4 counseling sessions during the 12-week pharmacotherapy course: 1

• First session within 2-3 weeks of starting medication
• Sessions should last 10-30+ minutes
• Include skills training, social support, and motivational interviewing

Follow-Up Schedule

Arrange follow-up within 2-3 weeks after starting pharmacotherapy to assess: 1, 2

• Smoking status
• Medication side effects and tolerability
• Need for dose adjustments

Additional follow-up at minimum 12-week intervals during therapy and after completion. 1, 2

Management of Treatment Failure

If the patient fails to quit or relapses: 4, 1

1. First approach: Try a different first-line medication not previously used (e.g., switch from varenicline to combination NRT or vice versa) 4
2. Second approach: Use combination therapy (e.g., varenicline plus NRT, or combination NRT plus bupropion) 4
3. Third approach: Extend treatment duration beyond 12 weeks 4

Before restarting therapy, identify and address factors contributing to failure: 1

• Inadequate behavioral support
• Living/working with smokers
• Alcohol or substance use
• Untreated depression or anxiety
• Insufficient medication dosing

Special Populations

Patients with cardiovascular disease: NRT and varenicline can be used safely, with no significant increase in cardiovascular adverse events. 1, 2

Patients with psychiatric disorders: Both varenicline and bupropion have been shown safe in large clinical trials, though monitoring remains essential. 1

Pregnant smokers: NRT is almost certainly safer than continued smoking, with oral forms (gum, lozenge) preferable to patches due to more rapid nicotine clearance if problems arise. 2

Severe renal impairment (CrCl <30 mL/min): Start varenicline at 0.5 mg once daily, titrate to 0.5 mg twice daily maximum. 3

Comparative Efficacy Summary

At 52 weeks, abstinence rates demonstrate clear superiority: 1, 6

• Varenicline: 21.8-23%
• Bupropion: 14.6-16.2%
• Nicotine patch: 15.7%
• Placebo: 9.4-10.3%

The combination of varenicline or combination NRT with behavioral counseling represents the most effective evidence-based approach to smoking cessation. 6