The single most impactful preventive intervention in medicine. Smoking cessation reduces all-cause mortality more than any drug you will ever prescribe. Ask every patient, every visit. Combination NRT + varenicline has the highest quit rate.
๐ญ Pharmacotherapy
5 A's Framework
Ask -about tobacco use at every visit
Advise -to quit in a clear, personalized way ("Quitting is the single best thing you can do for your health")
Assess -willingness to make a quit attempt
Assist -offer medication + counseling (combination is most effective)
Arrange -follow-up within 1 week of quit date
Agent
Dose
Quit Rate
Notes
Varenicline (Chantix) MOST EFFECTIVE
0.5 mg daily ร 3 days โ 0.5 mg BID ร 4 days โ 1 mg BID ร 12 weeks. Can extend to 24 weeks.
~30% at 1 year
Partial nicotine receptor agonist (reduces craving + blocks reward from smoking). FDA removed black box warning for neuropsych eventsEAGLES, 2016 -safe even in psychiatric patients. Start 1 week before quit date. GI side effects (nausea -take with food). Can combine with NRT for even higher efficacy.
Apply to clean, hairless skin, rotate sites. Combine patch (sustained) + lozenge or gum (acute cravings) for best results -combination NRT is as effective as varenicline.
NRT -gum/lozenge
2 mg or 4 mg (if first cigarette within 30 min of waking โ 4 mg). Use q1โ2h PRN.
~15โ20%
Best as add-on to patch for breakthrough cravings. Gum: "park and chew" technique. Lozenge: dissolve in mouth, don't chew.
Bupropion SR (Zyban)
150 mg daily ร 3 days โ 150 mg BID ร 12 weeks. Start 1โ2 weeks before quit date.
~20%
Also treats depression. Contraindicated in seizure disorders, eating disorders, MAOI use. Weight-neutral (unlike most cessation -patients often gain 5โ10 lbs). Can combine with NRT.
Highest quit rates: Varenicline + NRT patch (~35%), Varenicline alone (~30%), Combination NRT (patch + gum/lozenge, ~28%), Bupropion + NRT (~25%). All superior to counseling alone (~5โ10%). Always combine pharmacotherapy with behavioral counseling (quitline: 1-800-QUIT-NOW).
๐ On Rounds
Pimp Questions
A patient says 'I've tried quitting before and it didn't work.' How do you respond?
This is actually encouraging, not discouraging. Most successful quitters have tried 6โ8 times before finally quitting permanently. Each attempt teaches the patient about their triggers, cravings, and what strategies work or don't work for them. The response: 'That's actually great -it means you've been working at this. Most people need several attempts. Let's figure out what happened last time and try a different approach.' Then assess
Why is varenicline more effective than NRT alone?
Varenicline (Chantix) is a partial agonist at the ฮฑ4ฮฒ2 nicotinic acetylcholine receptor -the same receptor that nicotine binds. It works through a dual mechanism: (1) Agonist effect (~50% activation): provides a low level of dopamine release in the nucleus accumbens โ reduces craving and withdrawal symptoms (similar to NRT but via the same receptor)
What is the evidence for combining varenicline with NRT patch?
Combination therapy (varenicline + NRT patch) is the most effective smoking cessation strategy. A meta-analysis and the VARNIC trial showed ~35-40% quit rates at 12 weeks (vs ~25% for varenicline alone, ~20% for NRT alone, ~5-10% for counseling alone).
What does the USPSTF say about e-cigarettes/vaping for smoking cessation?
USPSTF has NOT endorsed e-cigarettes for cessation -evidence is insufficient. While some studies show higher quit rates with e-cigs vs NRT (particularly the UK NIHR trial), concerns remain: (1) Dual use: many smokers vape AND smoke โ no net benefit. (2) Long-term safety unknown: EVALI outbreak (2019) raised concerns, though most cases were linked to THC/vitamin E acetate, not nicotine e-cigs
Clinical Examples
๐ Case 1, Varenicline + Behavioral Counseling
Patient: 54M, 35-pack-year smoker, COPD, HTN. Failed NRT patch ร 2 prior attempts. Motivated to quit (Prochaska: preparation stage). No history of seizures or psychiatric illness.
Key findings: High nicotine dependence (Fagerstrรถm score 7/10), multiple prior failures with NRT alone. Combination pharmacotherapy + counseling has highest quit rates.
