The four evidence-based options — NRT, varenicline, bupropion, and cytisine — all beat placebo. Choosing between them is about medical history, cost, and what you have tried before.
Effect size (Cochrane 2023 network meta-analysis)
Roughly ordered:
- Varenicline
- Combination NRT (patch + short-acting)
- Cytisine (comparable to varenicline in the 2024 head-to-head)
- Bupropion + NRT combined
- Single-form NRT
- Bupropion alone
- Placebo
The gap between varenicline and single-form NRT is meaningful; the gap between varenicline and combination NRT is small.
Side-effect comparison
| Medication | Common | Serious concerns |
|---|---|---|
| Varenicline | Vivid dreams, mild nausea | Mood changes rare; boxed warning removed 2016 |
| Bupropion | Insomnia, dry mouth | Seizures (dose-related), contraindicated in seizure/eating disorders |
| Cytisine | GI upset, mild insomnia | Very few |
| NRT | Skin irritation, hiccups, mouth soreness | Rare; safer than continued nicotine use |
Cost comparison (rough US 2026 out of pocket, generic)
| Medication | Full course |
|---|---|
| Varenicline (12 wk) | $150-400 |
| Bupropion SR (12 wk) | $50-150 |
| Cytisine (25 d) | Not available in US as FDA-approved |
| NRT (12 wk combination) | $150-300 |
All four are typically fully covered by ACA-compliant US insurance and by NHS Stop Smoking Services in the UK.
Decision guide
- First attempt, no contraindications: varenicline (or cytisine where available).
- Concurrent depression / ADHD: bupropion.
- Seizure or eating disorder history: avoid bupropion; choose varenicline, cytisine, or NRT.
- Recent MI / unstable angina: clinician-supervised NRT or varenicline; delay bupropion.
- Previous failed cold-turkey quit: add a medication.
- Previous failed NRT quit: try varenicline or cytisine.
- Previous failed varenicline quit (efficacy): combination NRT or bupropion.
See getting a prescription for how to open the conversation with a clinician.
