What are the recommended medications for smoking cessation?

Recommended Medications for Smoking Cessation

Varenicline is the most effective first-line medication for smoking cessation, followed by combination nicotine replacement therapy (nicotine patch + short-acting NRT), and bupropion with or without NRT as alternative options. 1, 2

First-Line Medications

1. Varenicline (Preferred Primary Therapy)

• Dosing regimen:
  • Initiate 1-2 weeks prior to quit date
  • Days 1-3: 0.5 mg once daily
  • Days 4-7: 0.5 mg twice daily
  • Weeks 2-12: 1 mg twice daily (if tolerated)
• Efficacy: Significantly higher abstinence rates compared to bupropion and nicotine replacement therapy 1, 3
• Key considerations:
  • Nausea is common (affects ~30% of patients) and may require management 2, 4
  • Contraindicated in patients with brain metastases due to seizure risk 1, 2
  • Acts as a partial agonist/antagonist at α4β2 nicotinic acetylcholine receptors 4, 5

2. Combination Nicotine Replacement Therapy (NRT)

• Components:
  • Long-acting: Nicotine patch (21 mg for smokers of >10 cigarettes/day)
  • Short-acting: Gum, lozenge, inhaler, or nasal spray
• Dosing approach:
  • Apply one patch daily to clean, dry skin
  • Use short-acting NRT as needed for breakthrough cravings
  • If 21 mg patch ineffective, consider increasing to 35 or 42 mg 1
• Key considerations:
  • Doubles the chance of successful smoking cessation 2
  • Lower risk of side effects compared to varenicline and bupropion 2
  • Risk of nicotine toxicity is rare, even when used with smoking 1

3. Bupropion ± NRT

• Dosing regimen:
  • Initiate 1-2 weeks prior to quit date
  • Days 1-3: 150 mg once daily
  • Day 4-12 weeks: 150 mg twice daily (if tolerated)
  • Maximum 300 mg per day
• Key considerations:
  • Contraindicated in patients with seizure risks (stroke, brain metastases) 1, 2
  • Common side effects: dry mouth, insomnia, headaches, nausea 1, 6
  • May be particularly beneficial for patients with depression history 1

Comparative Efficacy

1. Varenicline vs. Bupropion:

   • Varenicline shows significantly higher continuous abstinence rates at 12,24, and 52 weeks 3
   • Odds ratio for abstinence with varenicline vs. bupropion at 52 weeks: 1.60 (95% CI: 1.22-2.12) 3

2. Varenicline vs. NRT:

   • Higher continuous abstinence rate at 52 weeks (25.9% vs 19.8%, p=0.040) 4

3. Combination NRT vs. Single NRT:

   • Higher success rates with combination therapy 2

Treatment Duration and Follow-up

• Standard treatment duration: 12 weeks for all pharmacotherapies 1, 2
• May extend therapy to 6 months-1 year to promote continued abstinence 1
• Follow-up within 2-3 weeks of starting therapy to assess efficacy and side effects 2
• Continue periodic monitoring at minimum 12-week intervals 2

Safety Considerations

1. Neuropsychiatric Safety:

   • Large EAGLES trial (n=8,144) found no significant increase in neuropsychiatric events with varenicline or bupropion compared to nicotine patch or placebo 1
   • Monitor for development or worsening of depression and suicidal ideation 1, 2

2. Cardiovascular Safety:

   • Systematic reviews have not identified significant link between varenicline and increased cardiovascular risks 1
   • NRT can be used safely in patients with coronary heart disease 2

3. Drug Interactions:

   • Varenicline does not inhibit cytochrome P450 enzymes, limiting drug interactions 7
   • No clinically meaningful interactions identified with digoxin, warfarin, metformin, or cimetidine 7

Algorithm for Medication Selection

1. First choice: Varenicline (if no contraindications)
2. If varenicline contraindicated or not tolerated: Combination NRT
3. If both varenicline and combination NRT unsuccessful or contraindicated: Bupropion ± NRT
4. Special populations:
   • Depression history: Consider bupropion
   • Cardiovascular disease: Any option (with monitoring)
   • Seizure risk/brain metastases: Avoid varenicline and bupropion; use NRT

Common Pitfalls to Avoid

1. Inadequate treatment duration: Continuing for less than 12 weeks reduces success rates
2. Improper dosing: Failure to titrate varenicline properly increases nausea risk
3. Monotherapy NRT: Less effective than combination NRT
4. Lack of follow-up: Monitoring is essential to manage side effects and adjust treatment
5. Overlooking contraindications: Particularly seizure risk with varenicline and bupropion
6. Stopping medication too early after achieving abstinence: Continuing medication reduces relapse risk

Remember that despite the efficacy of these medications, continuous abstinence rates remain relatively low (18-30% with varenicline vs. 4-10% with placebo at one year) 5, highlighting the importance of comprehensive treatment including behavioral support alongside pharmacotherapy.