Management:
Varenicline 0.5 mg daily ร 3 days โ 0.5 mg BID ร 4 days โ 1 mg BID ร 12 weeks (most effective single agent, 33% quit rate vs 14% placebo)
Set quit date 1-2 weeks after starting (allows drug to reach steady state)
Behavioral counseling: 1-800-QUIT-NOW (quitline doubles quit rates when combined with meds)
Consider combo: varenicline + nicotine patch (JAMA 2014: combo superior to varenicline alone)
Warn: nausea (most common side effect, take with food). Vivid dreams. Psychiatric monitoring
Teaching point: Varenicline is the most effective single cessation agent. The old FDA black box warning for psychiatric events was REMOVED in 2016 after the EAGLES trial showed no increased risk. Do not withhold from patients with psychiatric history.
๐ Case 2, Inpatient Smoking Cessation After ACS
Patient: 48M admitted for NSTEMI, underwent PCI. 25-pack-year smoker. Currently nicotine-deprived and motivated. Asking about quitting.
Key findings: Hospitalization for ACS is a "teachable moment", quit rates are highest when cessation is initiated during admission. Continued smoking post-ACS doubles the risk of recurrent MI and death.
Management:
Start NRT in hospital: nicotine patch 21 mg/day + nicotine lozenge 2 mg PRN (combo NRT during admission)
Add varenicline before discharge if no contraindication (start during admission โ continue outpatient)
Brief motivational interviewing: "How important is quitting to you on a scale of 1-10? What would make it higher?"
Arrange follow-up: smoking cessation clinic or quitline within 1 week of discharge
Document smoking status and cessation plan in discharge summary
Teaching point: Every admission is an opportunity. The 5 A's: Ask (smoking status), Advise (quit), Assess (readiness), Assist (meds + counseling), Arrange (follow-up). NRT is safe in ACS, nicotine from patches causes far less cardiovascular harm than nicotine from cigarettes.
๐ Case 3, Pregnant Smoker
Patient: 28F, 10-pack-year smoker, newly pregnant (8 weeks). Smoking 10 cigarettes/day. Concerned about harm to baby but unable to quit cold turkey.
Key findings: Smoking during pregnancy: risk of preterm birth (2ร), low birth weight, placental abruption, SIDS, and childhood asthma. Behavioral counseling is first-line in pregnancy. Pharmacotherapy options are limited.
If counseling alone fails: nicotine patch (lowest effective dose), benefits of quitting likely outweigh NRT risks, but discuss shared decision-making
Varenicline and bupropion are NOT recommended in pregnancy (insufficient safety data)
Motivational framing: "Quitting before 15 weeks eliminates most of the excess risk to your baby"
Postpartum relapse prevention, 70% of women who quit during pregnancy relapse within 6 months postpartum
Teaching point: Behavioral counseling is first-line for pregnant smokers. NRT can be used if counseling fails, the risk of continued smoking far outweighs NRT risk. The critical window is quitting before 15 weeks, which nearly eliminates the excess risk of preterm birth and low birth weight.
๐ฃ Sample Presentation
One-Liner
"Ms. Davis is a 52-year-old with 30-pack-year smoking history, COPD, and HTN. She wants to quit but has tried cold turkey twice and relapsed within 2 weeks both times. Ready to try medication."
Key Points to Cover on Rounds
Pack-year: 30. Prior quit attempts: 2 (cold turkey -no pharmacotherapy). Stage of change: preparation (ready to set quit date). Pharmacotherapy plan: varenicline 0.5 mg daily ร 3 days โ 0.5 mg BID ร 4 days โ 1 mg BID (start 1 week before quit date, continue ร 12 weeks). Added NRT patch 21 mg/day for combination therapy (varenicline + NRT = highest quit rate ~35%). Quit date set: 2 weeks from today. Behavioral counseling: quitline referral (1-800-QUIT-NOW), trigger avoidance strategies discussed. LDCT lung cancer screening: eligible (50-80 yo, โฅ20 pack-years) -ordered. Plan: follow-up call at 1 week post-quit date, office visit at 4 weeks.
๐ Overview
Overview
See the tabs above for the complete smoking cessation reference: Workup, Management, Medications, Rounds, Summary, and One Pager.
๐งช Workup
Workup
See the Overview and Management tabs for the smoking cessation assessment framework (5 A's, Ask, Advise, Assess, Assist, Arrange; pack-year history; readiness-to-quit stages; triggers; co-morbid psychiatric/substance use).
โก Management
Management
See the Management tab for the full stepwise smoking cessation algorithm, behavioral counseling + pharmacotherapy combinations, follow-up timing, and relapse management.
๐ Medications
Medications
Medication details (varenicline, bupropion, NRT combinations, patch + gum/lozenge) with evidence-based dosing and trial citations are in the Management tab.