What is the first‑line pharmacologic regimen for smoking cessation in an adult, including nicotine replacement therapy options and non‑nicotine medications?

First-Line Pharmacologic Regimen for Smoking Cessation in Adults

All adults attempting to quit smoking should receive combination nicotine replacement therapy—a 21 mg/24-hour nicotine patch plus a short-acting form (gum, lozenge, nasal spray, or inhaler)—combined with intensive behavioral counseling for a minimum of 12 weeks. 1, 2

Evidence-Based Treatment Algorithm

Step 1: Initiate Combination NRT as First-Line Therapy

• Combination NRT (patch + short-acting form) achieves 36.5% abstinence at 6 months versus 23.4% for patch alone, representing a 34% increase in quit rates (RR 1.34,95% CI 1.18–1.51). 1, 2
• Start with a 21 mg/24-hour patch for smokers consuming ≥10 cigarettes/day; apply each morning to clean, dry, hairless skin on the upper body or outer arm, rotating sites daily. 1, 2
• For lighter smokers (<10 cigarettes/day), begin with a 14 mg (24-hour) or 15 mg (16-hour) patch. 2

Step 2: Add Short-Acting NRT for Breakthrough Cravings

• Nicotine gum: Use 4 mg for highly dependent smokers (first cigarette within 30 minutes of waking) or 2 mg for lighter smokers; chew slowly until peppery taste emerges, then "park" between cheek and gum for absorption; use 8–12 pieces daily as needed. 1, 2
• Alternative short-acting options (lozenge, nasal spray, inhaler) have similar efficacy to gum and may be substituted based on patient preference. 2
• All single forms of NRT significantly improve cessation rates: gum (RR 1.49), patch (RR 1.64), lozenges (RR 1.95). 1

Step 3: Prescribe Minimum 12-Week Course with Extended Duration Option

• Continue combination NRT for at least 12 weeks for the initial quit attempt; longer duration (>14 weeks) shows superior results to standard 8–12 week courses. 1, 2
• Therapy may be extended to 6–12 months to prevent relapse in patients who remain abstinent but experience persistent cravings. 2

Step 4: Combine with Intensive Behavioral Counseling

• Combination pharmacotherapy plus intensive behavioral counseling increases abstinence from 8.3% to 14.5% (RR 1.82,95% CI 1.66–2.00) compared to usual care or brief advice alone. 1
• Provide at least 4 counseling sessions totaling 91–300 minutes of contact time; greatest effect is seen with 8+ sessions. 1, 2
• Counseling should include practical problem-solving skills, identification of high-risk situations, development of coping strategies, and strong personalized quit advice. 1

Step 5: Schedule Follow-Up Within 2 Weeks

• Arrange follow-up within 2 weeks after starting pharmacotherapy to monitor adherence, manage side effects, and adjust treatment if needed. 1, 2
• Nicotine withdrawal symptoms typically peak within 1–2 weeks of quitting and then subside—encourage continued therapy through brief slips. 2

Alternative First-Line Medications (When NRT Is Contraindicated or Patient Preference)

Varenicline

• Varenicline achieves 28.0% abstinence at 6 months versus 12.0% with placebo (RR 2.27,95% CI 2.02–2.55), making it the most effective single-agent pharmacotherapy. 1
• Standard dosing: 0.5 mg once daily for 3 days, then 0.5 mg twice daily for 4 days, then 1 mg twice daily for 12 weeks. 1
• Varenicline is superior to bupropion SR (RR 0.68 favoring varenicline, 95% CI 0.56–0.83). 1

Bupropion SR

• Bupropion SR achieves 19.7% abstinence at 6 months versus 11.5% with placebo (RR 1.62,95% CI 1.49–1.76). 1
• No significant difference in efficacy between NRT and bupropion SR when used as monotherapy. 1

Escalation Strategy for Treatment Failure

If Combination NRT Fails:

• Switch to varenicline 1 mg twice daily for 12 weeks as the alternative primary therapy. 2
• Alternatively, increase patch dose to 35–42 mg while continuing short-acting NRT. 2
• Ensure behavioral counseling intensity is adequate (≥4 sessions, 91–300 minutes total contact). 1

If Varenicline or Bupropion Fails:

• Add combination NRT (patch + short-acting form) if not already using it. 1, 2
• Consider extending treatment duration beyond 12 weeks. 2

Safety Considerations and Common Pitfalls

Safety Profile

• NRT is safe even in patients with cardiovascular disease; blood nicotine levels from combination NRT remain significantly lower than from smoking cigarettes, making toxicity rare. 2, 3
• Common side effects: local skin reactions from patches, mouth irritation from gum/lozenges, nausea, mood changes, sleep disturbances. 2
• Very few people become addicted to NRT itself; concerns about NRT dependence should not prevent appropriate prescribing. 2

Critical Pitfalls to Avoid

• Inadequate dosing: Ensure patients use sufficient nicotine doses to control withdrawal symptoms; underdosing is a common cause of treatment failure. 2
• Premature discontinuation: Encourage continued therapy for the full 12-week minimum even if patients experience brief slips to smoking. 2
• Monotherapy when combination is indicated: Single-form NRT is substantially less effective than combination therapy; do not prescribe patch alone as first-line treatment. 1, 2
• Failure to combine with behavioral support: Pharmacotherapy alone achieves 18.3% abstinence versus 21.4% when combined with behavioral counseling (RR 1.16,95% CI 1.09–1.24). 1
• Avoiding acidic beverages: Instruct patients to avoid food or beverages 15 minutes before and after using nicotine gum, as acidic drinks interfere with absorption. 2

Special Populations

Pregnant Women

• Intensive behavioral counseling is the only first-line treatment with established safety and effectiveness in pregnancy, increasing cessation from 11% to 15% in late pregnancy. 4
• If counseling fails, intermittent-dose NRT (nicotine gum) may be considered under physician supervision, as NRT is likely safer than continued smoking despite FDA Pregnancy Category D classification. 4
• Bupropion, varenicline, and e-cigarettes are not recommended in pregnancy due to insufficient safety and efficacy data. 4

Cardiovascular Disease

• NRT, varenicline, and bupropion are all safe in patients with established coronary artery disease, including those with recent acute coronary syndromes when used under physician supervision. 2, 5
• Do not discontinue NRT during acute viral illnesses (e.g., influenza); abrupt cessation can provoke nicotine-withdrawal-related sympathetic activation. 2